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{\f234\fscript\fcharset0\fprq2{\*\panose 03080302020302020206}Gradl;}{\f235\fdecor\fcharset0\fprq2{\*\panose 04040505050a02020702}Harrington;}{\f236\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Holidays MT;}
{\f237\fdecor\fcharset0\fprq2{\*\panose 04020605060303030202}Imprint MT Shadow;}{\f238\fdecor\fcharset0\fprq2{\*\panose 04040403040a02020202}Juice ITC;}{\f239\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Keystrokes MT;}
{\f240\fdecor\fcharset0\fprq2{\*\panose 040307050d0c02020703}Kino MT;}{\f241\froman\fcharset0\fprq2{\*\panose 020a0a07050505020404}Wide Latin;}{\f242\fnil\fcharset0\fprq2{\*\panose 00000000000000000000}Lucida Blackletter;}
{\f243\froman\fcharset0\fprq2{\*\panose 02040602050505020304}Lucida Bright;}{\f244\fscript\fcharset0\fprq2{\*\panose 03010101010101010101}Lucida Calligraphy;}{\f245\froman\fcharset0\fprq2{\*\panose 02060602050505020204}Lucida Fax;}
{\f246\fscript\fcharset0\fprq2{\*\panose 03010101010101010101}Lucida Handwriting;}{\f247\fmodern\fcharset0\fprq1{\*\panose 020b0509030504030204}Lucida Sans Typewriter;}{\f248\fswiss\fcharset0\fprq2{\*\panose 020e0502030308020204}Maiandra GD;}
{\f249\froman\fcharset0\fprq2{\*\panose 00050102010706020507}Map Symbols;}{\f250\fscript\fcharset238\fprq2{\*\panose 03020702040402020504}Marigold;}{\f251\fnil\fcharset0\fprq2{\*\panose 00000000000000000000}Marquee Engraved;}
{\f252\fdecor\fcharset0\fprq2{\*\panose 04040403030d02020704}Matisse ITC;}{\f253\fscript\fcharset0\fprq2{\*\panose 03020802060602070202}Matura MT Script Capitals;}{\f254\fnil\fcharset0\fprq2{\*\panose 00000000000000000000}Mead Bold;}
{\f255\fnil\fcharset0\fprq2{\*\panose 01010101010101010101}Mercurius Script MT Bold;}{\f256\fscript\fcharset0\fprq2{\*\panose 03090702030407020403}Mistral;}{\f257\froman\fcharset0\fprq2{\*\panose 02070704070505020303}Modern No. 20;}
{\f258\fnil\fcharset2\fprq2{\*\panose 01010601010101010101}Monotype Sorts;}{\f259\fswiss\fcharset0\fprq2{\*\panose 020b0504020203020204}News Gothic MT;}{\f260\fmodern\fcharset0\fprq2{\*\panose 02010509020102010303}OCR A Extended;}
{\f261\fdecor\fcharset0\fprq2{\*\panose 04050602080702020203}Onyx;}{\f262\fnil\fcharset2\fprq2{\*\panose 05000000000000000000}MS Outlook;}{\f263\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Parties MT;}
{\f264\froman\fcharset0\fprq2{\*\panose 02020502060401020303}Perpetua;}{\f265\froman\fcharset0\fprq2{\*\panose 02020502060505020804}Perpetua Titling MT;}{\f266\fswiss\fcharset0\fprq2{\*\panose 020b0606030402050204}Placard Condensed;}
{\f267\fdecor\fcharset0\fprq2{\*\panose 040506030a0602020202}Playbill;}{\f268\fdecor\fcharset0\fprq2{\*\panose 040c0101020201010102}Ransom;}{\f269\froman\fcharset0\fprq2{\*\panose 02060603050405020104}Rockwell Condensed;}
{\f270\froman\fcharset0\fprq2{\*\panose 02060603020205020403}Rockwell;}{\f271\froman\fcharset0\fprq2{\*\panose 02060903040505020403}Rockwell Extra Bold;}{\f272\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Signs MT;}
{\f273\fdecor\fcharset0\fprq2{\*\panose 04040a07060a02020202}Snap ITC;}{\f274\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Sports Two MT;}{\f275\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Sports Three MT;}
{\f276\fdecor\fcharset0\fprq2{\*\panose 040409050d0802020404}Stencil;}{\f277\fdecor\fcharset0\fprq2{\*\panose 04020404030d07020202}Tempus Sans ITC;}{\f278\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Transport MT;}
{\f279\fmodern\fcharset0\fprq1{\*\panose 020b0609020202020204}Monospac821 DL;}{\f280\fmodern\fcharset0\fprq1{\*\panose 020b0609020202090204}Monospac821 BT;}{\f281\fnil\fcharset0\fprq2{\*\panose 00000000000000000000}Ultra Shadow;}
{\f282\fnil\fcharset2\fprq2{\*\panose 05010101010101010101}Vacation MT;}{\f283\fscript\fcharset0\fprq2{\*\panose 03070502030502020203}Viner Hand ITC;}{\f284\fnil\fcharset0\fprq2{\*\panose 00000400000000000000}Sydnie;}
{\f285\froman\fcharset0\fprq0{\*\panose 00000000000000000000}TimesNewRoman;}{\f286\fnil\fcharset0\fprq0{\*\panose 00000000000000000000}AdvTimes;}{\f287\froman\fcharset238\fprq2 Times New Roman CE;}{\f288\froman\fcharset204\fprq2 Times New Roman Cyr;}
{\f290\froman\fcharset161\fprq2 Times New Roman Greek;}{\f291\froman\fcharset162\fprq2 Times New Roman Tur;}{\f292\froman\fcharset177\fprq2 Times New Roman (Hebrew);}{\f293\froman\fcharset178\fprq2 Times New Roman (Arabic);}
{\f294\froman\fcharset186\fprq2 Times New Roman Baltic;}{\f295\froman\fcharset163\fprq2 Times New Roman (Vietnamese);}{\f297\fswiss\fcharset238\fprq2 Arial CE;}{\f298\fswiss\fcharset204\fprq2 Arial Cyr;}{\f300\fswiss\fcharset161\fprq2 Arial Greek;}
{\f301\fswiss\fcharset162\fprq2 Arial Tur;}{\f302\fswiss\fcharset177\fprq2 Arial (Hebrew);}{\f303\fswiss\fcharset178\fprq2 Arial (Arabic);}{\f304\fswiss\fcharset186\fprq2 Arial Baltic;}{\f305\fswiss\fcharset163\fprq2 Arial (Vietnamese);}
{\f307\fmodern\fcharset238\fprq1 Courier New CE;}{\f308\fmodern\fcharset204\fprq1 Courier New Cyr;}{\f310\fmodern\fcharset161\fprq1 Courier New Greek;}{\f311\fmodern\fcharset162\fprq1 Courier New Tur;}
{\f312\fmodern\fcharset177\fprq1 Courier New (Hebrew);}{\f313\fmodern\fcharset178\fprq1 Courier New (Arabic);}{\f314\fmodern\fcharset186\fprq1 Courier New Baltic;}{\f315\fmodern\fcharset163\fprq1 Courier New (Vietnamese);}
{\f399\fmodern\fcharset0\fprq1 MS Mincho Western{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}{\f397\fmodern\fcharset238\fprq1 MS Mincho CE{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}
{\f398\fmodern\fcharset204\fprq1 MS Mincho Cyr{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}{\f400\fmodern\fcharset161\fprq1 MS Mincho Greek{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}
{\f401\fmodern\fcharset162\fprq1 MS Mincho Tur{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}{\f404\fmodern\fcharset186\fprq1 MS Mincho Baltic{\*\falt \'82\'6c\'82\'72 \'96\'be\'92\'a9};}
{\f409\froman\fcharset0\fprq2 Batang Western{\*\falt \'b9\'d9\'c5\'c1};}{\f407\froman\fcharset238\fprq2 Batang CE{\*\falt \'b9\'d9\'c5\'c1};}{\f408\froman\fcharset204\fprq2 Batang Cyr{\*\falt \'b9\'d9\'c5\'c1};}
{\f410\froman\fcharset161\fprq2 Batang Greek{\*\falt \'b9\'d9\'c5\'c1};}{\f411\froman\fcharset162\fprq2 Batang Tur{\*\falt \'b9\'d9\'c5\'c1};}{\f414\froman\fcharset186\fprq2 Batang Baltic{\*\falt \'b9\'d9\'c5\'c1};}
{\f419\fnil\fcharset0\fprq2 SimSun Western{\*\falt \'cb\'ce\'cc\'e5};}{\f429\froman\fcharset0\fprq2 PMingLiU Western{\*\falt \'b7\'73\'b2\'d3\'a9\'fa\'c5\'e9};}
{\f439\fmodern\fcharset0\fprq1 MS Gothic Western{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}{\f437\fmodern\fcharset238\fprq1 MS Gothic CE{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}
{\f438\fmodern\fcharset204\fprq1 MS Gothic Cyr{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}{\f440\fmodern\fcharset161\fprq1 MS Gothic Greek{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}
{\f441\fmodern\fcharset162\fprq1 MS Gothic Tur{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}{\f444\fmodern\fcharset186\fprq1 MS Gothic Baltic{\*\falt \'82\'6c\'82\'72 \'83\'53\'83\'56\'83\'62\'83\'4e};}
{\f449\fswiss\fcharset0\fprq2 Dotum Western{\*\falt \'b5\'b8\'bf\'f2};}{\f447\fswiss\fcharset238\fprq2 Dotum CE{\*\falt \'b5\'b8\'bf\'f2};}{\f448\fswiss\fcharset204\fprq2 Dotum Cyr{\*\falt \'b5\'b8\'bf\'f2};}
{\f450\fswiss\fcharset161\fprq2 Dotum Greek{\*\falt \'b5\'b8\'bf\'f2};}{\f451\fswiss\fcharset162\fprq2 Dotum Tur{\*\falt \'b5\'b8\'bf\'f2};}{\f454\fswiss\fcharset186\fprq2 Dotum Baltic{\*\falt \'b5\'b8\'bf\'f2};}
{\f469\fmodern\fcharset0\fprq1 MingLiU Western{\*\falt \'b2\'d3\'a9\'fa\'c5\'e9};}{\f489\fswiss\fcharset0\fprq2 Gulim Western{\*\falt \'b1\'bc\'b8\'b2};}{\f487\fswiss\fcharset238\fprq2 Gulim CE{\*\falt \'b1\'bc\'b8\'b2};}
{\f488\fswiss\fcharset204\fprq2 Gulim Cyr{\*\falt \'b1\'bc\'b8\'b2};}{\f490\fswiss\fcharset161\fprq2 Gulim Greek{\*\falt \'b1\'bc\'b8\'b2};}{\f491\fswiss\fcharset162\fprq2 Gulim Tur{\*\falt \'b1\'bc\'b8\'b2};}
{\f494\fswiss\fcharset186\fprq2 Gulim Baltic{\*\falt \'b1\'bc\'b8\'b2};}{\f516\froman\fcharset222\fprq2 Angsana New (Thai);}{\f526\fswiss\fcharset222\fprq2 Cordia New (Thai);}{\f547\froman\fcharset238\fprq2 Sylfaen CE;}
{\f548\froman\fcharset204\fprq2 Sylfaen Cyr;}{\f550\froman\fcharset161\fprq2 Sylfaen Greek;}{\f551\froman\fcharset162\fprq2 Sylfaen Tur;}{\f554\froman\fcharset186\fprq2 Sylfaen Baltic;}{\f637\fswiss\fcharset238\fprq2 Tahoma CE;}
{\f638\fswiss\fcharset204\fprq2 Tahoma Cyr;}{\f640\fswiss\fcharset161\fprq2 Tahoma Greek;}{\f641\fswiss\fcharset162\fprq2 Tahoma Tur;}{\f642\fswiss\fcharset177\fprq2 Tahoma (Hebrew);}{\f643\fswiss\fcharset178\fprq2 Tahoma (Arabic);}
{\f644\fswiss\fcharset186\fprq2 Tahoma Baltic;}{\f645\fswiss\fcharset163\fprq2 Tahoma (Vietnamese);}{\f646\fswiss\fcharset222\fprq2 Tahoma (Thai);}{\f647\froman\fcharset238\fprq2 Bookman Old Style CE;}
{\f648\froman\fcharset204\fprq2 Bookman Old Style Cyr;}{\f650\froman\fcharset161\fprq2 Bookman Old Style Greek;}{\f651\froman\fcharset162\fprq2 Bookman Old Style Tur;}{\f654\froman\fcharset186\fprq2 Bookman Old Style Baltic;}
{\f657\fswiss\fcharset238\fprq2 Verdana CE;}{\f658\fswiss\fcharset204\fprq2 Verdana Cyr;}{\f660\fswiss\fcharset161\fprq2 Verdana Greek;}{\f661\fswiss\fcharset162\fprq2 Verdana Tur;}{\f664\fswiss\fcharset186\fprq2 Verdana Baltic;}
{\f665\fswiss\fcharset163\fprq2 Verdana (Vietnamese);}{\f729\fscript\fcharset0\fprq2 Coronet;}{\f757\fmodern\fcharset238\fprq1 Lucida Console CE;}{\f758\fmodern\fcharset204\fprq1 Lucida Console Cyr;}{\f760\fmodern\fcharset161\fprq1 Lucida Console Greek;}
{\f761\fmodern\fcharset162\fprq1 Lucida Console Tur;}{\f767\fswiss\fcharset238\fprq2 Lucida Sans Unicode CE;}{\f768\fswiss\fcharset204\fprq2 Lucida Sans Unicode Cyr;}{\f770\fswiss\fcharset161\fprq2 Lucida Sans Unicode Greek;}
{\f771\fswiss\fcharset162\fprq2 Lucida Sans Unicode Tur;}{\f772\fswiss\fcharset177\fprq2 Lucida Sans Unicode (Hebrew);}{\f777\fswiss\fcharset238\fprq2 Arial Black CE;}{\f778\fswiss\fcharset204\fprq2 Arial Black Cyr;}
{\f780\fswiss\fcharset161\fprq2 Arial Black Greek;}{\f781\fswiss\fcharset162\fprq2 Arial Black Tur;}{\f784\fswiss\fcharset186\fprq2 Arial Black Baltic;}{\f787\fscript\fcharset238\fprq2 Comic Sans MS CE;}{\f788\fscript\fcharset204\fprq2 Comic Sans MS Cyr;}
{\f790\fscript\fcharset161\fprq2 Comic Sans MS Greek;}{\f791\fscript\fcharset162\fprq2 Comic Sans MS Tur;}{\f794\fscript\fcharset186\fprq2 Comic Sans MS Baltic;}{\f797\fswiss\fcharset238\fprq2 Impact CE;}{\f798\fswiss\fcharset204\fprq2 Impact Cyr;}
{\f800\fswiss\fcharset161\fprq2 Impact Greek;}{\f801\fswiss\fcharset162\fprq2 Impact Tur;}{\f804\fswiss\fcharset186\fprq2 Impact Baltic;}{\f807\froman\fcharset238\fprq2 Georgia CE;}{\f808\froman\fcharset204\fprq2 Georgia Cyr;}
{\f810\froman\fcharset161\fprq2 Georgia Greek;}{\f811\froman\fcharset162\fprq2 Georgia Tur;}{\f814\froman\fcharset186\fprq2 Georgia Baltic;}{\f817\fswiss\fcharset238\fprq2 Franklin Gothic Medium CE;}
{\f818\fswiss\fcharset204\fprq2 Franklin Gothic Medium Cyr;}{\f820\fswiss\fcharset161\fprq2 Franklin Gothic Medium Greek;}{\f821\fswiss\fcharset162\fprq2 Franklin Gothic Medium Tur;}{\f824\fswiss\fcharset186\fprq2 Franklin Gothic Medium Baltic;}
{\f827\froman\fcharset238\fprq2 Palatino Linotype CE;}{\f828\froman\fcharset204\fprq2 Palatino Linotype Cyr;}{\f830\froman\fcharset161\fprq2 Palatino Linotype Greek;}{\f831\froman\fcharset162\fprq2 Palatino Linotype Tur;}
{\f834\froman\fcharset186\fprq2 Palatino Linotype Baltic;}{\f835\froman\fcharset163\fprq2 Palatino Linotype (Vietnamese);}{\f837\fswiss\fcharset238\fprq2 Trebuchet MS CE;}{\f838\fswiss\fcharset204\fprq2 Trebuchet MS Cyr;}
{\f840\fswiss\fcharset161\fprq2 Trebuchet MS Greek;}{\f841\fswiss\fcharset162\fprq2 Trebuchet MS Tur;}{\f844\fswiss\fcharset186\fprq2 Trebuchet MS Baltic;}{\f877\fswiss\fcharset238\fprq2 Microsoft Sans Serif CE;}
{\f878\fswiss\fcharset204\fprq2 Microsoft Sans Serif Cyr;}{\f880\fswiss\fcharset161\fprq2 Microsoft Sans Serif Greek;}{\f881\fswiss\fcharset162\fprq2 Microsoft Sans Serif Tur;}{\f882\fswiss\fcharset177\fprq2 Microsoft Sans Serif (Hebrew);}
{\f883\fswiss\fcharset178\fprq2 Microsoft Sans Serif (Arabic);}{\f884\fswiss\fcharset186\fprq2 Microsoft Sans Serif Baltic;}{\f885\fswiss\fcharset163\fprq2 Microsoft Sans Serif (Vietnamese);}{\f886\fswiss\fcharset222\fprq2 Microsoft Sans Serif (Thai);}
{\f891\fdecor\fcharset162\fprq2 Allegro BT Tur;}{\f897\fswiss\fcharset238\fprq2 AvantGarde Md BT CE;}{\f900\fswiss\fcharset161\fprq2 AvantGarde Md BT Greek;}{\f901\fswiss\fcharset162\fprq2 AvantGarde Md BT Tur;}
{\f907\fswiss\fcharset238\fprq2 AvantGarde Bk BT CE;}{\f910\fswiss\fcharset161\fprq2 AvantGarde Bk BT Greek;}{\f911\fswiss\fcharset162\fprq2 AvantGarde Bk BT Tur;}{\f917\fswiss\fcharset238\fprq2 BankGothic Md BT CE;}
{\f920\fswiss\fcharset161\fprq2 BankGothic Md BT Greek;}{\f921\fswiss\fcharset162\fprq2 BankGothic Md BT Tur;}{\f927\froman\fcharset238\fprq2 Benguiat Bk BT CE;}{\f930\froman\fcharset161\fprq2 Benguiat Bk BT Greek;}
{\f931\froman\fcharset162\fprq2 Benguiat Bk BT Tur;}{\f941\fdecor\fcharset162\fprq2 BernhardFashion BT Tur;}{\f951\froman\fcharset162\fprq2 BernhardMod BT Tur;}{\f961\fdecor\fcharset162\fprq2 Bremen Bd BT Tur;}
{\f987\fswiss\fcharset238\fprq2 CopprplGoth Bd BT CE;}{\f990\fswiss\fcharset161\fprq2 CopprplGoth Bd BT Greek;}{\f991\fswiss\fcharset162\fprq2 CopprplGoth Bd BT Tur;}{\f1011\fscript\fcharset162\fprq2 English111 Vivace BT Tur;}
{\f1021\fdecor\fcharset162\fprq2 FuturaBlack BT Tur;}{\f1031\fswiss\fcharset162\fprq2 Futura Md BT Tur;}{\f1041\fswiss\fcharset162\fprq2 Futura XBlk BT Tur;}{\f1051\fswiss\fcharset162\fprq2 Futura Lt BT Tur;}
{\f1061\fdecor\fcharset162\fprq2 GoudyHandtooled BT Tur;}{\f1071\froman\fcharset162\fprq2 GoudyOlSt BT Tur;}{\f1081\fswiss\fcharset162\fprq2 Humanst521 BT Tur;}{\f1087\fswiss\fcharset238\fprq2 Kabel Bk BT CE;}
{\f1090\fswiss\fcharset161\fprq2 Kabel Bk BT Greek;}{\f1091\fswiss\fcharset162\fprq2 Kabel Bk BT Tur;}{\f1097\fswiss\fcharset238\fprq2 Kabel Ult BT CE;}{\f1100\fswiss\fcharset161\fprq2 Kabel Ult BT Greek;}
{\f1101\fswiss\fcharset162\fprq2 Kabel Ult BT Tur;}{\f1141\fscript\fcharset162\fprq2 OzHandicraft BT Tur;}{\f1147\froman\fcharset238\fprq2 PosterBodoni BT CE;}{\f1150\froman\fcharset161\fprq2 PosterBodoni BT Greek;}
{\f1151\froman\fcharset162\fprq2 PosterBodoni BT Tur;}{\f1161\froman\fcharset162\fprq2 Serifa BT Tur;}{\f1171\froman\fcharset162\fprq2 Serifa Th BT Tur;}{\f1177\froman\fcharset238\fprq2 Souvenir Lt BT CE;}
{\f1180\froman\fcharset161\fprq2 Souvenir Lt BT Greek;}{\f1181\froman\fcharset162\fprq2 Souvenir Lt BT Tur;}{\f1191\fscript\fcharset162\fprq2 Staccato222 BT Tur;}{\f1201\fswiss\fcharset162\fprq2 Swiss911 XCm BT Tur;}
{\f1211\fscript\fcharset162\fprq2 TypoUpright BT Tur;}{\f1461\froman\fcharset162\fprq2 ZapfEllipt BT Tur;}{\f1471\fswiss\fcharset162\fprq2 Zurich Ex BT Tur;}{\f1477\fswiss\fcharset238\fprq2 Arial Narrow CE;}
{\f1478\fswiss\fcharset204\fprq2 Arial Narrow Cyr;}{\f1480\fswiss\fcharset161\fprq2 Arial Narrow Greek;}{\f1481\fswiss\fcharset162\fprq2 Arial Narrow Tur;}{\f1484\fswiss\fcharset186\fprq2 Arial Narrow Baltic;}
{\f1487\froman\fcharset238\fprq2 Book Antiqua CE;}{\f1488\froman\fcharset204\fprq2 Book Antiqua Cyr;}{\f1490\froman\fcharset161\fprq2 Book Antiqua Greek;}{\f1491\froman\fcharset162\fprq2 Book Antiqua Tur;}
{\f1494\froman\fcharset186\fprq2 Book Antiqua Baltic;}{\f1497\fswiss\fcharset238\fprq2 Century Gothic CE;}{\f1498\fswiss\fcharset204\fprq2 Century Gothic Cyr;}{\f1500\fswiss\fcharset161\fprq2 Century Gothic Greek;}
{\f1501\fswiss\fcharset162\fprq2 Century Gothic Tur;}{\f1504\fswiss\fcharset186\fprq2 Century Gothic Baltic;}{\f1507\froman\fcharset238\fprq2 Garamond CE;}{\f1508\froman\fcharset204\fprq2 Garamond Cyr;}{\f1510\froman\fcharset161\fprq2 Garamond Greek;}
{\f1511\froman\fcharset162\fprq2 Garamond Tur;}{\f1514\froman\fcharset186\fprq2 Garamond Baltic;}{\f1517\fswiss\fcharset238\fprq2 Haettenschweiler CE;}{\f1518\fswiss\fcharset204\fprq2 Haettenschweiler Cyr;}
{\f1520\fswiss\fcharset161\fprq2 Haettenschweiler Greek;}{\f1521\fswiss\fcharset162\fprq2 Haettenschweiler Tur;}{\f1524\fswiss\fcharset186\fprq2 Haettenschweiler Baltic;}{\f1527\fscript\fcharset238\fprq2 Monotype Corsiva CE;}
{\f1528\fscript\fcharset204\fprq2 Monotype Corsiva Cyr;}{\f1530\fscript\fcharset161\fprq2 Monotype Corsiva Greek;}{\f1531\fscript\fcharset162\fprq2 Monotype Corsiva Tur;}{\f1534\fscript\fcharset186\fprq2 Monotype Corsiva Baltic;}
{\f1596\fswiss\fcharset222\fprq2 Browallia New (Thai);}{\f1849\fmodern\fcharset0\fprq1 @MS Mincho Western;}{\f1847\fmodern\fcharset238\fprq1 @MS Mincho CE;}{\f1848\fmodern\fcharset204\fprq1 @MS Mincho Cyr;}
{\f1850\fmodern\fcharset161\fprq1 @MS Mincho Greek;}{\f1851\fmodern\fcharset162\fprq1 @MS Mincho Tur;}{\f1854\fmodern\fcharset186\fprq1 @MS Mincho Baltic;}{\f1859\froman\fcharset0\fprq2 MS PMincho Western;}{\f1857\froman\fcharset238\fprq2 MS PMincho CE;}
{\f1858\froman\fcharset204\fprq2 MS PMincho Cyr;}{\f1860\froman\fcharset161\fprq2 MS PMincho Greek;}{\f1861\froman\fcharset162\fprq2 MS PMincho Tur;}{\f1864\froman\fcharset186\fprq2 MS PMincho Baltic;}{\f1869\froman\fcharset0\fprq2 @MS PMincho Western;}
{\f1867\froman\fcharset238\fprq2 @MS PMincho CE;}{\f1868\froman\fcharset204\fprq2 @MS PMincho Cyr;}{\f1870\froman\fcharset161\fprq2 @MS PMincho Greek;}{\f1871\froman\fcharset162\fprq2 @MS PMincho Tur;}{\f1874\froman\fcharset186\fprq2 @MS PMincho Baltic;}
{\f1879\fmodern\fcharset0\fprq1 @MS Gothic Western;}{\f1877\fmodern\fcharset238\fprq1 @MS Gothic CE;}{\f1878\fmodern\fcharset204\fprq1 @MS Gothic Cyr;}{\f1880\fmodern\fcharset161\fprq1 @MS Gothic Greek;}{\f1881\fmodern\fcharset162\fprq1 @MS Gothic Tur;}
{\f1884\fmodern\fcharset186\fprq1 @MS Gothic Baltic;}{\f1889\fswiss\fcharset0\fprq2 MS PGothic Western;}{\f1887\fswiss\fcharset238\fprq2 MS PGothic CE;}{\f1888\fswiss\fcharset204\fprq2 MS PGothic Cyr;}{\f1890\fswiss\fcharset161\fprq2 MS PGothic Greek;}
{\f1891\fswiss\fcharset162\fprq2 MS PGothic Tur;}{\f1894\fswiss\fcharset186\fprq2 MS PGothic Baltic;}{\f1899\fswiss\fcharset0\fprq2 @MS PGothic Western;}{\f1897\fswiss\fcharset238\fprq2 @MS PGothic CE;}{\f1898\fswiss\fcharset204\fprq2 @MS PGothic Cyr;}
{\f1900\fswiss\fcharset161\fprq2 @MS PGothic Greek;}{\f1901\fswiss\fcharset162\fprq2 @MS PGothic Tur;}{\f1904\fswiss\fcharset186\fprq2 @MS PGothic Baltic;}{\f1909\fswiss\fcharset0\fprq2 MS UI Gothic Western;}
{\f1907\fswiss\fcharset238\fprq2 MS UI Gothic CE;}{\f1908\fswiss\fcharset204\fprq2 MS UI Gothic Cyr;}{\f1910\fswiss\fcharset161\fprq2 MS UI Gothic Greek;}{\f1911\fswiss\fcharset162\fprq2 MS UI Gothic Tur;}
{\f1914\fswiss\fcharset186\fprq2 MS UI Gothic Baltic;}{\f1919\fswiss\fcharset0\fprq2 @MS UI Gothic Western;}{\f1917\fswiss\fcharset238\fprq2 @MS UI Gothic CE;}{\f1918\fswiss\fcharset204\fprq2 @MS UI Gothic Cyr;}
{\f1920\fswiss\fcharset161\fprq2 @MS UI Gothic Greek;}{\f1921\fswiss\fcharset162\fprq2 @MS UI Gothic Tur;}{\f1924\fswiss\fcharset186\fprq2 @MS UI Gothic Baltic;}{\f1929\fswiss\fcharset0\fprq2 @Gulim Western;}{\f1927\fswiss\fcharset238\fprq2 @Gulim CE;}
{\f1928\fswiss\fcharset204\fprq2 @Gulim Cyr;}{\f1930\fswiss\fcharset161\fprq2 @Gulim Greek;}{\f1931\fswiss\fcharset162\fprq2 @Gulim Tur;}{\f1934\fswiss\fcharset186\fprq2 @Gulim Baltic;}{\f1939\fmodern\fcharset0\fprq1 GulimChe Western;}
{\f1937\fmodern\fcharset238\fprq1 GulimChe CE;}{\f1938\fmodern\fcharset204\fprq1 GulimChe Cyr;}{\f1940\fmodern\fcharset161\fprq1 GulimChe Greek;}{\f1941\fmodern\fcharset162\fprq1 GulimChe Tur;}{\f1944\fmodern\fcharset186\fprq1 GulimChe Baltic;}
{\f1949\fmodern\fcharset0\fprq1 @GulimChe Western;}{\f1947\fmodern\fcharset238\fprq1 @GulimChe CE;}{\f1948\fmodern\fcharset204\fprq1 @GulimChe Cyr;}{\f1950\fmodern\fcharset161\fprq1 @GulimChe Greek;}{\f1951\fmodern\fcharset162\fprq1 @GulimChe Tur;}
{\f1954\fmodern\fcharset186\fprq1 @GulimChe Baltic;}{\f1959\fswiss\fcharset0\fprq2 @Dotum Western;}{\f1957\fswiss\fcharset238\fprq2 @Dotum CE;}{\f1958\fswiss\fcharset204\fprq2 @Dotum Cyr;}{\f1960\fswiss\fcharset161\fprq2 @Dotum Greek;}
{\f1961\fswiss\fcharset162\fprq2 @Dotum Tur;}{\f1964\fswiss\fcharset186\fprq2 @Dotum Baltic;}{\f1969\fmodern\fcharset0\fprq1 DotumChe Western;}{\f1967\fmodern\fcharset238\fprq1 DotumChe CE;}{\f1968\fmodern\fcharset204\fprq1 DotumChe Cyr;}
{\f1970\fmodern\fcharset161\fprq1 DotumChe Greek;}{\f1971\fmodern\fcharset162\fprq1 DotumChe Tur;}{\f1974\fmodern\fcharset186\fprq1 DotumChe Baltic;}{\f1979\fmodern\fcharset0\fprq1 @DotumChe Western;}{\f1977\fmodern\fcharset238\fprq1 @DotumChe CE;}
{\f1978\fmodern\fcharset204\fprq1 @DotumChe Cyr;}{\f1980\fmodern\fcharset161\fprq1 @DotumChe Greek;}{\f1981\fmodern\fcharset162\fprq1 @DotumChe Tur;}{\f1984\fmodern\fcharset186\fprq1 @DotumChe Baltic;}{\f1989\froman\fcharset0\fprq2 @Batang Western;}
{\f1987\froman\fcharset238\fprq2 @Batang CE;}{\f1988\froman\fcharset204\fprq2 @Batang Cyr;}{\f1990\froman\fcharset161\fprq2 @Batang Greek;}{\f1991\froman\fcharset162\fprq2 @Batang Tur;}{\f1994\froman\fcharset186\fprq2 @Batang Baltic;}
{\f1999\fmodern\fcharset0\fprq1 BatangChe Western;}{\f1997\fmodern\fcharset238\fprq1 BatangChe CE;}{\f1998\fmodern\fcharset204\fprq1 BatangChe Cyr;}{\f2000\fmodern\fcharset161\fprq1 BatangChe Greek;}{\f2001\fmodern\fcharset162\fprq1 BatangChe Tur;}
{\f2004\fmodern\fcharset186\fprq1 BatangChe Baltic;}{\f2009\fmodern\fcharset0\fprq1 @BatangChe Western;}{\f2007\fmodern\fcharset238\fprq1 @BatangChe CE;}{\f2008\fmodern\fcharset204\fprq1 @BatangChe Cyr;}{\f2010\fmodern\fcharset161\fprq1 @BatangChe Greek;}
{\f2011\fmodern\fcharset162\fprq1 @BatangChe Tur;}{\f2014\fmodern\fcharset186\fprq1 @BatangChe Baltic;}{\f2019\froman\fcharset0\fprq2 Gungsuh Western;}{\f2017\froman\fcharset238\fprq2 Gungsuh CE;}{\f2018\froman\fcharset204\fprq2 Gungsuh Cyr;}
{\f2020\froman\fcharset161\fprq2 Gungsuh Greek;}{\f2021\froman\fcharset162\fprq2 Gungsuh Tur;}{\f2024\froman\fcharset186\fprq2 Gungsuh Baltic;}{\f2029\froman\fcharset0\fprq2 @Gungsuh Western;}{\f2027\froman\fcharset238\fprq2 @Gungsuh CE;}
{\f2028\froman\fcharset204\fprq2 @Gungsuh Cyr;}{\f2030\froman\fcharset161\fprq2 @Gungsuh Greek;}{\f2031\froman\fcharset162\fprq2 @Gungsuh Tur;}{\f2034\froman\fcharset186\fprq2 @Gungsuh Baltic;}{\f2039\fmodern\fcharset0\fprq1 GungsuhChe Western;}
{\f2037\fmodern\fcharset238\fprq1 GungsuhChe CE;}{\f2038\fmodern\fcharset204\fprq1 GungsuhChe Cyr;}{\f2040\fmodern\fcharset161\fprq1 GungsuhChe Greek;}{\f2041\fmodern\fcharset162\fprq1 GungsuhChe Tur;}{\f2044\fmodern\fcharset186\fprq1 GungsuhChe Baltic;}
{\f2049\fmodern\fcharset0\fprq1 @GungsuhChe Western;}{\f2047\fmodern\fcharset238\fprq1 @GungsuhChe CE;}{\f2048\fmodern\fcharset204\fprq1 @GungsuhChe Cyr;}{\f2050\fmodern\fcharset161\fprq1 @GungsuhChe Greek;}
{\f2051\fmodern\fcharset162\fprq1 @GungsuhChe Tur;}{\f2054\fmodern\fcharset186\fprq1 @GungsuhChe Baltic;}{\f2059\fnil\fcharset0\fprq2 @SimSun Western;}{\f2069\fmodern\fcharset0\fprq1 NSimSun Western;}{\f2079\fmodern\fcharset0\fprq1 @NSimSun Western;}
{\f2099\fmodern\fcharset0\fprq1 @MingLiU Western;}{\f2109\froman\fcharset0\fprq2 @PMingLiU Western;}{\f2517\fswiss\fcharset238\fprq2 Franklin Gothic Book CE;}{\f2518\fswiss\fcharset204\fprq2 Franklin Gothic Book Cyr;}
{\f2520\fswiss\fcharset161\fprq2 Franklin Gothic Book Greek;}{\f2521\fswiss\fcharset162\fprq2 Franklin Gothic Book Tur;}{\f2524\fswiss\fcharset186\fprq2 Franklin Gothic Book Baltic;}{\f2527\fswiss\fcharset238\fprq2 Franklin Gothic Demi CE;}
{\f2528\fswiss\fcharset204\fprq2 Franklin Gothic Demi Cyr;}{\f2530\fswiss\fcharset161\fprq2 Franklin Gothic Demi Greek;}{\f2531\fswiss\fcharset162\fprq2 Franklin Gothic Demi Tur;}{\f2534\fswiss\fcharset186\fprq2 Franklin Gothic Demi Baltic;}
{\f2537\fswiss\fcharset238\fprq2 Franklin Gothic Demi Cond CE;}{\f2538\fswiss\fcharset204\fprq2 Franklin Gothic Demi Cond Cyr;}{\f2540\fswiss\fcharset161\fprq2 Franklin Gothic Demi Cond Greek;}
{\f2541\fswiss\fcharset162\fprq2 Franklin Gothic Demi Cond Tur;}{\f2544\fswiss\fcharset186\fprq2 Franklin Gothic Demi Cond Baltic;}{\f2547\fswiss\fcharset238\fprq2 Franklin Gothic Heavy CE;}{\f2548\fswiss\fcharset204\fprq2 Franklin Gothic Heavy Cyr;}
{\f2550\fswiss\fcharset161\fprq2 Franklin Gothic Heavy Greek;}{\f2551\fswiss\fcharset162\fprq2 Franklin Gothic Heavy Tur;}{\f2554\fswiss\fcharset186\fprq2 Franklin Gothic Heavy Baltic;}{\f2557\fswiss\fcharset238\fprq2 Franklin Gothic Medium Cond CE;}
{\f2558\fswiss\fcharset204\fprq2 Franklin Gothic Medium Cond Cyr;}{\f2560\fswiss\fcharset161\fprq2 Franklin Gothic Medium Cond Greek;}{\f2561\fswiss\fcharset162\fprq2 Franklin Gothic Medium Cond Tur;}
{\f2564\fswiss\fcharset186\fprq2 Franklin Gothic Medium Cond Baltic;}{\f3077\fmodern\fcharset238\fprq1 Monospac821 DL CE;}{\f3080\fmodern\fcharset161\fprq1 Monospac821 DL Greek;}{\f3081\fmodern\fcharset162\fprq1 Monospac821 DL Tur;}
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{\title The Office of Combination Products:}{\author  }{\operator Computing Services}{\creatim\yr2005\mo6\dy13\hr9\min49}{\revtim\yr2005\mo6\dy13\hr9\min49}{\printim\yr2005\mo2\dy3\hr16\min57}{\version2}{\edmins1}{\nofpages79}{\nofwords20154}
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{\*\ftnsep \pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\insrsid7417172 \chftnsep 
\par }}{\*\ftnsepc \pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\insrsid7417172 \chftnsepc 
\par }}{\*\aftnsep \pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\insrsid7417172 \chftnsep 
\par }}{\*\aftnsepc \pard\plain \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\insrsid7417172 \chftnsepc 
\par }}\sectd \pgnrestart\linex0\endnhere\titlepg\pgnhn1\sectlinegrid360\sectdefaultcl\sectrsid2832133\sftnbj {\footer \pard\plain \s21\ql \li0\ri0\widctlpar
\tqc\tx4320\tqr\tx8640\pvpara\phmrg\posxc\posy0\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2832133 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\field{\*\fldinst {\cs22\insrsid16284404 PAGE  }}{\fldrslt {
\cs22\lang1024\langfe1024\noproof\insrsid9520680 79}}}{\cs22\insrsid16284404 
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\par }}{\*\pnseclvl1\pnucrm\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl2\pnucltr\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl3\pndec\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl4\pnlcltr\pnstart1\pnindent720\pnhang {\pntxta )}}
{\*\pnseclvl5\pndec\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl6\pnlcltr\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl7\pnlcrm\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl8
\pnlcltr\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl9\pnlcrm\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}\pard\plain \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11404391 
\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\insrsid11404391 
\par 
\par 
\par 
\par 
\par 
\par 
\par 
\par 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11404391 {\b\fs40\insrsid11404391 The Office of Combination Products:
\par Its Roots, Its Creation, and Its }{\b\fs40\insrsid5184722 Role}{\fs28\insrsid11404391 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11404391 {\fs28\insrsid11404391 
\par 
\par 
\par 
\par Danielle C. Schillinger
\par Food and Drug Law Winter 2004
\par }{\fs28\insrsid5184722 Class of 2005
\par }{\fs28\insrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5184722 {\insrsid4736782 This paper is submi}{\insrsid5184722 tted in satisfaction of both the course requirement and the third-year written work requirement.}{
\insrsid5184722\charrsid5184722 
\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\fs28\insrsid13313884 \page }{\b\insrsid13313884 TABLE OF CONTENTS}{\insrsid13313884 
\par }\pard \qc \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\insrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx9360\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\i\ul\insrsid13839632 Abstract}{\insrsid13839632 \tab 3}{\insrsid13839632\charrsid13839632 
\par }{\insrsid13839632 
\par }{\i\ul\insrsid13313884\charrsid13313884 Introduction}{\insrsid5525780 \tab 3}{\insrsid13313884\charrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx8640\tqr\tx9360\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\insrsid13313884\charrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx9360\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\i\ul\insrsid13313884\charrsid13313884 I. Basic Definitions and Regulatory Procedures for Drugs, Medical Devices, and Biologics}{
\insrsid3084911 \tab 6}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 I. A. Drugs}{\insrsid3084911 \tab 7}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 I. B. Medical Devices}{\insrsid3084911 \tab 9}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 I.C. Biological Products}{\insrsid4801255 \tab 13}{\insrsid13313884\charrsid13313884 
\par 
\par }{\i\ul\insrsid13313884\charrsid13313884 II. 1938-1990: The Changing Landscape of FDA-Regulated Products}{\insrsid3084911 \tab 14}{\insrsid13313884\charrsid13313884 
\par                
\par }{\i\ul\insrsid13313884\charrsid13313884 III. The Safe Medical Devices Act (SMDA) of 1990: Its Origins and Its Impact}{\insrsid3084911 \tab 19}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 III.A.  Section 16 of the SMDA}{\insrsid3084911 \tab 19}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 III.B. The Effect of the SMDA on the FDA\rquote s Regulatory Framework}{\insrsid11546220 \tab 26}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid16284404 III.}{\i\ul\insrsid13313884\charrsid13313884 C. 1991: The New Intercenter Agreements}{\insrsid11546220 \tab 31}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III. C. 1. CBER-CDRH Intercenter Agreement}{\insrsid11546220 \tab 32}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III.C. 2. CDER-CDRH Intercenter Agreement}{\insrsid3084911 \tab 33}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III. C. 3. CDER-CBER Intercenter Agreement}{\insrsid11546220 \tab 35}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 III.D. The Middle 1990\rquote s: The Continuing Effect of the SMDA}{\insrsid2041994 \tab 37}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III.D.I. To Move or Not to Move the FDA Centers?}{\insrsid3084911 \tab 37}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III.D.2. The Common Sense Product Liability Act of 1996}{\insrsid3084911 \tab 40}{\insrsid13313884\charrsid13313884 
\par                           }{\i\ul\insrsid13313884\charrsid13313884 III.D.3. Up in Smoke: Combination Products and the Supreme Court}{\insrsid3084911 \tab 42}{\insrsid13313884 
\par }{\insrsid8203118 
\par }{\i\ul\insrsid8203118 IV. Food and Drug Administration Modernization Act (FDAMA) of 1997}{\insrsid2041994 \tab 48}{\insrsid8203118\charrsid8203118 
\par }{\insrsid13313884\charrsid13313884 
\par }{\i\ul\insrsid13313884\charrsid13313884 V. MDUFMA of 2002: The Advent of the Office of Combination Products}{\insrsid3084911 \tab 49}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 V.A. The First Step: The Combination Products Program}{\insrsid3084911 \tab 50}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 V.B. The Next Step: The Office of Combination Products}{\insrsid3084911 \tab 52}{\insrsid13313884\charrsid13313884 
\par                
\par }{\i\ul\insrsid13313884\charrsid13313884 V}{\i\ul\insrsid8203118 I}{\i\ul\insrsid13313884\charrsid13313884 . The Current Status of the Office of Combination Products}{\insrsid2041994 \tab 61}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 V}{\i\ul\insrsid11021331 I}{\i\ul\insrsid13313884\charrsid13313884 .A. The First Public Hearing}{\insrsid2041994 \tab 62}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\insrsid13313884\charrsid13313884 V}{\i\ul\insrsid11021331 I}{\i\ul\insrsid13313884\charrsid13313884 .B. The First Six Month}{\i\ul\insrsid3084911 s}{\insrsid2041994 \tab 66}{\insrsid13313884\charrsid13313884 
\par                }{\i\ul\cf1\insrsid13313884\charrsid13313884 V}{\i\ul\cf1\insrsid11021331 I}{\i\ul\cf1\insrsid13313884\charrsid13313884 .C. The First Year Draws to a Close}{\cf1\insrsid3084911 \tab 71}{\cf1\insrsid13313884\charrsid13313884 
\par }{\insrsid13313884\charrsid13313884                           }{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 V}{\cs17\i\ul\cf1\insrsid11021331 I}{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 .C.I. \'93Prompt Assignment of Combination Products\'94}{
\cs17\cf1\insrsid2041994 \tab 72}{\cs17\cf1\insrsid13313884\charrsid13313884 
\par                           }{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 V}{\cs17\i\ul\cf1\insrsid11021331 I}{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 .C.II. \'93Timely and Effective Premarket Review\'94}{\cs17\cf1\insrsid3084911 \tab 73}{
\cs17\cf1\insrsid13313884\charrsid13313884 
\par                           }{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 V}{\cs17\i\ul\cf1\insrsid11021331 I}{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 .C.III. \'93Consistent and Appropriate Postmarket Regulation\'94}{\cs17\cf1\insrsid3084911 
\tab 75}{\cs17\cf1\insrsid13313884 
\par }{\cs17\cf1\insrsid16324738                }{\cs17\i\ul\cf1\insrsid16324738 VI.D. Moving Forward}{\cs17\cf1\insrsid2041994 \tab 76}{\cs17\cf1\insrsid16324738\charrsid16324738 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx8640\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\cs17\cf1\insrsid13313884\charrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx9360\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 VI}{\cs17\i\ul\cf1\insrsid8203118 I}{\cs17\i\ul\cf1\insrsid13313884\charrsid13313884 
. Conclusion}{\cs17\cf1\insrsid13313884\charrsid13313884 \tab 7}{\cs17\cf1\insrsid3084911 7}{\insrsid13313884\charrsid13313884 
\par }\pard \ql \li0\ri0\widctlpar\tqr\tldot\tx8640\tqr\tx9360\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13313884 {\insrsid13313884\charrsid13313884 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11404391 {\insrsid11404391 \page }{\i\ul\insrsid10948351 Abstract}{\insrsid10948351\charrsid10948351 
\par }\pard \qj \li360\ri360\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin360\lin360\itap0\pararsid6833360 {\insrsid12062990 The Office of Combination Products}{\insrsid6833360  (OCP)}{\insrsid12062990 
, within the Food and Drug Administration (FDA), was created formally by statute in December, 2002.  Upon its creation, the Office became broadly responsible for overseeing the regulation of combination products, or products that involve components that 
would normally be regulated under different FDA Centers}{\insrsid9117351 .  }{\insrsid7346762 But the statutory creation of this Office in one day represented the culmination of nearly}{\insrsid9117351  sixty-five years of }{\insrsid7346762 
both technological advancement }{\insrsid5073918 in the products submitted to the FDA }{\insrsid7346762 and amassed }{\insrsid9117351 experience within the FDA and its administrative predecessors}{\insrsid5073918  for managing those products}{
\insrsid7545196  in the name of the public safety}{\insrsid7346762 .}{\insrsid9117351  }{\insrsid7346762  To understand the need for this Office and its primary goals of timely, effective and clear regulation of }{\insrsid5073918 these }{\insrsid7346762 
groundbreaking technologies, the history of the FDA with respect to the advent of these combination products must be examined}{\insrsid5073918  chronologically}{\insrsid7346762 .}{\insrsid5073918 
  Drafts of statutes, administrative proposals offered for public comment, and lengthy debates from Capitol Hill all illustrate the}{\insrsid6833360  journey 
that led inevitably to the OCP as a final destination.  Nearly twenty-four months have passed since the OCP was created, so an analysis of its }{\insrsid5266172 initial }{\insrsid6833360 
progress through an explanation of the changes it has effected is necessary.  }{\insrsid12401616 Both combination product manufacturers and FDA jurisdiction officers }{\insrsid11417444 have }{\insrsid15945552 benefited}{\insrsid11417444 
 from industry guidances, enhanced}{\insrsid5266172  inter-Center communication, and a wealth of expertise }{\insrsid11417444 provided by }{\insrsid5266172 FDA employees }{\insrsid11417444 eager to streamline the regulatory pathways to be navigated}{
\insrsid6833360 .}{\insrsid13726595   Th}{\insrsid11417444 us, th}{\insrsid13726595 e next three years within the OCP }{\insrsid11417444 would seem to }{\insrsid13726595 promise similar success}{\insrsid7545196 
 for product manufacturers, the FDA and the American public}{\insrsid13726595 .}{\insrsid10948351 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11404391 {\i\ul\insrsid4358008 Introduction}{\insrsid4358008 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid4461383 {\insrsid4461383 The [Office of Combination Products] \'93is a significant step to increase the efficiency and timeliness of the procedures that m
ake these important products available to patients.  I also believe that the activities of this new office will help provide insights into how the Commissioner's office can better support a range of issues that cut across the three product centers, and th
us bring greater uniformity and coherence to our processes."}{\cs16\super\insrsid4461383 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 FDA Establishes Office of Combination Products}{\insrsid16284404\charrsid7211990  (December 31, 2002), }{
\i\insrsid16284404\charrsid7211990 available at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/bbs/topics/NEWS/2002/NEW00862.html" }{\insrsid16284404\charrsid7211990 
{\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f004e004500570053002f0032003000300032002f004e0045005700300030003800360032002e00
680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b6c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f004e004500570053002f0032003000300032002f004e0045005700300030003800360032002e
00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/bbs/topics/NEWS/2002/NEW00862.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid4461383 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4461383 {\insrsid4461383 \tab \tab \tab Mark B. McClellan, M.D., Ph.D., Commissioner of Food and Drugs. 
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4461383 {\insrsid11301554 By 2002, the Food and Drug Administration (FDA) had spent nearly two decades attempting to regulate }{\insrsid3635577 
in an orderly and thorough manner}{\insrsid9905777  }{\insrsid3635577 those }{\insrsid15943946 new }{\insrsid9905777 products that seemed to be more than just a }{\insrsid3635577 new }{\insrsid9905777 drug}{\insrsid3635577  or a new biological product}{
\insrsid9905777 , or }{\insrsid3635577 simply}{\insrsid9905777  a medical device}{\insrsid3635577 ,}{\insrsid9905777  }{\insrsid11301554 but rather a combination of more than one of those categories.  The }{\insrsid3635577 
Medical Device User Fee and Modernization Act}{\insrsid7953880  }{\insrsid14685545 (MDUFMA), }{\insrsid7953880 signed }{\insrsid3297364 into law}{\insrsid11301554  on October 26, 2002 }{\insrsid7953880 by President George W. }{\insrsid3297364 Bush}{
\insrsid14685545 ,}{\cs16\super\insrsid3297364 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Medical Device User Fee and Modernization Act of 2002 (hereinafter \'93MDUFMA\'94), Pub. L. No. 107-250, 21 U.S.C. }{\cs18\fs19\insrsid16284404\charrsid7211990 \'a7
 301 }{\cs18\i\fs19\insrsid16284404\charrsid7211990 et seq.}{\cs18\fs19\insrsid16284404\charrsid7211990  (2002); }{\insrsid16284404\charrsid7211990 President\rquote s Statement on Signing the Medical Device User Fee and Modernization Act of 2002, 38 }{
\scaps\insrsid16284404\charrsid7211990 Weekly Comp. Pres. Doc. }{\insrsid16284404\charrsid7211990 1874 (November 4, 2002). }}}{\insrsid14685545  explicitly called for a formalization of that regulation.}{\insrsid3297364   }{\insrsid11301554 
Among the other amendments that MDUFMA made to the statutory framework of the }{\insrsid16273608 Federal }{\insrsid11301554 Food, Drug}{\insrsid16273608 ,}{\insrsid11301554  and Cosmetic Act of 1938 (FDCA), }{\insrsid13829404 the o
rganic statute of the FDA, }{\insrsid11301554 it}{\insrsid3297364  }{\insrsid7953880 requir}{\insrsid3297364 ed}{\insrsid7953880  the FDA to establish an Office of Combination Products within sixty days \'93}{\cf1\insrsid7953880\charrsid7953880 
to ensure the prompt assignment of combination products to agency centers, the timely and effective premarket review of such products, and cons
istent and appropriate postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law}{\cf1\insrsid7953880 .\'94}{\cs16\cf1\super\insrsid3297364 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  MDUFMA }{
\cs18\insrsid16284404\charrsid7211990 \'a7 204(3), 21 U.S.C. \'a7 353 (2004).  Interestingly, the President\rquote s statement, }{\cs18\i\insrsid16284404\charrsid7211990 supra}{\cs18\insrsid16284404\charrsid7211990  note 2, made no mention of the new Offi
ce or its role.}}}{\cf1\insrsid7953880   }{\cf1\insrsid12547042 O}{\cf1\insrsid9994089 n December 31, 2002, }{\cf1\insrsid8999185 FDA }{\cf1\insrsid9994089 Commissioner }{\cf1\insrsid8999185 Mark }{\cf1\insrsid9994089 
McClellan notified the American public that this Office had indeed been created and that}{\cf1\insrsid10113953 ,}{\cf1\insrsid9994089  }{\cf1\insrsid10113953 as a new}{\insrsid9994089  part of the Office of the Commissioner, its responsibilities}{
\insrsid10113953  would}{\insrsid9994089  includ}{\insrsid10113953 e}{\insrsid9994089  the regulation of the entire \'93life cycle of combination products, including jurisdiction decisions as well as the timeliness and effectiveness of pre-mark
et review, and the consistency and appropriateness of post-market regulation}{\cf1\insrsid9994089 .\'94}{\cs16\cf1\super\insrsid9994089 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404\charrsid7211990  n.1.}}}{\cf1\insrsid9994089 
  }{\cf1\insrsid8856189 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8856189 {\cf1\insrsid8856189 \tab }{\cf1\insrsid9117351 Nearly twenty-four}{\cf1\insrsid3283153  months later, this Office}{\cf1\insrsid8999185 
 of Combination Products (OCP)}{\cf1\insrsid3283153  has survived}{\cf1\insrsid15342310  public hearings and opportunities for comment regarding }{\cf1\insrsid8999185 its}{\cf1\insrsid15342310  structure and }{\cf1\insrsid8999185 regulatory policies}{
\cf1\insrsid15342310 ,}{\cf1\insrsid3283153  }{\cf1\insrsid15342310 as well as }{\cf1\insrsid3283153 its first }{\cf1\insrsid12855723 mandatory }{\cf1\insrsid3283153 Annual Report to Congress}{\cf1\insrsid15342310 .}{\cs16\cf1\super\insrsid3283153 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Office of Combination Products Annual Report to Congress (October 26, 2003), }{\i\insrsid16284404\charrsid7211990 available at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/Congressreport.pdf" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003500000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0043006f006e00670072006500730073007200650070006f00720074002e00
7000640066000000e0c9ea79f9bace118c8200aa004ba90b6a00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0043006f006e00670072006500730073007200650070006f00720074002e0070
00640066000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/Congressreport.pdf}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\cf1\insrsid15342310  }{\cf1\insrsid14950376  }{
\cf1\insrsid15342310 In addition, it }{\cf1\insrsid11749157 has promulgated multiple regulations to m}{\cf1\insrsid12855723 anage its Congressional responsibilities}{\cf1\insrsid11749157 .}{\cs16\cf1\super\insrsid11749157 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 C.F.R. }{\cs18\insrsid16284404\charrsid7211990 \'a7\'a7 3.1-3.7, 5.7 (2004).}}}{\cf1\insrsid11749157   }{\cf1\insrsid12539947 Thus, the time is right to }{\cf1\insrsid8999185 
undertake}{\cf1\insrsid12539947  a critical review of the}{\cf1\insrsid8999185  initial}{\cf1\insrsid12539947  steps taken by the FDA to institute the OCP}{\cf1\insrsid10314179 .  }{\insrsid9975762\charrsid9975762 The goal of this}{\insrsid6907751 
 paper is to}{\insrsid9975762\charrsid9975762  }{\insrsid10314179 elucidate}{\insrsid6907751  the current structure of the OCP by examining the chain of historical developments that ultimately required }{\insrsid10314179 its}{\insrsid6907751  creation}{
\insrsid10314179 .}{\insrsid8999185\charrsid13069564 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8999185 {\insrsid8999185 \tab }{\insrsid4358008 Section I introduces the pertinent provisions of the FDCA}{\cs16\super\insrsid4003204 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4003204 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Federal Food, Drug, and Cosmetic Act}{\cs18\insrsid16284404\charrsid7211990 , 21 U.S.C. \'a7\'a7 321 }{\cs18\i\insrsid16284404\charrsid7211990 et seq.}{\cs18\insrsid16284404\charrsid7211990  (1938).}}}{\insrsid4358008  and 
traces the statutory development of how the}{\insrsid8999185  FDA}{\insrsid4358008  }{\insrsid3218507 has }{\insrsid4358008 define}{\insrsid3218507 d}{\insrsid4358008  a drug, a medical device, and a biological product}{\insrsid3218507 
 since the inception of the FDCA}{\insrsid4358008 .}{\insrsid8222120   Armed wi}{\insrsid4746465 th those definitions, Section I}{\insrsid8222120  then traces the }{\insrsid16273608 regulatory}{\insrsid8222120  }{\insrsid14427343 procedures }{
\insrsid16273608 for}{\insrsid14427343  each of}{\insrsid8222120  those three}{\insrsid3218507  product }{\insrsid14427343 categories}{\insrsid3218507  to illustrate}{\insrsid4746465  the diversity of approval procedur}{\insrsid16273608 
es that exist within the FDA.  This}{\insrsid4746465  illustration throws into relief }{\insrsid3218507 the}{\insrsid8222120  }{\insrsid14427343 long-felt}{\insrsid4746465  }{\insrsid8222120 need for }{\insrsid1317001 the OCP }{\insrsid8222120 to }{
\insrsid4746465 coordinate}{\insrsid8222120  the regulation of }{\insrsid4746465 products}{\insrsid14427343  that implicate more than one product category}{\insrsid4746465 .}{\insrsid3218507  }{\insrsid4746465  Section II
 details the historical and noteworthy developments surrounding the }{\insrsid14427343 initial appearance of and subsequent increase in }{\insrsid4746465 combination products during }{\insrsid3218507 the latter half of the 20}{
\super\insrsid3218507\charrsid3218507 th}{\insrsid3218507  Century}{\insrsid8222120 .}{\insrsid3218507   }{\insrsid14515834 This chronological treatment highlights the gradual change in the FDA\rquote s sophistication }{\insrsid11090332 towards the}{
\insrsid14515834  regulati}{\insrsid11090332 on of}{\insrsid14515834  this new product category.  }{\insrsid16273608 Section III}{\insrsid1126830  }{\insrsid3218507\charrsid216622 explore}{\insrsid16273608 s}{\insrsid3218507\charrsid216622  the }{
\insrsid14635512 legislative history surrounding the passage of the Safe Medical Devices Act (SMDA) of 1990, and the provision that led to numerous changes in the way the FDA regulates thousands of products each year.  Section IV explains }{
\insrsid4149806 the }{\insrsid1250504 contribution of the Food and Drug Administration Modernization Act (FDAMA) of 1997 to the regulation of combination products.  Section V describes the }{\insrsid4149806 latest and most dramatic changes accompany
ing the regulation of combination products: the Medical Device User Fee and Modernization Act (MDUFMA) of 2002.  From this Act, the OCP was born.  }{\insrsid14635512 Section V}{\insrsid1250504 I}{\insrsid14635512  examines the }{
\insrsid3218507\charrsid216622 current statu}{\insrsid216622 s of the }{\insrsid3218507\charrsid216622 OCP}{\insrsid216622  and}{\insrsid14635512  Section V}{\insrsid1250504 I}{\insrsid14635512 I concludes the analysis.}{\b\insrsid3218507   }{
\insrsid4358008\charrsid3218507 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid6122459 {\i\ul\insrsid12270558 I. }{\i\ul\insrsid8930057 Basic Definitions}{\i\ul\insrsid5523092  and Regulatory}{\i\ul\insrsid6122459 
 Procedures for Drugs, Medical Devices, and Biologic}{\i\ul\insrsid5523092 s}{\insrsid8930057 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8930057 {\insrsid8930057 \tab }{\insrsid5929100 The FDCA}{\insrsid10372633  }{\insrsid9855239 was }{\insrsid3342990 first }{\insrsid9855239 
enacted in 1938 }{\insrsid1510825 as a measure to protect}{\insrsid10372633  the}{\insrsid15930233  health and safety }{\insrsid10372633 of the American public }{\insrsid15930233 through}{\insrsid1510825  the}{\insrsid7889177  uniform}{\insrsid1510825 
 federal}{\insrsid15930233  regulation of food, drugs, }{\insrsid10036680 medical devices }{\insrsid15930233 and cosmetics. }{\insrsid10372633  }{\insrsid4358008 The }{\insrsid8944489 FDA, while existing in a variety of forms and under }{\insrsid1510825 
different monikers within multiple }{\insrsid8944489 federal departments since 1862}{\cs16\super\insrsid8944489 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Peter Barton Hutt, }{
\i\insrsid16284404\charrsid7211990 A Historical Introduction}{\insrsid16284404\charrsid7211990 , 45 FDC L.J. 17 (1990).}}}{\insrsid8944489 , was statutorily recognized in 1988.}{\cs16\super\insrsid8944489 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  102 Stat. 3048, 3120-22 (1988).}}
}{\insrsid8944489   Now a division of the Department of Health and Human Services, the FDA }{\insrsid7155175 is responsible for }{\insrsid6899421 executing and }{\insrsid7155175 enforcing}{\insrsid8944489  the FDCA}{\cs16\super\insrsid3342990 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3342990 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 C.F.R. }{\cs18\insrsid16284404\charrsid7211990 \'a7 5.10(a)(1) (2004).}}}{\insrsid3342990  and }{\insrsid7889177 portions of }{\insrsid3342990 the Public Health Service Act}{\insrsid8944489 .}{
\cs16\super\insrsid3342990 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  Public Health Service Act, 42 U.S.C. }{\cs18\insrsid16284404\charrsid7211990 \'a7 201 (2004). }}}{\insrsid8944489   }{\insrsid10509508 
Most drugs (for human or animal use), medical devices, and biological products introduced int}{\insrsid3342990 o American interstate commerce}{\insrsid10509508  must first survive a lengthy approval process overseen by the FDA.}{
\cs16\super\insrsid10509508 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 U.S.C. }{\cs18\insrsid16284404\charrsid7211990 \'a7\'a7 355, 360b, 360e (2004); 42 U.S.C. \'a7 262(a) (2004).}}}{\insrsid7889177   A}{\insrsid15546923 
ny food, drug, medical device, cosmetic or biological product that is adulterated or misbranded}{\insrsid5388980  potentially subjects the manufacturer, shipper, and seller }{\insrsid15546923 of that product to a variety of civil and criminal penalties.}{
\cs16\super\insrsid15546923 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. }{\cs18\insrsid16284404\charrsid7211990 \'a7\'a7 342-43, 351-52, 361-62 (2004); 42 U.S.C. \'a7
 262 (2004).  Violations of the FDCA and the accompanying penalties are codified at 21 U.S.C. \'a7\'a7 331-37 (2004).}}}{\insrsid13763168   The choice o
f the FDA to prosecute a violation of the FDCA is usually reviewed only to ensure that the choice was not \'93arbitrary or capricious}{\insrsid1510825 ,}{\insrsid13763168 \'94}{\cs16\super\insrsid13763168 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Administrative Procedure Act, 5 U.S.C. }{\cs18\insrsid16284404\charrsid7211990 \'a7 706(2)(A) (2004).}}}{\insrsid13763168  and the selective }{\insrsid13763168\charrsid1510825 
nonenforcement}{\insrsid13763168  of the FDCA }{\insrsid7412044 by the FDA }{\insrsid13763168 is nearly unreviewable.}{\cs16\super\insrsid13763168 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 Heckler v. Chaney, 470 U.S. 821 (1985).}}}{\insrsid15089287 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid15089287 {\i\ul\insrsid12270558 I. A. Drugs}{\insrsid15089287 \tab }{\insrsid12270558 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12270558 {\insrsid12270558 \tab }{\insrsid15089287 Pursuant to the FDC}{\insrsid10968101 A}{\insrsid15089287 , a}{\insrsid10968101  }{\insrsid8933934 
\'93}{\insrsid10968101 drug}{\insrsid8933934 \'94}{\insrsid10968101  is any article}{\insrsid8933934 , or component thereof,}{\insrsid10968101  \'93intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man\'94 or \'93
intended to affect the structure or any function of the body of man.\'94}{\cs16\super\insrsid10968101 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7\'a7 321(g)(1)(B)-(C), (g)(2) (1938).}}}{\insrsid10968101   }{\insrsid4609363 
Drugs were originally defined in 1938 to exclude devices, but the Safe Medical Devices Act of 1990 }{\insrsid12867625 (SMDA) }{\insrsid4609363 eliminated that exclusion.}{\cs16\super\insrsid6899421 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 321(g)(1), }{
\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  Safe Medical Devices Act of 1990, Pub. L. No. 101-629, sec. 16(b)(1), 104 Stat. 4511 (November 28, 1990); }{\i\insrsid16284404\charrsid7211990 see infra}{
\insrsid16284404\charrsid7211990  Section I.B.}}}{\insrsid10290628   Other than the single}{\insrsid12679794  amendment in 1990, the definition of a \'93drug\'94 has remained the same since 1938.}{\insrsid4486913   }{\insrsid12270558 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12270558 {\insrsid12270558 \tab }{\insrsid4486913 The regulation of premarket approval and postmarket surv
eillance of FDA-approved drugs rests with the Center for Drug Evaluation and Research (CDER).}{\cs16\super\insrsid8794611 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7
 314 et seq., 21 C.F.R. \'a7 5.701(a)(3) (2004).}}}{\insrsid4486913   }{\insrsid12325240 A portion of the FDA staff has been devoted to studying and approving new drugs since t}{\insrsid4486913 he enac}{\insrsid7889177 tment of the FDCA in 1938.}{
\cs16\super\insrsid15430111 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Donna Hamilton, }{\i\insrsid16284404\charrsid7211990 Brief History of CDER}{\insrsid16284404\charrsid7211990 , }{
\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cder/about/history/Histext.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00610062006f00750074002f0068006900730074006f00720079002f0048006900730074006500780074002e00680074006d00
0000e0c9ea79f9bace118c8200aa004ba90b6400000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00610062006f00750074002f0068006900730074006f00720079002f0048006900730074006500780074002e00680074006d000000}}
}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cder/about/history/Histext.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).  }}}{\insrsid4486913  }{\insrsid7889177  T}{\insrsid12325240 he }{\insrsid7889177 
current form of }{\insrsid12325240 CDER}{\insrsid10121463 , however, is the result of multiple institutional changes within the FDA.}{\insrsid12325240  }{\insrsid10121463  The Center for Biologics }{\insrsid10774716 Evaluation and Research (CBER) }{
\insrsid10121463 was transferred from the National Institutes of Health (NIH) to the FDA in 1972 while }{\insrsid12598400 it }{\insrsid10121463 still }{\insrsid12598400 bore }{\insrsid10121463 the name of the Bureau of Biologics.}{
\cs16\super\insrsid10121463 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 peter barton hutt & richard a. merrill, food and drug law}{\insrsid16284404\charrsid7211990 
 664 (2d ed. Foundation Press 1991) (hereinafter \'93}{\scaps\insrsid16284404\charrsid7211990 hutt & merrill\'94}{\insrsid16284404\charrsid7211990 ).}}}{\insrsid10698581 
  At this time, CDER was actually titled the Bureau of Drugs.  In 1982, the two Bureaus were united within the }{\insrsid15348071 FDA to form the }{\insrsid10698581 National Center for Drugs and Biologics, later renamed the Center for Drugs and Biologics.
}{\cs16\super\insrsid10698581 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid14449701   }{\insrsid6186619 Their union was formal, not functional.  Th}{\insrsid14449701 e union}{\insrsid6186619 , moreover,}{\insrsid14449701 
 was temporary; the two groups were divided in 1988}{\insrsid4538992  when the Center for Drugs and Biologics was split into CDER and}{\insrsid15348071  }{\insrsid8794611 CBER.}{\cs16\super\insrsid8794611 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.  See supra}{\insrsid16284404\charrsid7211990  n.19}{\i\insrsid16284404\charrsid7211990 .  }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990 
 53 Fed. Re}{\insrsid16284404 g. 8978 (March 18, 1988).}{\insrsid16284404\charrsid7211990   }}}{\insrsid4538992   CBER}{\insrsid8794611  now oversees the premarket approval of biologics, as discussed }{\i\insrsid8794611 infra}{\insrsid14704033 
 at Section I.C}{\insrsid8794611 .}{\insrsid7614668   CDER is the largest Center within the FDA, boasting over one thousand employees}{\insrsid534253 , eleven major Offices and seven subsidiary Divisions.}{\cs16\super\insrsid534253 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 
19;  U.S. Food and Drug Administration, Center for Drug Evaluation and Research, CDER Offices and Divisions Page, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/cder/office.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002300000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f006f00660066006900630065002e00680074006d000000e0c9ea79f9bace118c8200aa004ba90b460000006800740074007000
3a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f006f00660066006900630065002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cder/office.htm}}}{\insrsid16284404\charrsid7211990 
 (last visited April 16, 2004).}}}{\insrsid13774851   }{\insrsid8016991 Just recently,}{\insrsid8016991\charrsid7211990  }{\insrsid597630 CBER and CDER partially reunited once again.  The latest division of }{\insrsid8016991\charrsid7211990 CBER\rquote 
s jurisdiction}{\insrsid597630  was finalized}{\insrsid8016991\charrsid7211990  }{\insrsid597630 in late 2004 }{\insrsid8016991\charrsid7211990 into a CBER-only review reg}{\insrsid946332 ime and a }{\insrsid8016991\charrsid7211990 review }{
\insrsid946332 regime under CDER}{\insrsid8016991\charrsid7211990 .  CDER now bears the responsibility for the review of }{\insrsid8016991 therapeutic biologics (excepting cell and gene therapy products and therapeutic vaccines)}{
\insrsid8016991\charrsid7211990  that traditionally were reviewed }{\insrsid6704926 only }{\insrsid8016991\charrsid7211990 by CBER.}{\cs16\super\insrsid12325240 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 68 Fed. Reg. 38067, 38068 (June 26, 2003).  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404  CBER Transfer of Therapeutic Products to CDER, }{\i\insrsid16284404 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cber/transfer/transfer.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002e00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f007400720061006e0073006600650072002f007400720061006e0073006600650072002e00680074006d000000e0c9ea79f9ba
ce118c8200aa004ba90b5c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f007400720061006e0073006600650072002f007400720061006e0073006600650072002e00680074006d000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cber/transfer/transfer.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}{\insrsid16284404   }{\i\insrsid16284404\charrsid7211990 See, e.g.}{
\insrsid16284404\charrsid7211990  CBER Annual Report FY 2003, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cber/inside/annrpt.htm" 
}{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002a00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f0069006e0073006900640065002f0061006e006e007200700074002e00680074006d000000e0c9ea79f9bace118c8200aa004b
a90b5400000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f0069006e0073006900640065002f0061006e006e007200700074002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 
http://www.fda.gov/cber/inside/annrpt.htm}}}{\insrsid16284404\charrsid7211990  (last visited February 3, 2005).}}}{\insrsid12325240   }{\insrsid12734806 
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12734806 {\insrsid13774851 Currently, }{\insrsid5389376 the}{\insrsid13774851  role}{\insrsid5389376  of CDER is}{\insrsid13774851 
 divided among four major activities: new drug development and review, generic drug review, over-the-counter drug review, and post drug approval activities.}{\cs16\super\insrsid13774851 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  CDER Handbook, }{
\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cder/handbook" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002100000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b000000e0c9ea79f9bace118c8200aa004ba90b4200000068007400740070003a002f00
2f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cder/handbook}}}{\insrsid16284404\charrsid7211990 
 (last visited April 16, 2004).}}}{\insrsid14366538   The approval of a new drug is the most scientifically rigorous, time-con
suming and expensive process that CDER, and the FDA, undertakes.  A drug manufacturer, or sponsor, who wishes to have a new drug marketed within the United }{\insrsid15945552 States,}{\insrsid14366538  must file an Investigational New}{\insrsid11810527 
 Drug Application (IND) with}{\insrsid14366538  CDER.}{\cs16\super\insrsid14366538 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 ; Investigational New Drug Application, }{\i\insrsid16284404\charrsid7211990 at}{
\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cder/handbook/index.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002b00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b002f0069006e006400650078002e00680074006d000000e0c9ea79f9bace118c8200aa
004ba90b5600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b002f0069006e006400650078002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 
http://www.fda.gov/cder/handbook/index.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7 314.1 et seq.}}}{\insrsid14366538 
   The IND contains animal pharmacology and toxicology data that (hopefully) }{\insrsid16589730 demonstrates}{\insrsid14366538 
 that the drug will be initially safe in humans, and proposed clinical trial and manufacturing information.  If CDER approves the IND, the sponsor}{\insrsid8197923  may}{\insrsid14946548  proceed with clinical tr}{\insrsid8197923 ials using humans and}{
\insrsid14946548  ship the drug in interstate commerce as part of those clinical trials.}{\cs16\super\insrsid14946548 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid16073204 
  At the close of the clinical trials, the sponsor may file a New Drug Application (NDA) with CDER.}{\cs16\super\insrsid16073204 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 355 (1938); }{
\i\insrsid16284404\charrsid7211990 see also }{\insrsid16284404\charrsid7211990 Kefauver-Harris Amendments, Pub. L. No. 87-781, 76 Stat. 780 (October 10, 1962).}}}{\insrsid16073204   The sponsor must show, through clinical data resulting}{\insrsid2512138 
 from two}{\insrsid11810527  human trials}{\insrsid16073204 , that the drug is both safe and effective for human use.}{\cs16\super\insrsid2512138 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 321(p) (2004); 21 U.S.C. \'a7 355(d)-(e); 21 C.F.R. \'a7
 314.50, 34 Fed. Reg. 14596 (September 19, 1969).}}}{\insrsid16725285   In addition, the sponsor must now contribute a user fee }{\insrsid14359912 to accompany the NDA and any later }{\insrsid8197923 application }{\insrsid14359912 supplements }{
\insrsid8197923 in exchange for}{\insrsid16725285  CDER}{\insrsid8197923 \rquote s}{\insrsid16725285  review}{\insrsid8197923  of the}{\insrsid16725285  NDA.}{\cs16\super\insrsid2258376 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7
 379j(a) (2004); FDA Modernization Act of 1997, Pub. L. No. 105-115, 111 Stat. 2296, sec. 103 (November 21, 1997).}}}{\insrsid13904165   }{\insrsid5592294 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5592294 {\insrsid5592294 \tab }{\insrsid13904165 The sponsor of a new generic, or \'93me-too\'94}{\cs16\super\insrsid13904165 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990  at 478.}}}{\insrsid13904165  version, of a }{\insrsid14763718 \'93pioneer\'94 }{
\insrsid13904165 drug that already has  premarket approval from CDER does not need to file a }{\insrsid11810527 full}{\insrsid13904165  NDA.}{\insrsid14763718   Rather, those \'93me-too\'94 drugs are permitted to pursue an abbreviated NDA approval (ANDA)}
{\cs16\super\insrsid14763718 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 355(j).}}}{\insrsid11810527  once the patent and period of market exclusivity for}{\insrsid14763718  the \'93pioneer\'94 drug has expired.}{\cs16\super\insrsid14763718 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 355(j(2)(A)(vii).}}}{\insrsid8197923   Approval of an}{\insrsid14763718  ANDA }{\insrsid8197923 prior to marketing of the \'93me-too\'94 drug }{\insrsid14763718 
simply requires evidence of the drug\rquote s bioequivalence to the \'93pioneer\'94 drug.}{\cs16\super\insrsid14763718 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 355(j)(2)(A)(iv).}}}{
\insrsid11486961  Once a drug has been approved by CDER, ongoing postmarket surveillance of the dru
g takes place, with input from the medical profession, the pharmaceutical industry, the World Health Organization, other federal agencies (both foreign and domestic), and cooperative agreements with drug safety evaluation databases.}{
\cs16\super\insrsid11486961 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  Drug Experience/Epidemiologic Sources Available to FDA (for Post-Marketing Surveillance and Risk Assessment), }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cder/handbook/index.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002b00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b002f0069006e006400650078002e00680074006d000000e0c9ea79f9bace118c8200aa
004ba90b5600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400650072002f00680061006e00640062006f006f006b002f0069006e006400650078002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 
http://www.fda.gov/cder/handbook/index.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid4609363\charrsid8794611 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4609363 {\i\ul\insrsid12734806 I. B. Medical Devices}{\insrsid4609363 \tab }{\insrsid12734806 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12734806 {\insrsid12734806 \tab }{\insrsid10036680 Medical devices were also subject to the original FDCA as it was en}{\insrsid10178672 
acted in 1938.  A \'93device\'94 included}{\insrsid10036680  
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid10036680 {\insrsid10036680 \'93
instruments, apparatus, and contrivances, including their components, parts, and accessories, intended (1) for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; or (2) to affect the structur}{
\insrsid2305082 e or any function of the body of}{\insrsid10036680  man or other animals.\'94}{\cs16\super\insrsid10036680 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 321(h) (1938).}}}{\insrsid10036680  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid15089287 {\insrsid10036680 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4670537 {\insrsid10372633 In 1976, Congress amended the FDCA through the passage of the Medical Device Amendments.}{\cs16\super\insrsid10372633 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Medical Device Amendments of 1976, Pub. L. No. 94-295, 90 Stat. 539 (May 28, 1976) (codified as amended in scattered sections of 21 U.S.C.).}}}{\insrsid4344831   T}{\insrsid10036680 he definition of a}{\insrsid8331958  }{\insrsid8933934 \'93}{
\insrsid10036680 device}{\insrsid8933934 \'94}{\insrsid8331958  }{\insrsid10036680 was altered}{\insrsid3891666  in part}{\insrsid10036680 
 to reflect the increasing sophistication that the FDA witnessed in the design and capability of proposed medical devices.  A \'93device\'94 }{\insrsid2958961 was more broadly defined to }{\insrsid10036680 include an \'93implement,\'94 \'93machine,\'94 
\'93implant,\'94 \'93}{\i\insrsid10036680 in vitro}{\insrsid10036680  reagent, or other similar or related article.\'94}{\cs16\super\insrsid10036680 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7321(h) (2004), }{
\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  Pub. L. No. 94-295, sec. 3(a)(1)(A), 90 Stat. 539.}}}{\insrsid10036680   }{\insrsid4129014 More importantly,}{\insrsid10036680  the }{\insrsid2305082 broadened}{
\insrsid10910549  }{\insrsid10036680 definition of a \'93device\'94}{\insrsid4129014  modified}{\insrsid10036680  the language \'93intended to affect the structure or any function of the body of man.\'94  To }{\insrsid13394477 eliminate overlap in }{
\insrsid2958961 the }{\insrsid13394477 regulation of drugs, biologics, and devices, Congress }{\insrsid2305082 used the 1976}{\insrsid2958961  Amendments }{\insrsid10910549 to require that a device}{\insrsid13394477  \'93not achiev}{\insrsid10910549 e}{
\insrsid6899421  any of its principal}{\insrsid13394477  intended purposes through chemical action within or on the body . . .}{\insrsid6165824 \'94}{\insrsid13394477  }{\insrsid6165824 nor be \'93}{\insrsid13394477 
dependent upon being metabolized for the achievement of }{\insrsid6899421 any of }{\insrsid13394477 its pri}{\insrsid6899421 ncipal}{\insrsid13394477  intended purposes.}{\insrsid8331958 \'94}{\cs16\super\insrsid8331958 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
  The 1976 Amendments, by eliminating this definitional overlap, served to overrule the 1969 decision in United States v. An Article of Drug . . . Bacto-Unidisk . . ., 394 U.S. 784, 793, 797 (1969).  That decision defined \'93drug\'94
 within the FDCA to be much broader than the medical profession would define it, and then considered a \'93device\'94 to have a parallel definition with only semantic differences.}}}{\insrsid13394477   }{\insrsid6899421 
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid6899421 {\insrsid6585529 Devices }{\insrsid1533862 were}{\insrsid6585529  }{\insrsid10493104 classified under}{\insrsid6899421  the}{
\insrsid10493104  1976}{\insrsid6899421  Amendments}{\insrsid6585529  to belong to one of three classes}{\insrsid11747088  (I, II, or III)}{\insrsid6585529 , depending upon the amount of }{\insrsid1533862 clinical information that existed}{
\insrsid6585529  to reasonably assure the FDA of the safety and effectiveness of the device.}{\cs16\super\insrsid6585529 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360c(a) (2004), }{\i\insrsid16284404\charrsid7211990 amended by}{
\insrsid16284404\charrsid7211990  Pub. L. No. 94-295, sec. 2, 90 Stat. 539.}}}{\insrsid6585529   }{\insrsid985421 
Class I devices required neither a standard nor premarket approval because the general regulatory controls that the FDCA provided sufficiently guaranteed the device\rquote s safety and effectiveness}{\insrsid1533862 .}{\cs16\super\insrsid985421 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid985421 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360c(h); }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990  at 745.}}}{\insrsid985421  }{
\insrsid1533862   A device that required}{\insrsid6296116  more specialized controls}{\insrsid11367502  (or \'93performance standards\'94}{\cs16\super\insrsid11367502 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360d.}}}{\insrsid11367502 )}{\insrsid6296116  to ex}{\insrsid1533862 hibit safety and effectiveness }{\insrsid10178672 under the FDCA }{\insrsid1533862 wa}{
\insrsid6296116 s a Class II device, and those devices that require}{\insrsid1533862 d}{\insrsid6296116  premarket approval}{\cs16\super\insrsid11367502 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360e.}}}{\insrsid6296116  to provide reasonable assurance of their safety and effectivene}{\insrsid1533862 ss we}{\insrsid6296116 re Class III devices.}{
\cs16\super\insrsid11367502 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11367502 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360c(a)(1)(A)-(C).}}}{\insrsid985421   Class III also originally included all devices that were introduced for FDA approval following the 1976 Amendments (\'93postenactment devices\'94
) that were not substantially equivalent to \'93preenactment devices.\'94}{\cs16\super\insrsid985421 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990  at 745.}}}{\insrsid13508550 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13508550 {\insrsid13508550 \tab }{\insrsid8927137 With the passage of the }{\insrsid6379882 SMDA}{\insrsid9119629  in 1990}{\insrsid8927137 
, Congress once again modified the definition of a \'93device}{\insrsid3172612 .\'94  Rathe}{\insrsid13396229 r than }{\insrsid4344831 barring}{\insrsid13396229  a device }{\insrsid4344831 from achieving}{\insrsid3172612  \'93any of its principal\'94
 intended purposes through chemical action or being metabolized by the body, a device }{\insrsid4344831 is now barred from achieving}{\insrsid3172612  \'93its primary\'94 intended purposes through those enumerated means.}{\cs16\super\insrsid3172612 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See infra}{\insrsid16284404\charrsid7211990  section II.A., note 102; 21 U.S.C. \'a7 321(h)(3), }{\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  Saf
e Medical Devices Act of 1990 (hereinafter \'93SMDA\'94), Pub. L. No. 101-629, sec. 16(b)(2), 104 Stat. 4511 (November 28, 1990).}}}{\insrsid8927137  }{\insrsid12867625  }{\insrsid11873122 
The SMDA of 1990 also required the FDA to undertake a massive reclassification of currently regulated medical devices.}{\cs16\super\insrsid10553577 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990  at 750-51.}}}{\insrsid11873122  }{\insrsid14501310 
 Section 515 of the FDCA was amended to require}{\insrsid10553577  the FDA}{\insrsid14501310 \rquote s}{\insrsid10553577  reconsider}{\insrsid14501310 ation of}{\insrsid10553577  its classification of all }{\insrsid14501310 preenactment }{
\insrsid10553577 Class III devices and mandated that those devices be reclassified as Class I}{\insrsid14501310  or Class II, unless the FDA could}{\insrsid10553577  show that the device pr}{\insrsid14501310 operly belonged}{\insrsid10553577 
 in Class III.}{\cs16\super\insrsid10553577 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7\'a7 360c(e)-(f), 360e(i) (2004), }{\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  SMDA, Pub. L. No. 101-629, sec. 4(b), sec. 5, 104 Stat. 4511.}}}{
\insrsid11873122 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13508550 {\insrsid14188188 \tab Currently, the }{\insrsid15485003 regulation}{\insrsid10493104  of medical devices in}{\insrsid15485003 
 the United States rests with}{\insrsid14188188  the Center for Devices and Radiological Health (CDRH)}{\insrsid15485003  within the FDA}{\insrsid14188188 .}{\cs16\super\insrsid14188188 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 5.701(a)(2) (2004).  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Center for Devices and Radiological Health, Device Advice, Overview of Regulations, }{\i\insrsid16284404\charrsid7211990 at}{
\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cdrh/devadvice/overview.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400720068002f006400650076006100640076006900630065002f006f0076006500720076006900650077002e00680074006d006c000000e0c9
ea79f9bace118c8200aa004ba90b6000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400720068002f006400650076006100640076006900630065002f006f0076006500720076006900650077002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cdrh/devadvice/overview.html}}}{\insrsid16284404\charrsid7211990  (last visited January 24, 2004).}}}{\insrsid15489033 
  Class I devices do not require premarket approval (PMA) nor do most Class I devices require any premarket notification (PMN)}{\insrsid16461234 .}{\cs16\super\insrsid1917831 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 A list of Class I and II devices that are exempt from a PMN can be found at }{\field\fldedit{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm" }}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm}}}{\insrsid16284404\charrsid7211990  (last visited January 24, 2004).}}}{\insrsid16461234   Most Class II devices, however, do require a PMN, 
often known }{\insrsid2255026 through}{\insrsid16461234  its statutory shorthand as a \'93510(k)\'94}{\insrsid2848779  because }{\insrsid4808405 the PMN provision}{\insrsid2848779 s}{\insrsid4808405  are codified}{\insrsid2848779 
 within section 510(k) of the FDCA.}{\cs16\super\insrsid16461234 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360(k) (2004).}}}{\insrsid15999582  }{\insrsid4808405  A 510(k)}{\insrsid15999582  must be filed with and }{\insrsid10493104 cleared}{\insrsid15999582 
 by the CDRH prior to marketing of the device}{\insrsid5331785  in the United States}{\insrsid15999582 .  The 510(k) must }{\insrsid10493104 demonstrate}{\insrsid15999582  that the device seeking FDA approval is either \'93substantially equivalent\'94}{
\cs16\super\insrsid15999582 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid15999582 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360c(i) (2004); 21 C.F.R. \'a7 807(e) (2004); }{\i\insrsid16284404\charrsid7211990 see supra}{\insrsid16284404\charrsid7211990  note 48.}}}{\insrsid15999582 
 to a device that has received premarket approval prior to the enactment of the 1976 Amendments, or to another device that the CDRH has already determined to be substantially equivalent.}{\insrsid15879354   }{\insrsid3420104 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3420104 {\insrsid3420104 \tab }{\insrsid15879354 
A device that requires a PMA is a Class III device that poses a significant injury or illness risk, or a Class III device that was not substantially equivalent to a Class I or Class II device already approved under the 510(k) process.}{
\cs16\super\insrsid15879354 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 48; }{\i\insrsid16284404\charrsid7211990 see}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7\'a7
 360c(a)(1)(C(ii)(II), 360e(a)-(b) (2004); 21 C.F.R. \'a7 814 (2004).}}}{\insrsid15879354   Although a PMA is not as time-consuming or as expensive as a}{\insrsid10493104 n}{\insrsid15879354 
 NDA for a new drug, the PMA is more difficult to obtain than a PMN and represents an actual approval by the CDRH.}{\cs16\super\insrsid15879354 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid4656569   }{\insrsid7283640 
Single-use Class III devices may also now be reprocessed and marketed in the United State}{\insrsid4204158 s, but the manufacturer must prepare first a premarket report (PMR) for submission to the FDA.  The PMR }{\insrsid7283640 is similar to a PMA, but }
{\insrsid4204158 it }{\insrsid7283640 does not require }{\insrsid11880389 the inclusion of }{\insrsid7283640 information }{\insrsid11880389 that explains how the device was}{\insrsid7283640  original}{\insrsid11880389 ly}{\insrsid7283640  manufactur}{
\insrsid11880389 ed}{\insrsid7283640  }{\insrsid11880389 or}{\insrsid7283640  process}{\insrsid11880389 ed}{\insrsid7283640 .}{\cs16\super\insrsid7283640 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 379i(2) (2004), }{
\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  MDUFMA, Pub. L. No. 107-250, sec. 102(a), 116 Stat. 1588 (October 26, 2002); }{\i\insrsid16284404\charrsid7211990 see }{\insrsid16284404\charrsid7211990 21 U.S.C. \'a7\'a7
 360e(c)(1)-(2)(A) (2004), }{\i\insrsid16284404\charrsid7211990 amended by }{\insrsid16284404\charrsid7211990 MDUFMA, sec. 302(c)(2)(B).}}}{\insrsid7283640   }{\insrsid14752921 A}{\insrsid4656569 
n unapproved medical device may be used in clinical trials on human subjects pursuant to an investigational device exemption (IDE).  The proposed clinical trials must be first approved, however, by CDRH and an institutional review board (IRB).}{
\cs16\super\insrsid4656569 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\i\insrsid16284404\charrsid7211990  See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 48; 21 U.S.C. \'a7 360j(g) (2004); 21 C.F.R. \'a7 812 (2004).}}}{\insrsid14496085   }{\insrsid1332362 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1332362 {\insrsid1332362 \tab }{\insrsid14496085 For }{\insrsid5244305 both}{\insrsid14496085  a PMN }{\insrsid5244305 and}{\insrsid14496085 
 a PMA (and some PMA supplements), the device manufacturer must also submit a user fee in exchange for CDRH\rquote s review of the application.}{\cs16\super\insrsid14496085 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 379(j) (2004), }{
\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  MDUFMA, Pub. L. No. 107-250, sec. 738, 116 Stat. 1588 (October 26, 2002).}}}{\insrsid14496085 
  Currently, the fee to file a PMA is roughly one hundred times greater than the fee that accompanies the filing of a PMN.}{\cs16\super\insrsid14496085 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Center for Devices and Radiological Health, Device Advice, PMA Review Fees, }{\i\insrsid16284404\charrsid7211990 at }{\insrsid16284404\charrsid7211990 
http://www.fda.gov/cdrh/devadvice/pma/userfees.html (last visited April 16, 2004).}}}{\insrsid14496085   Between 1976 and 1991, more than 98 percent of new medical devices sought a PMN through substantial equivalence}{\insrsid5244305 
 with a preenactment device}{\insrsid14496085 .}{\cs16\super\insrsid14496085 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990 
 at 752.}}}{\insrsid13771816   The CDRH also performs varying levels of postmarket surveillance, rangin}{\insrsid12352478 g from mandatory surveillance of}{\insrsid13771816 
 certain life-sustaining devices to discretionary surveillance of devices when it is necessary to protect the public health.}{\cs16\super\insrsid13771816 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7\'a7
 360l(a)(1)-(2) (2004); }{\i\insrsid16284404\charrsid7211990 see}{\insrsid16284404\charrsid7211990  Center for Devices and Radiological Health, Postmarket Surveillance Studies, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }
{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cdrh/devadvice/352.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002b00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400720068002f006400650076006100640076006900630065002f003300350032002e00680074006d006c000000e0c9ea79f9bace118c8200aa
004ba90b5600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400720068002f006400650076006100640076006900630065002f003300350032002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://w
ww.fda.gov/cdrh/devadvice/352.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid14188188 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8927137 {\i\ul\insrsid12734806 I. C. Biological Products}{\insrsid8927137 \tab }{\insrsid12734806 
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12734806 {\insrsid2234743 The}{\insrsid4670537  }{\insrsid8027375 federal }{\insrsid5251016 Biologics}{\insrsid8027375  Act}{\insrsid4670537 , }{
\insrsid8933934 as }{\insrsid8027375 originally passed in 1902}{\insrsid8933934 ,}{\insrsid8027375  }{\insrsid5910035 prohibited the interstate }{\insrsid14363549 commercial sale or production}{\insrsid5910035  of 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid5910035 {\insrsid5910035 \'93
any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or its derivatives (or any other trivalent organic arsenic compound), a
pplicable to the prevention, treatment, or cure of disease or injuries of man . . .\'94}{\cs16\super\insrsid14363549 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Biologics Act, 32 Stat. 728 (1902).}}}{\insrsid5910035  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4670537 {\insrsid8933934 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4670537 {\insrsid5910035 This language was }{\insrsid8027375 recodified }{\insrsid14363549 within section 351 of}{\insrsid8027375 
 the Public Health Services Act (PHSA) in 1944}{\insrsid2234743 .}{\cs16\super\insrsid5910035 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  42 U.S.C. \'a7 262(a) (1944).}}}{\insrsid8933934  }{\insrsid2234743  In 1972, enforcement o}{\insrsid2112030 
f the PHSA was delegated to the }{\insrsid4670537 FDA}{\cs16\super\insrsid5251016 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. }{\cs18\insrsid16284404\charrsid7211990 \'a7 5.10 (2004); }{\insrsid16284404\charrsid7211990 37 Fed. Reg. 12865 (June 29, 1972).}}}{\insrsid16127746 
 and in 1997, the FDA Modernization Act of 1997 (}{\insrsid14706681 FDAMA) }{\insrsid3961900 codified}{\insrsid14706681  this language}{\insrsid8930057 , with minor changes,}{\insrsid14706681  to }{\insrsid3961900 define}{\insrsid14706681  a}{
\insrsid16127746  \'93biological product}{\insrsid14706681 .}{\insrsid16127746 \'94}{\cs16\super\insrsid16127746 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  42 U.S.C. \'a7 262(i) (1997), }{\i\insrsid16284404\charrsid7211990 amended by}{
\insrsid16284404\charrsid7211990  Food and Drug Administration Modernization Act of 1997 (hereinafter \'93FDAMA\'94), Pub. L. No. 105-115, sec. 123(d), 111 Stat. 2296 (November 21, 1997).}}}{\insrsid5181694   }{\insrsid7623269 One important distinction}{
\insrsid13261361  between biological products and drugs}{\insrsid7623269  is that biological products are derived from living sources, whereas drugs are chemically synthesized.}{\cs16\super\insrsid7623269 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Center for Biologics Evaluation and Research, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cber/about.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f00610062006f00750074002e00680074006d000000e0c9ea79f9bace118c8200aa004ba90b4400000068007400740070003a00
2f002f007700770077002e006600640061002e0067006f0076002f0063006200650072002f00610062006f00750074002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cber/about.htm}}}{\insrsid16284404\charrsid7211990 
 (last visited April 16, 2004).}}}{\insrsid1212048   At the same time, many biological products can also be classified as a \'93drug\'94 under section 321(g)(1) of the FDCA and thus, the authority }{\insrsid2112030 of the FDA }{\insrsid1212048 
to regulate biological products comes from two statutory sources.}{\cs16\super\insrsid1212048 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid7623269   }{\insrsid2688461 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2688461 {\insrsid2688461 \tab }{\insrsid5181694 As indicated above}{\insrsid9717739  in section I.A.}{\insrsid5181694 , the approval and }{
\insrsid3961900 marketing}{\insrsid5181694  of biological products }{\insrsid3961900 (excepting therapeutic biologi}{\insrsid14752921 cs, which have been transferred to}{\insrsid3961900  the jurisdiction of CDER) }{\insrsid5181694 in the United States is 
}{\insrsid3961900 regulated}{\insrsid5181694  by the Center for }{\insrsid14699868 Biologics Evaluation and Research (CBER).}{\cs16\super\insrsid14699868 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  53 Fed. Reg. 8978 (March 18, 1988); 21 C.F.R. \'a7 5.701(a)(1) (2004).}}}{\insrsid11102978   An investigational new drug application (IND) may be }{\insrsid1917628 sought and }{
\insrsid11102978 obtained for a biological product as well as}{\insrsid15935580  for}{\insrsid11102978  a drug}{\insrsid8220748 .}{\cs16\super\insrsid11102978 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 312.2(a) (2004).}}
}{\insrsid8220748   }{\insrsid13530063 A}{\insrsid15935580  new biological product}{\insrsid1917628 , however,}{\insrsid15935580  may be marketed within the United States }{\insrsid1917628 only }{\insrsid15935580 after CBER approves the}{\insrsid9508078 
 manufacturer\rquote s}{\insrsid15935580  biologics license application (BLA)}{\insrsid5384358 .  T}{\insrsid3563357 he approval of the BLA is conditioned upon }{\insrsid9508078 demonstration of the}{\insrsid3563357  safe}{\insrsid9508078 
ty, purity and potency of the new biological product}{\insrsid3563357 .}{\cs16\super\insrsid15935580 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 601.2(d) (2004).}}}{\insrsid15935580   }{\insrsid4804486 This}{\insrsid13905027  single}{
\insrsid4804486  BLA procedure replaced the old regime of licensing for biological products in 1999, }{\insrsid1917628 when}{\insrsid4804486  the }{\insrsid3278624 requirement that}{\insrsid13905027  the manufacturer obtain both an }{\insrsid4804486 
establishment license application (ELA) and }{\insrsid3278624 a}{\insrsid4804486  product license application (PLA)}{\insrsid1917628  was eliminated}{\insrsid4804486 .}{\cs16\super\insrsid4804486 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  42 U.S.C. \'a7\'a7
 262(a)(2)(A)-(B) (2004), }{\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  Pub. L. No. 105-115, sec. 123(a)(1), 111 Stat. 2296; 64 Fed. Reg. 56441 (October 20, 1999).}}}{\insrsid14090648   }{\insrsid9205247 Review of a }{
\insrsid13530063 BLA }{\insrsid9205247 by CBER is analogous to the review that CDER undertakes with each}{\insrsid13530063  NDA.  In fact, w}{\insrsid14090648 
hen Congress enacted FDAMA in 1997, it charged the FDA with the task of minimizing the differences in the review and the approval of NDAs and BLAs.}{\cs16\super\insrsid13530063 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Pub. L. No. 105-115, sec. 123(f), 111 Stat. 2296, 2324 (November 21, 1997).}}}{\insrsid14090648   }{\insrsid12745080 Finally}{\insrsid9205247 , p}{\insrsid8220748 ostmarket reporting }{\insrsid9717739 by the manufacturer }{\insrsid8220748 
of any adverse experie}{\insrsid9205247 nces with the biological product }{\insrsid8220748 is required.}{\cs16\super\insrsid8220748 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 600.80(c) (2004).}}}{\insrsid1069526 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11341947 {\i\ul\insrsid8222120 II. }{\i\ul\insrsid8023933 1938-1990: }{\i\ul\insrsid1204164 The Changing Landscape of FDA-Regulated}{
\i\ul\insrsid1069526  Products}{\insrsid1069526 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2688461 {\insrsid1069526 \tab }{\insrsid6502338 
As enacted, neither the original FDCA of 1938 nor the Medical Device Amendments of 1976 contemplated the regulation }{\insrsid14095572 by the FDA }{\insrsid6502338 of a product that was not solely a drug, a device, or a biological product}{
\insrsid3885062 , but}{\insrsid14095572  was}{\insrsid3885062  a combination of two or more of those categories}{\insrsid6502338 .}{\insrsid8220748  }{\insrsid10963380  T}{\insrsid6502338 his result is }{\insrsid14095572 perhaps }{\insrsid5384358 
not surprising in light of the prevalent technology when}{\insrsid6502338  the original FDCA}{\insrsid5384358  was enacted}{\insrsid3891666 .  T}{\insrsid14095572 he regulation of medical devices}{\insrsid6502338  was added to the FDCA }{\insrsid14095572 
in 1938 not because of the technological advances in the field, but }{\insrsid6502338 in large part to deter the marketing of fraudulent devices}{\insrsid343108  }{\insrsid14501974 that }{\insrsid4399175 increasingly }{\insrsid14501974 occurred }{
\insrsid343108 during the 1930s}{\insrsid6502338 .}{\cs16\super\insrsid6502338 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990 
 at 720; }{\scaps\insrsid16284404\charrsid7211990 S. Rep. No. }{\insrsid16284404\charrsid7211990 94-33, at 2-5 (1975).  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 supra}{
\insrsid16284404 , n.}{\insrsid16284404\charrsid7211990 11.  Biologics are still defined under the Public Health Service Act, }{\insrsid16284404 the administration of }{\insrsid16284404\charrsid7211990 which was delegated to the FDA in 1972.}}}{
\insrsid343108   }{\insrsid16015430 Further}{\insrsid14501974 , t}{\insrsid13461469 he original FDCA did not }{\insrsid4399175 provide for}{\insrsid13461469  the regulation of biological products.}{\cs16\super\insrsid13461469 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404 , n.61}{\insrsid16284404\charrsid7211990 .}}}{\insrsid13461469   }{\insrsid16015430 Moreover}{\insrsid6901851 
, the FDCA of 1938 expressly defined a \'93drug\'94 and a \'93device\'94 as exclusive of one another}{\insrsid5384358 .  I}{\insrsid15751402 t was not until }{\insrsid16015430 the passage of the SMDA in }{\insrsid15751402 1990 that the}{\insrsid1195267 se
}{\insrsid15751402  two regulated categories were statutorily defined to be nonexclusive.}{\cs16\super\insrsid6901851 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404\charrsid7211990 , n}{\insrsid16284404 .17}{
\insrsid16284404\charrsid7211990 .}}}{\insrsid6901851   }{\insrsid16015430 One decade after the enactment of the FDCA, however}{\insrsid343108 , technological innovation }{\insrsid16015430 on the heels of World War II }{\insrsid343108 
resulted in a near doubling of the number of }{\insrsid16015430 domestic }{\insrsid343108 medical device manufacturers and a near quadrupling in the total value of }{\insrsid16015430 domestic }{\insrsid3885062 industry }{\insrsid343108 shipments.}{
\cs16\super\insrsid343108 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Theodore H. Cooper, }{\i\insrsid16284404\charrsid7211990 Device Legislation}{\insrsid16284404\charrsid7211990 
, 26 FDC L. J. 165 (1971)(from 1937 to 1947,
 the number of American medical device manufacturers increased from 463 to 980 and the total value of medical device shipments within the United States increased from a little over one million dollars to $3.72 million annually).}}}{\insrsid10963380   }{
\insrsid134018 Especially during the 1960\rquote s, the medical device industry blossomed with the development of the pacemaker, kidney dialysis systems, and artificial cardiac valves and blood vessels.}{\cs16\super\insrsid134018 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 S. Rep. No.}{\insrsid16284404\charrsid7211990  94-33, at 5 (1975).}}}{\insrsid134018   }{\insrsid4093036 Yet updated regulation over these increasingly sophisticated devices }{\insrsid1195267 that }{\insrsid13453760 
often }{\insrsid1195267 involved }{\insrsid5384358 implantation}{\insrsid3293201  in patients}{\insrsid1195267  or accompanying medication }{\insrsid13453760 regimens }{\insrsid4093036\charrsid1195267 remained}{\insrsid4093036  nonexistent, as }{
\insrsid3293201 the }{\insrsid4093036 FDA had to furlough stricter regulation of medical devices }{\insrsid4274181 in}{\insrsid11233793  a legislative concession }{\insrsid4093036 to ensure the passage of the 1962 Drug Amendments.}{
\cs16\super\insrsid4939501 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 hutt & merrill}{\insrsid16284404\charrsid7211990  at 743.}}}{\insrsid4093036   
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid15814195 {\insrsid4093036 Once}{\insrsid10963380  the 1976 }{\insrsid210708 Medical Device }{\insrsid10963380 Amendments }{\insrsid13453760 
were passed,}{\insrsid4093036  there was }{\insrsid13453760 still }{\insrsid4093036 no mention of, or provision}{\insrsid10963380  for, a scheme of regulation to control the approval of products}{\insrsid210708 
 that fit into more than one regulated category}{\insrsid10963380 .  Perhaps this is so }{\insrsid4399175 for two reasons.  T}{\insrsid14501974 he FDA }{\insrsid14187542 had only recently been}{\insrsid15802525  delegated the responsibility}{
\insrsid4399175  of regulating}{\insrsid14501974  biological products}{\insrsid988500 .}{\cs16\super\insrsid14501974 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404 , n.63}{\insrsid16284404\charrsid7211990 .}}}{
\insrsid10963380  }{\insrsid988500  Second, the }{\insrsid10963380 1976 Amendments }{\insrsid11820151 were}{\insrsid4399175  narrowly focused upon}{\insrsid8147142  moderniz}{\insrsid4399175 ing}{\insrsid10833319  the }{\insrsid8147142 FDCA}{
\insrsid10963380  }{\insrsid10833319 by broadening its regulatory reach }{\insrsid10963380 sufficiently }{\insrsid8147142 to }{\insrsid10833319 respond to}{\insrsid10963380  the medical devices }{\insrsid988500  }{\insrsid10963380 that resulted from the t
echnological boom.}{\cs16\super\insrsid10963380 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Cooper, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404 , n.76}{
\insrsid16284404\charrsid7211990  (nearly 1500 medical device manufacturers, with total annual shipments in excess of $1.5 billion, in 1967).}}}{\insrsid15814195   }{\insrsid6760964 Hence the}{\insrsid15945552 re was the}{\insrsid6760964 
 creation of the device classes and the corresponding approval procedures for each class.  }{\insrsid8147142 Despite }{\insrsid9449363 the }{\insrsid11494231 continued }{\insrsid9449363 lack of }{\insrsid14368036 explicit }{\insrsid9449363 statutory }{
\insrsid11820151 guidance,}{\insrsid8147142  the FDA }{\insrsid5012334 forged ahead.  Through}{\insrsid8147142  }{\insrsid5012334 numerous cas}{\insrsid5384358 e-by-case decisions in the 1970}{\insrsid5012334 s and 1980s, the FDA }{\insrsid8147142 assign}
{\insrsid5012334 ed or adjusted to the three main Centers}{\insrsid8147142  approval jurisdi}{\insrsid6632263 ction }{\insrsid11820151 over tho}{\insrsid9449363 se products }{\insrsid11820151 occupying the border between drugs, devices, and biological p}{
\insrsid5012334 roducts}{\insrsid8147142 .  }{\insrsid6632263 A few examples}{\insrsid11432212  illustrate the diversity of the situations that }{\insrsid15281868 the }{\insrsid11432212 FDA encountered}{\insrsid6632263 .  }{\insrsid10760606 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10760606 {\insrsid10760606 \tab }{\insrsid9904662 In the early 1970\rquote s, the first sign of combination products appeared on the FDA\rquote 
s regulatory landscape.  }{\insrsid158712 Products such as r}{\insrsid5987734 adiobiologicals, radiopharmaceuticals, and }{\i\insrsid5987734 in vitro}{\insrsid5987734  diagnostic products}{\insrsid158712  explicitly}{\insrsid5987734  }{\insrsid158712 
required}{\insrsid5987734  the FDA to determine in which Center each of those products would be regulated.}{\cs16\super\insrsid5987734 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  56 Fed. Reg. 58754-01, 1991 WL 242348 (November 21, 1991).}}}{\insrsid5987734   }{\insrsid6173596 
Pursuant to the passage of the 1976 }{\insrsid15281868 Medical Device }{\insrsid6173596 Amendments, certain \'93transitional\'94 devices that the FDA had traditionally }{\insrsid11739073 regulated}{\insrsid6173596 
 as drugs were redesignated automatically as Class III devices, requiring an approved PMA to enter the market.}{\cs16\super\insrsid6173596 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360j(l) (2004), }{
\i\insrsid16284404\charrsid7211990 amended by}{\insrsid16284404\charrsid7211990  Pub. L. No. 94-295, sec. 520, 90 Stat. 539 (May 28, 1976); 42 Fed. Reg. 63472 (December 16, 1977) (listing transitional devices).}}}{\insrsid6173596   }{\insrsid7763276 
In 1979, the Bureau of Biologics (a predecessor of CBER) was assigned the lead jurisdiction for the regulation of medical devices that processed or administered biological products.}{\cs16\super\insrsid7763276 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  44 Fed. Reg. 24236 (April 24, 1979), 47 Fed. Reg. 15412-01 (April 9, 1982).}}}{\insrsid8158553   The predecessor of CDRH, the Bureau of Medical Devices, }{\insrsid1002530 initially 
}{\insrsid8158553 received lead jurisdiction to regulate }{\i\insrsid8158553 in vitro}{\insrsid8158553  }{\insrsid5012334 biological }{\insrsid8158553 diagnostic products in 1980.}{\cs16\super\insrsid8158553 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  45 Fed. Reg. 51226 (August 1, 1980), 45 Fed. Reg. 58964-02 (September 5, 1980), 47 Fed. Reg. 34532-01 (August 10, 1982), 51 Fed. Reg. 37976-03 (October 27, 1986).  }{
\i\insrsid16284404\charrsid7211990 But see infra}{\insrsid16284404\charrsid7211990  Section III.D.3.}}}{\insrsid15939994   }{\insrsid10760606 The FDA decided that it could not regulate attached cigarette filters as medical devices in 1982.}{
\cs16\super\insrsid10760606 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  47 Fed. Reg. 31130, 31132 (July 16, 1982).}}}{\insrsid10760606   }{\insrsid3493650 In 1986, }{\insrsid10560456 analytical }{\insrsid3493650 
products }{\insrsid10560456 that were }{\insrsid3493650 used to }{\insrsid10560456 test for}{\insrsid3493650  a certain chemical allergy }{\insrsid10560456 in humans }{\insrsid3493650 were designated as biological products.}{\cs16\super\insrsid3493650 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  51 Fed. Reg. 33664-01 (September 22, 1986).}}}{\insrsid3493650   }{\insrsid1002577 By 1989, the FDA}{\insrsid983591 \rquote s regulatory practices}{\insrsid1002577 
 had established a trend that treated combination products }{\insrsid2363160 that consiste}{\insrsid11432212 d of a medical device and a drug}{\insrsid2363160  }{\insrsid1002577 as a device only, as long as the drug was }{\insrsid13336246 employed}{
\insrsid1002577  according to the use}{\insrsid7415586  that was}{\insrsid1002577  approved by the FDA.}{\cs16\super\insrsid1002577 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See e.g.,}{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 876.5820 (2004)(regulation of hemodialysis system and accessories).}}}{\insrsid1002577   }{\insrsid15939994 In 1990, }{\i\insrsid15939994 in vitro}{\insrsid15939994 
 diagnostic products that detected antibodies to hepatitis B core antigens were switched from regulation as medical devices to}{\insrsid11432212  regulation as biological produc}{\insrsid15939994 ts because they }{\insrsid13336246 began to be}{
\insrsid15939994  used primarily to screen blood}{\insrsid6632263  transfusions}{\insrsid15939994 .}{\cs16\super\insrsid15939994 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See }{\insrsid16284404\charrsid7211990 
55 Fed. Reg. 5892-02 (February 20, 1990).}}}{\insrsid6632263   }{\insrsid10760606 In contrast, }{\insrsid8913525 an }{\i\insrsid10760606 in vitro }{\insrsid8913525 radioimmunoassay test}{\insrsid10760606  that detect}{\insrsid8913525 ed}{\insrsid10760606 
 the abuse of certain drugs through human hair analysis was designated as a medical device}{\insrsid6180125 ,}{\insrsid10760606  requiring a PMA.}{\cs16\super\insrsid10760606 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  55 Fed. Reg. 23985-01 (June 13, 1990).}}}{\insrsid10760606   }{\insrsid6632263 To this day, }{\insrsid12461643 any application that is made by a drug manufacturer to the FDA for}{
\insrsid11432212  a}{\insrsid6632263  }{\insrsid12418791 new }{\insrsid6632263 drug }{\insrsid11432212 that}{\insrsid12461643  also}{\insrsid11432212  contains}{\insrsid1002577  biological components }{\insrsid6632263 must be addressed to }{
\insrsid1002577 CBER}{\insrsid11432212 ,}{\insrsid1002577  rather than CDER.}{\cs16\super\insrsid1002577 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 312.140; 21 C.F.R. 
\'a7 312.440 (2004).}}}{\insrsid8147142 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1204164 {\insrsid1204164 \tab }{\insrsid6180125 Faced wit}{\insrsid15945552 h a product market that was}{\insrsid6180125  increasing}{\insrsid15945552 
ly}{\insrsid6180125  divers}{\insrsid15945552 e and sophisticated, as well as }{\insrsid6180125 an ad hoc regime of assigning responsibil}{\insrsid15288354 ity for those products, e}{\insrsid1204164 
ach of the three Centers entered into Intercenter Agreements with each of }{\insrsid14090403 the other Centers}{\insrsid15945552 , beginning in 1982.}{\insrsid14090403  }{\insrsid15945552  The agreements were designed }{\insrsid1204164 to}{\insrsid277289 
 minimize repetitive and conflicting regulation, to inform manufacturers, and to conserve agency resources}{\insrsid1204164 .}{\cs16\super\insrsid1204164 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1204164 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 U.S. Food and Drug Administration, Office of Combination Products, Intercenter Agreements, }{\i\insrsid16284404\charrsid7211990 at }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/intercenter.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003300000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0069006e00740065007200630065006e007400650072002e00680074006d00
6c000000e0c9ea79f9bace118c8200aa004ba90b6600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0069006e00740065007200630065006e007400650072002e00680074006d006c000000}}
}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/intercenter.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid1204164   All three }{\insrsid14090403 of these }{\insrsid1204164 
agreements }{\insrsid14090403 first }{\insrsid277289 determined which Center would have}{\insrsid1204164  approval jurisdiction for a given type of product and }{\insrsid14090403 then }{\insrsid1204164 provide}{\insrsid277289 d}{\insrsid1204164 
 guidance to the product manufacturer as to the working relationship between each Center during the approval process.
\par }\pard \ql \fi720\li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13179294 {\insrsid16727929 Coordination }{\insrsid604891 
between the Bureau of Biologics (BoB), the Bureau of Medical Devices (BMD), and the Bureau of Radiological Health (BRH) }{\insrsid144150 was the }{\insrsid16727929 first}{\insrsid144150  cooperative agreement to exist}{\insrsid16727929  when }{
\insrsid144150 the three bureaus}{\insrsid14090403  }{\insrsid144150 signed}{\insrsid14090403  an}{\insrsid16727929  agreement}{\insrsid604891  }{\insrsid144150 in 1982 }{\insrsid604891 
to identify separate responsibilities in the oversight of medical devices.}{\cs16\super\insrsid604891 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 47 Fed. Reg. 15412-01 (April 9, 1982).}}}{\insrsid16727929   The agreement was}{\insrsid604891  still in effect, }{\insrsid16727929 even }{\insrsid684842 after}{\insrsid604891  BMD and BRH }{\insrsid4550530 first}{\insrsid604891  united }{
\insrsid16727929 in March,}{\insrsid604891  1982 }{\insrsid144150 to form CDRH }{\insrsid604891 a}{\insrsid4550530 nd BoB eventually became}{\insrsid604891  CBER.}{\cs16\super\insrsid3101781 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 ; U.S. Food and Drug Administration, Office of Combination Products, Intercenter Agreements, Biologics & Devices Intercenter Agreement,}{\insrsid16284404  }{\i\insrsid16284404 at}{
\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/ombudsman/bio-dev.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f00620069006f002d006400650076002e00680074006d000000e0c9ea79f9bace118c82
00aa004ba90b5800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f00620069006f002d006400650076002e00680074006d000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 
http://www.fda.gov/oc/ombudsman/bio-dev.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004) (hereinafter \'93CBER-CDRH Intercenter Agreement\'94).}}}{\insrsid9442996   }{\insrsid13179294 
The agreement that arose between CDER and CBER did not predat}{\insrsid144150 e this}{\insrsid684842  CBER-CDRH agreement because}{\insrsid3429210  CDER and CB}{\insrsid13179294 ER }{\insrsid684842 did not separate}{\insrsid13179294  from one another }{
\insrsid684842 again }{\insrsid13179294 until 198}{\insrsid10635475 8}{\insrsid13179294 .}{\cs16\super\insrsid13179294 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404 , n.22}{\insrsid16284404\charrsid7211990 .}}}{
\insrsid144150   Their}{\insrsid13179294  agreement, however, represented }{\insrsid144150 simply }{\insrsid13179294 a continuation of an existing working relationship to regulate the frontier between drugs and biological products.}{
\cs16\super\insrsid13179294 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  U.S. Food and Drug Administration, Office of Combination Products, Intercenter Agreements, Intercenter Agreement between CDER and CBER,}{\insrsid16284404  }{\i\insrsid16284404 at}{\insrsid16284404\charrsid7211990  }
{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/ombudsman/drug-bio.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002d00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f0064007200750067002d00620069006f002e00680074006d000000e0c9ea79f9bace11
8c8200aa004ba90b5a00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f0064007200750067002d00620069006f002e00680074006d000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/ombudsman/drug-bio.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004) (hereinafter \'93CDER-CBER Intercenter Agreement\'94).}}}{\insrsid13179294 
  Finally, the agreement between CDER and CDRH was the }{\insrsid144150 formal }{\insrsid16206919 culmination}{\insrsid13179294  of multiple, previous ad hoc collaborations (a few examples of which were illustrated above).}{\cs16\super\insrsid10042770 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 U.S. Food and Drug Administration, Office of Combination Products, Intercenter Agreements, Intercenter Agreement between CDER and CDRH,}{\insrsid16284404  }{\i\insrsid16284404 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/ombudsman/drug-dev.htm" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002d00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f0064007200750067002d006400650076002e00680074006d000000e0c9ea79f9bace11
8c8200aa004ba90b5a00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f006f006d0062007500640073006d0061006e002f0064007200750067002d006400650076002e00680074006d000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/ombudsman/drug-dev.htm}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004) (hereinafter \'93CDER-CDRH Intercenter Agreement\'94).}}}{\insrsid13179294   }{\insrsid9263712 It b}{
\insrsid13179294 ecame effective in late October, 1991, as did t}{\insrsid9442996 he latest version of }{\insrsid13179294 the other two}{\insrsid16727929  }{\insrsid9442996 agreement}{\insrsid16727929 s}{\insrsid13179294 ,}{\insrsid9442996  }{
\insrsid16727929 because changes were necessary}{\insrsid9442996  to reflect the }{\insrsid2374433 mandatory }{\insrsid9442996 provisions of the SMDA.}{\cs16\super\insrsid16471273 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 56 Fed. Reg. 58760-01 (November 21, 1991).}}}{\insrsid13179294   The working relationship between each Center will be explored in more detail }{\i\insrsid13179294 infra}{\insrsid13179294 .}{\insrsid1204164 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12913133 {\insrsid11432212 \tab }{\insrsid14310844 By 1990}{\insrsid11432212 , }{\insrsid11347144 the number of }{\insrsid7894735 sophisticated}{
\insrsid131877  new}{\insrsid7894735  }{\insrsid11432212 product}{\insrsid4611262 s that sought FDA approval and }{\insrsid11432212 that }{\insrsid4611262 also }{\insrsid11432212 potentially }{\insrsid9187428 implicated}{\insrsid11432212  the }{
\insrsid9187428 expertise}{\insrsid11432212  of more than one Center}{\insrsid1797037  continued to increase.}{\insrsid11432212  }{\insrsid1797037  }{\insrsid4733477 An extensive Congressional hearing before the Subcommittee on Oversight a
nd Investigations of the House Committee on Energy and Commerce occurred early in 1990 to address the failure of the Bjork-Shiley Convexo-Concave heart valves, previously approved by CDRH and the FDA.}{\cs16\super\insrsid4733477 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 FDA and the Medical Device Industry: Hearing Before the Subcomm. on Oversight and Investigations of the House Comm. on Energy and Commerce}{\insrsid16284404\charrsid7211990 , 101st Cong. 203 (1990).}}}{\insrsid2893415   
}{\insrsid16323199 During that hearing, a report was introduced by CDRH highlighting some of the devices that had recently received approval}{\insrsid11347144 .  This report served}{\insrsid131877  }{\insrsid11347144 as an}{\insrsid16323199  indicat}{
\insrsid11347144 ion of}{\insrsid16323199  the level of complex}{\insrsid11347144 ity that CDRH experienced in regulating devices that}{\insrsid16323199  interact}{\insrsid11347144 ed}{\insrsid16323199  with the human body.}{\insrsid4733477  }{
\insrsid16323199  }{\insrsid815097 A few of the examples included anesthesia machines that delivered }{\insrsid131877 certain }{\insrsid815097 anesthetic ga}{\insrsid11296353 ses and oxygen to humans in patient-specific }{\insrsid815097 dosages,}{
\cs16\super\insrsid815097 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 242-43.}}}{\insrsid815097  hemodialysis machines that intravenously filter}{\insrsid131877 ed}{\insrsid815097 
 wastes from the blood of a patient (who }{\insrsid131877 was}{\insrsid815097  often totally dependent upon that machine for survival)}{\cs16\super\insrsid815097 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 259-60.}}}{\insrsid5777598  and}{\insrsid92540  home use}{\insrsid5777598  }{\i\insrsid5777598 in vitro}{\insrsid5777598  diagnostic (IVD) devices}{\insrsid815097  }{
\insrsid5058588 that screened}{\insrsid5777598  for medical conditions such as pregnancy, blood glucose, urinary tract infections, and gonorrhea.}{\cs16\super\insrsid5777598 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 261-62.}}}{\insrsid10574661   }{\insrsid5047480 The CDRH report at the Shiley heart valve hearing made clear that the FDA needed a more sophistica
ted statutory grant to acknowledge the changing horizon of its approval landscape.  }{\insrsid6172878 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11341947 {\i\ul\insrsid11341947 III. }{\i\ul\insrsid6172878 The Safe Medical Devices Act}{\i\ul\insrsid10059263  (SMDA)}{\i\ul\insrsid6172878  of 1990}{
\i\ul\insrsid10059263 : Its Origins and Its Impact}{\insrsid6172878 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid12913133 {\i\ul\insrsid10059263 III.A. }{\i\ul\insrsid11492884  Section 16 of the SMDA}{\insrsid11492884\charrsid11492884 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid5058588 \tab }{\insrsid3278730 The Shiley heart valve}{\insrsid600042  hearing took place just nine months b}{\insrsid11296353 ef
ore the passage of the SMDA of 1990}{\insrsid600042 .}{\insrsid9064451  }{\insrsid11432212  }{\insrsid9705096 
In the intervening months, both Houses of Congress worked independently on bills meant to modernize the regulation of medical devices by amending the provisions of the FDCA.  The result was the SMDA.  Within the SMDA, 
a provision appeared that finally and formally recognized the presence of the combination product on the FDA\rquote s regulatory radar}{\insrsid4550530 .  Congress for the first time}{\insrsid9705096  codified }{\insrsid4550530 how FDA was to exercise its
}{\insrsid9705096  jurisdiction }{\insrsid4550530 over}{\insrsid9705096  a product that was not solely a drug, a med
ical device, or a biological product within section 353(f) of the FDCA.  The Secretary of Health and Human Services was delegated the power to \'93designate a component of the Food and Drug Administration to regulate products that constitute a }{
\i\insrsid9705096 combination of a drug, device, or biological product}{\insrsid9705096 .\'94}{\cs16\super\insrsid9705096 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9705096 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 353(g)(1) (2004); 21 C.F.R. \'a7 3.2(e) (2004).}}}{\insrsid9705096 
 (emphasis added).  Some explanation of the drafting of this pertinent provision and its inclusion within the SMDA may illustrate how slowly both }{\insrsid9322940 our }{\insrsid9705096 administr}{\insrsid9322940 ative and legislative mechanism }{
\insrsid9705096 responded to the onslaught of combination products. 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid9705096 \tab }{\insrsid4550530 During August}{\insrsid2171688  1990, Senator Edward Kennedy}{\insrsid13134884 
, as the Chair of the Labor a}{\insrsid1988871 nd Human Resources Committee, joined by}{\insrsid2171688  fo}{\insrsid8665373 ur other Senators introduced a Senate }{\insrsid4550530 bill}{\insrsid8665373  entitled}{\insrsid2171688  }{\insrsid7671953 the }{
\insrsid8665373 \'93}{\insrsid2171688 Comprehensive Medical Device Improvement Act}{\insrsid8665373 \'94}{\insrsid4550530  (S. 3006}{\insrsid2171688 ).}{\cs16\super\insrsid2171688 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Comprehensive Medical Device Improvement Act, S. Res. 3006, 101st Cong. (1990).  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  135 Cong. Rec. S12476-02, S12487 (August 4, 1990).}}}{\insrsid2171688   }{\insrsid7824661 
As the title of the bill made clear, }{\insrsid7671953 one purpose of }{\insrsid7824661 this legislation was to build upon the improvements to the FDCA made through the Med}{\insrsid4095874 ical Device Amendments of 1976}{\insrsid7824661  }{
\insrsid4095874 by allowing }{\insrsid7824661 the medical device industry to \'93benefit from}{\insrsid15025320  more consistent FDA regulation}{\insrsid7824661 \'94}{\insrsid15025320  while \'93encourag[ing] technological innovation\'94 and \'93
providing improved protections for public health.\'94}{\cs16\super\insrsid7824661 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at S12487-89.}}}{\insrsid15025320   }{\insrsid4095874 
One further purpose of S. 3006, as pointed out by }{\insrsid15025320 Senator Kennedy}{\insrsid4095874 , }{\insrsid15025320 was to \'93improve efficiency in the FDA review process by providing that the Secreta
ry will require only one market clearance route for products which are combinations of devices, drugs, or biologics.\'94}{\cs16\super\insrsid15025320 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at S12489.}}}{\insrsid16599118   }{\insrsid9847967 Senator Dodd echoed Senator Kennedy\rquote s sentiments and added that the \'93
tremendous diversity in the medical devices industry\'94 }{\insrsid13904879 made this bill necessary.  More particularly, he noted that this diversity had }{\insrsid9847967 stood in the way of the FDA\rquote 
s effective implementation of the Medical Device Amendments of 1976 because of the complexities of those Amendments, the FDA\rquote s interpretation of the Amendments, and the FDA\rquote s limited resources.}{\cs16\super\insrsid9847967 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid9847967   }{\insrsid14307838 
One other sponsor, Senator Durenberger from Minnesota, supported the new provisions related to combination product regulation because his constituency was comprised in part of medical device companies.}{\cs16\super\insrsid14307838 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at S12495.}}}{\insrsid14307838   }{\insrsid16599118 To that end, section 20 of S. 3006 was drafted to amend section 503 of the FDCA with the following language:}{\insrsid7824661 

\par }\pard \ql \li1440\ri1440\sa240\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid16599118 {\fs22\cf1\insrsid16599118\charrsid16517808 
SEC. 20. REVIEW OF MARKET APPLICATIONS FOR ARTICLES COMPRISING COMBINATIONS OF DRUGS, DEVICES OR BIOLOGICS\line \line Section 503 (21 U.S.C. 353) is amended-\line (1) by striking the section heading and inserting the following:
\par }\pard \qc \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid16599118 {\i\fs22\cf1\insrsid16599118\charrsid3351584 "SPECIAL CONSIDERATION FOR CERTAIN DRUGS, DEVICES, AND BIOLOGICAL PRODUCTS";
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid16599118 {\fs22\cf1\insrsid16599118\charrsid16517808 \line and\line {\*\bkmkstart SDU_125}{\*\bkmkend SDU_125}
(2) by adding at the end the following new subsection:\line "(f)(1) }{\i\fs22\cf1\insrsid16599118\charrsid16599118 The Secretary shall require only one market clearance route for
 an article that constitutes a combination of a device, drug, or biological product. }{\i\fs22\cf1\insrsid16599118\charrsid9373832 If the Secretary determines that the primary mode of action of the combination article is that of-\line 
"(A) a drug (other than a biological product), neither the combination article nor any part of the article shall be treated as a device or as a biological product for market clearance purposes;\line 
"(B) a device, neither the combination article nor any part of the article shall be treated as a drug or a biological product for market clearance purposes; or\line 
"(C) a biological product, neither the combination article nor any part of the article shall be treated as a drug or a device for market clearance purposes.\line }{\fs22\cf1\insrsid16599118\charrsid16517808 "(2) }{
\i\fs22\cf1\insrsid16599118\charrsid16599118 Nothing in this paragraph shall prevent the Secretary from using any
 agency resource of the Food and Drug Administration necessary to assure adequate review of the safety, effectiveness, or substantial equivalence of an article, if the Secretary employs a single market clearance mechanism.}{
\fs22\cf1\insrsid16599118\charrsid16517808 \line "(3) The Secretary shall promulgate regulations to implement market approval procedures in accordance with paragraph (1) not later than 1 year after the date of enactment of this subsection.\line 
{\*\bkmkstart SDU_126}{\*\bkmkend SDU_126}"(4) As used in this subsection:\line "(A) The term 'biological product' has the meaning given the term in section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)).\line 
"(B) The term 'market clearance' includes approval of an application under section 505, 507, 515, or 520(g), an order determining substantial equivalence under this subchapter, and app
roval of a product or establishment license under subsection (a) or (d) of section 351 of the Public Health Service Act (42 U.S.C. 262)."}{\cs16\fs22\cf1\super\insrsid16599118 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at S12489.}}}{\fs22\cf1\insrsid16599118  (emphasis added).}{\insrsid16599118 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid7824661 \tab }{\insrsid16599118 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid16599118 \tab }{\insrsid14560893 Just over two months later, }{\insrsid16154534 on October 5, 1990, }{\insrsid14560893 
the Committee on Energy and Commerce within the House of Representatives presented its report on }{\insrsid9913175 a }{\insrsid14560893 House }{\insrsid9913175 bill}{\insrsid14560893  (H.R. 3095), otherwise known as the Safe Medical Devices Act of 1990.}{
\cs16\super\insrsid14560893 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  H.R. 3095, 101st Cong. (1990) (enacted).  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 H. Rep. No.}{\insrsid16284404\charrsid7211990 
 101-808, 1990 WL 200530 (October 5, 1990).}}}{\insrsid14560893   This report was presented to the House just one month before the passage of the SMDA by Congress, }{\insrsid14187695 containing the major pro
visions that would eventually be codified within the FDCA.  Y}{\insrsid14560893 et no pro}{\insrsid11542848 vision within H.R. 3095 mentioned}{\insrsid14560893  combination products in any way.  }{\insrsid16154534 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid16154534 \tab Four days later, the Senate was presented with a report from the Committee on Labor and Human Resources recommending
 passage of an amended version of S. 3006.}{\cs16\super\insrsid24892 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 S. Rep. No.}{\insrsid16284404\charrsid7211990  101-513, 1990 WL 201762 (October 9, 1990).}}}{\insrsid16154534   }{
\insrsid4984748 The pertinent language from }{\insrsid9523763 the amended section 20 of S. 3006}{\insrsid4984748  is reprinted below, }{\insrsid9523763 so as }{\insrsid4984748 to be contrasted with the }{\insrsid16078379 earlier }{\insrsid4984748 
version reproduced}{\insrsid15280011  in italics}{\insrsid4984748  }{\i\insrsid4984748 supra}{\insrsid4984748 .
\par }\pard \ql \li1440\ri1440\sa240\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid3351584 {\fs22\cf1\insrsid3351584\charrsid6898785 SEC. 20. REVIEW OF MARKET APPLICATIONS FOR ARTICLES 
COMPRISING COMBINATIONS OF DRUGS, DEVICES, AND BIOLOGICS. \line \line Section 503 (21 U.S.C. 353) is amended- \line (1) by striking the section heading and inserting the following:{\*\bkmkstart SDU_38}{\*\bkmkend SDU_38}
\par }\pard \qc \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid3351584 {\i\fs22\cf1\insrsid3351584\charrsid3351584 "EXEMPTIONS AND C}{\i\fs22\cf1\insrsid3351584 ONSIDERATION FOR CERTAIN DRUGS, }{
\i\fs22\cf1\insrsid3351584\charrsid3351584 DEVICES, AND BIOLOGICAL}{\i\fs22\cf1\insrsid3351584  }{\i\fs22\cf1\insrsid3351584\charrsid3351584 PRODUCTS";
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid3351584 {\fs22\cf1\insrsid3351584\charrsid6898785 \line and \line (2) by adding at the end the following new subsection: \line 
"(f)(1) The Secretary shall designate a component of the Food and Drug Administration to regulate products that constitute a combination of a drug, device, or biological product. The Secretary shall d
etermine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of- \line 
"(A) a drug (other than a biological product), the persons charged with premarket review of drugs shall have primary jurisdiction; \line "(B) a device, the persons charged with premarket review of devices shall have primary jurisdiction; or \line 
"(C) a biological product, the persons charged with premarket review of biological products shall have primary jurisdiction. \line "(2) Nothing
 in this subsection shall prevent the Secretary from using any agency resources of the Food and Drug Administration necessary to ensure adequate review of the safety, effectiveness, or substantial equivalence of an article. {\*\bkmkstart SDU_39}
{\*\bkmkend SDU_39}"(3) The Secretary shall promulgate regulations to implement market approval procedures in accordance with paragraphs (1) and (2) not later than 1 year after the date of enactment of this subsection. \line 
"(4) As used in this subsection: \line "(A) The term 'biological product' has the meaning given the term in section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)). \line "(B) The term 'market clearance' includes- \line 
"(i) approval of an application under section 505, 507, 515, or 520(g); \line "(ii) a finding of substantial equivalence under this subchapter; and \line 
"(iii) approval of a product or establishment license under subsection (a) or (d) of section 351 of the Public Health Service Act (42 U.S.C. 262)."}{\cs16\fs22\cf1\super\insrsid3351584 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid4984748 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid3351584 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid3351584 \tab }{\insrsid16078379 This amendment to S. 3006 contains the final version of the provision }{\insrsid9583338 that }{
\insrsid2969586 explicitly }{\insrsid9583338 governs}{\insrsid2969586  }{\insrsid9583338 the FDA\rquote s pre-existing }{\insrsid2969586 regulatory control over}{\insrsid16078379  com}{\insrsid1340886 bination products}{\insrsid9583338 ,}{\insrsid1340886 
 as it }{\insrsid9583338 also }{\insrsid1340886 appeared}{\insrsid16078379  within section 16 of the SMDA and as it }{\insrsid1340886 was}{\insrsid16078379  codified within section 503 of the FDCA.}{\cs16\super\insrsid7041417 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 SMDA, Pub. L. No. 101-629, sec. 16(a), 21 U.S.C. \'a7 353(f) (1990).}}}{\insrsid16078379   }{\insrsid7041417 The most }{\insrsid15992510 obvious and }{\insrsid7041417 noteworthy difference between the two versions }{\insrsid1340886 was}{\insrsid7041417 
 the removal of the }{\insrsid1008703 earlier }{\insrsid7041417 language \'93requir[ing] one market clearance route\'94 in favor of a more broad designation }{\insrsid13711276 directing}{\insrsid7041417  the FDA to \'93regulate products}{\insrsid11413736 
 that constitute a combination}{\insrsid15992510 .\'94  }{\insrsid1008703 In addition}{\insrsid15992510 , the earlier version required that once the }{\insrsid1008703 FDA determined the }{\insrsid15992510 primary mode of action of the p}{\insrsid1008703 
roduct}{\insrsid15992510 , that primary mode would guide the product\rquote s approval}{\insrsid1008703  process}{\insrsid15992510  to such an extent that \'93neither the combination article nor any part of the article\'94
 would be treated as anything other than pertaining to that primary mode for market clearance purposes.}{\cs16\super\insrsid15992510 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.108}{\insrsid16284404\charrsid7211990 .}}}{\insrsid15992510   As the later version }{\insrsid1008703 of section 20 }{\insrsid15992510 
makes clear, the Senate eased those restrictions by granting \'93primary jurisdiction\'94}{\insrsid12402703  to the Center that normally oversees products with that primary mode of action.}{\cs16\super\insrsid12402703 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.111}{\insrsid16284404\charrsid7211990 .}}}{\insrsid1008703   }{\insrsid1966960 That Center would be responsible for reviewing the premarket submission of the entire combination product.}{
\cs16\super\insrsid1966960 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 S. Rep. No.}{\insrsid16284404\charrsid7211990  101-513, VI. Section-By-Section Analysis, Section 20, 1990 WL 201762 (October 9, 1990).}}}{\insrsid1966960   }{\insrsid1008703 
Such language allows for the cooperative input of the other Centers during the approval process.}{\insrsid15992510 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid8222561 \tab The report that accompanied the amended version of S. 3006 echoed Senator Kennedy\rquote 
s statements two months earlier with regard to }{\insrsid1796707 lessening product over-regulation by the FDA }{\insrsid10683309 
while maintaining an innovative medical device industry.  Yet the report went further than the previous comments on the Senate floor as it }{\insrsid8222561 explain}{\insrsid10683309 ed}{\insrsid8222561  the intent behind adding }{\insrsid1796707 
section 20 to regulate }{\insrsid8222561 combination products.  }{\insrsid10683309 The Labor and Human Resources Committee recognized the \'93
difficulty under the present law in determining the jurisdictional base for regulating products that are comprised of combinations of drugs, devices, or biologics,\'94}{\insrsid13711276  and made note of the industry}{\insrsid10683309  view that the FDA
\rquote s premarket review process }{\insrsid16319483 was}{\insrsid13711276  weak in }{\insrsid10683309 determining how to regulate combination products.}{\cs16\super\insrsid10683309 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at IV. Committee Views, Sections 19 and 20.}}}{\insrsid12207360   }{\insrsid12716520 The delays that combination product manufacturers felt due to this regulatory we
akness spurred the Senate to \'93provide the Secretary with firm ground rules to direct products promptly to that part of the FDA responsible for reviewing the article that provides the primary mode of action,\'94
 especially since the number of combination products coming before the FDA for approval was increasing.}{\cs16\super\insrsid12716520 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid12716520   }{\insrsid12207360 Section 20 was drafted to 
\'93eliminate the need to receive clearances from both the device and drug review divisions, and will vest authority in one agency group to conduct a premarket review.\'94}{\cs16\super\insrsid12207360 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid16319483   The C
ommittee was quick to caution, however, that the goal of administrative efficiency within the FDA would not exempt the manufacturer from producing the same level of safety and effectiveness data for each component of the combination product.}{
\cs16\super\insrsid16319483 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid8222561 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5058588 {\insrsid1398508 \tab Just over two weeks later, Representative Waxman submitted a conference report to the House of Representatives.}{
\cs16\super\insrsid1398508 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 H.R. Conf. Rep. No.}{\insrsid16284404\charrsid7211990  101-959 (1990).  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 136 Cong. Rec. H13251-01, 1990 WL 290412 (October 26, 1990).}}}{\insrsid1398508   The report was the result of a conference that was necessary to}{\insrsid13711276  resolve the differences between H.R. 3095 and}{\insrsid1398508  S. 3006.  The }{
\insrsid7275190 Senate}{\insrsid9309514 , when presented with H.R. 3095,}{\insrsid7275190  had replaced all}{\insrsid9309514  }{\insrsid7275190 of }{\insrsid11478148 the provisions with the text of S. 3006;}{\insrsid7275190 
 the House had responded by amending S. 3006 }{\insrsid11478148 and replacing some of the language of H.R. 3095 }{\insrsid7275190 again}{\insrsid11478148 .}{\cs16\super\insrsid9309514 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at H13256.}}}{\insrsid7275190   The conference}{\insrsid1398508  v}{\insrsid7275190 ersion of H.R. 3095}{\insrsid1398508  that resul}{\insrsid11022610 ted was}{\insrsid9309514 
 an amalgamation of the two bills, }{\insrsid13711276 and}{\insrsid9309514  it was}{\insrsid11022610  the final bill that would be passed }{\insrsid1398508 by both Houses}{\insrsid12261567 ,}{\cs16\super\insrsid9309514 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  136 Cong. Rec. H13008-01 (October 26, 1990) (House acceptance of the conference report); }{\i\insrsid16284404\charrsid7211990 see}{\insrsid16284404\charrsid7211990 
 136 Cong. Rec. S17456-01, S17458 (October 27, 1990) (Senate acceptance of the conference report).   Sen. Durenberger in particular expressed his gratitude toward the }{\cs17\insrsid16284404\charrsid7211990  \'93
inclu[sion] of the Senate provision on products which are comprised of combinations of devices, drugs, or biologics. These so-called co
mbination products are, and will continue to be, of great benefit to health care consumers, and I think it is important that we acted to streamline the regulatory barriers facing such products.\'94}}}{\insrsid1398508  presented to the President}{
\insrsid12261567 , and enacted at the close of 1990}{\insrsid7275190  as the SMDA}{\insrsid9309514 .  With respect to combination products, this conference report is of note because }{\insrsid11022610 the conference managers from both Houses agreed to }{
\insrsid9309514 the inclusion of}{\insrsid11022610  }{\insrsid9309514 section 20 of S. 3006 within the final bill}{\insrsid1398508 .}{\cs16\super\insrsid7275190 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  136 Cong. Rec. at H13259.}}}{
\insrsid1398508\charrsid6237644 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3898803 {\insrsid15992510 \tab }{\insrsid11499337 In the aftermath of the passage of the SMDA}{\insrsid12913133 , }{\insrsid6760672 
the definition of a medical device itself }{\insrsid3495744 had to be}{\insrsid6760672  altered}{\insrsid3495744  }{\insrsid11499337 because}{\insrsid5661193  }{\insrsid9705096 section 16 }{\insrsid5661193 of the SMDA}{\insrsid5510824 , }{\insrsid9705096 
formerly section 20 of S. 3006}{\insrsid9322940 , provided for }{\insrsid11499337 combination }{\insrsid9322940 product regulation }{\insrsid7550277 by a specific Center }{\insrsid9322940 based upon the}{\insrsid9568940  product\rquote s}{\insrsid9322940 
 \'93primary mode of action.\'94}{\cs16\super\insrsid5661193 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5661193 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Pub. L. No. 101-629, sec. 16(a)(2), 104 Stat. 4511; 56 Fed. Reg. 58754 (November 21, 1991); 21 C.F.R. \'a7 3.1 (2004).}}}{\insrsid5661193   The primary}{
\insrsid16515956  mode of action of the product wa}{\insrsid5661193 s determined once the product\rquote s effect upon the body and the relative contribu}{\insrsid16515956 tion of each of its components wa}{\insrsid5661193 s assessed.}{
\cs16\super\insrsid5661193 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5661193 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.4(a) (2004); 56 Fed. Reg. 58754 (November 21, 1991); 67 Fed. Reg. 34722 (May 15, 2002).}}}{\insrsid5661193  }{\insrsid16515956  If the primary mode of action wa}{\insrsid5661193 
s not determinable}{\insrsid16515956  in that manner}{\insrsid5661193 ,}{\insrsid16515956  then}{\insrsid5661193  other fac}{\insrsid9568940 tors such as guidance from the Intercenter A}{\insrsid5661193 
greements or a determination of the most innovative com}{\insrsid16515956 ponent of the product that posed}{\insrsid5661193  the greatest safety risk or }{\insrsid3812763 clearest }{\insrsid5661193 indication of use }{\insrsid16515956 would}{
\insrsid5661193  guide the FDA in deciding to which Center jurisdiction }{\insrsid16515956 would}{\insrsid5661193  be granted.}{\cs16\super\insrsid5661193 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5661193 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 3.5; }{\i\insrsid16284404\charrsid7211990 see}{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7 3.7(a)-(b) (2004).}}}{\insrsid5661193   Once approval and oversight jurisdiction of each product was thus awarded, Congress needed to redefine a \'93
device\'94 in terms of \'93its primary\'94 purpose rather than \'93any of its principal purposes\'94 to comply.  In 1991, Congress ame}{\insrsid8787066 nded the FDCA to move section 16 of the SMDA and its}{\insrsid5661193  \'93primary mode of action\'94 }
{\insrsid8787066 language}{\insrsid5661193  to its current }{\insrsid8787066 resting place }{\insrsid5975604 within}{\insrsid8787066  }{\insrsid5661193 section 353(g).}{\cs16\super\insrsid5661193 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5661193 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Nutrition 
Labeling and Education Act of 1990, Amendment, Pub. L. No. 102-108, sec. 2(d)(4), \'a7 353(g), 105 Stat. 549, 550 (August 17, 1991).}}}{\insrsid11432212  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3898803 {\i\ul\insrsid10059263 III.B.}{\i\ul\insrsid11492884  The Effect of the SMDA on the FDA\rquote s Regulatory Framework}{\insrsid11492884 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3898803 {\insrsid11492884 \tab }{\insrsid5975604 With the statutory mandate of the SMDA to oversee and approve combination products added to the FDA
\rquote s responsibilities, the FDA next undertook admini}{\insrsid6648845 strative proceedings}{\insrsid5975604  to adapt its regulatory framework}{\insrsid6648845  by}{\insrsid6231227  November 29, 1991,}{\insrsid6648845  the one-year deadline se}{
\insrsid6231227 t by the SMDA}{\insrsid5975604 .}{\cs16\super\insrsid6648845 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  56 Fed. Reg. 58754-01, 1991 WL 242348 (November 21, 1991).}}}{\insrsid5975604   Such an adaptation would give each Center and }{\insrsid15945552 
each product manufacturer}{\insrsid5975604  guidelines to }{\insrsid16656332 adhere}{\insrsid5975604  to throughout the approval process}{\insrsid2496902 .}{\insrsid5989300   On Novemb}{\insrsid13711276 er 21, 1991, the FDA announced final regulations}{
\insrsid5989300  containing the new provisions}{\insrsid13711276  in}{\insrsid15687635  21 C.F.R. \'a7\'a7 3.1-.10 (1991)}{\insrsid5989300  \'93}{\cf1\insrsid5989300\charrsid5989300 
to describe how the agency will determine which component within FDA will have primary jurisdiction for the premarket review and regulation of: (1) A combination drug, device, or biologic product or (2) any drug, d
evice, or biologic product where the center with primary jurisdiction is unclear or in dispute.  This rule describes how to identify the agency's assigned review component which will, in most cases, eliminate the need for a sponsor to obtain approval from
 more than one FDA component for a combination product.}{\cf1\insrsid5989300 \'94}{\cs16\cf1\super\insrsid11293452 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid2848985   In light of }{\cf1\insrsid12409384 this}{
\cf1\insrsid2848985  change in its approval procedures, the FDA decided that }{\cf1\insrsid12409384 its approval efficiency would be enhanced by }{\cf1\insrsid6231227 also }{\cf1\insrsid12409384 applying }{\cf1\insrsid2848985 these new }{
\cf1\insrsid12409384 rules}{\cf1\insrsid2848985  in the future to any product}{\cf1\insrsid2306962  whose approval jurisdiction was disputed or unclea}{\cf1\insrsid13711276 r.  T}{\cf1\insrsid2306962 
he rules would not be limited to only those combination products }{\cf1\insrsid16656332 as defined}{\cf1\insrsid2306962  by the SMDA}{\cf1\insrsid2848985 .}{\cs16\cf1\super\insrsid2848985 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7
 3.1, 3.3 (1991).  56 Fed. Reg. at 58756.  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 353(g)(1) (2004).}}}{\cf1\insrsid6648845   }{\cf1\insrsid2439548 The FDA explicitly excluded from that }{
\cf1\insrsid6650562 regulation}{\cf1\insrsid2439548 , however,}{\insrsid5975604  }{\insrsid2439548 most drugs, devices or biological products that are used concomitantly a
s well as products that are comprised exclusively of two or more drugs, two or more devices, or two or more biological products.}{\cs16\super\insrsid2439548 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 58755.}}}{\insrsid11492884 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3898803 {\insrsid3231555 \tab 
Since these new regulations would bind both the Centers within the FDA and the combination product manufacturers, the FDA ste
pped beyond the basic definition of a combination product as provided by the SMDA, and used the new regulations to provide a few illustrative examples of how the SMDA definition could be interpreted.}{\cs16\super\insrsid3231555 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 58754-55.}}}{\insrsid3231555   The term \'93combination product\'94 now encompassed
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\insrsid3231555 \tab }{\cf1\insrsid3231555\charrsid3231555 (1) A 
product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;}{
\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555  (2) Two or more separate p
roducts packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;}{\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555  (3) A drug, device, or biological product packaged separately that according to its inv
estigational plan or proposed labeling is intended for use only with {\*\bkmkstart Document0zzSDUNumber16}{\*\bkmkend Document0zzSDUNumber16}
an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed p
roduct the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or}{\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid3231555 {\cf1\insrsid3231555\charrsid3231555  (4) Any investigational drug, device, or biological product
 packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.}{
\cs16\cf1\super\insrsid3231555 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7 3.2(e)(1)-(4) (1991); 56 Fed. Reg. at 58756.}}}{\insrsid3231555   
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid3231555 {\insrsid5973337\charrsid11492884 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\insrsid5973337 Paragraph (1) comports }{\insrsid3681300 as expected }{\insrsid5973337 
with the literal definition of a combination product as given by the SMDA.  Paragraphs (2) \endash  (4), }{\insrsid3681300 by contrast}{\insrsid5973337 , represent the influence of other industry considerations uniquely within the purview of FDA\rquote 
s regulatory knowledge.  }{\insrsid1901021 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\insrsid1901021 \tab }{\insrsid5973337 One explanation for}{\insrsid2379241  the inclusion of paragraphs (2) \endash  (4), regulating}{
\insrsid5973337  both products that are packaged together an}{\insrsid13007504 d products that are packaged sep}{\insrsid5973337 arately but labeled in such a manner so as to be used together, is the influence of the other }{\insrsid2379241 
administrative }{\insrsid5973337 responsibilities of the FDA.}{\insrsid3681300   The SMDA was enacted in part to ensure the safety and }{\insrsid9837647 
effectiveness of medical devices by modernizing the standards of premarket review applied to those devices.}{\cs16\super\insrsid9837647 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 102.}}}{
\insrsid2176590   As these regulations stated, though, \'93}{\cf1\insrsid2176590\charrsid2176590 nothing in this section }{\cf1\insrsid2176590 [16}{\cf1\insrsid12858940  of the }{\cf1\insrsid3629274 SMD}{\cf1\insrsid12858940 A}{\cf1\insrsid2176590 ] }{
\cf1\insrsid2176590\charrsid2176590 prevents FDA from using any agency resources it deems necessary to ensure adequate review of the safety and effectiveness of any product}{\cf1\insrsid2176590 .\'94}{\cs16\cf1\super\insrsid2176590 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 3.1 (1991).}}}{\cf1\insrsid6768318   As mentioned }{\i\cf1\insrsid6768318 supra}{\cf1\insrsid6768318 , t}{\cf1\insrsid2176590 he FDA also monitors the labeling and packaging of drugs, medical devices, and bi
ological products as part of its administrative role.}{\cs16\cf1\super\insrsid2176590 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 13.}}}{\cf1\insrsid6714361   Thus, }{\cf1\insrsid4522747 
Congress may have considered a product to represent a combination only i}{\cf1\insrsid3629274 f the parts of the combination we}{\cf1\insrsid4522747 re in physical proximity to one another, }{\cf1\insrsid3629274 given the }{\cf1\insrsid6714361 
original language of section 20 of S. 3006 and the final codified }{\cf1\insrsid3629274 lan}{\cf1\insrsid6714361 guage of section 16 of the SMDA.  }{\cf1\insrsid6773431 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\cf1\insrsid6773431 \tab }{\cf1\insrsid6714361 But}{\cf1\insrsid3629274  }{\cf1\insrsid4522747 the FDA}{\cf1\insrsid6714361 , through this rule,
}{\cf1\insrsid4522747  }{\cf1\insrsid6714361 expressed an understanding}{\cf1\insrsid6650562  that}{\cf1\insrsid1901021  classification as a}{\cf1\insrsid4522747  combination}{\cf1\insrsid1901021  product}{\cf1\insrsid4522747  may extend }{
\cf1\insrsid1901021 beyond the}{\cf1\insrsid6714361  immediate appearance}{\cf1\insrsid6768318  of the product (or its parts) }{\cf1\insrsid4522747 to the manner in which the product }{\cf1\insrsid6714361 is }{\i\cf1\insrsid1901021\charrsid9699803 
employed}{\cf1\insrsid6714361  by}{\cf1\insrsid4522747  the end consumer.}{\cf1\insrsid3629274   Two items that are packaged separately, but are }{\cf1\insrsid6650562 intended}{\cf1\insrsid3629274 
 to be used in conjunction with one another for the benefit of the patient, }{\cf1\insrsid15749482 will be treated as a combination product by the }{\cf1\insrsid6650562 health }{\cf1\insrsid15749482 professional
 administering the product.  The separate parts, then, are best regulated as}{\cf1\insrsid3629274  a combination product }{\cf1\insrsid9699803 by the FDA as well to ensure the}{\cf1\insrsid3629274  overall safety}{\cf1\insrsid15749482  }{
\cf1\insrsid9699803 of the product and the patient, }{\cf1\insrsid15749482 in accordance with the statutory charge of the SMDA}{\cf1\insrsid3629274 .    }{\cf1\insrsid5973337 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\cf1\insrsid14357459 \tab After explaining th
e purpose of these new regulations in response to the SMDA, providing definitions to industry terms appearing within the regulations, and clarifying their scope, the FDA reiterated }{\cf1\insrsid14353845 that the product\rquote s}{\cf1\insrsid14357459  
\'93primary mode of action\'94 }{\cf1\insrsid14353845 would be}{\cf1\insrsid14357459  the primary determinant }{\cf1\insrsid4721725 in assigning}{\cf1\insrsid14357459  Center premarket review jurisdiction.}{\cs16\cf1\super\insrsid14357459 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. 
\'a7 3.4 (1991).  56 Fed. Reg. at 58756-57.  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 353(g)(1) (2004).}}}{\cf1\insrsid10554915   The FDA did make one }{\cf1\insrsid14106735 important}{
\cf1\insrsid10554915  addition, however, to the provisions of the SMDA regardin}{\cf1\insrsid15753019 g the primary mode}{\cf1\insrsid4617629  of action}{\cf1\insrsid15753019 .  }{\cf1\insrsid4617629 T}{\cf1\insrsid9572089 
he original language of section 20 of S. 3006 granted approval jurisdiction to only one Center for \'93market clearance purposes.\'94}{\cs16\cf1\super\insrsid9572089 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9572089 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  III.A.}{\insrsid16284404\charrsid7211990 , n}{\insrsid16284404 .}{\insrsid16284404\charrsid7211990 10}{\insrsid16284404 8}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid9572089 
  Yet that language was softened, perhaps in response to the disagreement by the House in H.R. 3095}{\cf1\insrsid14962930  and as a concession by the Conference Committee}{\cf1\insrsid9572089 , such that section 16 of the SMDA gave }{\cf1\insrsid14962930 
to }{\cf1\insrsid9572089 the}{\cf1\insrsid10554915  Center responsible for reviewing the product}{\cf1\insrsid14962930 \rquote s }{\cf1\insrsid10554915 primary mode of action onl}{\cf1\insrsid14962930 y \'93primary jurisdiction.\'94}{\cf1\insrsid10554915 
 }{\cf1\insrsid14962930 To cement this new statutory position within the FDCA,}{\cf1\insrsid16669550  }{\cf1\insrsid9076284 the FDA }{\cf1\insrsid15753019 provided that \'93t}{\cf1\insrsid15753019\charrsid15753019 
he designation of one agency component as having primary jurisdiction for the premarket review and regulation of a combination product }{\i\cf1\insrsid15753019\charrsid3438006 
does not preclude consultations by that component with other agency components or, in appropriate cases, the requirement by FDA of separate applications}{\cf1\insrsid15753019 \'94}{\cs16\cf1\super\insrsid15753019 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 3.4(b) (1991).  56 Fed. Reg. at 58756-57.}}}{\cf1\insrsid3438006  (emphasis added).}{\cf1\insrsid14106735   }{\cf1\insrsid6824659 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\cf1\insrsid6824659 \tab }{\cf1\insrsid14106735 In a corresponding fashion, the three Intercenter Agreements}{\cf1\insrsid1774791 ,}{
\cs16\cf1\super\insrsid14106735 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See also supra}{\insrsid16284404  n. 91}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid1774791  discussed }{\i\cf1\insrsid1774791 infra}{\cf1\insrsid1774791 
 in II.C., were updated at approximately the same time that these regula}{\cf1\insrsid4617629 tions were promulgated}{\cf1\insrsid4853823  to reflect the }{\cf1\insrsid1774791 changes effected by the SMDA}{\cf1\insrsid4853823  in favor of g}{
\cf1\insrsid4617629 reater intercenter cooperation}{\cf1\insrsid1774791 .}{\cf1\insrsid9466035   The FDA drew attention to the existence of these non-binding documents to inform combination product manufacturers}{\cf1\insrsid14106735  }{
\cf1\insrsid9466035 and the public by citing them in the new regulations.}{\cs16\cf1\super\insrsid9466035 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.5 (1991); 56 Fed. Reg. at 58757.}}}{\cf1\insrsid6492409 
  Section 3.5(a)(3) of these regulations encouraged the manufacturer to contact the appropriate Center before beginning the premarket review process to discuss the Center\rquote 
s jurisdiction and to settle any questions.  This provision evinces the policy that initially motivated the SMDA: greater communication between the industry manufacturer and the FDA to enhance the effici
ency of the regulatory process and to increase the public safety.}{\cf1\insrsid14357459 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\cf1\insrsid16211425 \tab The }{\cf1\insrsid4617629 remaining regulations, }{\cf1\insrsid16211425 published in Novembe}{\cf1\insrsid4617629 r}{
\cf1\insrsid2574295  1991}{\cf1\insrsid4617629 ,}{\cf1\insrsid16211425  elucidate}{\cf1\insrsid11042255 d}{\cf1\insrsid16211425  the actual steps to be taken by a product manufacturer prior to a premarket review.}{\cs16\cf1\super\insrsid16211425 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. 
\'a7\'a7 3.7-.10 (1991); 56 Fed. Reg. at 58757-58.}}}{\cf1\insrsid7037958   Section 3.7 detailed the \'93who, when, what and where\'94 }{\cf1\insrsid2574295 for the product manufacturer wishing }{\cf1\insrsid7037958 to file a }{\cf1\insrsid13269000 
letter of }{\cf1\insrsid7037958 request for designation}{\cf1\insrsid2574295 .}{\cs16\cf1\super\insrsid13269000 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.7 (1991).  A \'93
letter of request means an applicant's written submission to the product jurisdiction officer seeking the designation of the agency component with primary jurisdiction.\'94 21 C.F.R. \'a7 3.2(j) (1991); 56 Fed. Reg. at 58756.}}}{\cf1\insrsid2574295   S}{
\cf1\insrsid13269000 ection 3.8 explained that a letter of designation would be sent}{\cf1\insrsid2574295  back}{\cf1\insrsid13269000  to the manufacturer within sixty days}{\cf1\insrsid2574295  of the request}{\cf1\insrsid11042255  \'93}{
\cf1\insrsid11042255\charrsid11042255 specifying the agency component designated to have primary jurisdiction for the premarket review and regulation of the product at issue, and any consulting agency components}{\cf1\insrsid11042255 .\'94}{
\cs16\cf1\super\insrsid11042255\charrsid11042255  }{\cs16\cf1\super\insrsid11042255 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11042255 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.8(b) (1991).  A \'93
letter of designation means the written notice issued by the product jurisdiction officer specifying the agency component with primary jurisdiction for a combination product.\'94 21 C.F.R. \'a7 3.2(i) (1991); 56 Fed. Reg. at 58756.}}}{\cf1\insrsid9639182 
  The product manufacturer, if unhappy with the agency\rquote s decision, could request a reconsideration within fifte
en days of receiving the letter of designation; the agency would then be given fifteen additional days to review the designation and respond.}{\cs16\cf1\super\insrsid9639182 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.8(c) (1991).}}}{
\cf1\insrsid2574295   Finally, a letter of designation }{\cf1\insrsid1445271 would }{\cf1\insrsid2574295 represent a final FDA determination unless the product jurisdiction officer (in this case, the FDA Ombudsman}{\cs16\cf1\super\insrsid2574295 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. 
\'a7 3.6 (1991); 56 Fed. Reg. at 58757.}}}{\cf1\insrsid1445271 ) changed the designation with the manufacturer\rquote s consent or without the manufacturer\rquote s consent because of concerns about the public health \'93or other compelling reasons.\'94}{
\cs16\cf1\super\insrsid1445271 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 C.F.R. \'a7 3.9 (1991); 56 Fed. Reg. at 58757.}}}{\cf1\insrsid6117105   The manufacturer would be entitled to object to
 such a nonconsensual change and the FDA would be required to respond in writing with reasons for the change.}{\cs16\cf1\super\insrsid6117105 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 3.9(b) (1991).  As an extra administrative check on a nonconsensual change in designation, the product jurisdiction officer\rquote s decision \'93requires the concurrence of the Deputy Commissioner for Operations or the Deputy Commissioner for Policy.
\'94  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid16211425\charrsid5973337 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\i\ul\insrsid8222120 I}{\i\ul\insrsid10059263 I}{\i\ul\insrsid8222120 I.}{\i\ul\insrsid6172878  }{\i\ul\insrsid11492884 C}{\i\ul\insrsid8222120 
. }{\i\ul\insrsid1838767 1991: The New}{\i\ul\insrsid8023933  }{\i\ul\insrsid944874 Intercenter Agreements}{\insrsid944874 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\insrsid15026085 \tab }{\insrsid9243286 In }{\insrsid3937128 response}{\insrsid9243286 
 to the statutory and regulatory changes that the SMDA effected within the FDA as a whole, each Center within the FDA needed to modernize its }{\insrsid9654707 individual }{\insrsid9243286 approach toward combination products.  }{\insrsid3937128 
The Intercenter Agreements that resulted late in 1991}{\insrsid15026085  }{\insrsid3937128 thus }{\insrsid15026085 determine}{\insrsid3937128 d}{\insrsid15026085  the role of each Center when the expertise of two}{\insrsid12808956  or more}{
\insrsid12456206  Centers was involved}{\insrsid15026085  }{\insrsid10109419 in}{\insrsid15026085  the approval of a combination product.  }{\insrsid14450235 Predictably}{\insrsid15026085 , e}{\insrsid3937128 ach of their traditional roles wa}{
\insrsid15026085 s }{\insrsid12456206 maintained.}{\insrsid3937128  }{\insrsid12456206  }{\insrsid3937128 CDRH still maintained}{\insrsid15026085  lead jurisdiction for approving medical devices, CDER still over}{\insrsid3937128 saw}{\insrsid11935897 
 the approval of new}{\insrsid15026085  drugs, and }{\insrsid3937128 CBER still regulated}{\insrsid15026085  the presence of biological products in the American market.}{\insrsid11088206   }{\insrsid3937128 
The modernization efforts that were set into motion by the SMDA, however, could not be fully realized without the cooperation of each of the other Centers.  As a result, the Intercenter Agreements specified that premarket review of }{\insrsid11088206 
combination product}{\insrsid3937128 s}{\insrsid11088206  }{\insrsid3937128 would require the}{\insrsid11088206  Centers either}{\insrsid3937128  to}{\insrsid11088206  divide their jurisdiction }{\insrsid8004616 
pursuant to the guidelines established by the }{\insrsid11935897 pertinent }{\insrsid8004616 Agreement }{\insrsid11088206 or work cooperatively to oversee the }{\insrsid11935897 tailored}{\insrsid11088206  approval process.}{\insrsid734543   }{
\insrsid12808956 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid944874 {\insrsid12808956 \tab }{\insrsid8727003 Each Agreement also provided}{\insrsid734543 
 for an Intercenter Jurisdictional Committee, an ad hoc group comprised of one}{\insrsid7155176  regular}{\insrsid734543  member and one alternate from each Center.  The committee }{\insrsid8727003 would }{\insrsid8004616 resolve}{\insrsid734543 
 questions }{\insrsid8727003 that aro}{\insrsid8004616 se over}{\insrsid734543  the manner in which juris}{\insrsid8727003 diction for prod}{\insrsid12456206 uct approval had been assigned.  A}{\insrsid734543 ny disagreement within the committee }{
\insrsid8727003 would }{\insrsid734543 result in }{\insrsid8727003 an }{\insrsid734543 application of the product jurisdiction procedures.  These procedures, }{\insrsid11147869 sometimes}{\insrsid734543  called the \'93request for designation\'94
 (RFD) process,}{\cs16\super\insrsid8727003 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  III.B., n.143}{\insrsid16284404\charrsid7211990 .}}}{\insrsid536363  also would be}{\insrsid734543  available at the }{\insrsid8004616 initial }{
\insrsid734543 reque}{\insrsid536363 st of the product manufacturer }{\insrsid12456206 for}{\insrsid8004616  }{\insrsid734543 a formal agency determination }{\insrsid8004616 of which}{\insrsid734543  Center }{\insrsid4747425 would}{\insrsid8004616  }{
\insrsid12456206 have}{\insrsid8004616  approval}{\insrsid734543  jurisdiction.}{\cs16\super\insrsid734543 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 U.S. Food and Drug Administration, Office of Combination Products, Jurisdictional Updates, }{\i\insrsid16284404 at}{\insrsid16284404  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLIN
K "http://www.fda.gov/oc/combination/updates.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002f00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0075007000640061007400650073002e00680074006d006c000000e0c9ea79
f9bace118c8200aa004ba90b5e00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0075007000640061007400650073002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/updates.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid15026085 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13179294 {\i\ul\insrsid8592177 III. }{\i\ul\insrsid2629406 C}{\i\ul\insrsid8222120 . 1. }{\i\ul\insrsid13179294 CBER-CDRH Intercenter Agreement}{
\insrsid13179294 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13179294 {\insrsid9263712 \tab }{\insrsid11088206 Combinat}{\insrsid11735535 ion products that we}{\insrsid12456206 re subject to the CBER-CDRH A}{
\insrsid11088206 greement include}{\insrsid11735535 d}{\insrsid11088206  those products that represent}{\insrsid11735535 ed}{\insrsid11088206 
 advances in medical device technology for biological applications or biological products coupled with medical devices for therapeutic use.}{\cs16\super\insrsid11088206 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  CBER-CDRH Intercenter Agreement, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.93}{\insrsid16284404\charrsid7211990 .}}}{\insrsid11088206   CDRH }{
\insrsid11735535 was designated the lead C}{\insrsid11088206 enter to manage any good manufacturing practices (GMP) problems }{\insrsid11735535 in addition to}{\insrsid11088206  all}{\insrsid11735535  of the}{\insrsid11088206  medical }{\insrsid11735535 
device reporting issues that aro}{\insrsid11088206 se as a result of the }{\insrsid11735535 premarket review}{\insrsid11088206  process.}{\cs16\super\insrsid11088206 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section III.}}}{\insrsid11088206   }{\insrsid11735535 In contrast, both CBER and CDRH would}{\insrsid8473134  }{\i\insrsid8473134\charrsid11613470 share}{\insrsid8473134 
 jurisdiction }{\insrsid11088206 over other aspects of the }{\insrsid11735535 approval }{\insrsid11088206 process, including}{\insrsid14823598  surveillance and FDCA compliance, informal a
nd formal sanctions, PMNs, IDEs, PMAs and petitions for device reclassification and exemptions.}{\cs16\super\insrsid14823598 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section IV.}}}{\insrsid8473134 
  }{\insrsid11613470 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8473134 {\insrsid11613470 \tab }{\insrsid8473134 Formal approval responsibility}{\insrsid16393501  for medical devices}{\insrsid11613470 , however, wa}{
\insrsid8473134 s }{\i\insrsid8473134\charrsid11613470 divided}{\insrsid8473134  between the Centers in the following ways.  }{\insrsid5589481 CDRH would retain}{\insrsid16393501  general approval responsibility, but }{\insrsid8473134 CBER }{
\insrsid5589481 became}{\insrsid8473134  generally responsible for regulating \'93}{\cf1\insrsid8473134\charrsid1914569 
medical devices used or indicated for the collection, processing, storage or administration of blood products, blood components or analogous products, as well as screening or confirmatory cl
inical laboratory tests associated with blood banking practices and other process testing procedures}{\cf1\insrsid14449292 \'94}{\insrsid5589481  }{\insrsid8473134 as}{\insrsid14449292  well as any }{\i\insrsid14449292 in vitro}{\insrsid14449292 
 test kits and any medical devices intended for use for HIV and other retroviruses.}{\cs16\cf1\super\insrsid14449292 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid14449292 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VI.}}}{\insrsid7682694 
  }{\insrsid12016055 The Agreement provided a few e}{\insrsid7682694 xamples of these devices}{\insrsid12016055 , including}{\insrsid7682694 
 collection devices, specimen containers, components of test kits and those devices used for the inactivation of HIV and other retroviruses.}{\cs16\super\insrsid7682694 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid8602721   }{\insrsid333772 CBER was also assigned the approval jurisdiction to regulate some generic medical devices that the CDRH originally classified in its hematology category.}{
\cs16\super\insrsid333772 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VII.}}}{\insrsid333772  }{\insrsid8602721 CDRH }{\insrsid12016055 would regain}{\insrsid8602721  responsib}{\insrsid13137248 
ility, though, if the device had}{\insrsid8602721  a therapeutic purpose, meaning }{\insrsid13137248 that the device wa}{\insrsid11863803 s}{\insrsid13137248  }{\insrsid11863803 intended}{\insrsid13137248  for a}{\insrsid333772 
 specific use on a particular patient with a specific ailment to provide a direct clinical benefit for that patient.}{\cs16\super\insrsid333772 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VI.}}}{
\insrsid8473134\charrsid5589481 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 {\i\ul\insrsid2629406 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid2629406 I.C}{\i\ul\insrsid8222120 . 2. }{\i\ul\insrsid10159429 
CDER-CDRH Intercenter Agreement}{\insrsid10159429\charrsid12847204 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 {\insrsid10159429 \tab These two Centers were accustomed to cooperating prior to their 1991 Agreement,}{\cs16\super\insrsid11863803 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.93}{\insrsid16284404\charrsid7211990 .}}}{\insrsid10159429  but both recognized}{\insrsid10825715  that the statutory amendments created the SMDA would}{\insrsid11285519  require a co}{
\insrsid10159429 dification of their working rel}{\insrsid10825715 ationship}{\insrsid10159429  rather than a continuation of their history of ad hoc }{\insrsid15945552 decision-making}{\insrsid10159429 .}{\cs16\super\insrsid10159429 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  CDER-CDRH Intercenter Agreement, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 9}{\insrsid16284404 6}{
\insrsid16284404\charrsid7211990 .}}}{\insrsid10159429   To som}{\insrsid11285519 e extent, this A}{\insrsid10825715 greement mirrored}{\insrsid10159429  the CBER-CDRH agreement, in that CDRH and CDER share}{\insrsid10825715 d}{\insrsid10159429  the same 
}{\insrsid10825715 subelements}{\insrsid10159429  of jurisdiction over the general aspects of the approval process as do CBER and CDRH.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section IV.}}}{\insrsid10159429   }{\insrsid4226021 Similarly, }{\insrsid10825715 t}{\insrsid10159429 he tw}{\insrsid10825715 o Centers in this }{\insrsid11285519 A}{
\insrsid10825715 greement stro}{\insrsid10159429 ve to assure manufacturers that}{\insrsid10825715  approval for their product }{\insrsid4226021 usually }{\insrsid10825715 would}{\insrsid10159429  be necessary from only one Center.}{
\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section V.  }{\i\insrsid16284404\charrsid7211990 See also id.}{\insrsid16284404\charrsid7211990 
 at section VI; CBER-CDRH Intercenter Agreement, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.93}{\insrsid16284404\charrsid7211990  at section V. (allowing f
or the possibility of a collaborative review between the two Centers, even though the regulations contained within 21 C.F.R. Part 3 encourage the grant of approval jurisdiction to just one Center).}}}{\insrsid10159429   To }{\insrsid10825715 
that end, the Agreement provided}{\insrsid10159429  in some detail the }{\insrsid10825715 criteria that CDER and CDRH would}{\insrsid10159429 
 consider in designating a product as a drug, device, or a combination thereof before assigning approval jurisdiction.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VIII.}}}{\insrsid10159429  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 {\insrsid10159429 \tab In }{\insrsid22789 addition, the Agreement explained how the two Centers would}{\insrsid10159429  manage the app}{
\insrsid22789 roval of a few}{\insrsid10159429  important}{\insrsid22789 ,}{\insrsid10159429  common product designs.  Th}{\insrsid22789 e category that the product would}{\insrsid10159429 
 be placed in (drug, device, or combination product), the steps of approval (including the appropriate application mechanism) and the}{\insrsid22789  subsequent role of each Center wa}{\insrsid10159429 s outlined.  F}{\insrsid22789 
irst, the Agreement indicated}{\insrsid10159429  in what special circumstances}{\insrsid22789  the approval of both Centers}{\insrsid10159429  still}{\insrsid22789  would be}{\insrsid10159429  requ}{\insrsid22789 ired, such as when the product wa}{
\insrsid10159429 s }{\insrsid22789 a device that primarily delivered or helped}{\insrsid10159429  to deliver a drug, but that drug is not distributed with the device.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VII.A.1(a).}}}{\insrsid2701349   Another example wa}{\insrsid10159429 s a device}{\insrsid2701349  that was}{\insrsid10159429 
 used concurrently with a drug to activate or improve the benefit of the drug.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VII.B.1.}}}{
\insrsid10159429  }{\insrsid2701349  Second, the Agreement maintained}{\insrsid10159429  a default category}{\insrsid2701349  in }{\insrsid10159429 wh}{\insrsid2701349 ich}{\insrsid10159429  ad hoc jurisdictional decisions still }{\insrsid2701349 
would be }{\insrsid10159429 appropriate.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VII.E.}}}{\insrsid10159429   Products traditionally considered to be drugs}{
\insrsid11285519  and devices, respectively, }{\insrsid4412659 would}{\insrsid10159429  re}{\insrsid11285519 tain that designation, except}{\insrsid10159429  those drugs that were affected by the Transitional Device Notice in 1977.}{
\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section VII.C.-D.  }{\i\insrsid16284404\charrsid7211990 See also supra}{\insrsid16284404 , n.82}{\insrsid16284404\charrsid7211990 . }
}}{\insrsid10159429   
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 {\insrsid10159429 \tab Finally, the Agreement indicate}{\insrsid14352447 d what types of new products could}{\insrsid10159429  antici
pate being categorized as combinati}{\insrsid14352447 on products and what Center would}{\insrsid10159429  have subsequent }{\insrsid14352447 primary}{\insrsid10159429  jurisdiction over their a}{\insrsid14352447 pproval.  Medical devices that we}{
\insrsid10159429 re pre}{\insrsid15945552 -}{\insrsid10159429 filled with drugs to deliver, or devices that incorporate}{\insrsid14352447 d}{\insrsid10159429  the drug in general within the overall product as part of}{\insrsid14352447 
 the functioning of the device}{\insrsid12943062 ,}{\insrsid14352447  we}{\insrsid10159429 re both examp}{\insrsid14352447 les of combination products, except that CDER would oversee}{\insrsid10159429  the former and CDRH }{\insrsid14352447 would oversee 
}{\insrsid10159429 the latter.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section VII.A.1(b)-A.2.}}}{\insrsid10159429   Further examples include}{
\insrsid12943062 d a drug that incorporated}{\insrsid10159429  a device component to effect the function of the drug (}{\insrsid16009777 overseen by }{\insrsid10159429 CDER),}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section VII.A.3.}}}{\insrsid10159429  a drug and a de}{\insrsid16009777 vice combined together that would process the}{\insrsid10159429 
 drug into its final packaged form (CDER),}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section VII.A.4(b).}}}{\insrsid16009777  and a device kit that wa}{\insrsid10159429 
s both labeled f}{\insrsid16009777 or use with a certain drug and wa}{\insrsid10159429 s packaged with that drug as a means of effectuating the function of the device (CDRH).}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section VII.B.2.}}}{\insrsid10159429   An interesting exception }{\insrsid16009777 to these standards was a device that would be used to produce a drug that wa}{
\insrsid10159429 s delive}{\insrsid16009777 red directly to the patient or wa}{\insrsid10159429 s used at }{\insrsid13395492 a}{\insrsid10159429  }{\insrsid13395492 medical facility.  T}{\insrsid16009777 he product would be classified a device, yet}{
\insrsid10159429  regulated by CDER.}{\cs16\super\insrsid10159429 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid10159429 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section VII.A.4(a).}}}{\insrsid10159429\charrsid5143005 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13179294 {\i\ul\insrsid2629406 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid2629406 I. C}{\i\ul\insrsid8222120 . 3. }{\i\ul\insrsid13179294 
CDER-CBER Intercenter Agreement}{\insrsid13179294 :
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13179294 {\insrsid16285674 \tab Taking }{\insrsid16262037 yet }{\insrsid16285674 a}{\insrsid16262037 nother}{\insrsid16285674  approach than the }{
\insrsid16262037 CDER-CDRH }{\insrsid13395492 A}{\insrsid16285674 greement}{\insrsid16262037 , CDER and CBER ch}{\insrsid16285674 ose to designate approval jur}{\insrsid2248516 i}{\insrsid16285674 
sdiction for a drug or biological product depending upon the product class.}{\cs16\super\insrsid16285674 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See }{\insrsid16284404\charrsid7211990 
CDER-CBER Intercenter Agreement, section III, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.95}{\insrsid16284404\charrsid7211990 .}}}{\insrsid16262037   A product class wa}{\insrsid10181232 s}{\insrsid16262037  defined to be}{
\insrsid10181232  a \'93distinct category of agents recognizable by physical characteristics, source materials or pharmacologic properties.\'94}{\cs16\super\insrsid10181232 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid13395492   The A}{\insrsid16262037 greement provided}{\insrsid10625316  a few exampl}{\insrsid1533845 es}{\insrsid16262037  of these classes}{\insrsid1533845 : vaccines, hormones, and anti}{
\insrsid16262037 biotics.  When one Center wa}{\insrsid10625316 s given regulatory responsibility, that Center}{\insrsid16262037  would oversee}{\insrsid10625316  both the manufacture of the product and its resulting quality}{\insrsid16262037 
, but the other Center would}{\insrsid1533845  not }{\insrsid16262037 be }{\insrsid1533845 precluded from participating in the oversight.}{\cs16\super\insrsid10625316 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid10625316  }{\insrsid16262037  CDER was given the}{\insrsid6511877  responsibil}{\insrsid16262037 ity of regulating}{\insrsid6511877  }{\insrsid16262037 products from nonhuman animal,}{\insrsid6511877 
 solid human tissue sources}{\insrsid16262037 ,}{\insrsid6511877  chemically synthesized molecules (excluding vaccines or allergenics), antibiotics, certain fungi and bacteria products, and hormone products.}{\cs16\super\insrsid6511877 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section III.A.}}}{\insrsid16262037   CBER, in contrast, would regulate}{\insrsid1121360  biological products that we}{\insrsid6511877 re subject to BLAs (such as vaccines, }{
\i\insrsid6511877 in vivo}{\insrsid6511877  diagnostic allergenic products, human blood or immunoglobulin products, protein}{\insrsid15945552 s}{\insrsid6511877 
, peptide or carbohydrate products), synthetically produced allergenic products, and certain drugs associated with blood banking.}{\cs16\super\insrsid6511877 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section III.B.}}}{\insrsid6776642   }{\insrsid7865820 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid7865820 \tab }{\insrsid1121360 For}{\insrsid6776642  co}{\insrsid1121360 mbination products that possessed}{\insrsid6776642 
 both drug and biological components}{\insrsid1121360 , the product would}{\insrsid6776642  fall under CDER\rquote s jurisdiction if th}{\insrsid1121360 e biological component \'93enhanced the efficacy or ameliorated}{\insrsid6776642  the toxicity\'94
 of the drug comp}{\insrsid13395492 onent.  A}{\insrsid1121360  reverse result would place}{\insrsid6776642  the product under CBER\rquote s jurisdiction.}{\cs16\super\insrsid6776642 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section III.D.1.-2.}}}{\insrsid6776642   A c}{\insrsid1121360 ombination product that contained}{\insrsid6776642 
 a biological product coupled with either a radioactive component or a toxin com}{\insrsid1121360 ponent (that is not a drug) would}{\insrsid6776642  be subject to CBER regulation, whereas a biological component }{\insrsid1121360 that was }{
\insrsid6776642 used to affect distribution of the product coupled with a no}{\insrsid1121360 nradioactive drug component would}{\insrsid6776642  be subject to CDER regulation.}{\cs16\super\insrsid15142931 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid13179294 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid7865820 \tab One un}{\insrsid1121360 ique aspect of this Agreement was}{\insrsid7865820 
 the designation of responsibility for medical reviews and pharmacology/toxicology reviews.}{\insrsid13395492   Products}{\insrsid2568208  approved by CDER and CBER implicate concerns for human }{\insrsid1121360 health, }{\insrsid2568208 safety}{
\insrsid1121360 ,}{\insrsid2568208  and exposure in a way that medical devices often do not.  Thus, }{\insrsid3083797 approval of the product by }{\insrsid2568208 either Center }{\insrsid1121360 would be conditioned upon the}{\insrsid3083797  }{
\insrsid1121360 inclusion of}{\insrsid3083797  an}{\insrsid2568208  analysis of the product\rquote s effect in the fields of allergy, clinical immunology and rheumatology, hematology, oncology and infectious diseases.}{\cs16\super\insrsid2568208 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section IV.}}}{\insrsid3083797   Since multiple}{\insrsid1121360  clinical}{\insrsid3083797  subsets of each of those fields}{\insrsid1121360  exist, the Agreement enumerated}{
\insrsid3083797  in more detail which Center }{\insrsid1121360 would have}{\insrsid3083797  primary medical review jurisdiction over each subset.  Both Centers }{\insrsid1121360 retained}{\insrsid3083797 
 concurrent review jurisdiction over a third group of products, but the Center that }{\insrsid1121360 would be}{\insrsid3083797  assigned overall approval jurisdiction of the product }{\insrsid13395492 was}{\insrsid3083797  also}{\insrsid1121360 
 responsible for the product\rquote s medical review}{\insrsid3083797 .}{\cs16\super\insrsid3083797 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See id.}{\insrsid16284404\charrsid7211990  at section IV.A.-C.}}}{
\insrsid14098595   If the medical review of a product }{\insrsid1121360 was}{\insrsid14098595  not }{\insrsid16409232 delegated}{\insrsid14098595  }{\insrsid16409232 to}{\insrsid14098595  the Center with the overall approval jurisdiction for that product}
{\insrsid16409232  (so-called \'93collaborative review\'94}{\cs16\super\insrsid16409232 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 id.}{\insrsid16284404\charrsid7211990  at section VI.}}
}{\insrsid16409232 )}{\insrsid14098595 , then both Centers }{\insrsid1121360 would}{\insrsid14098595  share the responsibility of completing the pharmacology/toxicology review.}{\cs16\super\insrsid14098595 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section V.A.1.}}}{\insrsid13395492   I}{\insrsid1121360 f CDER received}{\insrsid16409232  approval jurisdiction for a product containing human source material, }{
\insrsid1121360 then }{\insrsid16409232 CBER }{\insrsid1121360 would be}{\insrsid16409232  expected to consult on appropriate tests for unexpected agents within the product.}{\cs16\super\insrsid16409232 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at section V.B.}}}{\insrsid1121360   \'93Collaborative review\'94 differed}{\insrsid2391950  from}{\insrsid1121360  a more informal}{\insrsid2391950 
 consultation in that the Center with collaborative jurisdiction }{\insrsid1121360 was bound to}{\insrsid2391950  produce a definitive result from its}{\insrsid15796426  review that }{\insrsid1121360 would}{\insrsid15796426 
 be included in the final administrative record, }{\insrsid1121360 even if that Center did}{\insrsid2391950  not have final product jurisdiction.}{\cs16\super\insrsid2391950 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See id. }{\insrsid16284404\charrsid7211990 at section VI.}}}{\insrsid7865820 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\i\ul\insrsid2629406 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid2629406 I.D. The Middle 1990\rquote s}{\i\ul\insrsid7225859 
: The Continuing Effect of the SMDA}{\insrsid2629406 
\par }{\i\ul\insrsid2230315 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid2230315 I.D.I. To Move or Not to Move the FDA Centers?}{\insrsid2230315\charrsid2230315 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid2629406 \tab }{\insrsid75930 F}{\insrsid7225859 ollowing the passage of the SMDA and the promulgation of the corre}{\insrsid75930 
sponding regulations by the FDA, }{\insrsid12672170 the recognition of combination products as a separate class }{\insrsid6901971 deserving of separate regulatory procedures}{\insrsid12672170  by the FDA took a quantum leap forward.  Yet, }{
\insrsid6901971 once this change evolved into a common feature of the FDA\rquote s approval landscape, }{\insrsid12672170 a familiar and still unresolved}{\insrsid13395492  challenge rose}{\insrsid12672170  once again for }{\insrsid13395492 
CDRH, CBER, and CDER: how}{\insrsid15692572  actually}{\insrsid13395492  to}{\insrsid15692572 
 implement the statutory and administrative mandates that were set out for the Centers with three separate staffs that were increasingly inundated with premarket review requests}{\insrsid3756417  and were physically separated i}{\insrsid15692572 
n different FDA }{\insrsid3756417 buildings}{\insrsid15692572 .}{\insrsid6901971   }{\insrsid5113377 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid5113377 \tab }{\insrsid10910021 At a hearing before the }{\insrsid6901971 Subcommittee on Public Buildings and Economic Development }{
\insrsid10910021 of}{\insrsid6901971  the }{\insrsid10910021 House }{\insrsid6901971 Committee on Transpor}{\insrsid3756417 tation and Infrastructure, }{\insrsid6901971 Commissioner of Food and Drugs, Dr. David A. Kessler, informed the
 Subcommittee that the FDA was still receiving an increasing number of requests for combination product premarket review.}{\cs16\super\insrsid6901971 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Heari}{\i\insrsid16284404 ng Before the Subcomm. on Pub. Bldg}{\i\insrsid16284404\charrsid7211990 s}{\i\insrsid16284404 . and Econ. Dev.}{\i\insrsid16284404\charrsid7211990  of t}{\i\insrsid16284404 
he House Comm. on Transp.}{\i\insrsid16284404\charrsid7211990  and Infrastructure}{\insrsid16284404\charrsid7211990 , 1995 WL 89247 (March 6, 1995) (statement of Dr. David A. Kessler, Commissioner, Food and Drug 
Administration).  Commissioner Kessler also gave examples of some of the more recent applications for combination products, including \'93
drug delivery systems, medicated wound dressing, bone cement containing an antibiotic, and dental composites with fluoride.\'94}}}{\insrsid5113377   More notably, his appearance before this particular Subcommittee was in conjunction with the FDA\rquote 
s campaign to consolidate its operations on two, as yet unapproved, central}{\insrsid3823002 ized}{\insrsid5113377  campuses in Maryland.  According to Commissioner Kessler, \'93
the current fragmentation of FDA review staff among many scattered facilities result[ed] in unnecessary approval delays for these [combination] products.\'94}{\cs16\super\insrsid5113377 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid11096721   His support for consolidation of the FDA facilities was motivated in part by the same concerns that Senator Kennedy expressed in promoting the SMDA five years earlier: \'93
improvements in efficiencies\'94 and continued improvement in \'93the time frames for product approval decisions.\'94}{\cs16\super\insrsid11096721 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid7225859 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid13783668 \tab The administrative push for these two new FDA campuses, however, }{\insrsid10910021 
met with significant resistance from at least one source.}{\insrsid7015363   C. Boyden Gray, the Chairman }{\insrsid10910021 of Citizens for a Sound Economy, a non-profit research and education organ
ization formed to advocate market-based solutions for public policy problems, testified before the Treasury, Postal Service, and General Government Subcommittee of the House Committee on Appropriations just two weeks after Commissioner Kessler made his st
atements in favor of the consolidated campuses.}{\cs16\super\insrsid3823002 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Hearing Before the Subc}{\i\insrsid16284404 omm. on Treasury, Postal Serv., and General Gov\rquote }{
\i\insrsid16284404\charrsid7211990 t of the House Comm. on Appropriations}{\insrsid16284404\charrsid7211990 , 1995 WL 118134 (March 21, 1995) (statement of C. Boyden Gray, Chairman, Citizens for a Sound Economy).}}}{\insrsid11224164   Chairman Gray
\rquote s testimony focused upon the proposed expenditures for the two campuses, one of which would tentatively house CDRH, CBER}{\insrsid3756417 ,}{\insrsid11224164  and CDER.  He expressed skepticism at the FDA\rquote s insistence that its \'93di
spersed locations . . . have created both administrative and operations inefficiencies.\'94}{\cs16\super\insrsid11224164 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid543177 
  In particular, he criticized the need for inter-Center communication by noting that \'93the number of products affected by more than one evaluating center is small comp
ared to the total number of product applications evaluated by the agency each year.  In all likelihood, an $810 million campus will not significantly speed up the approval process for the relatively small number of products that need to be evaluated betwe
en centers.\'94}{\cs16\super\insrsid543177 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 
\chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid543177   Instead, Chairman Gray advocated the continued use of the FDA\rquote 
s state of the art, inter-agency computer network that allowed the premarket reviewers to communicate with each other via the World Wide Web.}{\cs16\super\insrsid543177 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See id.}}}{\insrsid13783668 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid3285378 \tab }{\insrsid15342116 The legislative record does not disc
lose an immediate response by the FDA, but the debate over the FDA campus consolidation continued.  Fourteen months after Chairman Gray\rquote 
s claims that the consolidation of CBER, CDRH, and CDER into one building would be a waste of government spending, espec
ially after the General Services Administration (GSA) was appropriated approximately $325 million between 1992 and 1995 for the project,}{\cs16\super\insrsid15342116 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid15342116  }{\insrsid3285378 FDA Deputy Commissioner for External Affairs Sharon Smith Holston also addressed the Subcommittee on Public Buildings and Economic Development}{\insrsid9202538 
 of the House Committee on Transportation and Infrastructure}{\insrsid3285378 .}{\cs16\super\insrsid3285378 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Hearing Before the Subc}{\i\insrsid16284404 omm. on Pub. Bldg}{
\i\insrsid16284404\charrsid7211990 s}{\i\insrsid16284404 . and Econ. Dev.}{\i\insrsid16284404\charrsid7211990  of t}{\i\insrsid16284404 he House Comm. on Transp.}{\i\insrsid16284404\charrsid7211990  and Infrastructure}{\insrsid16284404\charrsid7211990 
, 1996 WL 276588 (May 23, 1996) (statement of Sharon Smith Holston, Deputy Commissioner, Food and Drug Administration External Affairs).}}}{\insrsid9202538 
  Her response to Chairman Gray was an appeal grounded in the experience of the FDA in the regulation of these products.}{\insrsid10046253   She noted that }{\insrsid16475001 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid16475001 {\insrsid10046253 \'93[FDA\rquote s] experience demonstrates
 that the Agency is increasingly required to resolve policy questions involving multiple FDA Centers, differing or overlapping statutory jurisdiction, or complex emerging developments in new science or technology that affect more than one of our Centers. 
 This emerging trend means that there is a greater need for collaboration across Center lines, and for sharing resources, including personnel, equipment, and scientific expertise.}{\insrsid16475001 
 . . . Consolidation will allow FDA scientists to engage in collaborative efforts that are critical both to the advancement of knowledge and to the coordination of research and review functions performed by the Agency.}{\insrsid10046253 \'94}{
\cs16\super\insrsid10046253 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid3285378 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid2230315 \tab }{\insrsid7225859 \tab }{\insrsid16475001 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid15945552 While Ms. Ho}{\insrsid2230315 lston\rquote s comments did not disclose a radical de}{\insrsid12545634 velopment in FDA }{
\insrsid12335603 regulatory }{\insrsid12545634 policy, they arguably}{\insrsid2230315  indicate}{\insrsid12545634 d}{\insrsid2230315  a frustration within the Agency}{\insrsid12335603  that had continued unresolved}{\insrsid2230315  fiv}{\insrsid12335603 
e years after the passage of section 16 of the}{\insrsid2230315  SMDA and four years after the }{\insrsid12335603 corresponding}{\insrsid2230315  premarket review regulations were published.}{\insrsid12545634 
  Despite the Congressional efforts through the SMDA to provide for more efficient product regulation}{\insrsid2230315  }{\insrsid12335603 to further the}{\insrsid12545634 
 public health, it appeared that the FDA was still struggling to realize the level of administrative efficiency and inter-Center informational collaboration that would need to exist before effective combination product regulation could exist.}{
\insrsid12335603   The debate over the physical location of the three Centers only threw that continuing struggle into relief.  Thus, the statutory recognition of combination products and the accompanying adjustments to the FDA\rquote 
s regulatory framework may have represented more of a quantum leap on paper than in practice.}{\cs16\super\insrsid12335603 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 After all of the debate surrounding the consolidation of the FDA campuses, construction is currently underway on the White Oak campus in Montgomery County, Maryland.  The consolidated campus is the result of explicit Congressional approval; in 1990, sect
i
on 101 of the FDA Revitalization Act authorized the Secretary of Health and Human Services in conjunction with the Administrator of the General Services Administration (GSA) to begin contracting for a consolidated FDA facility.  FDA Revitalization Act, Pu
b. L. No. 101-635, sec. 101, 104 Stat. 4583, 21 U.S.C. \'a7
 379b (November 28, 1990).  Through the combined efforts of the GSA and the FDA, the new White Oak facility will finally house CBER, CDER, and CDRH in one location.  The facility will provide updated l
aboratory space in addition to administrative office space for the FDA\rquote 
s research scientists and their support staff.  The construction will be completed in yearly phases, with the CDER facilities to be completed first in 2007, the CDRH facilities to follo
w in 2008, and the CBER facilities to be finished in 2009.  FDA Headquarters Consolidation at White Oak, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/whiteoak/" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f00770068006900740065006f0061006b002f000000e0c9ea79f9bace118c8200aa004ba90b4000000068007400740070003a002f002f00
7700770077002e006600640061002e0067006f0076002f006f0063002f00770068006900740065006f0061006b002f000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/whiteoak/}}}{\insrsid16284404\charrsid7211990 
 (last visited April 16, 2004); FDA Headquarters Consolidation at White Oak Frequently Asked Questions, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/whiteoak/faq.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f00770068006900740065006f0061006b002f006600610071002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b5000
000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f00770068006900740065006f0061006b002f006600610071002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda
.gov/oc/whiteoak/faq.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).}}}{\insrsid12335603 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\i\ul\insrsid12335603 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid3756417 I.D.2. The Biomaterials Access Assurance}{\i\ul\insrsid12335603 
 Act of 1996}{\insrsid2230315 \tab }{\insrsid10437054 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid10437054 \tab Combination products continued to be implicated in unexpected ways throughout 1996, }{\insrsid15944608 both}{
\insrsid10437054  in the debate over the FDA campus consolidation, and in the political battle over the legal limits of a }{\insrsid15944608 medical device }{\insrsid10437054 manufacturer\rquote s product liability in litigation.}{\insrsid15213835 
  On March 14, 1996, a conference report was published on H.R. 956, the Common Sense Product Liability Legal Reform Act of 1996.}{\cs16\super\insrsid16122884 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 H. Rep. No.}{\insrsid16284404\charrsid7211990  104-481, 142 Cong. Rec. H2238-05, 1996 WL 111996 (March 14, 1996).}}}{\insrsid15944608   Title II of this}{\insrsid16122884 
 Act contained the Biomaterials Access Assurance Act of 1996}{\insrsid483781  (\'93BAAA\'94)}{\insrsid16122884 .}{\cs16\super\insrsid9266859 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Biomaterials Access Assurance Act of 1996 (\'93BAAA\'94), Pub. L. No. 105-230, 112 Stat. 1519, 21 U.S.C. \'a7
\'a7 1601 et seq. (August 13, 1998).}}}{\insrsid483781   }{\insrsid15944608 The}{\insrsid483781  BAAA }{\insrsid15944608 found}{\insrsid483781  that }{\cf1\insrsid483781\charrsid483781 the suppliers of the raw materials and component parts}{
\cf1\insrsid15944608  used to make medical devices}{\cf1\insrsid483781\charrsid483781  }{\cf1\insrsid483781 that are included }{\cf1\insrsid15944608 later }{\cf1\insrsid483781 within}{\cf1\insrsid15944608  combination products }{\cf1\insrsid483781 
do not have a duty either to \'93}{\cf1\insrsid483781\charrsid483781 evaluate the safety and efficacy of the use of a raw material or compone}{\cf1\insrsid483781 nt part in a medical device\'94 or to \'93}{\cf1\insrsid483781\charrsid483781 
warn consumers concerning the safety and effectiveness of a medical }{\cf1\insrsid483781 {\*\bkmkstart SDU_33}{\*\bkmkend SDU_33}device.\'94}{\cs16\cf1\super\insrsid483781 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  BAAA, \'a7 202(13); 21 U.S.C. 
\'a7 1601(13) (2004); 142 Cong. Rec. at H2242.  Under the BAAA, a \'93medical device\'94 includes \'93any device component of any combination product as that term is {\*\bkmkstart SDU_37}{\*\bkmkend SDU_37}
used in section 503(g) of such Act (21 U.S.C. 353(g)).\'94  BAAA, \'a7 203(7); 142 Cong. Rec. at H2242.}}}{\cf1\insrsid483781   }{\cf1\insrsid1125213 Yet, to impose such a duty on those suppliers would \'93}{\cf1\insrsid1125213\charrsid1125213 
cause more harm than good by driving the suppliers to cease supplying manuf}{\cf1\insrsid1125213 acturers of medical devices.\'94}{\cs16\cf1\super\insrsid1125213 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  BAAA, \'a7
 203(14); 142 Cong. Rec. at H2242.  The BAAA, as enacted, did not employ the exact language of section 203(14).  Rather, a similar provision was codified at 21 U.S.C. \'a7 1601(8) that found that \'93
even though suppliers of raw materials and component parts have very rarely been held liable in such actions, such suppliers have ceased supplying certain r
aw materials and component parts for use in medical devices for a number of reasons, including concerns about the costs of such litigation.\'94}}}{\cf1\insrsid13644648   }{\cf1\insrsid483781 Thus, to}{\cf1\insrsid483781\charrsid483781  }{
\cf1\insrsid483781 \'93}{\cf1\insrsid483781\charrsid483781 safeguard the availability of a wide variety of lifesaving and life-enhancing medical devices}{\cf1\insrsid483781 \'94 and device components of combination products}{
\cf1\insrsid483781\charrsid483781 , }{\cf1\insrsid483781 Congress determined }{\cf1\insrsid2693046 that \'93immediate action [was]}{\cf1\insrsid483781  needed }{\cf1\insrsid483781\charrsid483781 
to clarify the permissible bases of liability for suppliers of raw materials and compo}{\cf1\insrsid483781 nent parts for medical devices . . . }{\cf1\insrsid483781\charrsid483781 and}{\cf1\insrsid483781  . . .}{\cf1\insrsid2693046  }{
\cf1\insrsid483781\charrsid483781 to provide expeditious procedures to dispose of unwarranted suits against the suppliers in such manner as to minimize litigation costs.}{\cf1\insrsid483781 \'94}{\cs16\cf1\super\insrsid16526829 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  BAAA, \'a7
 202(15); 21 U.S.C. \'a7 1601(15); 142 Cong. Rec. at H2242.}}}{\cf1\insrsid10182047   The }{\cf1\insrsid13644648 BAAA}{\cf1\insrsid10182047  thus imposed}{\cf1\insrsid13644648  product liability }{\cf1\insrsid15944608 up}{\cf1\insrsid13644648 
on biomaterials suppliers for harm caused to a person by a medical implant, but only if that supplier was also the manufacturer }{\cf1\insrsid1457897 or the seller }{\cf1\insrsid13644648 of the implant.}{\cs16\cf1\super\insrsid13644648 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  BAAA, \'a7\'a7
 205(a)(1), (b)(1), (c)(1); 21 U.S.C. \'a7\'a7 1604(a)(1), (b)(1), (c)(1); 142 Cong. Rec. at H2243.}}}{\cf1\insrsid2230315 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\cf1\insrsid5775959 \tab }{\cf1\insrsid9832689 While }{\cf1\insrsid5775959 Congress }{\cf1\insrsid9832689 sought}{\cf1\insrsid5775959 
 to provide a legal defense from product liability to suppliers of raw materials or parts that are included in implantable medi}{\cf1\insrsid9832689 cal devices, it}{\cf1\insrsid5775959  distinguish}{\cf1\insrsid9832689 ed}{\cf1\insrsid10514097  the }{
\i\cf1\insrsid5775959\charrsid10514097 device}{\cf1\insrsid5775959  parts from the other facets of a combination product, such as an active ingredient or drug.}{\cs16\cf1\super\insrsid5775959 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  142 Cong. Rec. at H2247.}}}{\cf1\insrsid16347509   By the terms of the BAAA, only the parts that qualified as medical devices were allowed to claim the legal defense, and not the}{
\cf1\insrsid9832689  parts provided by the}{\cf1\insrsid16347509  suppliers or manufacturers of the active ingredient or drug.}{\cf1\insrsid8158297   As the report stated, \'93}{\cf1\insrsid8158297\charrsid8158297 
this will ensure that the development and availability of such devices will not be impaired because of the same liability concerns affecting the availability of materials for other types of implants.}{\cf1\insrsid8158297 \'94}{
\cs16\cf1\super\insrsid8158297 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid10514097   The BAAA stood}{\cf1\insrsid16398902  as an}{\cf1\insrsid10514097 other}{\cf1\insrsid16398902 
 example of how the advent of combination products had changed more than just the immediate regulatory landscape of the FDA.  Congress found that a balance needed to be struck between the pressure felt by medical device
 and combination product manufacturers to stay ahead of the technological curve and the safety of patients receiving those products.  All of this legislation could be interpreted as an additional chapter in the pursuit of the original goal of the SMDA: to
 enable the financial and scientific growth of the combination product industry while }{\cf1\insrsid10514097 preserving}{\cf1\insrsid11031016  as preeminent}{\cf1\insrsid16398902  the safety of the American public.}{\cf1\insrsid5775959 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\i\ul\insrsid6650771 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid6650771 I.D.3. Up in Smoke: Combination Products and the Supreme Court}{
\insrsid2629406  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid7153423 \tab }{\insrsid14449331 Before 1996 drew to a close, the FDA }{\insrsid2845184 undoubt
edly classified multiple new products as combination products.  But one classification in particular, directed }{\insrsid8519778 at}{\insrsid2845184  }{\insrsid14449331 a politically and culturally charged product}{\insrsid2845184 , }{\insrsid14449331 
would become a }{\insrsid2845184 fateful administrative decision.  Never before }{\insrsid9788002 had the FDA chosen to regulate}{\insrsid2845184  tobacco products}{\insrsid5134371 , }{\insrsid6189824 but on }{\insrsid5134371 August 28, 1996}{
\insrsid6189824 , t}{\insrsid2845184 he FDA chose to classify}{\insrsid14449331  cigarettes}{\insrsid3756417  as combination products.  T}{\insrsid12607465 he nicotine }{\insrsid6189824 constitute}{\insrsid12607465 d}{\insrsid6189824  }{\insrsid12607465 
a drug }{\insrsid6189824 while the cigarette and smokeless tobacco formed the \'93}{\insrsid12607465 drug delivery }{\insrsid6189824 device\'94 to deliver the nicotine to the consumer}{\insrsid14449331 .}{\cs16\super\insrsid6189824 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  61 Fed. Reg. 44396, 44397, 45208-16. (August 28, 1996).  Nor did such a change in regulatory policy seem to be in conflict at the time that the Food and Drug 
Administration Modernization and Accountability Act of 1997 was being drafted.  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 143 Cong. Rec. S8851-01, S8859, 1997 WL 545415 (September 4, 1997) (statement of  Diane Duffy, Legislative Attorney, American Law Division to Senate Comm. on Labor and Human Resources).}}}{\insrsid12607465   Def
ining tobacco products to be combination products as such meant that the FDA }{\insrsid8921376 then }{\insrsid12607465 had jurisdiction under the FDCA to investigate the labeling of the cigarette packages \endash 
 labels that lacked claims of therapeutic benefits.}{\cs16\super\insrsid12607465 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 44402.}}}{\insrsid4553922   }{\insrsid8921376 More specifically,}{\insrsid11695887 
 pursuant to its jurisdiction to regulate \'93restricted devices}{\insrsid15945552 ,}{\insrsid11695887 \'94}{\cs16\super\insrsid11695887\charrsid11695887  }{\cs16\super\insrsid11695887 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11695887 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7
 360j(e) (2004), which allows the agency to "require that a device be restricted to sale, distribution, or use ... upon such other conditions as [the FDA] may prescribe in such regulation, if, because of its p
otentiality for harmful effect or the collateral measures necessary to its use, [the FDA] determines that there cannot otherwise be reasonable assurance of its safety and effectiveness."}}}{\insrsid11695887  }{\insrsid4553922 
and its reasoning that the establishment of such jurisdiction would be necessary to provide a reasonable assurance of safety for cigarettes,}{\cs16\super\insrsid4553922 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  61 Fed. Reg. at 44405-07.}}}{
\insrsid4553922  }{\insrsid8921376 the FDA }{\insrsid4553922 promulgated regulations to change cigarette package}{\insrsid9709822  labels}{\insrsid4553922 .}{\insrsid9709822  }{\insrsid4553922  All cigarette labels would be }{\insrsid3081047 require}{
\insrsid4553922 d to contain}{\insrsid3081047  the statement \'93A Nicotine-Delivery Device for Persons 18 and Older\'94 }{\insrsid9788002 to prevent}{\insrsid9709822  minors from }{\insrsid9788002 smoking}{\insrsid4553922 .}{
\cs16\super\insrsid5968977\charrsid5968977  }{\cs16\super\insrsid5968977 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5968977 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id. }{\insrsid16284404\charrsid7211990 at 44615-18.}}}{\insrsid4553922  }{\insrsid8921376 
 Such a regulation was in accord with the FDA\rquote s finding that }{\cf1\insrsid8921376\charrsid8921376 if "the number of children and adoles
cents who begin tobacco use can be substantially diminished, tobacco-related illness can be correspondingly reduced because data suggest that anyone who does not begin smoking in childhood or adolescence is unlikely ever to begin."}{
\cs16\cf1\super\insrsid8921376 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 44399.}}}{\f5\fs20\cf1\insrsid8921376  }{\insrsid4553922  }{\insrsid7153423 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid9716124 \tab In response, several
 tobacco manufacturers, advertisers and retailers filed suit in federal court against the FDA to challenge the}{\insrsid8519778  labeling}{\insrsid9716124  regulation.}{\cs16\super\insrsid9716124 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Coyne Beahm, Inc. v. FDA, 966 F.Supp. 1374 (M.D.N.C. 1996).}}}{\insrsid9716124   They m}{\insrsid5707226 oved for summary judgment on three}{\insrsid9716124  grounds}{
\insrsid5707226 : 1)}{\insrsid9716124  that the FDA lacked the statutory jurisdiction to regulate cigarettes and smokeless tobacco as normally }{\insrsid15945552 labeled}{\insrsid5707226 
, 2) that the FDA had exceeded its statutory authority under 21 U.S.C. \'a7 360j(e)}{\insrsid6975822  by attempting to regulate the advertisements and promotions of tobacco products}{\insrsid5707226 , and 3) that such mandatory advertising restrictions }{
\insrsid4391164 violated the }{\insrsid13381767 First Amendment.  Although the District C}{\insrsid4391164 ourt determined that the FDA had jurisdiction to regulate tobacco products}{\insrsid12456097  pursuant to the FDCA}{\insrsid4391164 ,}{
\cs16\super\insrsid9184084 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 1388.}}}{\insrsid4391164  t}{\insrsid5707226 he court }{\insrsid548651 granted}{\insrsid3756417  the motion }{\insrsid9184084 in part }{
\insrsid3756417 on the ground}{\insrsid5707226  that the mandatory advertising restrictions violated the FDA\rquote s statutory grant unde}{\insrsid8519778 r 21 U.S.C. \'a7 360j(e), thus staying}{\insrsid5707226  the promulgation of those regulations.}{
\cs16\super\insrsid15230900 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 1398-1401.}}}{\insrsid2689722   The Court of Appeals for the Fourth Circuit }{\insrsid672801 split, but it reversed the District Court, }{
\insrsid2689722 finding that the FDA lacked the statutory authority to regulate tobacco products as they were normally marketed.}{\cs16\super\insrsid2689722 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Coyne Beahm, Inc. v. FDA, 153 F.3d 155 (4th Cir. 1998).  In his dissent, Judge K.K. Hall stressed that \'93}{\chshdng0\chcfpat0\chcbpat8\insrsid16284404\charrsid7211990 
the FDCA was broadly worded by design. In an area i
n which complex new products (and old products, seen in the light of new evidence) pose the potential for grievous harm, Congress deemed it necessary to delegate to an expert--the FDA--the job of monitoring drugs.\'94  }{
\i\chshdng0\chcfpat0\chcbpat8\insrsid16284404\charrsid7211990 Id}{\chshdng0\chcfpat0\chcbpat8\insrsid16284404\charrsid7211990 . at 182.}}}{\insrsid2164271   The }{\insrsid8519778 Fourth Circuit}{\insrsid2164271 
 found that Congress did not intend for the FDA to regulate tobacco products }{\insrsid548651 as combination products }{\insrsid12083942 because,}{\insrsid2164271  if the FDA}{\insrsid8519778  had}{\insrsid2164271 
 found cigarettes to be unsafe, they would have}{\insrsid548651  had}{\insrsid2164271  to ban the product completely}{\insrsid8519778 , rather than }{\insrsid548651 just }{\insrsid8519778 requiring new}{\insrsid8412299  product labels}{\insrsid2164271 .}{
\cs16\super\insrsid2164271 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 164-67.  The FDA is statutorily authorized to prevent products that are \'93unsafe\'94 from reaching the market.}}}{\insrsid12083942   N}{
\insrsid9332638 o legislative intent could be found to support the theory that the FDA should regulate tobacco products, and the court pointed out that the FDA itself had explicitly rejected the regulation of tobacco products through 1995.}{
\cs16\super\insrsid9332638 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 168-76. In his dissent, Judge Hall reminded the majority of the \'93familiar canon\'94
 of administrative law that allows an administrative agency to change its regulatory position, especially when new facts are discovered.  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
 at 180 (citing Rust v. Sullivan, 500 U.S. 173, 186-87 (1991)).}}}{\insrsid9716124 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid8412299 \tab The case was argued before the Supreme Court late in 1999.  Four months later, the Supreme Court }{\insrsid548651 affirmed
}{\insrsid8412299 , 5-4, }{\insrsid12848994 the Middle District of North Carolina and }{\insrsid8412299 the Fourth Circuit\rquote s interpretation of the FDCA and the}{\insrsid11273069  }{\insrsid8519778 limits}{\insrsid11273069  of the}{\insrsid8412299 
 FDA\rquote s authority}{\insrsid548651  therein}{\insrsid8412299 .}{\cs16\super\insrsid807025 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 FDA v. Brown & Williamson Tobacco Corp., 529 U.S. 120 (2001).}}}{\insrsid16714375   }{\insrsid6454169 The FDA, like other f}{\insrsid16714375 ederal agencies}{\insrsid6454169 ,}{\insrsid16714375  }{\insrsid6454169 are}{\insrsid16714375 
 given wide latitude to interpret their statutory charge due to their }{\insrsid16675554 specific administrative }{\insrsid16714375 expertise, especially if Congress had not directly addressed the issue facing the agency}{\insrsid8519778 .}{
\cs16\super\insrsid16714375 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837 (1984).}}}{\insrsid8412299  }{\insrsid6454169  }{\insrsid8519778 
But here, }{\insrsid16675554 the Supreme Court found that the FDA\rquote s regulation of tobacco was inconsistent with the purpose of the provisions of the FDCA, including }{\insrsid8519778 the combination product provision of }{\insrsid16675554 
21 U.S.C. \'a7 353(g)(1)}{\insrsid8519778 ,}{\insrsid16675554  and Congress\rquote }{\insrsid8519778  tobacco}{\insrsid16675554  legislation }{\insrsid8519778 following}{\insrsid16675554  the passage of the FDCA.}{\insrsid12848994 
  The FDA could not define a cigarette to be a \'93drug delivery device,\'94 find the device to be \'93unsafe\'94 and \'93dangerous,\'94}{\cs16\super\insrsid12016062 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  61 Fed. Reg. at 44412.}}}{\insrsid12848994  but then subsequently allow it to remain on the market}{\insrsid8519778  without violating the mandate of the FDCA to protect th
e public health}{\insrsid12848994 .}{\cs16\super\insrsid9246532 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  467 U.S. at 135.}}}{\insrsid6094880   The majority opinion conveyed an \'93all or nothing\'94 understanding of the FDA\rquote s ability to regulate}{\insrsid6454169 
 the manufacture and packaging of}{\insrsid6094880  combination products.
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid7865820 {\insrsid6094880 \tab Justice Breyer, in his dissent, construed 21 U.S.C. \'a7 353(g)(1)}{\insrsid13050745  in concert with 21 U.S.C. \'a7
 360j(e)}{\insrsid6094880  in a different manner.  He wrote}{\insrsid11226579 :}{\insrsid6094880  
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid6094880 {\cf1\insrsid6094880\charrsid6094880 First, the }{\cf1\insrsid6094880 [FDCA]\rquote s}{\cf1\insrsid6094880\charrsid6094880 
 language does not restrict the FDA's remedial powers in this way.   The FDCA permits the FDA to regulate a "combination product"--}{\i\cf1\insrsid6094880\charrsid6094880 i.e.,}{\cf1\insrsid6094880\charrsid6094880 
 a "device" (such as a cigarette) that contains a "drug" (such as nicotine)-- under its "device" provisions.}{\cf1\insrsid6094880   21 U.S.C. }{\insrsid6094880 \'a7 353(g)(1).}{\cf1\insrsid6094880\charrsid6094880  }{\cf1\insrsid6094880  }{
\cf1\insrsid6094880\charrsid6094880 And the FDCA's "device" provisions explicitly grant the FDA wide remedial discretion.   For example, where the FDA cannot "otherwise" obtain "reasonable assurance" of a dev
ice's "safety and effectiveness," the agency may restrict by regulation a product's "sale, distribution, or use" upon "}{\i\cf1\insrsid6094880\charrsid6094880 such ... conditions as the Secretary may prescribe."}{\cf1\insrsid6094880\charrsid6094880  }{
\insrsid6094880 \'a7}{\cf1\insrsid6094880\charrsid6094880  }{\cf1\insrsid6094880 360j(e)(1) }{\cf1\insrsid6094880\charrsid6094880 (emphasis added).   And the statutory section that most clearly address
es the FDA's power to ban (entitled "Banned devices") says that, where a device presents "an unreasonable and substantial risk of illness or injury," the Secretary "}{\i\cf1\insrsid6094880\charrsid6094880 may}{\cf1\insrsid6094880\charrsid6094880 "--not }{
\i\cf1\insrsid6094880\charrsid6094880 must}{\cf1\insrsid6094880\charrsid6094880 -- {\*\bkmkstart Document0zzSDUNumber91}{\*\bkmkend Document0zzSDUNumber91}"initiate a proceeding ... to make such device a banned device."   \'a7  360f(a) (emphasis added).}{
\cs16\cf1\super\insrsid6094880 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  467 U.S. at 175.}}}{\cf1\insrsid8412299 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid6094880 {\cf1\insrsid11226579 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11226579 {\cf1\insrsid11226579 As this excerpt illustrates, Justice Breyer focused upon the permissive language of the FDCA to construe the FDA\rquote 
s authority}{\cf1\insrsid8257757  to }{\cf1\insrsid13050745 classify}{\cf1\insrsid8257757  tobacco products as combination products}{\cf1\insrsid11226579  broadly.  The disagreement within the Court over the proper classification of cigarettes as \'93
drug delivery devices\'94 presented no }{\cf1\insrsid8257757 statutory }{\cf1\insrsid11226579 obstacle to Justice Breyer}{\cf1\insrsid8257757 
. To begin, the Court did not dispute that nicotine was properly classified as a drug.  To further construe the cigarette as a device with which to convey the nicotine to the end user }{\cf1\insrsid9975326 not only seemed}{\cf1\insrsid8257757 
 appropriate to Justice Breyer}{\cf1\insrsid9975326 , but justified given the purpose of the FDCA}{\cf1\insrsid13050745  to protect the public health.}{\cs16\cf1\super\insrsid5523276 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5523276 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Indeed, Justice Breyer began his dissent, }{\i\insrsid16284404\charrsid7211990 id.}{\insrsid16284404\charrsid7211990  at 161, by pointing out that the FDCA, when read literally, provided for the regulation of tobacco products bec
ause those products contained nicotine, an \'93article (other than food) intended to affect the structure or any function of the body.\'94 21 U.S.C. \'a7 321(g)(1)(C).  Second, the FDCA\rquote 
s central purpose, to protect the public health, also argued for the inclusion of tobacco products within the FDA\rquote s regulatory jurisdiction.  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 162; }{
\i\insrsid16284404\charrsid7211990 see also}{\insrsid16284404\charrsid7211990  U.S. v. Article of Drug . . . Bacto-Unidisk, 394 U.S. 784, 798 (1969)(\'93FDCA "is to be given }{\i\insrsid16284404\charrsid7211990 
a liberal construction consistent with [its] overriding purpose to protect the public health}{\insrsid16284404\charrsid7211990  " (emphasis added)). The majority disputed neither point in its opinion.}}}{\cf1\insrsid5523276   }{\cf1\insrsid13050745 S}{
\cf1\insrsid11226579 uch a classification provided the FDA with a variety of administrative actions regarding the sale of those}{\cf1\insrsid13788601  restricted}{\cf1\insrsid11226579  devices on the market.}{\cf1\insrsid13050745   The FDA }{
\cf1\insrsid8257757 restrict}{\cf1\insrsid13050745 ed}{\cf1\insrsid8257757  the distribution of tobacco products to minors because the FDA could not obtain the necessary }{\cf1\insrsid13050745 assurance that tobacco products were}{\cf1\insrsid8257757 
 safe}{\cf1\insrsid13050745 ; }{\insrsid13050745 \'a7 360f(a) did not require the FDA to ban tobacco products completely}{\cf1\insrsid8257757 .}{\cf1\insrsid9975326 
  In other words, Justice Breyer found that the statutory framework provided by the FDCA allowed the FDA to provide adequate notice to consumers regarding the safety of cigarettes without requiring the FDA to completely remove an unsafe d
evice from the market}{\cf1\insrsid12539105 :}{\cs16\cf1\super\insrsid9975326 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid11226579 
\par }\pard \ql \li1440\ri1440\nowidctlpar\faauto\rin1440\lin1440\itap0\pararsid12539105 {\cf1\insrsid12539105\charrsid12539105 
Thus, the statute plainly allows the FDA to consider the relative, overall "safety" of a device in light of its regulatory alternatives, and where the FDA has chosen the least dangerous path, }{\i\cf1\insrsid12539105\charrsid12539105 i.e.,}{
\cf1\insrsid12539105\charrsid12539105  the safest path, then it can--and 
does--provide a "reasonable assurance" of "safety" within the meaning of the statute.   A good football helmet provides a reasonable assurance of safety for the player even if the sport itself is still dangerous.   And the safest regulatory choice by 
{\*\bkmkstart Document0zzSDUNumber92}{\*\bkmkend Document0zzSDUNumber92}definition offers a "reasonable" assurance of safety in a world where the other alternatives are yet more dangerous.}{\cs16\cf1\super\insrsid12539105 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 175-76 (J. Breyer, dissenting).}}}{\insrsid12539105\charrsid12539105 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11226579 {\cf1\insrsid12539105 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11226579 {\cf1\insrsid8414140 \tab Justice Breyer\rquote s dissent arguably supports the goals behind the}{\cf1\insrsid1521493 
 combination product provision of the}{\cf1\insrsid8414140  SMDA, even though the majority favored a narrower construction of }{\cf1\insrsid1521493 the FDCA with regards to public}{\cf1\insrsid8414140  }{\cf1\insrsid8260870 health and }{
\cf1\insrsid8414140 safety.}{\cf1\insrsid8260870   The majority emphasized the importance of the public health, but it determined that the public health was constrained by its interpretation of the authority that Congress delegat
ed to the FDA through the FDCA.  Thus, \'93}{\cf1\insrsid8260870\charrsid8260870 no matter how "important, conspicuous, and controversial" the issue, and regardless of how likely the public is to hold the Executive Branch politically accountable, }{
\i\cf1\insrsid8260870\charrsid8260870 post,}{\cf1\insrsid5462118  . . . }{\cf1\insrsid8260870\charrsid8260870 an administrative agency's power to regulate in the {\*\bkmkstart Document0zzSDUNumber71}{\*\bkmkend Document0zzSDUNumber71}
public interest must always be grounded in a valid gran}{\cf1\insrsid8260870 t of authority from Congress.}{\cf1\insrsid5462118 \'94}{\cs16\cf1\super\insrsid8260870 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 161.}}}{\cf1\insrsid8260870   }{\cf1\insrsid13788601 Despite its }{\i\cf1\insrsid13788601 Chevron}{\cf1\insrsid13788601 -like recognition of the FDA\rquote 
s expertise in regulating products that present a risk to the public health, the majority seemed to diverge from }{\i\cf1\insrsid13788601 Chevron}{\cf1\insrsid13788601 , a legally binding precedent, to focus upon Congress\rquote 
 explicit delegation to the FDA and Congress\rquote  subsequent, separate tobacco legislation.}{\cf1\insrsid8405828   }{\cf1\insrsid16322345 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2755294 {\cf1\insrsid16322345 \tab }{\cf1\insrsid5462118 Justice Breyer, in contrast, warned that the protection of the public health was}{
\cf1\insrsid7501780  not only a source of }{\i\cf1\insrsid7501780 Chevron}{\cf1\insrsid7501780 -like }{\cf1\insrsid10682576 deference due to }{\cf1\insrsid7501780 the FDA}{\cf1\insrsid7676294 \rquote s }{\cf1\insrsid10682576 depth}{\cf1\insrsid7676294 
 of expertise}{\cf1\insrsid7501780 , but}{\cf1\insrsid7676294  that it}{\cf1\insrsid7501780  was}{\cf1\insrsid5462118  }{\cf1\insrsid1585334 in fact }{\cf1\insrsid5462118 
at the heart of the valid delegation made by Congress to the FDA when it enacted the FDCA.  Thus, an action taken by the FDA to regulate a combination product that }{\cf1\insrsid7676294 markedly }{\cf1\insrsid5462118 
implicated the public health, even though the FDA had explicitly rejected such regulation in the past, was properly within the statutory authority of the FDA.}{\cs16\cf1\super\insrsid5462118 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 id.}{\insrsid16284404\charrsid7211990  at 163.  Justice Breyer attached \'93no legal significance\'94 to the FDA\rquote 
s regulatory change of heart, not only because controlling legal doctrine supported an administrative agency\rquote s change in policy{\*\bkmkstart Document0zzSDUNumber107}{\*\bkmkend Document0zzSDUNumber107}, }{\i\insrsid16284404\charrsid7211990 see}{
\insrsid16284404\charrsid7211990  }{\insrsid16284404\charrsid7211990 Chevron}{\i\insrsid16284404\charrsid7211990 ,}{\insrsid16284404\charrsid7211990 
 467 U.S. at 863 ("An initial agency interpretation is not instantly carved in stone"), but because the FDA obtained evidence throughout the late 1980\rquote s and early 1990\rquote s that the tobacco companies knew of nicotine\rquote 
s addictive qualities, that the scientific evidence of the adverse health effects of tobacco use grew (}{\i\insrsid16284404\charrsid7211990 see }{\insrsid16284404\charrsid7211990 
61 Fed. Reg. 44701-06 (August 28, 1996), and because the FDA regulatory policy simply changed with the advent of a new Administration and a new Commissioner.  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 188.}}}{
\cf1\insrsid5308883   }{\cf1\insrsid13788601 This interpretation supported}{\cf1\insrsid1585334  the goal of the SMDA because section 16 of the SMDA made the FDA\rquote s initial regulation of tobacco products in 1996 possible and because the SMDA }{
\cf1\insrsid5308883 further}{\cf1\insrsid10299018 ed}{\cf1\insrsid5308883  the }{\cf1\insrsid1585334 protection of the }{\cf1\insrsid5308883 public health}{\cf1\insrsid10299018  in part}{\cf1\insrsid5308883 
 by providing more stringent and efficient regulation of combination products.}{\cs16\cf1\super\insrsid15013680 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  In its decision to regulate tobacco products as combination products, the FDA applied 21 U.S.C. \'a7
 360j(e) to regulate tobacco products as restricted medical devices.  Such a designation allowed the FDA to restrict the sale and distribution of tobacco products to persons over the age of 18 because the FDA could not be assured of the products\rquote 
 safety.  See 21 U.S.C. \'a7 360j(e)(1)(B); 61 Fed. Reg. 44,396, 44,400 (August 28, 1996).  Thus, the FDA did not conclude that tobacco products were safe for human consumption by allowing their sale to the public. }}}{\cf1\insrsid533844 
  More broadly, Justice Breyer construed Congress\rquote  delegation to the FDA through the }{\cf1\insrsid10758117 general purpose of the }{\cf1\insrsid533844 FDCA and }{\cf1\insrsid10758117 section 16 of the}{\cf1\insrsid533844  SMDA to }{
\cf1\insrsid10758117 allow the FDA to }{\cf1\insrsid533844 regulate combination products that implicate}{\cf1\insrsid10758117 d}{\cf1\insrsid533844  the public health as a means of }{\cf1\insrsid10758117 efficiently }{\cf1\insrsid533844 
consolidating within one administrative agency the }{\i\cf1\insrsid533844 Chevron}{\cf1\insrsid533844 -like expertise needed to best regulate }{\cf1\insrsid10758117 such a}{\cf1\insrsid1866823  product}{\cf1\insrsid533844 .}{\cf1\insrsid1585334   }{
\cf1\insrsid1378943 This interpretation did not carry the day, however, and it appears the FDA thus may be limited to regulating as combination products, for example, those products that are more traditiona
lly identifiable as a drug/device combination. Yet this litigation and Justice Breyer\rquote s dissent illustrate}{\cf1\insrsid16322345 d}{\cf1\insrsid1378943  the impact that combination products have had on }{\cf1\insrsid16322345 redefining}{
\cf1\insrsid1378943  the role of the FDA in protecting the public health today.}{\cf1\insrsid6094880\charrsid2755294 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2755294 {\i\ul\insrsid8203118 IV. Food and Drug Administration Modernization Act (FDAMA) of 1997}{\insrsid8203118\charrsid8203118 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8203118 {\insrsid5331510 \tab 
As the preceding section illustrated, the changes that the SMDA effected were felt beyond the statutory prescriptions of the FDCA and the accompanying regulatory practice of the FDA.  Still, improvements in the manner
 in which combination products were reviewed prior to their market release remained to be made.  The Food and Drug Administration Modernization Act (FDAMA) of 1997, the next prominent round of amendments to the FDCA following the SMDA, did not amend the d
efinition of a combination product or the substance of those provisions at 21 U.S.C. \'a7 353(g).}{\insrsid8939321   In full, FDAMA made very little mention of the regulation of combination products in general or in detail.  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8203118 {\insrsid8939321 \tab FDAMA did provide, however, a measure of autonomy t
o combination product manufacturers seeking regulatory approval for their new products.}{\insrsid3413236   Section 416 of FDAMA, later codified at 21 U.S.C. \'a7 360bbb-2 within the FDCA}{\insrsid12477932 
, allowed the manufacturer to request that its product be classified as a drug, biological product, device or combination product.}{\cs16\super\insrsid12477932 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7
 360bbb-2(a) (2004).  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  Pub. L. No. 105-115, Title IV, sec. 416 (November 21, 1997).}}}{\insrsid16526589   }{\insrsid4153473 In the alternative}{\insrsid16526589 
, section 416 allowed the manufacturer to request that a particular component of the product guide the decision as to which Center }{\insrsid4153473 would}{\insrsid16526589  regulate the product.}{\cs16\super\insrsid16526589 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Id.}}}{\insrsid16348913 
  In response, the FDA would provide its determina}{\insrsid14449863 tion as to what product classification}{\insrsid16348913  was appropriate or what component would guide the overall regulation of the product to the manufacturer within sixty days.}{
\cs16\super\insrsid16348913 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  21 U.S.C. \'a7 360bbb-2(b) (2004).}}}{\insrsid14449863   If the FDA failed to make such a decision within sixty days, then the manufacturer\rquote 
s request would be considered the final determination of either the classification of the product or the component that guide the product\rquote s regulation.}{\cs16\super\insrsid14449863 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 U.S.C. \'a7
 360bbb-2(c) (2004).}}}{\insrsid14449863   Such a final decision could not be changed unless the manufacturer agreed to the change in writing or new evidence arose that indicated that the product threatened the public safety.}{\cs16\super\insrsid14449863 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 .}}}{\insrsid16004651   Thus, FDAMA in its entirety did not effect sweeping changes in the reg}{\insrsid11761056 ulation of combination products.   }{\insrsid1000027 
Through a statutorily imposed time limit on}{\insrsid11761056  the FDA\rquote s classification of each new product}{\insrsid1000027  seeking approval, FDAMA}{\insrsid16004651  did serve }{\insrsid11761056 nonetheless }{\insrsid16004651 to }{
\insrsid11761056 further the}{\insrsid1000027  SMDA\rquote s goal of an expedited}{\insrsid7475608 , efficient}{\insrsid16004651  regulatory process.}{\insrsid8203118 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2755294 {\i\ul\insrsid8592177 V}{\i\ul\insrsid12718403 .}{\i\ul\insrsid2629406  }{\i\ul\insrsid11032053 MDUFMA of }{\i\ul\insrsid2629406 2002}{
\i\ul\insrsid11608828 : The Advent of the Office of Combination Products}{\insrsid2629406 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2755294 {\insrsid11032053 \tab }{\insrsid7239918 In 200}{\insrsid5331510 1, }{\insrsid7239918 the Executive Director of the Med
ical Device Manufacturers Association, Stephen Northrup, addressed the House Committee on Energy and Commerce to discuss the effects }{\insrsid70880 and shortcomings of FDAMA}{\insrsid7239918 .}{\cs16\super\insrsid7239918 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Hearing Before the House Comm. on Energy and Commerce}{\insrsid16284404\charrsid7211990 , 2001 WL 475630 (May 3, 2001) (statement of Stephen Northrup, Executive Director, Medical Device Manufacturers Association).}}}{
\insrsid12466315   Specifically}{\insrsid16344015 , Northrup believed that the SMD}{\insrsid12466315 A and the FDAMA were only discrete steps on a continuous journey to keep the FDCA and the FDA\rquote 
s practices current with technological progress.  New and different combination products continued to arrive at the FDA\rquote s doorstep}{\cs16\super\insrsid12466315 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Northrup\rquote 
s testimony cited a few of the latest examples of combination products coming from the medical device arena: drug-coated stents to fight restenosis, implanted drug-delivery pumps, artificial organs (such as livers, pancreases, and kidneys), nerve regenera
tors, and devices to provide genetic therapies.  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid12466315  }{\insrsid16344015 such that the Center with primary premarket review jurisdiction often needed add
itional expertise from the other Centers.  Northrup predicted that the evolution of these }{\insrsid10631920 \'93hybrid\'94 }{\insrsid16344015 products would be such that their classification under one Center\rquote 
s primary jurisdiction would become increasingly difficult.}{\cs16\super\insrsid16344015 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
  To illustrate this point, Northrup pointed to the Tissue Reference Group (TRG), initially established in 1998 by CBER and CDRH and comprised of three members of each Center.  The TRG provided for 
device-biologic combination product manufacturers a single committee to draft guidance documents for these manufacturers and to answer their questions pertaining to approval jurisdiction and FDA regulations and policy.}}}{\insrsid7239918   }{
\insrsid1857143 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid10631920 \tab Northrup\rquote s primary suggestion to ameliorate these problems would }{\insrsid16741734 eventually }{\insrsid10631920 
prove visionary: }{\insrsid16741734 he recommended }{\insrsid10631920 an Office of Combination Products with \'93the authority to determine how a combination product will be reviewed and to coordinate all involvement by and interaction between the 
various FDA [C]enters in the review of specific marketing applications.\'94}{\cs16\super\insrsid10631920 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid10838799   With a goal reminiscent of }{\insrsid5458024 
Senator Kennedy\rquote s comments during the debates over the SMDA}{\insrsid10838799 , Northrup sought to encourage efficient use o}{\insrsid5458024 f the FDA\rquote s resources, increase}{\insrsid10838799  expertise within the FDA\rquote s staff, and }{
\insrsid5458024 establish}{\insrsid10838799  accountability for the agency\rquote s actions.  He testified that such an Office could efficiently operate with a small, \'93multi-disciplinary\'94
 staff that occasionally sought the additional input of experts from the three Centers.  Further, Northrup believed that one Office would help to minimize the delays that still haunted the FDA review process for these \'93hybrid\'94
 products because of disagreements between the staff at different Centers, despite the Intercenter Agreements of 1991.}{\cs16\super\insrsid10838799 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 .}}}{\insrsid16195633   An effective response to the appearance of these \'93hybrid\'94 products that blurred the lines between drugs, devices, and biological products, in Northrup
\rquote s mind, was the creation of an Office that was equally hybridized in expertise and resources.}{\insrsid10631920 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\i\ul\insrsid8272595 V.A. The First Step}{\i\ul\insrsid14380242 : The Combination Products Program}{\insrsid22912 \tab }{\insrsid14380242 

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid14380242 \tab }{\insrsid3240902 The FDA took the first step toward realizing Northrup\rquote 
s vision when it created the Combination Products Program }{\insrsid11226200 (hereinafter \'93CPP\'94) }{\insrsid13719232 in February}{\insrsid3240902  2002.}{\cs16\super\insrsid11226200 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Regulation of Combination Products: FDA Employee Perspectives, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/perspectives.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
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6d006c000000e0c9ea79f9bace118c8200aa004ba90b6800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007000650072007300700065006300740069007600650073002e00680074006d006c
000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/perspectives.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).  }{\i\insrsid16284404\charrsid7211990 See also}{
\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 H. R. Rep. No.}{\insrsid16284404\charrsid7211990  107-728, at 39 (2002).}}}{\insrsid4734283   The program was established within the Office of the Ombud
sman because the Ombudsman served as the product jurisdiction officer for combination products, designating which Center would have primary premarket review jurisdiction.}{\cs16\super\insrsid4734283 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See }{\insrsid16284404\charrsid7211990 21 C.F.R. \'a7 3.6 (1991) (designating Ombudsman as product jurisdiction officer pursuant to the SMDA).}}}{\insrsid11226200   The CPP was charged with \'93}{
\cf1\insrsid11226200\charrsid11226200 developing a number of initiatives to improve the review 
and regulation of combination products, including developing standard operating procedures to improve the management of the intercenter review process, monitoring the progress of premarket reviews of combination products, and developing guidance on a vari
ety of policy issues for combination products.}{\cf1\insrsid11226200 \'94}{\cs16\cf1\super\insrsid11226200 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 Regulation of Combination Products: FDA Employee Perspectives, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/perspectives.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003400000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007000650072007300700065006300740069007600650073002e0068007400
6d006c000000e0c9ea79f9bace118c8200aa004ba90b6800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007000650072007300700065006300740069007600650073002e00680074006d006c
000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/perspectives.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\cf1\insrsid11089163 
  To determine the most pressing issues needing immediate resolution by the CPP and to formulate a future approach that would improve the efficiency of combination product review, approximately 25 reviewers (b
oth premarket and postmarket) from all three Centers were interviewed by the CPP.}{\cs16\cf1\super\insrsid11089163 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid2895537   }{\cf1\insrsid22912 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\cf1\insrsid2895537 \tab 
Observations from the staff interviews, as well as the recommendations that were issued therein, were published by the FDA.}{\cs16\cf1\super\insrsid2895537 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   The findings by the CPP were extensive; in the name of brevity, only the most significant results are noted within this text.  In addition to the posting of these findings and r
ecommendations, the FDA also made available on its website a new, extensive Manual of Standard Operating Procedures and Policies (\'93SOPPs\'94) that would guide the \'93consultative and collaborative review process\'94
 between Centers when approving combination products.  These SOPPs were originally approved on July 31, 2002 and have since been updated twice.  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 Intercenter Consultative/Collaborative Review Process, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/consultative.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003400000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0063006f006e00730075006c007400610074006900760065002e0068007400
6d006c000000e0c9ea79f9bace118c8200aa004ba90b6800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0063006f006e00730075006c007400610074006900760065002e00680074006d006c
000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/consultative.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004). }}}{\cf1\insrsid14556348   The interviews focused upon four key areas: 
consultation and collaboration between Centers, product jurisdiction, postmarket regulation issues, and electronic submission tracking systems.  }{\cf1\insrsid9054510 To summarize, the employees }{\cf1\insrsid269961 noted}{\cf1\insrsid9054510 
 a lack of transparency within the Centers}{\cf1\insrsid269961  and stressed the need for continued intercommunication, education and \'93crosstraining\'94 of combination product reviewers}{\cf1\insrsid5395046 , especially since the employees }{
\cf1\insrsid11888369 believed that assigning }{\cf1\insrsid5395046 combination product review only to experienced reviewers}{\cf1\insrsid11888369  would enhance their efficiency and success in completing reviews}{\cf1\insrsid9054510 .  }{
\cf1\insrsid269961 Due to time and resource constraints, reviewers often felt pressured to complete the review within one Center rather than spending time to obtain a consultation from another Center}{\cf1\insrsid11888369 .  Some}{\cf1\insrsid16410709 
 reviewers were unsure even how}{\cf1\insrsid5395046  appropriately }{\cf1\insrsid16410709 to }{\cf1\insrsid5395046 contact another Center}{\cf1\insrsid269961 .  }{\cf1\insrsid9054510 
The Centers could not electronically track products within other Centers, nor electronically confer upon the status of that product.  While the request for designation (RFD) procedures worked well generally, the employees noted that the Interc
enter Agreements were outdated and in need of modernization because RFD procedures were employed rarely and \'93front-line reviewers\'94 often shouldered the responsibility for determining if product jurisdiction was appropriate for their Center}{
\cf1\insrsid269961 .  }{\cf1\insrsid9054510 Finally, when postmarket failures did occur, the Center with lead responsibility for such failure was not always apparent.  }{\cf1\insrsid14556348 The recommendations }{\cf1\insrsid15925364 
gleaned from the various Center employees }{\cf1\insrsid14556348 focused upon keeping stakeholders informed of the changes within the FDA and the CPP, continuing the development of and monitoring of \'93review programs, policies, [and] processes,\'94
 creating transparent procedures that would be easily understood and followed by product manufacturers, and presenting the CPP as an advocate for the improved efficiency of combination product review.}{\cs16\cf1\super\insrsid14556348 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid2895537\charrsid3240902 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\i\ul\insrsid8272595 V.B. The Next Step: The Office of Combination Products}{\insrsid14485506 \tab }{\insrsid8272595 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid8272595 \tab }{\insrsid15475243 
Nearly eighteen months later, both Houses of Congress were submerged in the final stages of sending a bill to the President that would, in part, incorporate Northrup\rquote s suggestions.}{\insrsid5458024   Originally sponsored by Represe}{
\insrsid16410709 ntative James C. Greenwood}{\insrsid5458024  and }{\insrsid8665373 presented to the House pursuant to a report from}{\insrsid5458024  the Committee on Energy and Commerce,}{\cs16\super\insrsid8665373 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 H. R. Rep. No. }{\insrsid16284404\charrsid7211990 107-728 (2002).}}}{\insrsid5458024  }{\insrsid16410709 H.R.}{\insrsid266508  3580}{\insrsid5458024  made its way to the House floor }{\insrsid12193910 
for consideration }{\insrsid5458024 on October 7, 2002.}{\cs16\super\insrsid5458024 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  H.R. 3580, 107th Cong., 148 Cong. Rec. H7153-03 (2002) (enacted).}}}{\insrsid12193910   }{\insrsid7738021 The }{\insrsid16410709 bill}{\insrsid7738021  was entitled 
\'93Medical Device User Fee and Modernization Act of }{\insrsid12935363 2002\'94 }{\insrsid14759027 (hereinafter \'93MDUFMA\'94) }{\insrsid7738021 
and it was drafted primarily to allow CDRH to charge fees to medical device manufacturers seeking market approval as a means of increasing both CDRH\rquote s funding and its approval rate.}{\insrsid11015634   }{\insrsid11611377 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid11611377 \tab }{\insrsid11015634 Section 203 of H.R. 3580, entitled \'93Designation and regulation of combination products,\'94 }{
\insrsid9728731 was primarily written to address the concerns of the medical device industry, but the resulting provision had a broader scope}{\insrsid11015634 .}{\insrsid8985770   The most 
extensive Congressional statement with respect to the regulation of combination products}{\insrsid11015634  }{\insrsid8985770 since the passage of the SMDA, section 203}{\insrsid6038097 ,}{\insrsid1249388  explicitly }{\insrsid16410709 required}{
\insrsid1249388  the creation of an Office of Combination Products}{\insrsid12935363  (hereinafter \'93OCP\'94)}{\insrsid1249388 .}{\cs16\super\insrsid1249388 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1249388 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at H7158.}}}{\insrsid4395268   Not only did section 203 amend some of the language introduced by section 16 of the SMDA}{\insrsid12935363 ,}{\cs16\super\insrsid4395268 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.112}{\insrsid16284404\charrsid7211990 .  The amendments to, and not the additions to, the preexisting language of section 16 of the SMDA, 21 U.S.C. \'a7
 353(g), by section 203 of H.R. 3580 were necessary to create future statutory agreement between the two amendments to the FDCA.  The modified language, however, was not revolutionary.  Rather, the language modifications simply provided that \'93}{
\cs17\insrsid16284404\charrsid7211990 Section 503(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353(g)) is amended-}{\insrsid16284404\charrsid7211990  
\par }\pard \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 {\cs17\insrsid16284404\charrsid7211990 (1) in paragraph (1) -}{\insrsid16284404\charrsid7211990 \line }{\cs17\insrsid16284404\charrsid7211990 
(A) in the first sentence, by striking "shall designate a component of the Food and Drug Administration" and inserting "shall in accordance with this subsection assign an agency center"; and}{\insrsid16284404\charrsid7211990 \line }{
\cs17\insrsid16284404\charrsid7211990 (B) in each of subparagraphs (A) through (C), by striking "the persons charged" and inserting "the agency center charged";}{\insrsid16284404\charrsid7211990 \line }{\cs17\insrsid16284404\charrsid7211990 
(2) by redesignating paragraph (4) as paragraph (5). . .\'94 148 Cong. Rec. at H7158.}}}{\insrsid12935363 
 it introduced the OCP, explained its mission, delineated the boundaries of its regulatory responsibility and provided for annual Congressional review of the performance of the OCP.}{\insrsid11611377   }{\insrsid14559901 The overall s
trategy of this provision was to deposit a layer of managerial responsibility and oversight, via the OCP, between the Commissioner\rquote 
s office and the three Centers implicated by combination product review.  In essence, the OCP would be charged with maintaini
ng the delicate balance between an agency head charged with protecting the national public health and three technologically sophisticated Centers operating at the outer boundaries of innovation.  }{\insrsid11158310 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid11158310 \tab }{\insrsid14559901 To that end, paragraphs (4)(A)-(C) gave the OCP the }{\insrsid16410709 authority}{\insrsid14559901 
 to assign primary premarket approval jurisdiction to one Center,}{\cs16\super\insrsid14559901 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  H.R. 3580, 107th Cong., \'a7 203(4)(B) (2002).}}}{\insrsid14559901 
 with the possibility of consultation from the Office of the Commissioner,}{\cs16\super\insrsid14559901 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(4)(A).}}}{
\insrsid14559901  while \'93overseeing and coordinating reviews\'94 that involved multiple Centers.}{\cs16\super\insrsid14559901 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 203(4)(C).}}}{
\insrsid14559901   Yet }{\insrsid11158310 this section also}{\insrsid14559901  barred the OCP from preempting the }{\i\insrsid14559901\charrsid2570280 postmarket}{\insrsid14559901  regulatory authority of any of those Centers.}{
\cs16\super\insrsid11158310 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(4)(D) (emphasis added).}}}{\insrsid2570280 
  Each Center, in return, would be responsible to the OCP for the timeliness of its product approvals}{\cs16\super\insrsid2570280 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(E).}}}{\insrsid2570280 
 and if a dispute arose regarding the rate at which that Center generate}{\insrsid2502275 d}{\insrsid2570280  approvals, those disputes would be resolved by the OCP.}{\cs16\super\insrsid2570280 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 203(F)(i).}}}{\insrsid3028064   Disputes over more substantive matters, however, such as the }{\insrsid15425971 claims within the ma}{\insrsid3352012 nufacturer\rquote 
s market application}{\insrsid15425971  that could not be resolved by the lead Center would be forwarded to the Office of the Commissioner for resol}{\insrsid3352012 ution}{\insrsid15425971  that could then request input from the OCP.}{
\cs16\super\insrsid15425971 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(F)(ii).}}}{\insrsid12270865   Section 203 also calle}{\insrsid6038097 d for a review}{\insrsid12270865 
 of the prior agreements and guidance document}{\insrsid6038097 s that had been generated by the FDA}{\insrsid12270865  with regard to the regulation of combination products.  That review was to engage the input of each Center\rquote 
s director.  If such agreements or documents }{\insrsid6038097 needed modification, reapproval, }{\insrsid12270865 or elimination, }{\insrsid6038097 FDA}{\insrsid12270865  was charged with fulfilling that duty.}{\cs16\super\insrsid12270865 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(G).}}}{\insrsid12270865   Finally, the section that gave birth to the OC}{\insrsid6038097 P required}{\insrsid12270865  an annual repo
rt with Congress on the progress of the OCP to date.  More specifically, the report }{\insrsid12997973 would}{\insrsid12270865  include \'93}{\cs17\cf1\insrsid12270865\charrsid11611377 provisions}{\cs17\cf1\insrsid12270865  }{
\cs17\cf1\insrsid12270865\charrsid11611377 (i) describing the numbers and types of combination products under review and the timeliness in days of such assignments, reviews, and dispute resolutions;}{\cf1\insrsid12270865  }{
\cs17\cf1\insrsid12270865\charrsid11611377 (ii) identifying the number of premarket reviews of such products that involved a consulting agency center; and}{\cf1\insrsid12270865  }{\cs17\cf1\insrsid12270865\charrsid11611377 
(iii) describing improvements in the consistency of postmarket reg}{\cs17\cf1\insrsid12270865 ulation of combination products.}{\cs17\cf1\insrsid12270865\charrsid11611377 "}{\cs16\cf1\super\insrsid12270865 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203(H).}}}{\cs17\cf1\insrsid14559901 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\cs17\cf1\insrsid922321 \tab When the report accompanying H.R. 3580 was submitted to the House on October 7, 2002, the legi}{
\cs17\cf1\insrsid6038097 slation had yet to be debated.  N}{\cs17\cf1\insrsid922321 o hearings were held }{\cs17\cf1\insrsid8468737 before }{\cs17\cf1\insrsid922321 the Committee on Energy and Commerce prior to the presentation of the report.}{
\cs16\cf1\super\insrsid922321 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\scaps\insrsid16284404\charrsid7211990 H.R. Rep. No. }{\insrsid16284404\charrsid7211990 107-728, at 21 (2002).}}}{\cs17\cf1\insrsid5728671   T}{\cs17\cf1\insrsid12796480 
he Committee stressed that the Office of the Ombudsman (within the Office of the Commissioner) would still make the initial determination as to whether a product was indeed a combination product}{\cs17\cf1\insrsid5728671 , but}{\cs17\cf1\insrsid13073061 
 that}{\cs17\cf1\insrsid5728671  the Ombudsman could consult with the OCP if necessary to determine the product\rquote s initial classification.}{\cs17\cf1\insrsid12796480  }{\cs17\cf1\insrsid5728671  T}{\cs17\cf1\insrsid16188937 he report}{
\cs17\cf1\insrsid5728671  also}{\cs17\cf1\insrsid16188937  made clear that section 203 }{\cs17\cf1\insrsid12796480 would continue the }{\cs17\cf1\insrsid16188937 administrative procedure that was originally introduced as the \'93primary mode of action\'94
 determination in the SMDA.}{\cs16\cf1\super\insrsid16188937 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at 39.}}}{\cs17\cf1\insrsid2819873   T}{\cs17\cf1\insrsid5728671 he section }{
\cs17\cf1\insrsid1902744 would still permit }{\cs17\cf1\insrsid5728671 a manufacturer }{\cs17\cf1\insrsid13073061 to}{\cs17\cf1\insrsid5728671  submit its application to the Center that it deemed most appropriate to retain lead approval jurisdiction.}{
\cs16\cf1\super\insrsid5728671 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 39-40.}}}{\cs17\cf1\insrsid1902744   In all, the Committee\rquote s report indicated that section 203 was aimed mostly at improving the \'93
timeliness\'94 of the premarket approval process of combination products.  Disput
es that arose that could not be managed solely within the Center with primary jurisdiction could be addressed to the Office of the Commissioner, but as a last resort.  Rather, as the report stated, \'93}{\cf1\insrsid1902744\charrsid1902744 
[t]he Committee does not intend for the new Office to be 
micro-managing line reviewers within the different Agency Centers. The bill instead contemplates that, with respect to the timeliness of reviews, the Centers themselves will be responsible to the new Office.}{\cf1\insrsid1902744 \'94}{
\cs16\cf1\super\insrsid1902744 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid922321 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\cf1\insrsid1902668 \tab An addendum to the Committee on Energy and Commerce\rquote s report was presented to }{\cf1\insrsid2819873 
the House on October 15, 2002.  T}{\cf1\insrsid1902668 he addendum contained the estimated cost (as prepared by the Congressional Budget Office}{\cf1\insrsid7622697 , or CBO}{\cf1\insrsid1902668 ) of enacting H.R. 3580.}{\cs16\cf1\super\insrsid1902668 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 H.R. Rep. No.}{\insrsid16284404\charrsid7211990  107-728(II) (2002).  As the report addendum explained, \'93CBO assumes that the bill will be enacted in the fall of 2002 and that outlays will follow historic
al spending rates for the authorized activities. Where H.R. 3580 specifies the amounts authorized to be appropriated, CBO assumes that such appropriations will be made. Where appropriations of such sums as necessary are authorized, CBO assumes that the es
timated amounts will be provided for each fiscal year.\'94  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 3.}}}{\cf1\insrsid7622697   In all, the CBO determined that H.R. 3580 }{\cf1\insrsid3559715 itself }{
\cf1\insrsid7622697 would cost $36 million to implement between 2003 and 2007, at which point the provisions would }{\cf1\insrsid616966 \'93}{\cf1\insrsid7622697 sunset}{\cf1\insrsid616966 ,\'94 or no longer be enforceable,}{\cf1\insrsid7622697 
 if unsuccessful.}{\cs16\cf1\super\insrsid7622697 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at 2.}}}{\cf1\insrsid3559715   }{\cf1\insrsid616966 
This estimate, however, did not provide the full picture.  For example, the }{\cf1\insrsid3559715 CBO also estimated that the user fee program}{\cf1\insrsid683896  would require an additional $78}{\cf1\insrsid3559715  million}{\cf1\insrsid683896 
 in Congressional appropriations}{\cf1\insrsid3559715  during the same time period to prevent early termination of the user fee program.}{\cs16\cf1\super\insrsid3559715 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid683896   }{\cf1\insrsid14759027 By sharp contrast, }{\cf1\insrsid683896 the CBO estimated that}{\cf1\insrsid14759027  the OCP would require}{\cf1\insrsid683896  $1 million in appropriations }{
\cf1\insrsid14759027 for the 2003 fiscal spending year}{\cf1\insrsid683896  and }{\cf1\insrsid14759027 that }{\cf1\insrsid683896 an additional $4 million would allow the OCP to operate through 2007.}{\cs16\cf1\super\insrsid8663236 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 6.}}}{\cf1\insrsid1005201   The first year of operation for the OCP would be more expensive than the following three years, the CBO estimated, because more staff would be neede
d to update data with regards to product tracking and to establish operating procedures for the OCP.}{\cs16\cf1\super\insrsid1005201 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid1902668 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\cf1\insrsid16207337 \tab The debate on the House floor that }{\cf1\insrsid2819873 followed}{\cf1\insrsid16207337 
 the presentation of the Committee\rquote s }{\cf1\insrsid14759027 initial }{\cf1\insrsid16207337 report was not extensive, but was }{\cf1\insrsid14759027 definitively }{\cf1\insrsid16207337 supportive of section 203.}{\cs16\cf1\super\insrsid16207337 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 148 Cong. Rec. at H7162.}}}{\cf1\insrsid16207337   Representative Eshoo noted that the provision would help to \'93shep}{\cf1\insrsid13073061 h}{\cf1\insrsid16207337 erd\'94
 combination products through the approval process, thereby allowing the FDA to focus upon approving the medical devices that patients needed most.}{\cs16\cf1\super\insrsid16207337 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid10294564   Representative Greenwood, H.R. 3580\rquote s sponsor, also echoed this theme of efficiency and protection of the public by pointing out that section 203 would eliminate the \'93
regulatory logjams\'94 that the FDA faced while ensuring that combination products were properly classified and assigned.}{\cs16\cf1\super\insrsid10294564 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at H7163.}}}{\cf1\insrsid15269923   In a unique extension of remarks on}{\cf1\insrsid2819873  the House floor, Representative }{\cf1\insrsid15269923 
Mark E. Souder of Indiana expressed his approval }{\cf1\insrsid2819873 of}{\cf1\insrsid15269923  the passage of H.R. 3580 because }{\cs17\cf1\insrsid15269923\charrsid15269923 Kosciusko County in Northern Indiana }{\cs17\cf1\insrsid15269923 was}{
\cs17\cf1\insrsid15269923\charrsid15269923  one of the nation's }{\cs17\cf1\insrsid15269923 leading sites for production of}{\cs17\cf1\insrsid15269923\charrsid15269923  medical device}{\cs17\cf1\insrsid15269923 s}{
\cs17\cf1\insrsid15269923\charrsid15269923 .}{\cs16\cf1\super\insrsid15269923 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  148 Cong. Rec. E1844 (2002).}}}{\cs17\cf1\insrsid1392460 
  He highlighted the streamlined approval procedures that the OCP would provide for product manufacturers while noting that }{\cs17\cf1\insrsid1392460\charrsid1392460 \'93
this expedited procedure will not sacrifice thoroughness for speed. This legislation carefully spells out strict standards to ensure the absolute highest level of safety.}{\cf1\insrsid1392460\charrsid1392460 \'94}{\cs16\cf1\super\insrsid1392460 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid15269923\charrsid15269923  }{\cf1\insrsid16207337\charrsid15269923  }{\insrsid16207337 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1857143 {\insrsid14559901 \tab }{\insrsid13257719 A little more than one week later, the House was again asked }{\insrsid4011069 
by the Committee on Energy and Commerce }{\insrsid13257719 to consider the MDUFMA, but in another form.  H.R. 3580 had been abandoned, or more properly, amended such that H.R. 5651 was now the legislation seeking passage.}{\cs16\super\insrsid13257719 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\scaps\insrsid16284404\charrsid7211990 H.R. Res.}{\insrsid16284404\charrsid7211990  5651, 107th Cong., 148 Cong. Rec. H7964 (2002) (enacted) (introduced by Rep. Armey).}}}{\insrsid13728035   }{\insrsid10301446 In fact, section 203 became section 20}{
\insrsid6445460 4 within H.R. 5651 because the Committee drafted}{\insrsid10301446  a new provision }{\insrsid6445460 as}{\insrsid10301446  section 203: the debarment of accredited third-party reviewers of premarket product applications.}{
\cs16\super\insrsid10301446 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 203.}}}{\insrsid6445460   }{\insrsid14890538 Section 204 in particular was}{\insrsid3336  amended, it could be argued,}{\insrsid14890538 
 more fully}{\insrsid3336  to}{\insrsid14890538  incorporate Rep. Greenwood\rquote s theme of timeliness and efficiency of review.  }{\insrsid6445460 Since section 204 of H.R. 5651 }{\insrsid4740931 was}{\insrsid6445460  the }{\insrsid4740931 final }{
\insrsid6445460 provision }{\insrsid14890538 allowing for the creation of the OCP as }{\insrsid6445460 enacted by Congress and signed by the President, the full text of this noteworthy legislative development is included here:  }{\insrsid11611377 
\par }\pard \ql \li1440\ri1440\widctlpar\aspalpha\aspnum\faauto\adjustright\rin1440\lin1440\itap0\pararsid11611377 {\cs17\cf1\insrsid6445460\charrsid6445460 SEC. 204. DESIGNATION AND REGULATION OF COMBINATION PRODUCTS.}{\cf1\insrsid6445460\charrsid6445460 
\line \line }{\cs17\cf1\insrsid6445460\charrsid6445460 Section 503(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353(g)) is amended-}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 (1) in paragraph (1) -}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
(A) in the first sentence, by striking "shall designate a component of the Food and Drug Administration" and inserting "shall in accordance with this subsection assign an agency center"; and}{\cf1\insrsid6445460\charrsid6445460 \line }{
\cs17\cf1\insrsid6445460\charrsid6445460 (B) in each of subparagraphs (A) through (C), by striking "the persons charged" and inserting "the agency center charged";}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
(2) by redesignating paragraph (4) as paragraph (5);}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 (3) by inserting after paragraph (3) the following paragraph:}{\cf1\insrsid6445460\charrsid6445460 \line }{
\cs17\cf1\insrsid6445460\charrsid6445460 "(4)(A) Not later than 60 days
 after the date of the enactment of this paragraph, the Secretary shall establish within the Office of the Commissioner of Food and Drugs an office to ensure the prompt assignment of combination products to agency centers, }{
\cs17\i\cf1\insrsid6445460\charrsid9326885 the timely and effective }{\cs17\cf1\insrsid6445460\charrsid6445460 premarke
t review of such products, and consistent and appropriate postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law. Additionally, the office shall, in determining whether a product is to be designate
d
 a combination product, consult with the component within the Office of the Commissioner of Food and Drugs that is responsible for such determinations. Such office (referred to in this paragraph as the 'Office') shall have appropriate scientific and medic
al expertise, and shall be headed by a director.}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
"(B) In carrying out this subsection, the Office shall, for each combination product, promptly assign an agency center with primary jurisdiction in accordance with paragraph (1) for the premarket review of such product.}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\i\cf1\insrsid6445460\charrsid9326885 
"(C)(i) In carrying out this subsection, the Office shall ensure timely and effective premarket reviews by overseeing the timeliness of and coordinating reviews involving more than one agency center.}{\i\cf1\insrsid6445460\charrsid9326885 \line }{
\cs17\i\cf1\insrsid6445460\charrsid9326885 "(ii) In order to ensure the timeliness of t
he premarket review of a combination product, the agency center with primary jurisdiction for the product, and the consulting agency center, shall be responsible to the Office with respect to the timeliness of the premarket review.}{
\i\cf1\insrsid6445460\charrsid9326885 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 "(D) In carrying out thi
s subsection, the Office shall ensure the consistency and appropriateness of postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law.}{\cf1\insrsid6445460\charrsid6445460 \line }{
\cs17\cf1\insrsid6445460\charrsid6445460 "(E)(i) Any dispute regarding the timeliness of the premarket review of a combination product may be presented to the Office for resolution, unless the dispute is clearly premature.}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 "(ii) During the review process, any dispute regarding the substance of the premarket review may be presented to the Commissioner of Food a
nd Drugs after first being considered by the agency center with primary jurisdiction of the premarket review, under the scientific dispute resolution procedures for such center. The Commissioner of Food and Drugs shall consult with the Director of the Off
ice in resolving the substantive dispute.}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
"(F) The Secretary, acting through the Office, shall review each agreement, guidance, or practice of the Secretary that is specific to the assignment of combination products to agency centers and shall determine whe
ther the agreement, guidance, or practice is consistent with the requirements of this subsection. In carrying out such review, the Secretary shall consult with stakeholders and the directors of the agency centers. After such consultation, the Secretary sh
a
ll determine whether to continue in effect, modify, revise, or eliminate such agreement, guidance, or practice, and shall publish in the Federal Register a notice of the availability of such modified or revised agreement, guidance or practice. Nothing in 
this paragraph shall be construed as preventing the Secretary from following each agreement, guidance, or practice until continued, modified, revised, or eliminated.}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
"(G) Not later than one year after the date of the enactment of this paragraph and annually thereafter, the Secretary shall report to the appropriate committees of Congress on the activities and impact of the Office. The report shall include provisions-}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 "(i) describing the numbers and types of combination products under review and the timeliness in days of such assignments, reviews, and dispute resolutions;}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 "(ii) identifying the number of premarket reviews of such products that involved a consulting agency center; and}{\cf1\insrsid6445460\charrsid6445460 \line }{
\cs17\cf1\insrsid6445460\charrsid6445460 "(iii) describing improvements in the consistency of postmarket regulation of combination products.}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\i\cf1\insrsid6445460\charrsid9326885 
"(H) Nothing in this paragraph shall be construed to limit the regulatory authority of any agency center."; }{\cs17\cf1\insrsid6445460\charrsid6445460 and}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
(4) in paragraph (5) (as redesignated by paragraph (2) of this section)-}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 (A) by redesignating subparagraphs (A) and (B) as subparagraphs (B) and (C), respectively; and}{
\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 (B) by inserting before subparagraph (B) the following subparagraph:}{\cf1\insrsid6445460\charrsid6445460 \line }{\cs17\cf1\insrsid6445460\charrsid6445460 
"(A) The term 'agency center' means a center or alternative organizational component of the Food and Drug Administration."}{\cs16\cf1\super\insrsid5989923 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 . at \'a7 204 (emphasis added).}}}{\cs17\cf1\insrsid12935363 
\par }\pard \ql \fi-1440\li1440\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin1440\itap0\pararsid11611377 {\insrsid11611377 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\insrsid8940371 The a}{\insrsid6445460 mendments to }{\insrsid8940371 s}{\insrsid6445460 ection 203 of H.R. 3580}{\insrsid12538843  that appear
}{\insrsid8940371  within section 204 of H.R. 5651}{\insrsid6445460  }{\insrsid12538843 above }{\insrsid6445460 have been italicized}{\insrsid9326885  to illustrate the thematic changes}{\insrsid13446791  in }{\insrsid8940371 agreement}{\insrsid13446791 
 with Rep. Greenwood\rquote s }{\insrsid3336 position}{\insrsid9326885 .}{\insrsid8940371   Paragraph (4)(A), that originally called for the \'93timely\'94 premarket review of combination products, now mandated their \'93timely and effective\'94
 premarket review.}{\cs16\super\insrsid8940371 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 204(4)(A).}}}{\insrsid12256993 
  Paragraph (4)(C) within H.R. 3580 became paragraph (4)(C)(i) within H.R. 5651, and the }{\insrsid12538843 word}{\insrsid12256993  \'93overseeing\'94 }{\insrsid12538843 as it related to reviews }{\insrsid12256993 was }{\insrsid12538843 modified}{
\insrsid12256993  to read \'93}{\cs17\cf1\insrsid12256993\charrsid12256993 overseeing the timeliness of }{\cs17\cf1\insrsid3816198 . . .}{\cs17\cf1\insrsid12256993 \'94}{\cs17\cf1\insrsid3816198  instead.}{\cs16\cf1\super\insrsid12256993 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 204(4)(C)(i).}}}{\cs17\cf1\insrsid3816198 
  Paragraph (4)(E) within H.R. 3580 became paragraph (4)(C)(ii) within H.R. 5651, and the last sentence of paragraph (4)(D) within H.R. 3580 became paragraph (4)(H) within H.R. 5651.  }{\cs17\cf1\insrsid12277848 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\cs17\cf1\insrsid12277848 \tab }{\cs17\cf1\insrsid3816198 Of note within paragraph (4)(H), however, is the removal of the word \'93postmarket
\'94 from the phrase \'93regulatory authority.\'94}{\cs16\cf1\super\insrsid3816198 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at \'a7 204(4)(H).  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.250}
{\insrsid16284404\charrsid7211990 .}}}{\cs17\cf1\insrsid621765   With this amendment, s}{\cs17\cf1\insrsid4541016 ection 204(4)(H) would seem to have narrowed the role of the new OCP before it was even statutorily created.  }{\cs17\cf1\insrsid12277848 
It is arguable that}{\cs17\cf1\insrsid4541016  this amendment occurred because the Committee }{\cs17\cf1\insrsid12277848 intended}{\cs17\cf1\insrsid4541016  the OCP }{\cs17\cf1\insrsid12277848 to occupy }{\cs17\cf1\insrsid4541016 
a uniquely supervisory role over the smooth functioning and intercommunication of the three Centers rather than conducting the premarket approval review of combination products itself.}{\cs17\cf1\insrsid12277848   Each of the three Cent
ers would still complete the premarket approval of the products appropriately classified to them, using the same staff and same approval procedures as in the past}{\cs17\cf1\insrsid621765 ,}{\cs17\cf1\insrsid12277848 
 while the OCP monitored their progress and collaboration.}{\cs17\cf1\insrsid1254359   Thus, it wa}{\cs17\cf1\insrsid621765 s appropriate, if not 
necessary, to vest continued regulatory authority in each Center (notably the Center with primary jurisdiction for combination products) because that }{\cs17\cf1\insrsid1254359 Center would}{\cs17\cf1\insrsid621765 
 be directly responsible for its decision to the OCP }{\cs17\cf1\insrsid1254359 pursuant to}{\cs17\cf1\insrsid621765  \'a7 204(4)(C)(ii).}{\cs17\cf1\insrsid16062729 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\cs17\cf1\insrsid12538843 \tab T}{\cs17\cf1\insrsid4805396 h}{\cs17\cf1\insrsid12538843 e amended }{\cs17\cf1\insrsid15945552 responsibilities}
{\cs17\cf1\insrsid12538843  of the OCP within section 204 of H.R. 5651 were passed by the House on October 16, 2002.}{\cs16\cf1\super\insrsid12538843 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  148 Cong. Rec. at H7964-65.}}}{
\cs17\cf1\insrsid12538843   The following day, the Senate continued the debate surrounding these provisions in anticipation of its own vote.}{\cs16\cf1\super\insrsid12538843 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 148 Cong. Rec. S10752 (October 17, 2002).}}}{\cs17\cf1\insrsid6895453   As Senator Kennedy pointed out, }{\cs17\cf1\insrsid6895453\charrsid6895453 \'93
We have been working on this legislation for 10 years. It has been a divisive issue, both the issue and as a public policy issue. . . I indicate [that] this is a public health matter of enormous importance and consequence.\'94}{
\cs16\cf1\super\insrsid6895453 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  148 Cong. Rec. at S10619.  Perhaps in a more pointed display of his support for H.R. 5651, Senator Kennedy proceeded, \'93}{\cs17\insrsid16284404\charrsid7211990 
If Members are going to object, they are going to have to come to the floor of the Senate and express those objections and reasons. We will not tolerate someone holding up this bill in hopes that they can get it carried back to the House.\'94  }{
\cs17\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid9771246   The }{\cs17\cf1\insrsid3336 bill}{\cs17\cf1\insrsid9771246  passed in the Senate
 that day as well, indicating the universal approval for the provisions that would amend the FDCA and \'93bring FDA regulation into the 21}{\cs17\cf1\super\insrsid9771246\charrsid9771246 st}{\cs17\cf1\insrsid9771246  century.\'94}{
\cs16\cf1\super\insrsid9771246 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  148 Cong. Rec. at 10754 (statement by Sen. Gregg).}}}{\cs17\cf1\insrsid9771246   H.R. 5651 was presented to President George W. Bush on October 25, 2002}{\cs16\cf1\super\insrsid9771246 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 148 Cong. Rec. H8043 (October 28, 2002).}}}{\cs17\cf1\insrsid9771246  }{\cs17\cf1\insrsid10425104 and the Medical Device User Fee and Modernization Act of 2002 became law on October 26, 2002.}{\cs16\cf1\super\insrsid10425104 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 2.}}}{\cf1\insrsid5905966\charrsid12061547 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\i\ul\insrsid14957811 V}{\i\ul\insrsid8203118 I}{\i\ul\insrsid14957811 . }{\i\ul\insrsid4475040 The Current }{\i\ul\insrsid14380242 Status}{
\i\ul\insrsid4475040  of the Office of Combination Products}{\insrsid14957811 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8863827 {\insrsid2832133 \tab With the President\rquote s signing of }{\insrsid10622499 the }{\insrsid2832133 
MDUFMA on October 26, 2002, the OCP became a sta}{\insrsid5929100 tutory responsibility of the FDA.}{\insrsid3351715   }{\insrsid3606836 There was no doubt that its advent was overdue}{\insrsid3336 . }{\insrsid3351715 
 FDA stakeholders reported that the number of new combination products seeking premarket approval was expected to continue to increase.}{\cs16\super\insrsid3351715 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Overview of the Office of Combination Products, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/overview.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
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ea79f9bace118c8200aa004ba90b6000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f006f0076006500720076006900650077002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/overview.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\insrsid6256328   }{\insrsid13382881 Recent examples of such sophisticated products }{
\insrsid3336 include}{\insrsid13382881  a glucose meter that integrated an insulin pump with a dose calculator,}{\cs16\super\insrsid13382881 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990 
 FDA Clears New Diabetes Device for Marketing, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/bbs/topics/NEWS/2003/NEW00918.html" }{
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680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b6c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f004e004500570053002f0032003000300033002f004e0045005700300030003900310038002e
00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/bbs/topics/NEWS/2003/NEW00918.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\insrsid13382881 
 dermal collagen implants for aesthetic use,}{\cs16\super\insrsid13382881 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  CosmoDerm\'99 1 Human-Based Collagen, CosmoDerm\'99 2 Human-Based Collagen, and CosmoPlast
\'99 Human-Based Collagen P800022S050, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/cdrh/pdf/p800022S050.html" }{
\insrsid16284404\charrsid7211990 {\*\datafield 
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8c8200aa004ba90b5a00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f0063006400720068002f007000640066002f00700038003000300030003200320053003000350030002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/cdrh/pdf/p800022S050.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\insrsid13382881  }{\insrsid6307642 and a drug-eluting stent used to unclog heart arteries.}{
\cs16\super\insrsid6307642 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  FDA Approves Drug-Eluting Stent for Clogged Heart Arteries, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }
{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/bbs/topics/NEWS/2003/NEW00896.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f004e004500570053002f0032003000300033002f004e0045005700300030003800390036002e00
680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b6c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f004e004500570053002f0032003000300033002f004e0045005700300030003800390036002e
00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/bbs/topics/NEWS/2003/NEW00896.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).  For more examples of recently appr
oved combination products, see Recent Examples of Combination Product Approvals, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/approvals.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003100000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0061007000700072006f00760061006c0073002e00680074006d006c000000
e0c9ea79f9bace118c8200aa004ba90b6200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0061007000700072006f00760061006c0073002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/approvals.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\insrsid6307642   }{\insrsid6256328 
Congress provided the OCP with a broad statutory grant to oversee the entire \'93regulatory life cycle\'94 of a co
mbination product, from assigning the product to one Center with primary review jurisdiction, to coordinating a timely and effective premarket review process when the product required input from }{\insrsid1052368 multiple Centers, to providing}{
\insrsid6256328  uniform postmarket procedures. }{\insrsid1052368 
 In addition, the OCP would be expected to resolve intercenter disputes arising over the proper review procedures to be applied by helping to guide and reformulate the procedures themselves.  Finally, such decisions as the OCP made would be subject to ann
ual Congressional review.}{\cs16\super\insrsid1052368 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid1052368 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid5393993   }{\insrsid5929100 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8863827 {\i\ul\insrsid31176 V}{\i\ul\insrsid8203118 I}{\i\ul\insrsid31176 .A. The First Public Hearing}{\insrsid5929100 \tab }{\insrsid31176 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8863827 {\insrsid31176 \tab }{\insrsid13382881 Despite these broad mandates, t}{\insrsid13657388 he }{\insrsid10507537 unavoidable}{\insrsid13657388 
 challenge for}{\insrsid5929100  the FDA}{\insrsid10507537  }{\insrsid13382881 still }{\insrsid10507537 came in making}{\insrsid2832133  the OCP a reality.}{\insrsid529738   }{\insrsid5929100 The discussion, }{\i\insrsid13382881 sup}{\i\insrsid5929100 ra}
{\insrsid5929100 , of }{\insrsid13657388 the findings and recommendations of the CPP, gleaned from the perspectives of }{\insrsid12603408 Center}{\insrsid13657388 
 employees, illustrated a multilayered problem of intercommunication breakdowns, outdated procedures used by a staff that was limited in time and resources, and a lack of crosstraining between Centers for different types of combination products. }{
\insrsid5929100  }{\insrsid13657388 Thus, the FDA approached the incorporation of the OCP into the Office of the Commissioner in a methodical, stepwise fashion.  }{\insrsid4216250 
At base, confusion surrounding and concerns about the manner in which the Centers within the FDA }{\insrsid13657388 should be}{\insrsid11952071  }{\insrsid4216250 regulat}{\insrsid13657388 ing}{\insrsid4216250  combination products }{\insrsid13657388 
day to day }{\insrsid4216250 would need resolution before the FDA }{\insrsid11952071 could establish the OCP to oversee the }{\insrsid13657388 subsequent, }{\insrsid11952071 smooth intercommunication }{\insrsid13657388 between}{\insrsid11952071 
 the Centers.  
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8863827 {\insrsid11952071 \tab }{\insrsid10622499 Although the Commissioner of Food and Drugs approved a press release about the new
 OCP on December 31, 2002,}{\cs16\super\insrsid10622499 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 1.}}}{\insrsid10622499 
 the FDA published a notice in the Federal Register just two days after the passage of the MDUFMA to invite public comment }{\insrsid7872953 at a hearing on November }{\insrsid10579346 25}{\insrsid7872953 , 2002 with regards to }{\insrsid10622499 the \'93
assignment, premarket review, and postmarket regulation of combination products.\'94}{\cs16\super\insrsid10622499 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  67 Fed. Reg. 65801 (October 28, 2002).}}}{\insrsid7872953   Within this notice, there wa}{\insrsid15140830 
s no men}{\insrsid7872953 tion of the OCP, but rather the notice cited }{\insrsid6506354 the CPP}{\insrsid7872953  within the Office of the Ombudsman.}{\cs16\super\insrsid10686988 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.237}{\insrsid16284404\charrsid7211990 .}}}{\insrsid7872953   That omission}{\insrsid15140830 , however, may }{\insrsid7872953 have been}{\insrsid4682080  either}{\insrsid15140830 
 the result of a public notice }{\insrsid7872953 that }{\insrsid12782705 had been}{\insrsid7872953  }{\insrsid15140830 drafted for the Federal Register prior to the passage of the MDUFMA}{\insrsid4682080  or a}{\insrsid12782705 n implicit}{
\insrsid4682080  recognition that, once the MDUFMA was enacted, the OCP would assume formally the duties of the CPP}{\insrsid15140830 .}{\cs16\super\insrsid4682080 \chftn {\footnote \pard\plain 
\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid11223891 \fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\fs20\super\insrsid16284404\charrsid7211990 \chftn }{\fs20\insrsid16284404\charrsid7211990  }{
\i\fs20\insrsid16284404\charrsid7211990 See}{\fs20\insrsid16284404\charrsid7211990  }{\scaps\fs20\insrsid16284404\charrsid7211990 H. R. Rep. No.}{\fs20\insrsid16284404\charrsid7211990  107-728, at 39 (2002) (expressing the Committee\rquote 
s intent that the OCP would continue the efforts of the CPP).  }{\i\fs20\insrsid16284404\charrsid7211990 See also}{\fs20\insrsid16284404\charrsid7211990  Overview of the Office of Combination Products, }{\i\fs20\insrsid16284404\charrsid7211990 at}{
\fs20\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\fs20\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/overview.html" }{\fs20\insrsid16284404\charrsid7211990 {\*\datafield 
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ea79f9bace118c8200aa004ba90b6000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f006f0076006500720076006900650077002e00680074006d006c000000}}}{\fldrslt {
\cs19\fs20\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/overview.html}}}{\fs20\insrsid16284404\charrsid7211990  (last visited April 15, 2004) (noting that \'93
The Office also has assumed the functions of the Combination Products Program begun in 2002 within the FDA
 Office of the Ombudsman.  Among these functions [are] working with FDA Centers to develop guidance or regulations to clarify the agency regulation of combination products [and] serving as a focal point for combination products issues for internal and ext
ernal stakeholders.\'94)}}}{\insrsid15140830   What the notice did allude to, however, were the concerns that product manufacturers had about the lack of clarity, efficiency, and predictability of the FDA\rquote s combination product approval mechanisms.}
{\cs16\super\insrsid15140830 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 65802.}}}{\insrsid15140830   }{\insrsid7872953 
To that end, the FDA requested that organizations interested in commenting on the current status of combination product review answer a variety of questions ranging from the flexibility of the Intercenter Agreements to the definition of \'93
primary mode of action\'94 to whether a product should be subject to one or more applications for premarket approval.}{\cs16\super\insrsid7872953 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  at 65803.}}}{\insrsid4475040 

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8863827 {\insrsid6434940 \tab }{\insrsid4933107 Attendees at the public hearing represented a wide variety of professional backgro}{\insrsid15688166 
unds and regulatory interests.  P}{\insrsid4933107 hysicians, laboratory researchers, attorneys and manufacturing executives all weighed in with their impressions of how the future of combination product review should be shaped.}{
\cs16\super\insrsid4933107 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  Transcript of the Public Hearing on November 25, 2002 on FDA Regulation of Combination Products, }{\i\insrsid16284404 at}{\insrsid16284404  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/transcript112502.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
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32002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007400720061006e007300630072006900700074003100310032
003500300032002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/transcript112502.html}}}{\insrsid16284404\charrsid7211990  (last visited April 11, 2004).}}}{\insrsid4928577   }{
\insrsid9513001 One of the FDA panelists overseeing the hearing was Dr. Mark Kramer, Director of the Combination Products Program within the Ombudsman\rquote s Office.  }{\insrsid4928577 
At least one participant noted that the outcome of this hearing was, in part, necessary to guide the immediate future of the OCP}{\insrsid9513001 .}{\cs16\super\insrsid4928577 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  (statement of Dr. Murray Lumpkin, FDA Principal Associate Commissioner).}}}{\insrsid16132748  }{\insrsid9513001  }{\insrsid12672421 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid12672421 \tab }{\insrsid9513001 
While many of the speakers encouraged the FDA to increase its efficiency and oversight procedures in general terms,}{\cs16\super\insrsid1392838 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  (}{
\i\insrsid16284404\charrsid7211990 see, e.g.}{\insrsid16284404\charrsid7211990 , statement of Dr. Owen Fields, Ph.D., Regulatory Affairs, Wyeth Pharmaceuticals).}}}{\insrsid9513001 
 a few participants made noteworthy suggestions.  Dr. Barbara D. Boyan, Ph.D., who spoke on behalf of the American Academy of Orthopaedic Surgeons, advocated for a \'93multidisciplinary\'94 approach,}{\cs16\super\insrsid8530874 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   Dr. Fields referred to this as an \'93intercenter review team.\'94}}}{\insrsid9513001 
 in which a team of physicians, scientists, and engineers would work cooperatively to review a combination product from the time that the product application is submitted to its final approval.}{\insrsid8286734   She also proposed that the \'93
primary mode of action\'94 of a product include its method of use.}{\cs16\super\insrsid9513001 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
  Ms. Ashley Whitesides, Esq., King & Spaulding, concurred that those products that were intended for identical uses should be categorized together and primarily regulated by the same Center.}}}{\insrsid12672421   }{\insrsid8070982 
Ultimately, Dr. Boyan, and }{\insrsid15553622 many of the}{\insrsid8070982  other speaker}{\insrsid15553622 s}{\insrsid8070982  at the hearing, }{\insrsid12672421 strongly urged the FDA to limit the review process to one applicatio
n for each combination product.}{\cs16\super\insrsid9456303 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   Oth
er speakers, however, argued that certain combinations contain two or more components that are diverse enough to require separate approval applications.  One example of such a product was a magnetic resonance system, where the drug that provided the imagi
ng effect, never physically contacted the device.}}}{\insrsid12672421   }{\insrsid9788512 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid9788512 \tab }{\insrsid2585480\charrsid9788512 Continuing a previous }{\insrsid12672421\charrsid9788512 
theme, Dr. Paul Goldfarb, M.D., who represented Genetronics, Inc., enco}{\insrsid14770407\charrsid9788512 uraged the FDA to consider the }{\insrsid12672421\charrsid9788512 primary }{\insrsid14770407\charrsid9788512 mode of action}{
\insrsid12672421\charrsid9788512  from the patient\rquote s perspective.}{\cs16\super\insrsid12672421\charrsid9788512 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid3673187\charrsid9788512 
  Dr. Goldfarb, in conjunction with Dr. Fields}{\insrsid15165558\charrsid9788512  and a few other speakers}{\insrsid3673187\charrsid9788512 , believed that the therapeutic effect of the product should weigh}{\insrsid15165558\charrsid9788512  heavily}{
\insrsid3673187\charrsid9788512  in the determination}{\insrsid14770407\charrsid9788512  of the primary mode of action.}{\cs16\super\insrsid9662120\charrsid9788512 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990  Mr. Michael Gross, Vice President of Worldwide Compliance for Aventis Behring, a biologics manufacturer, agreed.}}}{\insrsid2585480\charrsid9788512   }{
\insrsid15165558\charrsid9788512 Such an interpretation would continue the }{\insrsid14770407\charrsid9788512 historical approach}{\insrsid15165558\charrsid9788512  of the FDA}{\insrsid14770407\charrsid9788512  in determining the prima
ry mode of action and building the OCP\rquote s approach from that point.}{\cs16\super\insrsid14770407\charrsid9788512 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
 (statement of David Fox, Esq., Hogan & Hartson, LLP).  Mr. Fox disagreed tha
t multiple applications presented an efficiency problem for combination product review as the intercommunication and coordination between Centers had increased.  Ms. Patricia Shrader, Esq., Corporate Vice President of Regulatory Affairs and Compliance at 
B
ecton, Dickinson and the company spokesperson of AdvaMed, which is the largest medical technology association in the world, agreed that the historical approach to determining the primary mode of action was the most appropriate approach.  Her position, how
e
ver, was predicated upon an argument based in industrial and administrative inertia that thousands of manufacturers had come to rely upon the historical definition of the primary mode of action in filing their own applications, such that a change at this 
time would create unnecessary confusion.}}}{\insrsid1785705\charrsid9788512   }{\insrsid2585480\charrsid9788512 Another expert argued that premarket approval lead jurisdiction should be granted to the Center best equipped to }{
\insrsid4798665\charrsid9788512 assess the product\rquote s risk and to }{\insrsid2585480\charrsid9788512 assure the safety of the product to patients.}{\cs16\super\insrsid2585480\charrsid9788512 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990 
 (statement of Dr. Guy Chamberland, Ph.D., Vice President of Regulatory Affairs and Drug Development, Angiogene, Inc.).  Dr. Fields proposed a similar idea, as did Dr. Zorina Pitkin, Ph.D., Vice President of Reg
ulatory Affairs and Quality Systems at Nephros Therapeutics, Inc.  Mr. Fox, by contrast, largely discounted this consideration because any Center at FDA could provide the appropriate safety and effectiveness information, regardless of whether the Center h
ad primary review jurisdiction.}}}{\insrsid9788512\charrsid9788512   Finally, Dr. Stuart Portnoy, M.D., formerly a FDA Branch Chief of the Interventional Cardiology Devices Branch, voiced a unique position when he argued that }{\insrsid9788512 \'93}{
\insrsid9788512\charrsid9788512 it is essential for the reviewers of combination products to continue to work from within their respective centers, and not be pulled out to populate this new office.}{\insrsid9788512 \'94}{\cs16\super\insrsid9788512 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid11693437   He believed that the product reviewers within each Center would only maintain their specific expertise if they stayed within those Centers.  Thus, the \'93cross-center review teams\'94
 should not be abandoned in favor of the \'93multidisciplinary\'94 approach advanced by Dr. Boyan and the OCP should occupy the role intended for it by Congress: administrator of FDA inter-Center communication.}{\cs16\super\insrsid11693437 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid9788512 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid2629482 \tab From this hearing, the FDA promulgated a final ruling, published in the Federal Register on June 23, 2003.}{
\cs16\super\insrsid2629482 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  68 Fed. Reg. 37075-01 (June 23, 2003).}}}{\insrsid14117664   The ruling explained how some of the regulations that had been promulgated as the result of the passage of the SMDA, 21 C.F.R. \'a7\'a7 3}{\insrsid1726370 .1}{
\insrsid14117664  et seq., would require further amendment as a result of the MDUFMA.}{\insrsid1726370   }{\insrsid66532 Those changes, h}{\insrsid7537045 ow}{\insrsid15688166 ever, were mostly superficial.  T}{\insrsid7537045 
he major suggestions advanced by many of the speakers at the public hearing were not incorporated into the OCP\rquote s formal regulatory framework.  }{\insrsid1726370 Section 3.1, the statement of purpose behind these com
bination product regulations, was modified to cite the MDUFMA as }{\insrsid1579683 one source of }{\insrsid1726370 authority for the }{\insrsid1579683 combination product }{\insrsid1726370 regulations.}{\cs16\super\insrsid1726370 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7
 3.1 (2003); 68 Fed. Reg. at 37077.}}}{\insrsid1726370   Section 3.2 was amended to make the definitions of \'93agency component\'94 and \'93agency center}{\insrsid16145877 ,}{\insrsid1726370 \'94}{\insrsid16145877  (as both were used within the FDCA)}{
\insrsid1726370  compatible, and section 3.6 was revised to cite the OCP as the combination product jurisdiction officer, }{\insrsid66532 rather than}{\insrsid1726370  the Ombudsman.}{\cs16\super\insrsid1726370 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7
 3.2, 3.6 (2003); 68 Fed. Reg. at 37077.}}}{\insrsid10447813   }{\insrsid4090673 Designating the OCP as the new product jurisdiction officer meant that the OCP would now make the original determinatio
n as to which Center would have primary premarket review responsibility for combination products and for products whose review jurisdiction was in dispute.}{\cs16\super\insrsid4090673 \chftn {\footnote \pard\plain 
\s24\ql \li0\ri0\sb38\sa38\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4090673 \fs18\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\fs20\insrsid16284404\charrsid7211990 See}{\fs20\insrsid16284404\charrsid7211990  Assignment of Combination Products/Product Jurisdiction Program, }{\i\fs20\insrsid16284404 at}{\fs20\insrsid16284404  }{\field\flddirty{\*\fldinst {
\fs20\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/assignment.html" }{\fs20\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f00610073007300690067006e006d0065006e0074002e00680074006d006c00
0000e0c9ea79f9bace118c8200aa004ba90b6400000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f00610073007300690067006e006d0065006e0074002e00680074006d006c000000}}
}{\fldrslt {\cs19\fs20\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/assignment.html}}}{\fs20\insrsid16284404\charrsid7211990  (last visited }{\insrsid16284404\charrsid7211990 April 16}{\fs20\insrsid16284404\charrsid7211990 
, 2004).  }{\i\fs20\insrsid16284404\charrsid7211990 See also}{\fs20\insrsid16284404\charrsid7211990  Overview of the Office of Combination Products,}{\fs20\insrsid16284404  }{\i\fs20\insrsid16284404 at}{\fs20\insrsid16284404\charrsid7211990  }
{\field\flddirty{\*\fldinst {\fs20\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/overview.html" }{\fs20\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f006f0076006500720076006900650077002e00680074006d006c000000e0c9
ea79f9bace118c8200aa004ba90b6000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f006f0076006500720076006900650077002e00680074006d006c000000}}}{\fldrslt {
\cs19\fs20\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/overview.html}}}{\fs20\insrsid16284404\charrsid7211990  (last visited }{\insrsid16284404\charrsid7211990 April 16}{\fs20\insrsid16284404\charrsid7211990 , 2004).}}}{
\insrsid4090673   }{\insrsid10447813 Sections 3.7 and 3.9 were also modified in minor ways to correlate with the FDA\rquote s current organizational structure.}{\cs16\super\insrsid10447813 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  21 C.F.R. \'a7\'a7
 3.7,. 3.9 (2003); 68 Fed. Reg. at 37077.}}}{\insrsid2629482 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\i\ul\insrsid31176 V}{\i\ul\insrsid8203118 I}{\i\ul\insrsid31176 .B. The First Six Months}{\insrsid14380242 \tab }{\insrsid31176 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid31176 \tab }{\insrsid11418289 Between}{\insrsid14109380  the public hearing in November}{\insrsid11418289 
 2002 and the issuance of the final rule that modified the OCP\rquote s governing regulations, }{\insrsid14298323 the OCP issued two quarterly progress reports to its stakeholders.}{\cs16\super\insrsid14298323 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 First Quarterly Progress Report to Stakeholders, January \endash  March 2003 (\'93First Quarterly Report\'94), }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/firstquarter2003.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003800000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f00660069007200730074007100750061007200740065007200320030003000
33002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7000000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0066006900720073007400710075006100720074006500720032
003000300033002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/firstquarter2003.html}}}{\insrsid16284404\charrsid7211990 
 (last visited April 15, 2004).  Second Quarterly Progress Report to Stakeholders, April \endash  June 2003 (\'93Second Quarterly Report\'94), }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/secondquarter2003.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003900000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007300650063006f006e006400710075006100720074006500720032003000
300033002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f007300650063006f006e0064007100750061007200740065
00720032003000300033002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/secondquarter2003.html}}}{\insrsid16284404\charrsid7211990  (last visited April 15, 2004).}}}{\insrsid5009261 
  The first report explicitly stated that the OCP }{\insrsid4009065 was focusing on establishing }{\insrsid5009261 procedures in furtherance of its statutory responsibilities}{\insrsid4009065 
; to that end, it highlighted in a succinct fashion its actions during its first three months of existence.  During the first three months of 2003, }{\insrsid5653892 
the OCP received six requests for product assignment and issued four of those assignments.}{\insrsid5790736   Of those four assignments, all of them were issued within sixty days of the OCP\rquote s receipt of the request}{\insrsid15798207 
; the average review time was 37 days}{\cs16\super\insrsid5790736 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  First Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}
{\insrsid16284404\charrsid7211990 .}}}{\insrsid15798207   Two products were primarily assigned to CBER, and one of each of the remaining products was assigned to CDER and CDRH.}{\insrsid1789159   }{\insrsid6058304 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid6058304 \tab }{\insrsid1789159 In addition to this statistical data, the OCP stated that it was working to adapt the definition of \'93
primary mode of action,\'94 probably in response to the statements at the public hearing, and that proposed definitions were being used in test cases.}{\cs16\super\insrsid1789159 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid6058304   }{\insrsid6510748 A new \'93internal precedent documentation system\'94 was established to allow each Center to retroactively catalog old assignment decisions and to re
fer to prior relevant precedents when confronted with a new application.}{\cs16\super\insrsid2890385 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\insrsid6510748   }{\insrsid4356812 
More importantly, the OCP developed an electronic, web-based database}{\insrsid12193799  that would allow the Centers to track the progress of each consultation request made on a combination product.  }{\insrsid6058304 The OCP}{\insrsid6510748 
 also revised the SOPPs}{\insrsid12193799  of the Intercenter Consultative/Collaborative Review Process}{\cs16\super\insrsid12193799 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.241}{\insrsid16284404\charrsid7211990 .}}}{
\insrsid6510748  utilized by the Centers}{\insrsid8479828  to complement}{\insrsid12193799  the}{\insrsid8479828  use of the}{\insrsid12193799  electronic database}{\insrsid8479828 .}{\insrsid341479   }{\insrsid16406760 
Not forgetting that the OCP was charged with overseeing the \'93entire regulatory cycle\'94 o
f combination products, new working groups were formed within the OCP to create guidance documents that would inform manufacturers in advance of the role that the Centers expected to play in continuing }{\i\insrsid16406760\charrsid16406760 postmarket}{
\insrsid16406760  monitoring of specific combination products
.  The report noted that CDRH and CDER especially would be implicated by this new procedure because they anticipated a marked increase in a specific category of combination product that would require this monitoring in the future.  }{\insrsid8479828 
In essence, the first quarterly progress report captured the OCP at a \'93feet-wetting\'94
 stage, as it began its oversight responsibilities through meetings with various groups of stakeholders and debriefings with the staff of Center review teams, and as it responded to inquiries fielded by both FDA staff and product manufacturers.}{
\cs16\super\insrsid8479828 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  First Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{
\insrsid2699897   }{\insrsid341479 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid341479 \tab }{\insrsid2699897 One par}{\insrsid6181722 ticularly innovative approach that was tentatively adopted by the OCP}{
\insrsid2699897  }{\insrsid6181722 was}{\insrsid2699897  cited }{\insrsid11687508 briefly }{\insrsid2699897 in the report.  Section 204 of the MDUFMA charged the OCP with the \'93timely and effective\'94 premarket review of combination products.}{
\cs16\super\insrsid2699897 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.272}{\insrsid16284404\charrsid7211990 .}}}{\insrsid2699897   The OCP noted that two Centers interacted often }{\insrsid8656573 enough }{\insrsid2699897 
on a range of combination products}{\insrsid8656573  that a \'93two-Center, two-application collaborative premarket review\'94 could provide a more }{\insrsid6181722 appropriate}{\insrsid8656573  and efficient means of reviewing a new 
combination product without minimizing each Center\rquote s input or expertise.  After one such collaborative team had completed a premarket review with this new application, the OCP debriefed the }{\insrsid6181722 other Center review }{\insrsid8656573 
team}{\insrsid6181722 s and planned to debrief the manufacturer later}{\insrsid1769701  on the results of the trial inter-Center collaboration}{\insrsid8656573 .  The OCP hoped}{\insrsid8679760  that }{\insrsid9724896 the }{\insrsid8679760 feedback}{
\insrsid6181722  }{\insrsid9724896 that was generated }{\insrsid1769701 by the test review team }{\insrsid8679760 would help it to generate tools}{\insrsid8656573  to use }{\insrsid8679760 i}{\insrsid8656573 n furth}{\insrsid8679760 er }{\insrsid1769701 
collaborative }{\insrsid8679760 premarket reviews}{\insrsid9724896  with other teams}{\insrsid1080955 .}{\cs16\super\insrsid9521639 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  First Quarterly Report, }{
\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .  This inter-Center, team-oriented or \'93multidisciplinary\'94 approach also was advocated for by some of the speakers at the public hearing.  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.296}{\insrsid16284404\charrsid7211990 .}}}{\insrsid8479828 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\insrsid410005 \tab Another }{\insrsid2305253 noteworthy choice disclosed}{\insrsid410005 
 in the first quarterly report was the balancing act that }{\insrsid2305253 the infant OCP}{\insrsid410005  undertook}{\insrsid10687939 .}{\insrsid410005  }{\insrsid10687939 
 Many of the steps taken immediately following the enactment of the MDUFMA by the OCP were directed at mod}{\insrsid410005 ernizing current regulatory practices }{\insrsid10687939 by}{\insrsid410005  the Centers}{\insrsid10687939 
 and facilitating their intercommunication.  Yet the report also disclosed that the OCP jumped headlong}{\insrsid410005  }{\insrsid10687939 into break}{\insrsid6112747 ing new administrative ground}{\insrsid410005 .}{\insrsid6112747 
  Working groups were established to }{\insrsid6112747\charrsid6112747 \'93}{\cf1\insrsid6112747\charrsid6112747 clarify and develop the regulatory pathways for novel drug delivery systems and drug/test kit combination products b}{\cf1\insrsid6112747 
ased on pharmacogenomics. OCP [was]}{\cf1\insrsid6112747\charrsid6112747  also participating in the working groups being established to develop guidance documents for products for diabetes and obesity.\'94}{\cs16\super\insrsid10687939\charrsid6112747 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  First Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid83553   These steps were part of the 
\'93Commissioner\rquote s Technology Development Initiatives.\'94}{\cs16\cf1\super\insrsid83553 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cf1\insrsid3499078 
  Such an assertive move, to resolve old problems while simultaneously laying the groundwork to regulate cutting-edge technology, revealed an experienced sophistication and dedication that belied the brand-new veneer of the OCP.}{\cf1\insrsid410005 

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cf1\insrsid8677760 \tab 
The second quarterly progress report provided to stakeholders also drew a concise, yet illustrative, picture of the continuing evolution of the OCP.}{\cs16\cf1\super\insrsid12459305 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Second Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid8677760  }{\cf1\insrsid12281847  }{
\cf1\insrsid6448446 Product jurisdiction reviews were finally consolidated within the OCP, completing the transfer from the Office of the Ombudsman.  The OCP promulgated the final rule in the Federal Register on June 23, 2003.}{
\cs16\cf1\super\insrsid6448446 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid6448446 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.305}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid6448446   }{\cf1\insrsid13830574 
As expected, the OCP continued to oversee and facilit}{\cf1\insrsid12459305 at}{\cf1\insrsid14109380 e inter-Center }{\cf1\insrsid15945552 communication}{\cf1\insrsid14109380 .  I}{\cf1\insrsid12459305 t accomplished this,}{\cf1\insrsid13830574 
 in part, by completing a retrospective analysis of consultative reviews completed during the first six months of 2003.  }{\cf1\insrsid12459305 Regulatory challenges that still needed resolution included whether an updated definition of the \'93
primary mode of action\'94 was necessary and whether a single product application or separate applications}{\cf1\insrsid6495360 , managed by inter-Center review teams,}{\cf1\insrsid12459305  more effectively furthered the OCP\rquote 
s responsibility to approve combination products in a \'93timely and effective\'94 way.  }{\cf1\insrsid12518696 As before, the OCP forged ahead with creating regulatory pathways for new comb}{\cf1\insrsid15794492 ination products and establishing}{
\cf1\insrsid12518696  a new working group to consider whether cross-labeling of some combination products was feasible.}{\cs16\cf1\super\insrsid12518696 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Although no example is provided, cross-labeling issues may arise when a combination product consists of two physically distinct components that are intended for concomitant use.  }{\i\insrsid16284404\charrsid7211990 See, e.g.,}{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.133, 298}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid12518696   }{\cf1\insrsid15794492 
Postmarket review factors, such as adverse events, good manufacturing practices, and the registration of approved combination products, were elucidated further by OCP working groups.  }{\cf1\insrsid8478339 
Physically, the OCP consolidated itself into one location, added }{\cf1\insrsid7996537 and trained }{\cf1\insrsid8478339 new staff, and continued to expand its website }{\cf1\insrsid7996537 by providing links to guidance documents and examples o
f recently approved combination products}{\cf1\insrsid8478339 .}{\cf1\insrsid6448446   }{\cf1\insrsid13830574 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cf1\insrsid13830574 \tab }{\cf1\insrsid6448446 In fact, many of the changes }{\cf1\insrsid15945552 brought about}{\cf1\insrsid6448446 
 by the OCP in the second quarter dealt with enhancing its electronic }{\cf1\insrsid6495360 capabilities}{\cf1\insrsid6448446 .}{\cf1\insrsid7434033   The internal request for designation (RFD) database that contained prior approval pr
ecedents continued to be updated, as was the web-enabled database that allowed each of the Centers to track, monitor, and complete consultation requests between Centers.}{\cs16\cf1\super\insrsid7434033 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See }{\insrsid16284404\charrsid7211990 Second Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid4199969   Work began on an OCP \'93
intranet\'94 site that would allow OCP staff to access all the pertinent information related to the regulation of combination products.}{\cf1\insrsid15794492   An \'93algorithm and categorization scheme\'94
 was implemented also on the web to aid in describing how different types of combination products were currently defined by the OCP.}{\cf1\insrsid7434033  }{\cf1\insrsid8478339     }{\cf1\insrsid6448446 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cf1\insrsid6448446 \tab }{\cf1\insrsid13837877 Th}{\cf1\insrsid7434033 ree new }{\cf1\insrsid11943932 RFD}{\cf1\insrsid7434033 s}{
\cf1\insrsid13837877  were }{\cf1\insrsid4002164 submitted}{\cf1\insrsid13837877  to the OCP and f}{\cf1\insrsid8478339 ive more combination products were assigned to Centers, all of which were drug-device combinations.}{\cf1\insrsid13837877 
  Three of those assignments were holdovers from the first quarterly progress report.  }{\cf1\insrsid16006535 Again, all assignments were made within sixty days of receipt of the RFD from the manufacturer.  }{\cf1\insrsid13837877 
Thus, after six months of operation, the OCP had completed nine combination product assignments to the three Centers, with one assignment remaining.}{\cs16\cf1\super\insrsid13837877 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid11943932   }{\cf1\insrsid13248108 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cf1\insrsid13248108 \tab }{\cf1\insrsid14745992 Delving deeper into t}{\cf1\insrsid11943932 he statistics}{\cf1\insrsid14745992  provided}{
\cf1\insrsid11943932  in the second}{\cf1\insrsid14745992  quarterly report,}{\cf1\insrsid11943932  the mean}{\cs16\cf1\super\insrsid2978644 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  The \'93mean,\'94 in statistics, is the average value of a set of numbers.  }{
\scaps\insrsid16284404\charrsid7211990 American Heritage Dictionary of the English Language}{\insrsid16284404\charrsid7211990   (4th ed. 2000).}}}{\cf1\insrsid11943932  \'93total FDA review time,\'94
 or the time elapsed between receipt of the RFD from the manufacturer and the action letter generated by the OCP with the Center assignment for the product, was shortened by nearly a day.  The median}{\cs16\cf1\super\insrsid13248108 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  The \'93median,\'94
 in statistics, is the middle value in a distribution, above and below which lie an equal number of values.  }{\scaps\insrsid16284404\charrsid7211990 American Heritage Dictionary of the English Language}{\insrsid16284404\charrsid7211990   (4th ed. 2000).}
}}{\cf1\insrsid11943932  total review time}{\cf1\insrsid1855216 , however,}{\cf1\insrsid11943932  increased}{\cf1\insrsid2181760  }{\cf1\insrsid1855216 from 36.5 to 40 days}{\cf1\insrsid11943932 
.  While this trend would not comfort the supporters of the OCP because it did not indicate a more timely and effective review process, the import of this statistic was lessened 
when viewed against the range of total FDA review times.  In the first quarter, review times ranged between 29 and 46 days.}{\cs16\cf1\super\insrsid11943932 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  First Quarterly Report, }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{\cf1\insrsid16006535 
  In the second quarter, by contrast, review times ranged between 18 and 47 days.}{\cs16\cf1\super\insrsid10226923 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See }{\insrsid16284404\charrsid7211990 Second Quarterly Report, }{
\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.31}{\insrsid16284404\charrsid7211990 0.}}}{\cf1\insrsid2181760   }{\cf1\insrsid1855216 Thus, in the first quarter of 2003, half of the 
product assignment reviews were completed in 29 to 36.5 days and half were completed in 36.5 to 46 days.  In the second quarter of 2003, once the OCP had assumed completely the reins of product assignment from the Office of the Ombudsman, half of the prod
uct assignments took between 18 and 40 days, and the other half of the assignments were made in 40 to 47 days.}{\cf1\insrsid9382402   So the median shifted upwards from the first to the second quarter of 2003, but the }{\cf1\insrsid15099669 
mean review time changed a neglig}{\cf1\insrsid814879 i}{\cf1\insrsid15099669 ble amount, and the total }{\cf1\insrsid9382402 review time for at least one product }{\cf1\insrsid11697892 was shortened by}{\cf1\insrsid9382402 
 eleven days.  While the sample set}{\cf1\insrsid11697892  of combination products}{\cf1\insrsid9382402  used in these statistics }{\cf1\insrsid11697892 was}{\cf1\insrsid9382402  not extensive,}{\cs16\cf1\super\insrsid9382402 \chftn {\footnote 
\pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 Recall that the OCP completed only four product assignments in the first quarter of 2003 and five product assignments in the second quarter.  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{
\cf1\insrsid11697892  the }{\cf1\insrsid7558436 message conveyed by the statistics enhances the theme}{\cf1\insrsid13631791  of}{\cf1\insrsid7558436  the second quarterly progress report}{\cf1\insrsid4721382  outlined above}{\cf1\insrsid7558436 
: the undeniable advantages }{\cf1\insrsid4721382 in time and communication }{\cf1\insrsid7558436 that accrued}{\cf1\insrsid4721382  to both the FDA and combination product }{\cf1\insrsid15945552 manufacturers}{\cf1\insrsid7558436  }{\cf1\insrsid13631791 
as a result of}{\cf1\insrsid7558436  the}{\cf1\insrsid11697892  OCP\rquote s consolidate}{\cf1\insrsid7558436 d oversight}{\cf1\insrsid11697892 .}{\cf1\insrsid8677760 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\i\ul\cf1\insrsid31176 V}{\i\ul\cf1\insrsid8203118 I}{\i\ul\cf1\insrsid31176 .C. The First Year Draws to a Close}{\cf1\insrsid31176 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cf1\insrsid11881258 \tab }{\cf1\insrsid10380149 Although the OCP was officially cr
eated on December 24, 2002, the MDUFMA was enacted on October 26, 2002.  Included within the MDUFMA was section 204(4)(G), that required the OCP to file a report with the appropriate Congressional committee }{\cs17\cf1\insrsid10380149 \'93[n]}{
\cs17\cf1\insrsid10380149\charrsid6445460 ot later than one year after the date of the enactment of this pa}{\cs17\cf1\insrsid10380149 ragraph and annually thereafter. . .\'94}{\cs16\cf1\super\insrsid10380149 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990 
 MDUFMA, section 204(4)(G), 21 U.S.C. \'a7 353(g)(4)(G) (2004).  }{\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 supra}{\insrsid16284404  n.272}{\insrsid16284404\charrsid7211990 .}}}{
\cs17\cf1\insrsid10380149\charrsid6445460  }{\cs17\cf1\insrsid4939557  Also included within this }{\cs17\cf1\insrsid5856060 statutory }{\cs17\cf1\insrsid16211515 section were the }{\cs17\cf1\insrsid9517513 three }{\cs17\cf1\insrsid16211515 
requirements that the OCP must satisfy with}{\cs17\cf1\insrsid9517513 in}{\cs17\cf1\insrsid16211515  its}{\cs17\cf1\insrsid4939557  report, namely a description of the}{\cs17\cf1\insrsid9517513  (1)}{\cs17\cf1\insrsid4939557 
 types of reviews undertaken by the OCP and their timely completion, }{\cs17\cf1\insrsid9517513 (2) }{\cs17\cf1\insrsid4939557 the consultations undertaken between Centers, and }{\cs17\cf1\insrsid9517513 (3) }{\cs17\cf1\insrsid4939557 
the advances made in standardi}{\cs17\cf1\insrsid5464836 zi}{\cs17\cf1\insrsid4939557 ng postmarket product regulation.}{\cs16\cf1\super\insrsid4939557 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid4939557   }{\cs17\cf1\insrsid5464836 On October 26, 2003 the OCP presented its annual report to Congress to explain its progress}{\cs17\cf1\insrsid5856060  }{\cs17\cf1\insrsid5464836 
through July 31, 2003.}{\cs16\cf1\super\insrsid5464836 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  Annual Report to Congress, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/congressreport.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003600000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0063006f006e00670072006500730073007200650070006f00720074002e00
680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b6c00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0063006f006e00670072006500730073007200650070006f00720074002e
00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/congressreport.html}}}{\insrsid16284404\charrsid7211990  (last visited April 16, 2004).  The entire report is twenty-three pages and theref
ore, an exhaustive examination of each finding by the OCP is beyond the confines of this paper.  A summary of those findings, however, will still serve to illustrate the advances achieved by the OCP through July 31, 2003.}}}{\cs17\cf1\insrsid11881258 

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid10500756 \tab The annual report r}{\cs17\cf1\insrsid9723197 ead}{\cs17\cf1\insrsid10500756 
 much like an introductory primer to members of Congress}{\cs17\cf1\insrsid9723197  and the general public who had}{\cs17\cf1\insrsid10500756  not followed closely the creation and development of the OCP since late 2}{\cs17\cf1\insrsid9723197 
002.  In fact, the report voiced}{\cs17\cf1\insrsid10500756  the same }{\cs17\cf1\insrsid2577208 preliminary }{\cs17\cf1\insrsid10500756 concerns th
at were expressed at the beginning of the first quarterly progress report, produced at the end of March 2003.}{\cs16\cf1\super\insrsid10500756 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.310}{\insrsid16284404\charrsid7211990 .}}}{
\cs17\cf1\insrsid2577208   The broad responsibilities of the OCP, as well as its m}{\cs17\cf1\insrsid9723197 ore specific regulatory goals, we}{\cs17\cf1\insrsid2577208 re reiterated as well.}{\cs17\cf1\insrsid4002164   T}{\cs17\cf1\insrsid9723197 
he report explained}{\cs17\cf1\insrsid4063894  in more detail the OCP\rquote s }{\cs17\cf1\insrsid11277235 \'93}{\cs17\cf1\insrsid4063894 performance}{\cs17\cf1\insrsid11277235 \'94}{\cs17\cf1\insrsid4063894  and }{\cs17\cf1\insrsid11277235 its \'93
additional activities and impacts\'94 in each of the three statutorily specified areas}{\cs17\cf1\insrsid4063894 .}{\cs17\cf1\insrsid10500756 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\i\ul\cf1\insrsid5841562 V}{\cs17\i\ul\cf1\insrsid8203118 I}{\cs17\i\ul\cf1\insrsid5841562 .C.I. \'93
Prompt Assignment of Combination Products\'94}{\cs17\cf1\insrsid1453996 \tab }{\cs17\cf1\insrsid11277235 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid11277235 \tab }{\cs17\cf1\insrsid1453996 By July 31, 2003}{\cs17\cf1\insrsid859126 , the OCP had received twelve RFDs }{
\cs17\cf1\insrsid13397921 for}{\cs17\cf1\insrsid1453996  combination produ}{\cs17\cf1\insrsid13397921 cts and had assigned ten of those products}{\cs17\cf1\insrsid1453996 
 to one of the three Centers; one request was withdrawn and the final request had not be}{\cs17\cf1\insrsid8988967 en assigned but was not behind schedule.}{\cs16\cf1\super\insrsid10245698 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.332}{\insrsid16284404\charrsid7211990 .}}}{\cs17\cf1\insrsid859126   The ten assignments that had been made were all made within sixty days of the OCP\rquote s receipt of }{
\cs17\cf1\insrsid13397921 each}{\cs17\cf1\insrsid859126  RFD, as mandated by 21 C.F.R. \'a7 3.8.}{\cs17\cf1\insrsid13397921   In a minimal departure from the statistics of the second quarterly progress report, the mean total review time }{
\cs17\cf1\insrsid11154576 increased again to}{\cs17\cf1\insrsid13397921  36.9 days, the median total review time }{\cs17\cf1\insrsid11154576 decreased by one day to}{\cs17\cf1\insrsid13397921  39 days, and the range of review times increased }{
\cs17\cf1\insrsid11154576 again equal}{\cs17\cf1\insrsid13397921  to the range originally cited in the first quarterly progress report, between 29 and 46 days.}{\cs17\cf1\insrsid10245698 
  The minimal change in these statistics implied that the OCP may have settled into its expected rate of product assignment by the end of its seventh month.}{\cs17\cf1\insrsid1453996 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid10245698 \tab Aside from the performance statistics used to illustrate the OCP\rquote 
s initial success in assigning Center jurisdiction, the report detailed additional steps by the OCP to act on its assignment role.  }{\cs17\cf1\insrsid11477307 Many of the findin
gs were repetitive of what was cited in the first two quarterly progress reports}{\cs17\cf1\insrsid3157062 , such as the responses to stakeholder inquiries and the establishment of the RFD database to serve as prior assignment precedent}{
\cs17\cf1\insrsid11477307 .  }{\cs17\cf1\insrsid3157062 Of especial note in the annual report, however, wa}{\cs17\cf1\insrsid10245698 s the finding regarding the definition of the \'93primary mode of action.\'94
  The OCP stated that a team comprised of employees from the OCP, each Center, and the Office of Chief Counsel (OCC) was still working on creating a clearer standard to be employed when the FDA made jurisdictional decisions.}{
\cs16\cf1\super\insrsid10245698 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid11293665   The result of that work was expected to change 21 C.F.R. part 3 (the applicable combination product regulations) to include that new standard.}{
\cs17\cf1\insrsid3157062   Assignment letters sent to product manufacturers were modified to explain the full scope of regulatory requirements that each product would face.  Finally, the OCP reinstated monthly meetings between its \'93
jurisdictional and assignment specialists\'94 and the separate Center product jurisdiction officers to discuss pending RFDs and enhance the uniformity of cross-Center decisions.}{\cs16\cf1\super\insrsid3157062 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid10245698 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\i\ul\cf1\insrsid4852190 V}{\cs17\i\ul\cf1\insrsid8203118 I}{\cs17\i\ul\cf1\insrsid4852190 .C.II. \'93
Timely and Effective Premarket Review\'94}{\cs17\cf1\insrsid4852190 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid13435253 \tab The performance statistics provided by the OCP to illustrate its \'93timely and effective\'94
 actions were more complex than those cited in its assignment decisions.  First, }{\cs17\cf1\insrsid7824168 
the Centers had to adopt a system of designating applications as including a combination product; that adoption became effective on April 1, 2003.  In response, t}{\cs17\cf1\insrsid13435253 wo of the Centers, CBER and CDER}{\cs17\cf1\insrsid7824168 ,}{
\cs17\cf1\insrsid13435253  }{\cs17\cf1\insrsid7824168 made that designation }{\cs17\cf1\insrsid13435253 at the time that the application was submitted.  CDRH, by contrast, made that designation once the review decision about the product had been made.}{
\cs16\cf1\super\insrsid13435253 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid7824168   Thus, when the OCP reported that 49 applications between April 1, 2003 and July 31, 2003 were classified as combination p
roducts, 38 of those applications were }{\cs17\i\cf1\insrsid7824168 received}{\cs17\cf1\insrsid7824168  by CBER and CDER and the remaining eleven applications that came from CDRH were actually applications with final decisions attached to them.}{
\cs17\cf1\insrsid13570331   The OCP further noted that too little time had passed between the adoption of this classification scheme and the }{\cs17\cf1\insrsid15663772 preparation}{\cs17\cf1\insrsid13570331 
 of the annual report to draw any meaningful conclusion about the timeliness and effectiveness of the Centers\rquote  review procedures}{\cs17\cf1\insrsid15663772  for NDAs, BLAs, or PMAs involving combination products}{\cs17\cf1\insrsid13570331 .}{
\cs16\cf1\super\insrsid15663772 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{
\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   For information on NDAs, }{\i\insrsid16284404\charrsid7211990 see supra}{\insrsid16284404  n.28}{\insrsid16284404\charrsid7211990 
.  For information on PMAs, }{\i\insrsid16284404\charrsid7211990 see supra}{\insrsid16284404  n.50}{\insrsid16284404\charrsid7211990 .  For information on BLAs, }{\i\insrsid16284404\charrsid7211990 see supra}{\insrsid16284404  n.69}{
\insrsid16284404\charrsid7211990 .}}}{\cs17\cf1\insrsid13570331   The OCP did note that between May 1, 2003 and July 31, 2003, however, }{\cs17\cf1\insrsid15663772 all of the final decisions that CDRH issued with respect to four}{
\cs17\cf1\insrsid13570331  combination product 510(k) applications were reviewed within their statutory timeframes.}{\cs16\cf1\super\insrsid13570331 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   For information on 510(k) applications, }{\i\insrsid16284404\charrsid7211990 see supra}{\insrsid16284404  n.51}{\insrsid16284404\charrsid7211990 .}}}{\cs17\cf1\insrsid15668831   

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid15668831 \tab One other statistic compiled by the OCP
 for the report tracked the number of inter-Center consultations that were solicited }{\cs17\cf1\insrsid14493772 prior to}{\cs17\cf1\insrsid15668831 
 July 31, 2003.  CBER asked for 24 consultations (mostly with CDRH), CDER asked for 14 consultations (drawing heavily from CDRH too), and CDRH requested 43 consultations (}{\cs17\cf1\insrsid94492 forty }{\cs17\cf1\insrsid15668831 
of which were with CDER).  The OCP noted that many applications actually required multiple consultations and that }{\cs17\cf1\insrsid94492 applications received prior to April 1, 2003 for which consultations were soli}{\cs17\cf1\insrsid14493772 
cited were not reflected in these data.  N}{\cs17\cf1\insrsid15668831 ot all inter-Center consultations may have been recorded during the initialization of this procedure}{\cs17\cf1\insrsid94492  immediately after April 1, 2003}{\cs17\cf1\insrsid15668831 
.  Once the web-enabled database was completed, however, the OCP anticipated the automatic recording of these consultation requests.}{\cs16\cf1\super\insrsid15668831 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid4852190 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid94492 \tab 
The extensive nature of the changes that were documented by the OCP in this area indicated that the OCP had devoted much of its energy during the first half of 2003 to }{\cs17\cf1\insrsid15945552 completing}{\cs17\cf1\insrsid94492  more \'93
timely and effective\'94 product reviews.}{\cs16\cf1\super\insrsid9241501 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404  For an update of }{\insrsid16284404\charrsid7211990 the OCP\rquote s rate
 of product assignment between October 1, 2003 and March 31, 2004, see FY04 OCP Review Performance: Formal Requests for Designation Submitted by Industry, }{\i\insrsid16284404 at}{\insrsid16284404  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/fy04rfd.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002f00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0066007900300034007200660064002e00680074006d006c000000e0c9ea79
f9bace118c8200aa004ba90b5e00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0066007900300034007200660064002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/fy04rfd.html}}}{\insrsid16284404\charrsid7211990 
 (last visited September 6, 2004).  In that period, the OCP made 12 combination product assignments, mostly to CDRH, and spent between 20 and 58 days reviewing those requests for designation.}}}{\cs17\cf1\insrsid466338   Again, many of the cited ch
anges reiterated what had been explained to stakeholders in the quarterly progress reports.  Generally, the OCP worked strenuously to facilitate inter-Center communication}{\cs17\cf1\insrsid15753524 
, from the implementation of an inter-Center mail courier system, to repeated training sessions on inter-Center consultations, to active monitoring of those consultations and}{\cs17\cf1\insrsid466338  of}{\cs17\cf1\insrsid15753524 
 multidisciplinary review teams employing the revised Standard Operating Procedures,}{\cs16\cf1\super\insrsid15753524 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.241}{\insrsid16284404\charrsid7211990 .}}}{
\cs17\cf1\insrsid15753524  to }{\cs17\cf1\insrsid466338 modernized }{\cs17\cf1\insrsid15753524 internal }{\cs17\cf1\insrsid466338 electronic databases.  An internal working group was ch
arged with simplifying submission procedures, while another group was aided by OCP in establishing }{\cs17\cf1\insrsid14878597 specific }{\cs17\cf1\insrsid466338 review processes for \'93complex regulatory issues.\'94}{\cs16\cf1\super\insrsid466338 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.332}{\insrsid16284404\charrsid7211990 .}}}{\cs17\cf1\insrsid14878597   Finally, a retrospective review of these consultations and an analysis of the fee}{\cs17\cf1\insrsid4020409 d}{
\cs17\cf1\insrsid14878597 back solicited from Center employees involved in those product consultations informed the OCP as to how to coordinate future inter-Center communications.}{\cs17\cf1\insrsid94492 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\i\ul\cf1\insrsid4852190 V}{\cs17\i\ul\cf1\insrsid8203118 I}{\cs17\i\ul\cf1\insrsid4852190 .C.III. \'93
Consistent and Appropriate Postmarket Regulation\'94}{\cs17\cf1\insrsid12542251 \tab 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid9467845 \tab The third and final area}{\cs17\cf1\insrsid6169670  that}{\cs17\cf1\insrsid9467845  the OCP was assigned by
 statute to manage was the }{\cs17\cf1\insrsid1910997 consistent }{\cs17\cf1\insrsid9467845 oversight of combination product postmarket regulation.}{\cs17\cf1\insrsid6169670 
  Although the OCP did not effect as much change in this area as it did in the premarket review arena, new postmarket reporting requirements for combination products were conceived by drawing from other regulatory sources.}{\cs16\cf1\super\insrsid6169670 
\chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}{\insrsid16284404\charrsid7211990   Statistical analysis was not presented by the OCP in this area.}}}{\cs17\cf1\insrsid1910997   In essence, the OCP\rquote 
s actions indicated that a more uniform and more tailored postmarket regulation of combination products could occur only if product }{\cs17\cf1\insrsid15945552 manufacturers}{\cs17\cf1\insrsid1910997  were informed properly at ev
ery step of the regulatory cycle.  As mentioned }{\cs17\i\cf1\insrsid1910997 supra}{\cs17\cf1\insrsid1910997 , the OCP modified the}{\cs17\cf1\insrsid1910533  assignment}{\cs17\cf1\insrsid1910997  letters initially sent to manufa}{
\cs17\cf1\insrsid1910533 cturers to be more explicit about the regulatory }{\cs17\cf1\insrsid15417202 requirements}{\cs17\cf1\insrsid1910533  that a manufacturer could expect}{\cs17\cf1\insrsid1910997 .  Then, at the end of the regulatory revie
w process, the OCP saw a further chance to explain its expectations.  Not only would the OCP actively support the Centers in their specific postmarket regulatory requirements, but it had already formed a working group to update policy and guidance stateme
nts on good manufacturing practices, quality system regulations, adverse event reports, and registration and listing mechanisms for approved combination products.}{\cs16\cf1\super\insrsid1910997 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 Id.}}}{\cs17\cf1\insrsid1910533 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\i\ul\cf1\insrsid10948351 VI.D. Moving Forward}{\cs17\cf1\insrsid10948351 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid9788512 {\cs17\cf1\insrsid723722 \tab The regulation of combination products, while requiring a clear framewo
rk based upon common product classifications and accepted administrative channels, must be flexible enough to manage the ever increasing sophistication of new products.}{\cs17\cf1\insrsid15362361   To that end, the OC}{\cs17\cf1\insrsid6519106 
P has proposed}{\cs17\cf1\insrsid16607044  }{\cs17\cf1\insrsid8092121 at least two }{\cs17\cf1\insrsid16607044 change}{\cs17\cf1\insrsid6519106 s}{\cs17\cf1\insrsid16607044  in its own oversight procedures}{\cs17\cf1\insrsid15362361 .  }{
\cs17\cf1\insrsid6519106 It has drafted a guidance to manage timeliness disputes, when the lead Center has not reviewed and acted on the manufacturer\rquote s product submission in an appropriate time frame.}{\cs16\cf1\super\insrsid6519106 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  Draft Guidance for Industry: Combination Products Timeliness of Premarket Reviews Dispute Resolution Guidance, }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/dispute.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000002f00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0064006900730070007500740065002e00680074006d006c000000e0c9ea79
f9bace118c8200aa004ba90b5e00000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0064006900730070007500740065002e00680074006d006c000000}}}{\fldrslt {
\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/dispute.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{\cs17\cf1\insrsid6519106   }{\cs17\cf1\insrsid8092121 
The guidance would help to define when the dispute should be presented to the }{\cs17\cf1\insrsid11935544 OCP for resolution.  On another oversight front}{\cs17\cf1\insrsid8092121 ,}{\cs17\cf1\insrsid15362361  the OCP issued a proposed rule}{
\cs17\cf1\insrsid14223819  on May 7}{\cs17\cf1\insrsid8092121 , 2004}{\cs17\cf1\insrsid15362361  to codify the definition of \'93primary mode of action\'94}{\cs16\cf1\super\insrsid15362361 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See supra}{\insrsid16284404  n.}{\insrsid16284404\charrsid7211990 108.}}}{\cs17\cf1\insrsid11739648  and to expedite the process of assigning product regulation to one Center by giving a manufacturer }{
\cs17\cf1\insrsid869937 an \'93assignment algorithm\'94}{\cs17\cf1\insrsid11739648  to use when }{\cs17\cf1\insrsid869937 requesting}{\cs17\cf1\insrsid11739648  }{\cs17\cf1\insrsid869937 a product classification pursuant to }{\cs17\cf1\insrsid11739648 
the newly defined primary mode of action.}{\cs16\cf1\super\insrsid11739648 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  FDA Proposes Rule on Combination Products, }{\i\insrsid16284404\charrsid7211990 at}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {
\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01288.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
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380038002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006200620073002f0074006f0070006900630073002f0041004e00530057004500520053002f0032003000300034002f0041004e0053
00300031003200380038002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01288.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004); }{
\i\insrsid16284404\charrsid7211990 see}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld001.html" }{\insrsid16284404\charrsid7211990 
{\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003900000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073006c0064003000
300031002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300031002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld001.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).  }{
\i\insrsid16284404\charrsid7211990 See also}{\insrsid16284404\charrsid7211990  69 Fed. Reg. 25527 (May 7, 2004).}}}{\cs17\cf1\insrsid2753259   Providing a definition for \'93primary mode of}{\cs17\cf1\insrsid8680542  action,\'94 the OCP believes, would}{
\cs17\cf1\insrsid2753259  clarify the }{\cs17\cf1\insrsid869937 regulatory process}{\cs17\cf1\insrsid2753259 .}{\cs17\cf1\insrsid8680542   In addition, while the new definition would further the OCP\rquote 
s current practice of assigning jurisdiction based upon the primary mode of action, it would enhance that practice by providing a regulatory route when the primary mode of action can not be clearly determined.}{\cs16\cf1\super\insrsid16480149 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld007.html" }{\insrsid16284404\charrsid7211990 
{\*\datafield 
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300037002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300037002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld007.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{
\cs17\cf1\insrsid723722 
\par }{\cs17\cf1\insrsid6958277 \tab The OCP then allowed the}{\cs17\cf1\insrsid8198387  comment period }{\cs17\cf1\insrsid6958277 on its definition to }{\cs17\cf1\insrsid8198387 
extend through August 20, 2004, to permit product manufacturers and other interested parties to offer their alternative definitions or suggestions.}{\cs16\cf1\super\insrsid8198387 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  69 Fed. Reg. 35277 (June 24, 2004).}}}{\cs17\cf1\insrsid11812053   The primary mode of action would be \'93the single mo
de of action of a combination product that provides the most important therapeutic action of the combination product.\'94}{\cs16\cf1\super\insrsid11812053 \chftn {\footnote \pard\plain 
\s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld004.html" }{\insrsid16284404\charrsid7211990 
{\*\datafield 
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300034002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300034002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld004.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{
\cs17\cf1\insrsid13316267   If the most important therapeutic}{\cs16\cf1\super\insrsid10238464 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 
\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  The OCP would define \'93mode of action\'94 as \'93the means by which a product achieves a therapeutic effect.
\'94  The term \'93therapeutic\'94 would include \'93any effect of action of the combination product intended to diagnose, cure, mitigate, treat, or prevent disease, or affect the structure or any function of the body.\'94
  Combination products would be expected to have more than one mode of action.  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld002.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
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300032002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300032002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld002.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{
\cs17\cf1\insrsid13316267  action could not be determined, then the proposed assignment algorithm would be applied.  Any assignment of Center jurisdiction would seek first to maintain regulatory consistency.}{\cs16\cf1\super\insrsid13316267 \chftn 
{\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{
\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990  HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld005.html" }{\insrsid16284404\charrsid7211990 
{\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003900000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073006c0064003000
300035002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300035002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld005.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{
\cs17\cf1\insrsid11935164   In other words, a new combination product should be assigned to the Center that has experience in managing other products that raise the same questions of safety and effectiveness.}{\cs17\cf1\insrsid131883 
  If institutional consistency could not be preserved, perhaps because there are no similar older products, then the algorithm would dictate that the Center with the most related experience to the safety and effectiveness issues of the new product w
ould receive jurisdiction.}{\cs16\cf1\super\insrsid14047844 \chftn {\footnote \pard\plain \s15\ql \li0\ri0\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\cs16\super\insrsid16284404\charrsid7211990 \chftn }{\insrsid16284404\charrsid7211990  }{\i\insrsid16284404\charrsid7211990 See}{\insrsid16284404\charrsid7211990  }{\field\flddirty{\*\fldinst {\insrsid16284404\charrsid7211990 
 HYPERLINK "http://www.fda.gov/oc/combination/pmoaslides/sld006.html" }{\insrsid16284404\charrsid7211990 {\*\datafield 
00d0c9ea79f9bace118c8200aa004ba90b02000000170000003900000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073006c0064003000
300036002e00680074006d006c000000e0c9ea79f9bace118c8200aa004ba90b7200000068007400740070003a002f002f007700770077002e006600640061002e0067006f0076002f006f0063002f0063006f006d00620069006e006100740069006f006e002f0070006d006f00610073006c0069006400650073002f0073
006c0064003000300036002e00680074006d006c000000}}}{\fldrslt {\cs19\ul\insrsid16284404\charrsid7211990 http://www.fda.gov/oc/combination/pmoaslides/sld006.html}}}{\insrsid16284404\charrsid7211990  (last visited September 6, 2004).}}}{
\cs17\cf1\insrsid13832859   Such a definition and its accompanying}{\cs17\cf1\insrsid14763260  algorithm, if adopted by the OCP at all, would be effective after the date of any final rule based upon this proposal.}{\cs17\cf1\insrsid6298640 
  At this time, the OCP\rquote s final decision as to this definition and algorithm is pending, but the result will inevitably encompass the }{\cs17\cf1\insrsid14628145 input}{\cs17\cf1\insrsid6298640  of both private and public sector entities.}{
\cs17\cf1\insrsid8198387\charrsid723722 
\par }\pard \qc \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\i\ul\insrsid4475040 V}{\i\ul\insrsid8203118 I}{\i\ul\insrsid8592177 I}{\i\ul\insrsid4475040 . Conclusion}{\insrsid4475040\charrsid4475040 

\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\insrsid2629406 \tab }{\cs17\cf1\insrsid10487113 The }{\cs17\cf1\insrsid10948351 first }{\cs17\cf1\insrsid10487113 annual report}{
\cs17\cf1\insrsid13067495  to Congress, now nine}{\cs17\cf1\insrsid10487113  months old, in reality captured just the first seven months of the OCP\rquote s existe
nce.  Yet, it represented the culmination of decades of work on the part of the FDA to regulate the forefront of medical technology.  Such a broad delegation of authority as the OCP received from the MDUF}{\cs17\cf1\insrsid11669791 
MA, to restore the cooperation}{\cs17\cf1\insrsid10487113  between Centers confr
onted by divergent considerations while charting new administrative territory over combination products that defy traditional classifications, could have overwhelmed the infant Office before it could effect }{\cs17\cf1\insrsid11669791 even }{
\cs17\cf1\insrsid10487113 one significant change.  But the OCP drew on its greatest strength to bear that authority: the expertise and the cooperation of the staff already employed }{\cs17\cf1\insrsid11669791 by its sister Centers.  Perhaps}{
\cs17\cf1\insrsid10487113  in one regard}{\cs17\cf1\insrsid11669791 ,}{\cs17\cf1\insrsid10487113  then, the OCP was given a simpler task than it first appeared.  The dedication to regulatory integ
rity and procedural fairness was already present in the reviewers and the jurisdiction officers.  The OCP had just to bring these people together and to initiate a dialogue }{\cs17\cf1\insrsid11669791 among}{\cs17\cf1\insrsid10487113 
 them, whether through inter-Center review teams, or internal electronic databases, or employee training sessions.  }{\cs17\cf1\insrsid7432072 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\cs17\cf1\insrsid7432072 \tab }{\cs17\cf1\insrsid10487113 
To examine this relationship one step further, however, is to discover that such a reunion}{\cs17\cf1\insrsid7432072  of experience is not simple.  Decades of ad hoc decision making by the Centers, although tempered by the Intercenter Agreemen
ts of 1991, had created three unique pathways of approval that caused confusion }{\cs17\cf1\insrsid11669791 among}{\cs17\cf1\insrsid7432072  the Centers and consumed the temporal and financial resources of product manufacturers.  T}{
\cs17\cf1\insrsid10487113 he OCP had to interface different regulatory methods for markedly different prod
ucts from the point of application to the point of product approval.  Electronic resources had to be created.  Consultation and collaboration had to be initiated and nurtured consistently.}{\cs17\cf1\insrsid7432072 
  What the annual report provided was proof that such a reunion }{\cs17\cf1\insrsid7432072\charrsid7432072 could}{\cs17\cf1\insrsid11669791  occur, and in fact}{\cs17\cf1\insrsid7432072  it }{\cs17\i\cf1\insrsid7432072 had}{\cs17\cf1\insrsid7432072 
 occurred.}{\cs17\cf1\insrsid2629406 
\par }\pard \ql \li0\ri0\sl480\slmult1\widctlpar\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid5989923 {\cs17\cf1\insrsid7432072 \tab 
Several observations about the future of the OCP could be made with relative certainty.  The OCP will probably continue its web-enabled march to facilitate communication }{\cs17\cf1\insrsid15424956 among}{\cs17\cf1\insrsid7432072  the Centers, as}{
\cs17\cf1\insrsid5794107  the wireless I}{\cs17\cf1\insrsid7432072 nternet and other electronic advances make paper and telephones obsolete.  N}{\cs17\cf1\insrsid12470042 ew}{\cs17\cf1\insrsid7432072  products will challenge }{\cs17\cf1\insrsid12470042 
the strength of }{\cs17\cf1\insrsid7432072 that intercommunication routinely, as the forefront of science (especially with respect to drug-device combinations) }{\cs17\cf1\insrsid15424956 pushes into unexplored and unimagined}{\cs17\cf1\insrsid12470042 
 territory.}{\cs17\cf1\insrsid5794107   A new generation of FDA staff will be raised on such intercommunication without sacrificing its sense of responsibility toward the health of the American public.}{\cs17\cf1\insrsid7962109   }{
\cs17\cf1\insrsid9573589 Although the MDUFMA provides sunset provisions for the OCP, beginning in 2007, it is }{\cs17\cf1\insrsid11492164 acknowledged}{\cs17\cf1\insrsid9573589 
 currently that the OCP will become so integral to the efficient and effective operation of the }{\cs17\cf1\insrsid7962109 Centers }{\cs17\cf1\insrsid9573589 that its dissolution will not}{\cs17\cf1\insrsid11492164 , and in truth could not,}{
\cs17\cf1\insrsid9573589  occur}{\cs17\cf1\insrsid7962109 .}{\cs17\cf1\insrsid4984821   }{\cs17\cf1\insrsid11492164 Thus}{\cs17\cf1\insrsid4984821 , Congress should be content with the knowledge that, while the OCP would have been}{
\cs17\cf1\insrsid11492164  an }{\cs17\cf1\insrsid4984821 appropriate}{\cs17\cf1\insrsid11492164  addition to the FDA}{\cs17\cf1\insrsid4984821  even in 1990, its creation in 2002 came not a moment too soon.}{\insrsid7432072\charrsid7432072 
\par }}