Center for Drug Evaluation and Research

Office of Generic Drugs
Monthly Quantitative Report and Statistical Charts July 2005

M E M O R A N D U M

DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF GENERIC DRUGS

DATE: FROM:

August 11, 2005 LCDR Martin Shimer Branch Chief Division of Labeling and Program Support Peter Rickman Director Division of Labeling and Program Support Statistical Report – Month of July 2005 See Below

THROUGH:

SUBJECT: TO:

This memorandum represents the Office of Generic Drugs' statistical report for July 2005. Tables I through III detail quantitative information about OGD's receipts, actions, and pending review status for both original and supplemental (CMC and labeling) applications for the past month and for the 11 preceding months. Following the tables, graphic presentations of selective quantitative data are provided. In addition three new strength supplements were approved. These graphs allow comparisons to similar data dating back to 1998. Approvals for the month of July include 29 new generic full approvals and 14 tentative approvals. Of the 43 approvals, 15 applications were approved as first generics. Separate lists of the approvals for the month of July follow the graphic presentations.

cc:

Center for Drug Evaluation and Research - Office of Generic Drugs Quantitative Report ORIGINAL APPLICATIONS
Aug-04 Sep-04 Oct-04 Nov-04 Dec-04 Jan-05 Feb-05 Mar-05 Apr-05 May-05 Jun-05 Jul-05 TOTAL AVG LAST 12 MOS

Table I

AVG LAST 3 MOS

AVG PRIOR YEAR

-- RECEIPTS -TOTAL ORIGINALS AMENDMENTS - MAJOR - MINOR 47 285 121 164 45 259 117 142 70 282 140 142 73 264 119 145 113 273 117 156 55 231 109 122 66 222 123 99 85 299 149 150 41 308 148 160 39 292 163 129 55 296 145 151 73 312 143 169 762 3323 1594 1729 64 277 133 144 56 300 150 150 44 234 115 119

-- ACTIONS -APPROVALS TENTATIVE APPROVALS+ APPROVABLE+ NOT APPROVABLE REFUSE TO RECEIVE WITHDRAWALS - OF APPROVED - OF UNAPPROVED -- REVIEW STATUS -AWAITING OGD ACTION (TOTAL)*** AWAITING OGD ACTION (> 180 DAYS)*** AWAITING OGD ACTION (< 180 DAYS)*** 22 6 0 68 6 3 0 3 31 10 0 78 5 6 0 6 45 9 0 55 5 12 2 10 28 5 0 87 8 23 17 6 42 11 0 64 10 6 3 3 20 6 0 79 60 5 3 2 9 7 0 86 10 5 2 3 24 11 0 102 12 7 3 4 41 2 0 63 16 7 1 6 30 6 0 106 7 3 0 3 27 12 0 110 9 35 25 10 29 14 0 65 8 2 2 0 348 99 0 963 156 114 58 56 29 8 0 80 13 10 5 5 29 11 0 94 8 13 9 4 28 8 0 77 6 9 7 3

607 64 543

615 71 544

646 82 564

665 85 580

733 95 638

748 95 653

767 99 668

810 104 706

817 117 700

802 144 658

794 158 636

842 140 702

737 105 633

813 147 665

580 62 518

*** In September, 1991, the Office of Generic Drugs started implementation of its Application Integrity Policy by suspending review of applications suspected of being tainted by fraud. Review status figures reported since this date exclude suspended applications. As of July 31, 2005, 2 original application and 0 supplements were suspended. Upon completion of validity assessments, suspended applications may be returned to active pending status. + Note: Approvable and Tentative approvals are counted as approvals subsequently when approved.

Center for Drug Evaluation and Research - Office of Generic Drugs Quantitative Report POST APPROVAL SUBMISSIONS TO APPLICATIONS (CHEMISTRY)
Aug-04 --RECEIPTS-ORIGINAL SUPPLEMENTS AMENDMENTS TO SUPPLEMENTS 487 660 231 244 279 321 341 430 240 280 240 337 256 336 468 528 226 292 257 272 213 232 201 254 3439 4186 287 349 Sep-04 Oct-04 Nov-04 Dec-04 Jan-05 Feb-05 Mar-05 Apr-05 May-05 Jun-05 Jul-05 TOTAL AVG LAST 12 MOS

Table II

AVG LAST 3 MOS

AVG PRIOR YEAR

224 253

281 329

--SUPPLEMENTAL ACTIONS-APPROVALS APPROVABLE NOT APPROVABLE WITHDRAWALS 338 0 76 10 530 0 63 12 194 0 91 10 217 0 110 10 258 0 68 5 238 0 77 13 340 0 65 7 363 0 64 17 184 0 26 0 263 0 49 12 157 0 29 7 170 0 39 3 3252 0 757 106 271 0 63 9 197 0 39 7 232 0 84 11

--REVIEW STATUS-SUPPLEMENTS AWAITING OGD ACTION (TOTAL) SUPPLEMENTS AWAITING OGD ACTION (>180 DAYS) SUPPLEMENTS AWAITING OGD ACTION (<=180 DAYS)

1781

1444

1497

1586

1530

1548

1465

1567

1644

1490

1809

1809

1598

1703

1469

118 1663

109 1335

163 1334

165 1418

157 1373

186 1362

201 1264

173 1394

197 1447

222 1268

219 1590

348 1456

188 1409

263 1438

80 1389

Center for Drug Evaluation and Research - Office of Generic Drugs Quantitative Report POST APPROVAL SUBMISSIONS TO APPLICATIONS (LABELING)
Aug-04 --RECEIPTS-ORIGINAL SUPPLEMENTS AMENDMENTS TO SUPPLEMENTS 50 80 77 81 51 72 40 47 48 53 43 68 74 87 123 146 97 112 68 90 39 56 67 92 777 984 65 82 Sep-04 Oct-04 Nov-04 Dec-04 Jan-05 Feb-05 Mar-05 Apr-05 May-05 Jun-05 Jul-05 TOTAL AVG LAST 12 MOS

Table III

AVG LAST 3 MOS

AVG PRIOR YEAR

58 79

58 70

--SUPPLEMENTAL ACTIONSAPPROVALS APPROVABLE NOT APPROVABLE WITHDRAWALS 40 1 4 0 55 0 4 1 77 0 6 2 32 0 40 0 43 6 7 1 41 0 5 4 21 0 2 0 44 8 9 0 110 8 8 6 85 7 5 6 93 5 4 5 92 6 6 0 733 41 100 25 61 3 8 2 90 6 5 4 49 3 9 3

--REVIEW STATUS-SUPPLEMENTS AWAITING OGD ACTION (TOTAL) SUPPLEMENTS AWAITING OGD ACTION (>180 DAYS) SUPPLEMENTS AWAITING OGD ACTION (<=180 DAYS)

389

415

384

389

389

393

473

524

477

451

408

338

419

399

364

133 256

138 277

128 256

134 255

164 225

169 224

186 287

187 337

135 342

121 330

110 298

95 243

142 278

109 290

118 246

Office of Generic Drugs ANDA Full Approvals For Month of July 2005
1 . 40-594 MERCAPTOPURINE TABLETS USP, 50 MG MYLAN PHARMACEUTICALS, INC. AP'd on: 7/1/2005 DESMOPRESSIN ACETATE TABLETS, 0.1 MG AND 0.2 MG BARR LABORATORIES, INC. AP'd on: 7/1/2005 ISONIAZID INJECTION USP, 100 MG/ML; 10 ML VIALS SABEX 2002 INC. AP'd on: 7/5/2005 DIPHENHYDRAMINE HYDROCHLORIDE INJECTION USP, 50 MG/ML; 10 ML VIALS BIONICHE PHARMA AP'd on: 7/12/2005 METHIMAZOLE TABLETS USP, 15 MG CEDAR PHARMACEUTICALS LLC AP'd on: 7/12/2005 ALCLOMETASONE DIPROPIONATE CREAM USP, 0.05% ALTANA INC. AP'd on: 7/12/2005 METHADONE HYDROCHLORIDE TABLETS USP, 40 MG MALLINCKRODT INC. AP'd on: 7/12/2005 AMOXICILLIN TABLETS USP, 500 MG AND 875 MG SANDOZ INC. AP'd on: 7/13/2005 FEXOFENADINE HYDROCHLORIDE CAPSULES, 60 MG BARR LABORATORIES, INC. AP'd on: 7/13/2005 HYDROCHLOROTHIAZIDE CAPSULES, 12.5 MG IVAX PHARMACEUTICALS, INC. AP'd on: 7/13/2005 Full Approvals Page 1

2 . 76-470

3 . 40-648

4 . 40-498

5 . 40-619

6 . 76-973

7 . 77-142

8 . 65-228

9 . 76-169

10 . 77-005

11 . 77-074

LORAZEPAM INJECTION USP (PRESERVATIVE-FREE), 2 MG/ML AND 4 MG/ML; 1 ML VIALS BEDFORD LABORATORIES AP'd on: 7/13/2005 LORAZEPAM INJECTION USP, 2 MG/ML AND 4 MG/ML; 10 ML VIALS BEDFORD LABORATORIES AP'd on: 7/13/2005 BUPROPION HYDROCHLORIDE EXTENDED-RELEASE TABLETS USP, 150 MG SANDOZ INC. AP'd on: 7/14/2005 BUPROPION HYDROCHLORIDE EXTENDED-RELEASE TABLETS USP, 100 MG AND 150 MG SANDOZ INC. AP'd on: 7/14/2005 FOLIC ACID TABLETS USP, 1 MG MUTUAL PHARMACEUTICAL COMPANY, INC. AP'd on: 7/18/2005 ALCLOMETASONE DIPROPIONATE OINTMENT USP, 0.05% ALTANA INC. AP'd on: 7/18/2005 IBUPROFEN TABLETS USP, 400 MG, 600 MG, AND 800 MG PERRIGO R&D COMPANY AP'd on: 7/18/2005 IPRATROPIUM BROMIDE INHALATION SOLUTION, 0.02% RxELITE AP'd on: 7/19/2005 MILRINONE LACTATE IN 5% DEXTROSE INJECTION, 20 MG (BASE)/100 ML; 100 ML AND 200 ML PLASTIC CONTAINERS APOTEX CORP. AP'd on: 7/20/2005 FOLIC ACID TABLETS USP, 1 MG PHARMAX GROUP, INC. AP'd on: 7/21/2005

12 . 77-076

13 . 76-834

14 . 76-845

15 . 40-582

16 . 76-884

17 . 77-114

18 . 77-072

19 . 77-151

20 . 40-625

Full Approvals

Page 2

21 . 76-705

RANITIDINE TABLETS USP, 150 MG AND 300 MG DR. REDDY'S LABORATORIES LIMITED AP'd on: 7/27/2005 FAMOTIDINE TABLETS USP, 20 MG AND 40 MG PERRIGO R&D COMPANY AP'd on: 7/27/2005 BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE TABLETS USP, 50 MG/325 MG/40 MG MUTUAL PHARMACEUTICAL COMPANY, INC. AP'd on: 7/29/2005 CEFUROXIME AXETIL TABLETS USP, 125 MG (BASE), 250 MG (BASE), AND 500 MG (BASE) WOCKHARDT LIMITED AP'd on: 7/29/2005 RIFAMPIN AND ISONIAZID CAPSULES USP, 300 MG/150 MG WEST-WARD PHARMACEUTICAL CORP. AP'd on: 7/29/2005 DESOGESTREL AND ETHINYL ESTRADIOL TABLETS, 0.15 MG/0.03 MG (28-DAY) WATSON LABORATORIES, INC. AP'd on: 7/29/2005 VALPROIC ACID SYRUP USP, 250 MG/5 ML APOTEX INC. AP'd on: 7/29/2005 BACLOFEN TABLETS USP, 20 MG ALPHAPHARM PTY. LTD. AP'd on: 7/29/2005 BACLOFEN TABLETS USP, 10 MG ALPHAPHARM PTY. LTD. AP'd on: 7/29/2005

22 . 77-352

23 . 40-601

24 . 65-166

25 . 65-221

26 . 76-915

27 . 77-105

28 . 77-121

29 . 77-181

Full Approvals

Page 3

Office of Generic Drugs ANDA Tentative Approvals For Month of July 2005
1 . 77-672 STAVUDINE CAPSULES USP, 30 MG AND 40 MG AUROBINDO PHARMA LIMITED TA'd 7/1/2005 LAMIVUDINE AND ZIDOVUDINE TABLETS, 150 MG/300 MG AUROBINDO PHARMA LTD. TA'd 7/6/2005 MODAFINIL TABLETS, 100 MG AND 200 MG CARLSBAD TECHNOLOGY, INC. TA'd 7/13/2005 ZIDOVUDINE TABLETS USP, 300 MG RANBAXY LABORATORIES LIMITED TA'd 7/13/2005 TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN TABLETS, 37.5 MG/325 MG TEVA PHARMACEUTICALS USA TA'd 7/18/2005 FEXOFENADINE HYDROCHLORIDE TABLETS, 30 MG, 60 MG, AND 180 MG TEVA PHARMACEUTICALS, USA TA'd 7/19/2005 GLIMEPIRIDE TABLETS, 1 MG, 2 MG, 4 MG, AND 8 MG RANBAXY LABORATORIES LIMITED TA'd 7/20/2005 SERTRALINE HYDROCHLORIDE TABLETS, 25 MG (BASE), 50 MG (BASE), AND 100 MG (BASE) ANDRX PHARMACEUTICALS, LLC TA'd 7/21/2005 ZIDOVUDINE TABLETS USP, 300 MG ROXANE LABORATORIES, INC. TA'd 7/27/2005 GLIMEPIRIDE TABLETS, 3 MG AND 6 MG RANBAXY LABORATORIES LIMITED TA'd 7/27/2005 ONDANSETRON ORAL SOLUTION USP, 4 MG/5 ML TARO PHARMACEUTICAL INDUSTRIES, LTD. TA'd 7/28/2005

2 . 77-558

3 . 76-715

4 . 77-327

5 . 76-914

6 . 76-447

7 . 76-875

8 . 76-944

9 . 76-844

10 . 77-366

11 . 77-009

Tentative Approvals

Page 1

12 . 76-554

SUMATRIPTAN SUCCINATE TABLETS, 25 MG (BASE) AND 50 MG (BASE) RANBAXY LABORATORIES LIMITED TA'd 7/29/2005 SUMATRIPTAN SUCCINATE TABLETS, 100 MG (BASE) RANBAXY LABORATORIES LIMITED TA'd 7/29/2005 SUMATRIPTAN SUCCINATE TABLETS, 25 MG (BASE), 50 MG (BASE), AND 100 MG (BASE) COBALT PHARMACEUTICALS, INC. TA'd 7/29/2005

13 . 76-572

14 . 76-933

Tentative Approvals

Page 2

Office of Generic Drugs - First Generic Approvals
77-672 STAVUDINE CAPSULES USP, 30 MG AND 40 MG AUROBINDO PHARMA LIMITED Submitted: 4/6/2005 Innovator BRISTOL MYERS SQUIBB CO. PHARMACEUTICAL RESEARCH INSTITUTE RLD: ZERIT CAPSULES TENTATIVELY APPROVED: 7/1/2005 LAMIVUDINE AND ZIDOVUDINE TABLETS, 150 MG/300 MG AUROBINDO PHARMA LTD. Submitted: 2/4/2005 Innovator GLAXOSMITHKLINE RLD: COMIVIR TABLETS TENTATIVELY APPROVED: 7/6/2005 ZIDOVUDINE TABLETS USP, 300 MG RANBAXY LABORATORIES LIMITED Submitted: 10/22/2004 Innovator GLAXOSMITHKLINE RLD: RETROVIR TABLETS TENTATIVELY APPROVED: 7/13/2005 FEXOFENADINE HYDROCHLORIDE TABLETS, 30 MG, 60 MG, AND 180 MG TEVA PHARMACEUTICALS, USA Submitted: 7/1/2002 Innovator AVENTIS PHARMACEUTICALS, INC. RLD: ALLEGRA TABLETS TENTATIVELY APPROVED: 7/19/2005 SUMATRIPTAN SUCCINATE TABLETS, 25 MG (BASE) AND 50 MG (BASE) RANBAXY LABORATORIES LIMITED Submitted: 12/4/2002 Innovator GLAXOSMITHKLINE RLD: IMITREX TABLETS TENTATIVELY APPROVED: 7/29/2005 SUMATRIPTAN SUCCINATE TABLETS, 100 MG (BASE) RANBAXY LABORATORIES LIMITED Submitted: 12/17/2002 Innovator GLAXOSMITHKLINE RLD: IMITREX TABLETS TENTATIVELY APPROVED: 7/29/2005

* * * * * * *

77-558

* * * * * * *

77-327

* * * * * * *

76-447

* * * * * * *

76-554

* * * * * * *

76-572

* * * * * * *

First Generic Approvals

76-470

DESMOPRESSIN ACETATE TABLETS, 0.1 MG AND 0.2 MG BARR LABORATORIES, INC. Submitted: 8/1/2002 Innovator AVENTIS PHARMACEUTICAL PRODUCTS, INC. RLD: DDAVP TABLETS APPROVED: 7/1/2005 ISONIAZID INJECTION USP, 100 MG/ML; 10 ML VIALS SABEX 2002 INC. Submitted: 2/2/2005 Innovator SANDOZ INC. RLD: NYDRAZID INJECTION APPROVED: 7/5/2005 METHIMAZOLE TABLETS USP, 15 MG CEDAR PHARMACEUTICALS LLC Submitted: 8/24/2004 Innovator GENPHARM INC. RLD: METHIMAZOLE TABLETS, USP APPROVED: 7/12/2005 ALCLOMETASONE DIPROPIONATE CREAM USP, 0.05% ALTANA INC. Submitted: 12/22/2003 Innovator GLAXOSMITHKLINE RLD: ACLOVATE CREAM APPROVED: 7/12/2005 FEXOFENADINE HYDROCHLORIDE CAPSULES, 60 MG BARR LABORATORIES, INC. Submitted: 5/11/2001 Innovator AVENTIS PHARMACEUTICALS, INC. RLD: ALLEGRA CAPSULES APPROVED: 7/13/2005 SDOXYCYCLINE TABLETS, 150 MG PAR PHARMACEUTICAL, INC. Submitted: 12/17/2004 Innovator OCLASSEN PHARMACEUTICALS, INC. RLD: MONODOX CAPSULES APPROVED: 7/14/2005 DOXYCYCLINE CAPSULES USP, 150 MG PAR PHARMACEUTICAL, INC. Submitted: 12/17/2004 Innovator RLD: APPROVED: 7/15/2005

* * * * * * *

40-648

* * * * * * *

40-619

* * * * * * *

76-973

* * * * * * *

76-169

* * * * * * *

65-070

* * * * * * *

65-055

S-

* * * * * * *

First Generic Approvals

40-512

S-

PYRIDOSTIGMINE BROMIDE TABLETS USP, 30 MG BARR LABORATORIES, INC. Submitted: 12/19/2003 Innovator SOLVAY PHARMACEUTICALS RLD: PYRIDOSTIGMINE BROMIDE TABLETS USP, 30 MG APPROVED: 7/20/2005 RIFAMPIN AND ISONIAZID CAPSULES USP, 300 MG/150 MG WEST-WARD PHARMACEUTICAL CORP. Submitted: 4/5/2004 Innovator AVENTIS PHARMACEUTICALS, INC. RLD: RIFAMATE CAPSULES APPROVED: 7/29/2005

* * * * * * *

65-221

* * * * * * *

First Generic Approvals

Office Of Generic Drugs Supplement Approvals
Page 1 Wednesday, August 10, 2005 DOXYCYCLINE TABLETS, 150 MG DOXYCYCLINE CAPSULES USP, 150 MG PYRIDOSTIGMINE BROMIDE TABLETS USP, 30 MG PAR PHARMACEUTICAL, INC. PAR PHARMACEUTICAL, INC. BARR LABORATORIES, INC. 7/14/2005 1 . 65-070 S-009 2 . 65-055 S-006 3 . 40-512 S-002

7/15/2005

7/20/2005

Original ANDAs Received
110 100 90 80 70 60

Number of Submissions

50 40 30 20 10
O D F A J A O D F 99 99 00 00 00 00 00 00 01 A J A O D F A J A O D F A J A O D 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 F A J A O D F A J 04 04 04 04 04 04 05 05 05

by Month/Year

July 2005

Actions on Original ANDAs
160
Approvals Approvables Tentative Approvals Not Approvable FAX Amendments

140

120

100

80

60

40

20

0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05
Note: Tentative Approvals (TA) are applications that have been approved by the office pending patent expiration. TAs and Approvables(AE) are counted as approvals subsequently when approved.

July 2005

Original ANDAs Approved or Tentatively Approved
70 Approvables Tentative Approvals 60 Approvals

50

40

30

20

10

0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05
Note: Tentative Approvals (TA) are applications that have been approved by the office pending patent expiration. TAs and Approvables (AE) are counted as approvals subsequently when approved.

Original ANDAs Pending Per Month
900 850 800 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05

> 180 days

< 180 days

Chemistry, Manufacturing & Controls Supplements Awaiting OGD Action
2000 > 180 Days 1750 < 180 Days

1500

1250

1000

750

500

250

0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05
Please note that abrupt changes in the level of pending supplements are the result of global submissions to all applications held by a single firm. Changes other than these will be explained separately.

Labeling Supplements Awaiting OGD Action
600 < 180 Days 550 500 450 400 350 300 250 200 150 100 50 0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05

> 180 Days

ANDA Originals Percent Approved and Not-Approvable By Month
100% 90% Not Approvable 80% 70% 60% 50% 40% 30% 20% 10% 0%
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05

Approved

Median ANDA Review Cycle (Months)
Original Applications & Major Amendments
10

9

8

7

6

5

4

3

2
Oct 99 Jan 00 Apr 00 Jul 00 Oct 00 Jan 01 Apr 01 Jul 01 Oct 01 Jan 02 Apr 02 Jul 02 Oct 02 Jan 03 Apr 03 Jul 03 Oct 03 Jan 04 Apr 04 Jul 04 Oct 04 Jan 05 Apr 05 Jul 05

1 - Times correspond to actual applications received. The new ANDA/AADA submission policy that went into effect 1/1/91 allows certain variations in a drug product to be included in a single application. 2 - In September 1991, the OGD started implementation of the Application Integrity Policy by suspending review of applications suspected of being tainted by fraud. AIP time has therefore, been subtracted from review time after 9/91. However, before the AIP went into effect, the review of many applications suspected of containing fraudulent data were suspended. These suspensions were not recorded in the MIS and are reflected in the above chart.

Mean and Median ANDA Review Cycle (Months)
Original Applications & Major Amendments
10

Median
9

Mean

8

7

6

5

4

3

2
Oct 99 Jan 00 Apr 00 Jul 00 Oct 00 Jan 01 Apr 01 Jul 01 Oct 01 Jan 02 Apr 02 Jul 02 Oct 02 Jan 03 Apr 03 Jul 03 Oct 03 Jan 04 Apr 04 Jul 04 Oct 04 Jan 05 Apr 05 Jul 05

1 - Times correspond to actual applications received. The new ANDA/AADA submission policy that went into effect 1/1/91 allows certain variations in a drug product to be included in a single application. 2 - In September 1991, the OGD started implementation of the Application Integrity Policy by suspending review of applications suspected of being tainted by fraud. AIP time has therefore, been subtracted from review time after 9/91. However, before the AIP went into effect, the review of many applications suspected of containing fraudulent data were suspended. These suspensions were not recorded in the MIS and are reflected in the above chart.

Months 10 9 8 7

Median ANDA CMC Supplement Review Time

Original/Major Amendments

6 5 4 3
Expedited/Minor Amendments

2 1 0
Oct 99 Jan 00 Apr 00 Jul 00 Oct 00 Jan 01 Apr 01 Jul 01 Oct 01 Jan 02 Apr 02 Jul 02 Oct 02 Jan 03 Apr 03 Jul 03 Oct 03 Jan 04 Apr 04 Jul 04 Oct 04 Jan 05 Apr 05 Jul 05

1 - Times correspond to actual applications received. The new ANDA/AADA submission policy that went into effect 1/1/91 allows certain variations in a drug product to be included in a single application. 2 - In September 1991, the OGD started implementation of the Application Integrity Policy by suspending review of applications suspected of being tainted by fraud. AIP time has therefore, been subtracted from review time after 9/91. However, before the AIP went into effect, the review of many applications suspected of containing fraudulent data were suspended. These suspensions were not recorded in the MIS and are reflected in the above chart. 3 - Global Supplements are Collapsed

Mean 35

Percent of Original Submissions with Refuse to Receive Action

30

25

20

15

10

5

0
Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr Jul Oct Jan Apr 99 00 00 00 00 01 01 01 01 02 02 02 02 03 03 03 03 04 04 04 04 05 05
Status as of June 30, 2005. Percentages for recent months may increase due to future R/R actions

Original ANDAs Pending > 180 Days
150

125

100

75

50

25

0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05

ANDAs CMC Supplements Pending > 180 Days
300

250

200

150

100

50

0
O D F A J A O D F A J A O D F A J A O D F A J A O D F A J A O D F A J 99 99 00 00 00 00 00 00 01 01 01 01 01 01 02 02 02 02 02 02 03 03 03 03 03 03 04 04 04 04 04 04 05 05 05

Please note that abrupt changes in the level of pending supplements are the result of global submissions to all applications held by a single firm. Changes other than these will be explained separately.