Department of Health and Human Services
 

OFFICE OF 

INSPECTOR GENERAL 

THE FOOD AND DRUG 


ADMINISTRATION’S GENERIC 


DRUG REVIEW PROCESS
 

Daniel R. Levinson
 

Inspector General 


June 2008 


OEI-04-07-00280
 
 

 

 

 

 

 

Office of Inspector General 
 http://oig.hhs.gov 

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enforcement authorities. 
 

 

 

Δ EXECUTIVE SUMMARY 

OBJECTIVES 

1. To determine the percentage of new (i.e., original) generic drug 

applications approved, tentatively approved, or disapproved by the 

Food and Drug Administration (FDA) in 2006. 

2. To determine the extent to which FDA reviewed original generic 

drug applications within 180 days in 2006. 

3. To identify factors that affected review times for original and 

amended generic drug applications in 2006. 

BACKGROUND 

Pharmaceutical companies must submit Abbreviated New Drug 

Applications (ANDA) to FDA’s Office of Generic Drugs (OGD) and 

receive FDA’s approval before marketing new generic drugs. Three 

OGD divisions review all ANDAs: Chemistry, Bioequivalence, and 

Labeling. OGD’s Microbiology division also reviews some ANDAs. 

In addition, OGD may consult with other FDA offices during ANDA 

reviews. All OGD divisions involved in the ANDA review contribute to 

approval, but disapproval is primarily determined by Chemistry. 

According to FDA, almost all original ANDAs contain Chemistry 

deficiencies and are disapproved. 

OGD generally follows a first-in, first-reviewed policy for ANDAs. 

However, when Chemistry identifies no deficiencies in an ANDA 

(i.e., the ANDA is approvable by Chemistry), the other divisions assign 

high priority to the ANDA’s review. Pursuant to FDA policy, divisions 

should also assign high priority to ANDAs with minor deficiencies. 

In addition, some ANDA consults are assigned high priority. 

FDA’s timeliness in approving generic drugs has recently been a topic of 

scrutiny by both Congress and the media. Federal law requires that 

FDA approve, tentatively approve, or disapprove original ANDAs within 

180 days of receipt. 

We examined review times for 989 original ANDAs under review during 

2006. We also surveyed OGD division reviewers assigned to a sample of 

105 ANDAs with review times greater than 180 days in at least one 

division. Finally, we conducted structured interviews with OGD 

officials to determine factors affecting ANDA review times. 

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E X E CUTIVE S U MMAR Y 
 

FINDINGS 

The Food and Drug Administration approved or tentatively approved 

4 percent of original Abbreviated New Drug Applications under 

review in 2006; the remaining 96 percent did not meet review 

standards and were disapproved. FDA approved 1 percent and 

tentatively approved 3 percent of original ANDAs under review in 2006. 

FDA disapproved 96 percent of original ANDAs under review in 2006 

because they contained Chemistry deficiencies. 

The Food and Drug Administration exceeded the 180-day review 

requirement for nearly half of original Abbreviated New Drug 

Applications under review in 2006 because Chemistry reviews 

exceeded 180 days. In 2006, Chemistry did not review 46 percent of 

original ANDAs within 180 days as required by Federal law. For ANDAs 

taking more than 180 days for review, the median review time was 

217 days. Because almost all of these original ANDAs contained 

Chemistry deficiencies, Chemistry’s delay in reviewing these ANDAs 

resulted in FDA’s delay in disapproving them, regardless of the 

timeliness of the other divisions’ reviews. 

Microbiology, Bioequivalence, and Labeling reviews of original 

Abbreviated New Drug Applications generally exceeded 180 days in 

2006. In 2006, the percentages of ANDAs with review times exceeding 

180 days were 76 percent in Microbiology, 58 percent in Bioequivalence, 

and 56 percent in Labeling. For ANDAs taking more than 180 days to 

review, median review times were 361 days in Microbiology, 287 days in 

Bioequivalence, and 277 days in Labeling. 

Nearly 70 percent of sampled division reviews exceeding 180 days 

did not begin before the 180-day review periods expired. In a sample 

of 105 ANDAs with review times exceeding 180 days, reviews for 

69 percent did not begin within 180 days. Thus, the 180-day periods 

passed before division reviews began in most of the sample. 

The Food and Drug Administration’s prioritization practices affect 

Abbreviated New Drug Application review times. FDA prioritization 

practices contribute to longer review times for ANDAs that are close to 

approval. 

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E X E E X E CUTIVE S U MMAR Y 
 

RECOMMENDATIONS 

We found that FDA disapproved most original ANDAs under review in 

2006 because they did not meet FDA review standards. Nearly half of 

Chemistry review times exceeded the 180 days required by Federal law. 

Moreover, many review times in other OGD divisions exceeded 

180 days. In addition, for a sample of ANDA reviews exceeding 

180 days, most reviews did not begin before the 180-day period expired. 

Finally, we found that FDA prioritization practices affect ANDA review 

times. 

The ANDA submissions have increased at more than double the rate of 

review resources in the last 5 years. To better manage FDA’s current 

ANDA review resources and potentially improve ANDA review times, 

we recommend that FDA: 

Identify common original Abbreviated New Drug Application 

deficiencies and offer more guidance to industry to decrease the 

percentage disapproved. 

Increase the percentage of original Abbreviated New Drug Applications 

reviewed by all divisions within 180 days. 

Identify new prioritization practices to reduce review times for 

Abbreviated New Drug Applications close to approval. 

AGENCY COMMENTS 

In its comments to the draft report, FDA noted that it has already 

identified portions of the primary recommendations and is 

implementing process improvements that are the same as or similar to 

the recommendations. Specifically, FDA agreed with our first 

recommendation but did not indicate whether it concurred with the two 

additional recommendations. However, FDA has taken actions that 

address our recommendations by providing guidance to assist industry 

in submitting more easily reviewed applications, developing a focused 

hiring program to increase staff and decrease review times, and 

prioritizing some ANDAs based on potential market entry date. 

We ask that, in its final management decision, FDA more clearly 

indicate whether it concurs with each of our recommendations. 

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Δ TABLE OF CONTENTS 

EXECUTIVE SUMMARY ..................................... i 
 

INTRODUCTION ........................................... 1 
 

FINDINGS ................................................ 12 
 

FDA disapproved most original ANDAs..................... 12 
 

Chemistry reviews exceeded 180 days ...................... 13 
 

Review times in other divisions exceeded 180 days............ 15 
 

Sampled reviews did not start within 180 days............... 16 
 

ANDAs are not prioritized ............................... 17 
 

RECOMMENDATIONS ..................................... 21

 Agency Comments...................................... 23 
 

APPENDIXES ............................................. 25 
 

A: Additional Information on Methodology.................. 25 
 

B: 2006 Chemistry Review Time Ranges ................... 28 
 

C: 2006 Microbiology, Bioequivalence, and Labeling

Review Time Ranges................................. 29 
 

D: Frequency Distribution of Office of Generic Drugs 

Consults Pending as of June 2007 . . . . . . . . . . . . . . . . . . . . . . 30 

E: Agency Comments ................................... 31 
 

ACKNOWLEDGMENTS .................................... 36 
 
 

 

 

 

Δ INTRODUCTION 

OBJECTIVES 

1. To determine the percentage of new (i.e., original) generic drug 

applications approved, tentatively approved, or disapproved by the 

Food and Drug Administration (FDA) in 2006. 

2. To determine the extent to which FDA reviewed original generic 

drug applications within 180 days in 2006. 

3. To identify factors that affected review times for original and 

amended generic drug applications in 2006. 

BACKGROUND 

A generic drug is the same as a reference-listed (i.e., brand name) drug 

with respect to conditions of use, active ingredient(s), route of 

administration, dosage form, strength, and labeling.1 In addition, the 

generic drug must be bioequivalent to (i.e., perform in the same manner 

as) the brand name drug. 

A generic drug that is therapeutically equivalent is expected to have the 

same clinical effect and safety profile as the brand name drug when 

administered under the conditions specified in the labeling. If generic 

drugs are determined to be therapeutically equivalent, physicians and 

pharmacists can substitute them for brand name drugs. 

Generic drug applications are referred to as Abbreviated New Drug 

Applications (ANDA).2 Pharmaceutical companies must submit ANDAs 

and receive FDA’s approval before marketing new generic drugs.3 

1 21 U.S.C. § 355(j)(2) (§ 505(j)(2) of the Federal Food, Drug, and Cosmetic Act); 

21 CFR §§ 314.92 and 314.105(c). Some differences between generic and brand name drugs 

are permitted under 21 U.S.C. § 355(j)(2). See also “Abbreviated New Drug Application 

(ANDA) Process for Generic Drugs,” Center for Drug Evaluation and Research. Available 

online at http://www.fda.gov/cder/regulatory/applications/anda.htm. Accessed on 

November 29, 2007. 

2 The term “abbreviated” is used because FDA does not require generic drug 

manufacturers to submit the clinical studies necessary for brand name drug applications. 

Instead, the ANDA must demonstrate that the generic drug is the same as a brand name 

drug. 

3 21 CFR § 314.105(d). 

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INTRODUCTION 

FDA’s timeliness in approving generic drugs has recently been a topic of 

scrutiny by both Congress and the media.4 5 6 Federal law requires that 

FDA approve or disapprove ANDAs within 180 days of receipt.7 

Abbreviated New Drug Application Review Components 

Three divisions within FDA’s Center for Drug Evaluation and Research 

(CDER), Office of Generic Drugs (OGD), review all ANDAs: the 

Division of Bioequivalence (Bioequivalence), the Division of Chemistry 

(Chemistry), and the Division of Labeling and Program Support 

(Labeling).8 9 In addition, the Microbiology team (Microbiology) reviews 

some ANDAs.10 

Other offices within CDER also review ANDAs in certain instances. For 

example, safety evaluations of inactive ingredients, labeling and 

bioequivalence protocol reviews, and statistical reviews of 

bioequivalence studies require OGD to consult other offices within 

CDER. According to OGD officials, OGD typically sends requests for 

such reviews (i.e., consults) to the CDER’s Office of New Drugs because 

it has expertise in these areas. CDER policy provides timeframes for 

4 “The Generic Drug Maze: Speeding Access to Affordable, Life Saving Drugs.” Hearing 

of the United States Senate Special Committee on Aging. July 20, 2006. Available online 

at http://aging.senate.gov/hearing_detail.cfm?id=270735&. Accesssed on July 24, 2007. 

5 “Appropriations for the Food and Drug Administration.” Hearing of the United States 

House of Representatives Appropriations Committee, Agriculture, Rural Development, Food 

and Drug Administration and Related Agencies Subcommittee. February 16, 2006. 

6 Kaufman, Marc. “Generic Drugs Hit Backlog at FDA.” Washington Post. 

February 4, 2006, p. A01. Available online at http://www.washingtonpost.com/wpdyn/content/article/2006/02/03/AR2006020302598.html. Accesssed on July 25, 2007. 

7 21 U.S.C. § 355(j)(5)(A); 21 CFR § 314.101(f)(2). An approval becomes effective on the 

date of the issuance of the approval letter, except for certain approvals that have delayed 

effective dates. An approval with a delayed effective date is tentative and does not become 

final until the effective date. 21 CFR § 314.105(d). 

8 A CDER organizational chart is available online at 

http://www.fda.gov/cder/cderorg.htm. CDER provides general information on the ANDA 

review process online at http://www.fda.gov/cder/ogd/. CDER’s “Manuals of Policies and 

Procedures” (MaPP) provide official instructions to CDER staff on the drug review process. 

MaPP Chapter 5200 applies to OGD and is available online at 

http://www.fda.gov/cder/mapp.htm. Accesssed on January 3, 2008. 

9 In addition, the Office of Compliance evaluates the generic drug’s manufacturing, 

packaging, and testing facilities to determine whether they meet current Good 

Manufacturing Practices pursuant to 21 CFR § 211. 

10 Microbiology reviews drugs administered as injections, inhalations, or solutions to 

ensure their sterility. The Microbiology staff is officially housed within the Immediate 

Office of the OGD Director. When referring to OGD divisions throughout this report, 

Microbiology is included. 

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INTRODUCTION 

OGD to receive consult results from other CDER offices.11 Policy 

timeframes range from 15 to 90 days, based on the priority of the 

consult. A consult’s priority is based, in part, on how close the ANDA is 

to approval. 

Abbreviated New Drug Application Review Process 

OGD generally employs CDER’s first-in, first-reviewed policy for 

ANDAs.12 However, OGD grants expedited reviews of ANDAs in special 

circumstances.13 

When an applicant submits an original ANDA, OGD first conducts a 

review to determine whether the application is sufficiently complete to 

permit a substantive review.14 OGD refers to this period as the filing 

review. The filing review takes approximately 60 days from the ANDA’s 

receipt date to complete it. 

If OGD determines that an ANDA is sufficiently complete, it 

simultaneously assigns the ANDA to Bioequivalence, Chemistry, and 

Labeling, as well as Microbiology (if required).15 Each division begins 

its review when the ANDA reaches the top of the division’s waiting list 

(i.e., queue). Regardless of the outcome of one division’s review, the 

other divisions generally review the ANDA independently. 

According to OGD officials, each division follows CDER’s first-in, 

first-reviewed policy except when Chemistry determines that an ANDA 

contains no Chemistry deficiencies. In this case, divisions that have not 

finished reviewing the ANDA assign high priority to it and move it to 

the top of their queues. 

11 CDER MaPP 5200.6. “Issuing and Tracking of Consults.” Available online at 

http://www.fda.gov/Cder/mapp/5200-6.pdf. Accesssed on January 11, 2007. 

12 CDER MaPP 5240.3. “Review Order of Original ANDAs, Amendments, and 

Supplements.” Available online at http://www.fda.gov/Cder/mapp/5240-3R.pdf. Accesssed 

on December 5, 2007. 

13 Ibid. Expedited reviews are granted for products that respond to current and 

anticipated public health emergencies; are under special review programs, such as the 

President’s Emergency Plan for AIDS Relief (PEPFAR); have been identified as nationwide 

shortages; and are first-generic drugs for which there are no blocking patents or 

exclusivities. First generics are drugs that have never been approved before as generics 

and are generic products new to the market. 

14 21 CFR § 314.101(b). 

15 An OGD official indicated that if an ANDA is not sufficiently complete, OGD rejects it 

and sends a “refuse-to-file” letter to the applicant. OGD issued refuse-to-file letters for 

approximately 9 percent of ANDAs in fiscal year (FY) 2006. 

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INTRODUCTION 

In addition, Chemistry’s review outcome determines OGD’s response to 

the applicant. According to FDA, Chemistry results are the primary 

consideration during the ANDA review because Chemistry determines 

pharmaceutical equivalence, which is a key concept in assessing a 

generic’s therapeutic equivalence to a brand name drug. Chemistry’s 

influence on OGD’s response to the applicant and the review process in 

other divisions is explained in greater detail below.16 

The Office of Generic Drug’s response and review process if Chemistry 

identifies deficiencies in the Abbreviated New Drug Application. If an 

ANDA does not meet Chemistry’s review standards (i.e., Chemistry 

finds deficiencies in the ANDA), OGD disapproves the ANDA and sends 

a “not-approvable” letter to the applicant.17 The not-approvable letter 

summarizes the Chemistry deficiencies. According to OGD officials, 

most original ANDAs contain Chemistry deficiencies and are 

disapproved.18 19 

Even though OGD has issued a not-approvable letter and has 

disapproved the ANDA based on Chemistry deficiencies, the other 

divisions continue processing it. If an ANDA does not meet other 

divisions’ review standards (i.e., other divisions find deficiencies in the 

ANDA), they issue deficiency letters directly to the applicant 

summarizing the deficiencies. 

16 FDA provides various overviews of the ANDA review process. For example, the 

“Generic Drug (ANDA) Review Process” is a flowchart available online at 

http://www.fda.gov/cder/handbook/anda.htm. Accesssed on January 3, 2008. OGD officials 

indicated that the current review process is not accurately reflected in many of these 

overviews. We provide here our understanding of the current review process based on our 

contact with OGD officials. Our description may be inconsistent with previous FDA 

overviews of the process. 

17 21 U.S.C. § 505(j)(5)(A); 21 CFR § 314.120(a). 

18 Remarks by Scott Gottlieb, Deputy Commissioner for Medical and Scientific Affairs, 

FDA. Speech before the Annual Generic Drug Forum. April 7, 2006. Available online at 

http://www.fda.gov/oc/speeches/2006/genericdrug0407.html. Accesssed on October 9, 2007. 

According to these remarks, 98 percent of original ANDAs were disapproved in 2004 and 

93 percent were disapproved in 2005. 

19 FDA also refers to original ANDAs as ANDAs reviewed during the first review cycle. 

Throughout this report, our use of the term “original ANDAs” is synonymous with ANDAs 

reviewed during the first review cycle. Most ANDAs contain Chemistry deficiencies and are 

disapproved during the first review cycle. 

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INTRODUCTION 

Applicants do not submit new ANDAs in response to not-approvable or 

deficiency letters. Instead, applicants submit amendments to the 

appropriate division(s) to correct ANDA deficiencies.20 

OGD classifies amendments as major or minor.21 Major amendments 

contain significant new data. Major amendments have the same review 

priority as original, unreviewed ANDAs and are reviewed according to 

CDER’s first-in, first-reviewed policy.22 In contrast, minor amendments 

do not contain significant new data and often indicate that an ANDA is 

close to approval. When OGD receives a minor amendment, it assigns 

high priority to it. The division places the minor amendment at the top 

of its queue, and the reviewer assigned to the ANDA reviews it upon 

completing his or her current assignment. 

The Office of Generic Drugs response and review process if Chemistry 

does not identify deficiencies in the Abbreviated New Drug Application. If 

Chemistry does not find deficiencies in an ANDA, the other divisions 

must review it and resolve any deficiencies before OGD sends an 

approval letter. After each division determines that the ANDA contains 

no deficiencies, it notifies Chemistry that the ANDA is approvable 

within that division. Unlike not-approvable letters, OGD sends an 

approval letter only when all division reviews are complete and the 

ANDA contains no deficiencies.23 

If other divisions find deficiencies in an ANDA but Chemistry does not, 

OGD does not disapprove the ANDA. However, the applicant must 

resolve the deficiencies before OGD will approve the ANDA. Therefore, 

when Chemistry does not identify deficiencies in an ANDA and is ready 

to approve it, the other divisions assign high priority to that ANDA. 

20 21 CFR § 314.96(a). 

21 CDER, Guidance for Industry. “Major, Minor, and Telephone Amendments to 

Abbreviated New Drug Applications.” Available online at 

http://www.fda.gov/cder/guidance/4706fnl.pdf. Accesssed on December 13, 2006. 

22 Ibid. 

23 21 CFR § 314.105(d). 

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INTROD U C T U C T I O N I O N 

According to CDER, 535 ANDAs (and corresponding amendments) were 

approved in 2006.24 CDER indicates that median approval time for 

these ANDAs and amendments was nearly 17 months.25 

Abbreviated New Drug Applications With Valid Patents or Exclusivities 

In some cases, OGD can only “tentatively approve” an ANDA after all 

divisions have deemed the ANDA approvable.26 For example, OGD can 

only tentatively approve an ANDA if valid patents or exclusive 

marketing rights (exclusivities) exist for brand name drugs. 

The tentative-approval letter instructs the applicant to notify OGD of 

any updates to the ANDA within 90 days prior to the patent or 

exclusivity expiration date. OGD confirms that the ANDA is approvable 

by all divisions and sends an approval letter to the applicant once the 

patent or exclusivity expires. 

Patents on brand name drugs are granted by the U.S. Patent and 

Trademark Office and are typically valid for 20 years from the date on 

which the patent was submitted.27 Exclusivities are granted by FDA 

upon approval of a drug and may last up to 7 years.28 Generally, OGD 

does not prioritize ANDA reviews according to the dates on which the 

patents or exclusivities expire (i.e., market entry date). 

24 This includes ANDAs approved with delayed effective dates. “FDA 2006 

Accomplishments: Thousands of Safe and Effective Health Care Products Made Available 

for Patients.” Available online at http://www.fda.gov/oc/accomplishments/healthcare.html. 

Accesssed on May 5, 2008. 

25 Approval time is calculated from the time OGD receives the original ANDA to the time 

it is approved or tentatively approved. Approval time includes filing review time as well as 

the time necessary for applicants to prepare and submit, and for OGD to review and 

approve or tentatively approve, all amendments to the ANDA. Ted Sherwood, Office of 

Pharmaceutical Science in CDER at FDA. “Generic Drugs: Overview of ANDA Review 

Process.” Available online at.http://www.fda.gov/cder/ 

audiences/iact/forum/200704_sherwood.pdf. Accesssed on June 26, 2007. 

26 21 CFR §§ 314.105(d) and 314.107. Although the term “approval letters with delayed 

effective dates” is cited in regulation, OGD officials referred to these letters as 

tentative-approval letters. 

27 U.S. Patent and Trademark Office. “General Information Concerning Patents: Nature 

of Patent and Patent Rights.” Available online at http://www.uspto.gov/go/pac/doc/general/. 

Accesssed on July 27, 2007. 

28 FDA, CDER. “Frequently Asked Questions on Patents and Exclusivity.” Available 

online at http://www.fda.gov/cder/ob/faqs.htm. Accesssed on November 8, 2007. 

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INTROD U C T I O N 

The Food and Drug Administration’s 180-Day Review Requirement 

The Federal Food, Drug, and Cosmetic Act requires FDA to approve or 

disapprove an ANDA within 180 days of initial receipt.29 This 180-day 

period is called the “review clock.”30 

The 180-day review clock starts on the date on which OGD receives an 

ANDA (before the filing review) and stops on the date on which OGD 

sends an approval letter, a tentative-approval letter, or a 

not-approvable letter.31 32 If Chemistry identifies deficiencies in an 

original ANDA, OGD sends a not-approvable letter, and the 180-day 

review clock stops. If Chemistry identifies no deficiencies in the ANDA, 

OGD sends an approval or a tentative-approval letter once all 

remaining divisions deem the application approvable. According to 

OGD, Bioequivalence, Labeling, and Microbiology deficiency letters do 

not stop the 180-day review clock. 

Proposed rule requires all divisions to meet the 180-day review clock. FDA 

issued a proposed rule in 2004 that would require OGD to send a 

“complete response” letter to the applicant within 180 days of receipt if 

an ANDA contains deficiencies.33 The proposed rule specifies that a 

complete response letter will describe all of the deficiencies that the 

applicant must address before OGD can approve the ANDA. 

According to current OGD practice, all divisions must meet the 180-day 

review clock if Chemistry finds no deficiencies in the original ANDA. 

However, if Chemistry finds deficiencies, only Chemistry is required to 

29 Section 505(j)(5)(A) of the Federal Food, Drug, and Cosmetic Act 

(21 U.S.C. § 355(j)(5)(A)); 21 CFR § 314.100. 

30 21 CFR § 314.100(a). The law would permit the applicant and FDA to extend this 

180-day period by mutual agreement. However, OGD officials indicated that they do not 

extend the review clock. 

31 Ibid. If OGD deems an ANDA to be sufficiently complete under 21 CFR § 314.101(b), 

the 180-day review clock starts retroactively on the date of receipt. If OGD deems an 

ANDA not to be sufficiently complete, the 180-day review clock does not start. If OGD 

deems a revised and resubmitted ANDA to be sufficiently complete, the 180-day review 

clock retroactively starts on the date of the resubmission. 

32 Pursuant to 21 CFR § 314.100(a), FDA may also send an approvable letter under 

21 CFR § 314.110 to stop the 180-day review clock. However, OGD officials stated that they 

no longer send approvable letters. We confirmed this practice in OGD’s monthly statistics 

report, which provides data on OGD actions for original ANDAs in the past 5 years. 

According to this internal report, OGD has not sent an approvable letter since April 2004. 

Therefore, we did not include these letters in our review. 

33 Applications for Approval To Market a New Drug; Complete Response Letter; 

Amendments to Unapproved Applications, 69 Fed. Reg. 43352, 43355–43356 (proposed 

July 20, 2004). 

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INTROD U C T U C T I O N I O N 

meet the 180-day review clock. Therefore, when OGD sends a 

not-approvable letter based on Chemistry deficiencies, the 180-day 

review clock stops. 

In contrast, to comply with the proposed rule, all divisions will need to 

meet the 180-day review clock regardless of whether Chemistry finds 

deficiencies in the ANDA.34 

Review Resources at the Food and Drug Administration 

The number of ANDAs submitted to OGD has increased at more than 

double the rate of growth of OGD’s review resources for ANDAs in the 

last 5 years. Despite this disproportionate growth, OGD’s approval 

times have decreased.35 

Funding for the Generic Drugs Program has increased by 74 percent in 

the last 5 years, from $35.9 million in FY 2001 to $62.6 million in 

FY 2006.36 37 The number of full-time-equivalent positions in OGD 

increased by 50 percent during this same time period, from 134 in 

FY 2001 to 201 in FY 2006.38 

In contrast, according to CDER, the number of original ANDAs submitted 

between FYs 2001 and 2006 increased by 158 percent, from 307 to 793.39 40 

34 According to a recent Semiannual Regulatory Agenda published in the Federal 

Register, the Department of Health and Human Services estimated that it would publish 

the final rule in October 2007 (72 Fed. Reg. 22490 (Apr. 30, 2007)). Available online at 

http://frwebgate.access.gpo.gov/ cgibin/getdoc.cgi?dbname=2007_unified_agenda_&docid=f:ua070408.wais. Accesssed on 

August 29, 2007. As of January 16, 2008, FDA had not published the final rule. 

35 Ted Sherwood, Office of Pharmaceutical Science in CDER at FDA. “Generic Drugs: 

Overview of ANDA Review Process.” Available online at http://www.fda.gov/cder/ 

audiences/iact/forum/200704_sherwood.pdf. Accesssed on June 26, 2007. 

36 The Generic Drugs Program includes OGD and other FDA offices associated with the 

generic drug review process, such as the Office of Regulatory Affairs and CDER’s Office of 

Compliance, Office of Regulatory Policy, and Office of New Drugs. 

37 Generic Drugs Program budget figures were obtained from FDA officials in June 2007. 

38 Gary Buehler, OGD Director. “Improving Access to Generic Drugs.” Testimony before 

the United States Senate Special Committee on Aging. July 20, 2006. Available online at 

http://aging.senate.gov/events/hr161gb.pdf. Accesssed on July 25, 2007. 

39 Ted Sherwood, Office of Pharmaceutical Science in CDER at FDA. “Generic Drugs: 

Overview of ANDA Review Process.” Available online at 

http://www.fda.gov/cder/audiences/iact/forum/200704_sherwood.pdf. Accesssed on 

June 26, 2007. 

40 These 793 ANDAs were submitted to OGD in FY 2006. The number of ANDAs in our 

analysis—989—is greater than 793 because we included ANDAs that were submitted or 

were under review in calendar year 2006. Our analysis also includes ANDAs submitted 

before 2006. 

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INTRODUCTION 

FDA continues to revise the ANDA review process to improve approval 

times and has made progress since 2001.41 According to CDER, median 

approval time for ANDAs decreased nearly 2 months from 2001 to 2006.42 

Currently, congressional appropriations fund ANDA reviews. To 

supplement FDA’s budget, the President’s proposed budget for FY 2009 

includes over $16 million for ANDA reviews funded through a new user fee 

program.43 User fees would support CDER’s review by requiring 

applicants to pay fees when submitting original ANDAs. 

Related Office of Inspector General Work 

In 2003, the Office of Inspector General (OIG) reviewed the CDER 

Office of New Drugs’ management of the new drug application review 

process for brand name drugs.44 OIG found that there were general 

workload concerns but that the review process had several strengths. 

OIG recommended ways for FDA to manage review resources, including 

assessing workload pressures and rejecting poor-quality applications. 

In 1989, OIG reviewed FDA’s generic drug approval process.45 OIG 

concluded that the process for assigning ANDAs to reviewers was 

arbitrary and could permit favoritism to certain applicants. OIG 

recommended that FDA consistently apply its first-in, first-reviewed 

policy for reviewing ANDAs. OIG also recommended that FDA 

uniformly apply and properly document exceptions to this policy. 

41 For example, “FDA Announces Initiative To Bolster Generic Drug Program.” 

October 4, 2007. Available online at 

http://www.fda.gov/bbs/topics/NEWS/2007/NEW01719.html. Accesssed on 

November 2, 2007. This particular initiative was incorporated into CDER’s MaPP 5240.3 

and became effective October 18, 2006. 

42 Ted Sherwood, Office of Pharmaceutical Science in CDER at FDA. “Generic Drugs: 

Overview of ANDA Review Process.” Available online at 

http://www.fda.gov/cder/audiences/iact/forum/200704_sherwood.pdf. Accesssed on 

June 26, 2007. 

43 FDA. “Summary of FDA’s FY 2009 Budget.” Available online at 

http://www.fda.gov/oc/factsheets/budget2009.html. Accesssed on February 28, 2008. 

44 “FDA’s Review Process for New Drug Applications: A Management Review,” 

OEI-01-01-00590. 

45 “Vulnerabilities in the Food and Drug Administration’s Generic Drug Approval 

Process,” A-15-89-00051. 

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INTROD U C T I O N 
 

METHODOLOGY 

Scope 

We examined review times for 989 original ANDAs that were approved, 

tentatively approved, disapproved, or pending (i.e., the ANDAs had not 

been reviewed or the reviews were not complete) during 2006.46 47 See 

Appendix A for additional information about our methodology, including 

criteria for excluding ANDAs from our analyses. 

We surveyed OGD division reviewers and conducted structured 

interviews with OGD officials to determine factors that affect ANDA 

review times. 

Data Sources 

We obtained information about FDA’s generic drug review process from 

the following sources: 

• FDA statutes, regulations, policies, procedures, and guidance 

documents; 

• FDA’s Centerwide Oracle Management Information System 

(COMIS); 

• Surveys of OGD reviewers assigned to a sample of original ANDAs 

under review in 2006 with review times greater than 180 days; 

• Structured interviews with OGD officials involved in the generic 

drug review process; and 

• OGD’s consult database. 

Data Collection and Analysis 

We reviewed FDA law, policies, procedures, and guidance documents to 

understand the generic drug review process. We compared these 

documents with information obtained from OGD officials regarding 

OGD practices. In addition, we analyzed data obtained from COMIS to 

verify OGD practices. 

We analyzed 989 original ANDAs to determine review times in each 

division. Of the 989 original ANDAs, we identified those with review 

46 This includes ANDAs that were submitted in 2005 and were under review in 2006 or 

were submitted in 2006 but were reviewed or pending longer than 180 days in 2007. 

47 The term “original” refers to new, sufficiently complete ANDAs. It does not include 

amendments. 

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INTROD U C T I O N 

times greater than 180 days in each division and selected a sample of 

105 ANDAs. 

We surveyed OGD reviewers responsible for reviewing the sample of 

105 ANDAs. We surveyed reviewers about factors contributing to 

original ANDA review times exceeding 180 days. 

We conducted structured interviews with 12 OGD officials involved in 

the administration of the generic drug review process to identify factors 

contributing to longer review times throughout the review process, from 

ANDA receipt to approval. 

Finally, we examined the OGD consult database to determine the 

number of and review times for pending consults. 

Limitations 

We did not independently verify the COMIS data or the OGD consult 

data to ensure their accuracy. 

Almost all original ANDAs are disapproved because Chemistry finds 

deficiencies. Therefore, we determined the extent to which original 

ANDA review times exceeded the 180-day review clock by analyzing 

Chemistry review times. We did not determine the extent to which 

original ANDA review times exceeded the 180-day review clock in other 

divisions when Chemistry did not find deficiencies. 

The results from our sample of 105 ANDAs with review times greater 

than 180 days are not projectable. 

Shorter ANDA review times cannot be directly linked to faster market 

entry because of valid patents or exclusivities or applicants’ marketing 

decisions. For example, an ANDA can be approvable by all divisions 

within 180 days, but valid patents or exclusivities prevent OGD from 

approving the ANDA. OGD can only tentatively approve ANDAs before 

valid patents or exclusivities expire. Once OGD approves ANDAs, 

applicants’ marketing decisions may further delay or prevent drugs’ 

market entry. 

Standards 

We conducted this review in accordance with the “Quality Standards for 

Inspections” issued by the President’s Council on Integrity and 

Efficiency and the Executive Council on Integrity and Efficiency. 

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Δ FINDINGS 

The Food and Drug Administration approved or 

tentatively approved 4 percent of original 

Abbreviated New Drug Applications under 

review in 2006; the remaining 96 percent did not 

meet review standards and were disapproved 

FDA’s OGD approved 1 percent and 

tentatively approved 3 percent of 

original ANDAs under review in 

2006.48 49 OGD approves or 

tentatively approves ANDAs that 

meet each division’s review 

standards.50 If an ANDA does not meet all review standards (i.e., the 

ANDA contains deficiencies in at least one division), OGD cannot 

approve it. 

Generally, approval status (i.e., approved, tentatively approved, or 

disapproved) is based on whether (1) Chemistry identifies deficiencies in 

the ANDA and (2) valid patents or exclusivities exist for the 

brand name drug. 

OGD approved 1 percent of original ANDAs (9 of 989) under review in 

2006. No OGD divisions found deficiencies in these ANDAs, and valid 

patents or exclusivities did not exist for the brand name drugs.51 

Applicants could market these generic drugs as soon as OGD approved 

the ANDAs. 

OGD tentatively approved 3 percent of original ANDAs (34 of 989) 

under review in 2006. No divisions found deficiencies in these ANDAs, 

but valid patents or exclusivities existed for the brand name drugs.52 

Applicants cannot market generic drugs until patents or exclusivities 

expire or are deemed invalid through litigation. 

OGD disapproved 96 percent of original ANDAs (946 of 989) under 

review in 2006. OGD disapproves ANDAs and sends not-approvable 

letters to applicants when ANDAs do not meet Chemistry’s review 

standards. 

To correct the deficiencies noted in not-approvable or deficiency letters, 

applicants submit major or minor amendments. OGD receives a large 

48 FDA approved a total of 535 ANDAs in 2006. This included approved or tentatively 

approved original ANDAs and those requiring amendments. In contrast, our review 

included only original ANDAs. 

49 These original ANDAs were approved or tentatively approved during the first review 

cycle. 

50 21 CFR § 314.105(d). 

51 If Bioequivalence, Labeling, or Microbiology found deficiencies in these ANDAs, the 

deficiencies were resolved before OGD approved the ANDAs. 

52 If Bioequivalence, Labeling, or Microbiology found deficiencies in these ANDAs, the 

deficiencies were resolved before OGD tentatively approved the ANDAs. 

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FINDINGS 

 

 

 

 

 

 

 

FINDINGS 
 

number of amendments because most ANDAs do not meet OGD’s review 

standards and are initially disapproved. For example, OGD received 

828 original ANDAs under review in 2006 but received 4,174 major or 

minor Chemistry amendments.53 

Major and minor amendments compete for the same review resources as 

original ANDAs. Upon receipt, major amendments are placed at the 

end of the same queue as original ANDAs. Minor amendments are 

placed ahead of original ANDAs and major amendments in the queue. 

The Food and Drug Administration exceeded the 

180-day review requirement for nearly half of 

original Abbreviated New Drug Applications 

under review in 2006 because Chemistry reviews 

exceeded 180 days 

presented in Appendix B. 

Forty-six percent of original ANDA 

Chemistry reviews (456 of 989) 

exceeded the 180-day requirement 

in 2006.54 For these ANDAs, the 

median review time was 217 days. 

Chemistry review time ranges are 

Table 1 (on the next page) provides the number of original ANDAs 

under review by FDA’s OGD in 2006 as well as the number, percentage, 

and median review time for ANDAs having review times greater than 

180 days. Table 1 presents these data by ANDA approval status. 

Because Chemistry found deficiencies in most original ANDAs under 

review in 2006 and stopped the 180-day review clock, Table 1 contains 

data for Chemistry only.55 

53 These 828 ANDAs were submitted to OGD in 2006. The number of ANDAs in our 

analysis—989—is greater than 828 because we included ANDAs that were submitted or 

were under review in 2006. Thus, our analysis includes ANDAs submitted before 2006. 

54 Our analysis of the number of original ANDAs exceeding the 180-day review clock is 

conservative. Because of limitations in the COMIS database, we calculated compliance with 

the 180-day review clock based on Chemistry review time (from the date on which OGD 

received the ANDA to the date on which Chemistry completed its review) rather than OGD 

response time (from the date on which OGD received the ANDA to the date on which OGD 

sent an approval letter, a tentative-approval letter, or a not-approvable letter). For 

example, if Chemistry completed its review on Day 185 and found no deficiencies and OGD 

sent an approval letter on Day 210 (once other divisions deemed the ANDA approvable), our 

calculation of Chemistry review time would be 185 days. In contrast, pursuant to 

21 CFR § 314.100, the 180-day review clock would not stop until Day 210. 

55 One ANDA was pending longer than 180 days at the time we collected the data. FDA 

later indicated that this ANDA was disapproved and provided the date on which Chemistry 

completed its review. We used this date to calculate review time for this ANDA, which was 

included in our analysis of Chemistry’s ANDA review times. 

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FINDINGS 

Table 1: 2006 Chemistry Reviews of Original Abbreviated New Drug Applications 

Number of ANDAs Percentage of Median Review Time for 

Number of ANDAs With Review Time ANDAs With Review ANDAs With Review 

ANDA Approval Status Reviewed > 180 Days Time > 180 Days Time > 180 Days 

Approved 9 5 56% 268 days 

Tentatively Approved 34 23 68% 300 days 

Disapproved 946 428 45% 214 days 

All 989 456 46% 217 days 

Source: OIG analysis of FDA COMIS data, 2007. 

The percentage of ANDAs with review times longer than 180 days, and 

median review times for these ANDAs, varied according to ANDA 

approval status: 

•	 Approved Abbreviated New Drug Applications. Five of the nine original 

ANDAs approved in 2006 were not reviewed within 180 days. 

For these five ANDAs, applicants waited a median of 268 days 

(i.e., almost 3 months beyond the 180-day regulatory timeframe) 

before they received OGD’s approval and could market the drugs. 

•	 Tentatively Approved Abbreviated New Drug Applications. Reviews for 

23 of the 34 tentatively approved original ANDAs exceeded 180 

days. Applicants waited a median of 300 days (i.e., 4 months 

beyond the 180-day regulatory timeframe) for OGD to tentatively 

approve these ANDAs. 

Regardless of whether OGD reviewed these tentatively approved 

ANDAs within 180 days, applicants could not market these drugs 

immediately because of valid patents or exclusivities. For example, 

even though OGD tentatively approved 11 of the 34 ANDAs within 

180 days, the patent expiration dates for the brand name drugs 

ranged from 11 months to 12 years after the date of OGD’s tentative 

approval.56 57 58 

56 The earliest expiration date was November 22, 2007, but OGD tentatively approved 

this ANDA on December 29, 2006 (i.e., 11 months before the patent expired). The latest 

expiration date was November 14, 2018, and OGD tentatively approved this ANDA on 

November 6, 2006 (i.e., 12 years before the patent expired). 

57 Applicants for 2 of the 11 ANDAs were challenging the validity of the patents or 

exclusivities. 

58 Five of these ANDAs were expedited PEPFAR applications. Although patents prevent 

marketing these drugs in the United States, applicants can market them internationally. 

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FINDINGS 

•	 Disapproved Abbreviated New Drug Applications. Reviews for 

428 disapproved original ANDAs exceeded 180 days. For these 

ANDAs, applicants waited a median of 214 days (i.e., more than 

1 month beyond the expiration of the 180-day review clock) before 

OGD notified them of the ANDA disapproval. 

Microbiology, Bioequivalence, and Labeling 

reviews of original Abbreviated New Drug 

Applications generally exceeded 180 days 

in 2006 

In 2006, 77 percent of original 

ANDAs (760 of 989) had review 

times exceeding 180 days in 

divisions other than Chemistry. 

Of ANDAs taking more than 

180 days to review, median review times were 361 days in Microbiology, 

287 days in Bioequivalence, and 277 days in Labeling. Review time 

ranges in each division are presented in Appendix C. 

OGD does not hold these other divisions (i.e., Microbiology, 

Bioequivalence, and Labeling) to the 180-day review clock if Chemistry 

finds deficiencies in the original ANDA. However, FDA’s proposed rule 

will require all divisions to complete reviews within 180 days, 

regardless of whether Chemistry finds deficiencies.59 

Table 2 (on the next page) provides, by division, the number of original 

ANDAs under review in Microbiology, Bioequivalence, and Labeling in 

2006 as well as the number, percentage, and median review times for 

ANDAs having review times greater than 180 days.60 

59 Applications for Approval To Market a New Drug; Complete Response Letter; 

Amendments to Unapproved Applications, 69 Fed. Red. (proposed July 20, 2004). 

60 Data are not available in COMIS to determine the review outcome (i.e., approvable or 

deficient) in divisions other than Chemistry. 

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FINDINGS 

Table 2: 2006 Microbiology, Bioequivalence, and Labeling Reviews of Original Abbreviated 

New Drug Applications 

Number of ANDAs Percentage of Median Review Time for 

Total Number of ANDAs With Review Time ANDAs With Review ANDAs With Review 

OGD Division Reviewed > 180 Days Time > 180 Days* Time > 180 Days** 

Microbiology 229 175 76% 361 days 

Bioequivalence 989 576 58% 287 days 

Labeling 989 556 56% 277 days 

* Some ANDAs had reviews that exceeded 180 days in multiple divisions. 

** Median review times may be underestimated because review times for pending ANDAs in these divisions were accruing when we obtained the 

data. Of ANDAs with review times greater than 180 days, the percentages that were pending at the time we obtained the data were: 73 percent 

for Microbiology (127 of 175 ANDAs), 3 percent for Bioequivalence (16 of 576 ANDAs), and 32 percent for Labeling (178 of 556 ANDAs). 

Source: OIG analysis of FDA COMIS data, 2007. 

In our sample of ANDAs with Nearly 70 percent of sampled division reviews review times exceeding 180 days, exceeding 180 days did not begin before the 69 percent (72 of 105) of original 

180-day review periods expired ANDAs were in the queue longer 

 OEI-04-07-00280 

than 180 days.61 Thus, the 180-day 

periods passed before division reviews began in most of our sample of 

105 original ANDAs. 

Review time in each division is calculated from the date on which OGD 

receives an ANDA to the date on which each division completes its 

review of the original ANDA. Review times can be further divided into 

two components: the amount of time the ANDA waited in the queue 

(i.e., queue time) and the amount of time each division took to 

determine whether the ANDA met the division’s review standards 

(i.e., division review time).62 

Figure 1 (on the next page) compares medians for queue time and 

division review time for the sample of 105 ANDAs having review times 

greater than 180 days in each division. 

61 These data are available for the sample of 105 ANDAs only. The dates on which 

reviewers start their reviews (i.e., the dates on which ANDAs leave the queue) are not 

provided in the COMIS; reviewers in our sample provided these dates in their survey 

responses. 

62 Queue time consists of both the filing review time and the time the ANDA awaits 

review in the division queue. 

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F I NDING S 

FIGURE 1 

Comparison 

Between Queue 

Time and 

Division Review 

Time by Division 

Chemistry 

Bioequivalence 

Labeling 

Microbiology 

149 

227 

237 

264 

74 

21 

9 

0 180 

Queue Time 

Division Review Time 

37 

Number of Days 

Source: OIG analysis of FDA COMIS data and OGD reviewer responses, 2007. 

The Food and Drug Administration’s FDA prioritization practices 

prioritization practices affect Abbreviated New contribute to longer review times 

Drug Application review times for ANDAs close to approval. 

ANDAs that are close to approval 

include those that (1) have high-priority consults; (2) do not have valid 

patents or exclusivities, or have patents or exclusivities that will expire 

in the near future; (3) are deemed approvable in multiple divisions; or 

(4) contain only minor deficiencies. 

The Food and Drug Administration does not review consults within policy 

timeframes 

FDA’s CDER policy indicates that OGD should receive consult results 

for highest-priority consults within 15 days and lowest-priority 

consults within 90 days. Consult priority is based, in part, on how 

close the ANDA is to approval. In practice, however, consult results 

generally are not returned to OGD within the timeframes specified in 

policy, which prolongs ANDA review times. 

For the 100 pending OGD consults, days pending ranged from 3 to 

882.63 Of these pending consults, 78 percent (78 of 100) were not 

63 These consults were pending as of June 22, 2007, the date on which we received the 

OGD consult data. 

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FINDINGS 

returned to OGD within 90 days (i.e., the longest period of time 

specified by CDER policy). Sixty-eight percent (68 of 100) were not 

returned within 180 days. The number of days pending for all 

100 consults is presented in Appendix D. 

The Food and Drug Administration does not consider market entry date 

when prioritizing Abbreviated New Drug Applications 

FDA’s OGD generally maintains a first-in, first-reviewed policy for 

reviewing ANDAs. FDA grants exceptions to this policy, such as for 

first generic drugs that do not have valid patents or exclusivities at the 

time of submission.64 

However, FDA does not grant exceptions to this policy for ANDAs of 

non-first generic drugs without patents or exclusivities (i.e., ANDAs 

that are close to approval rather than tentative approval).65 Thus, OGD 

reviews ANDAs with valid patents or exclusivities while ANDAs that 

can immediately enter the market wait in the queue. 

Twenty-nine percent (291 of 989) of original ANDAs under review by 

OGD in 2006 could not immediately enter the market because of valid 

patents or exclusivities. Chemistry reviewed nearly 60 percent of 

these ANDAs (168 of 291) within 180 days. 

In contrast, 71 percent (698 of 989) of original ANDAs under review in 

2006 could enter the market as soon as OGD approved them.66 

Chemistry reviewed only 52 percent of these ANDAs (365 of 698) 

within 180 days. 

The Food and Drug Administration prioritizes Abbreviated New Drug 

Applications differently across divisions 

FDA’s OGD prioritizes ANDAs with approvable reviews differently 

across divisions. Divisions also classify and prioritize amendments 

differently. Differences in prioritizing ANDAs affect ANDA review 

times, as described below. 

64 First generics are drugs that have never been approved before as generics and are new 

to the market. 

65 According to FDA, the second and subsequent generic drugs to enter the market effect 

the greatest cost savings. First generic drugs are priced only slightly lower than brand 

name drugs. Available online at http://www.fda.gov/cder/ogd/generic_competition.htm. 

Accesssed on February 18, 2008. 

66 This includes ANDAs in which the applicants are challenging the validity of the 

patents or exclusivities. 

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FINDINGS 

Divisions in the Office of Generic Drugs do not consistently assign high 

priority to approvable Abbreviated New Drug Applications. Other OGD 

divisions assign high priority to an ANDA after Chemistry deems the 

ANDA approvable. However, Chemistry maintains CDER’s first-in, 

first-reviewed policy and does not change the priority of ANDAs deemed 

approvable by other divisions. 

For example, if Chemistry deems an ANDA approvable before other 

divisions, the ANDA is designated as high priority and reviewed ahead 

of other ANDAs in divisions’ queues.67 In contrast, if all three 

non-Chemistry divisions deem an ANDA approvable, Chemistry does 

not assign high priority to the ANDA. Rather, Chemistry reviews the 

ANDA according to CDER’s first-in, first-reviewed policy. 

Divisions in the Office of Generic Drugs do not consistently classify and 

prioritize amendments. Federal regulation recognizes that 

amendments that contain significant new data will require significant 

additional review time.68 Pursuant to CDER guidance, these major 

amendments have the same review priority as original, unreviewed 

ANDAs.69 CDER guidance also directs OGD to classify all other 

amendments as minor. When minor amendments are received, 

divisions should assign high priority to them to expedite the review of 

ANDAs that are near approval.70 

According to FDA, only Chemistry classifies amendments as major or 

minor.71 72 In addition, during our structured interviews, an OGD 

official stated that amendments in non-Chemistry divisions are 

treated as minor amendments and prioritized ahead of original 

67 The other divisions also assign high priority to any amendments they receive for the 

ANDA. 

68 21 CFR § 314.96(a). 

69 CDER, Guidance for Industry. “Major, Minor, and Telephone Amendments to 

Abbreviated New Drug Applications.” Available online at 

http://www.fda.gov/cder/guidance/4706fnl.pdf. Accesssed on December 13, 2006. 

70 Ibid. 

71 For example, see Ted Sherwood, Office of Pharmaceutical Science in CDER at FDA. 

“Generic Drugs: Overview of ANDA Review Process.” Available online at 

http://www.fda.gov/cder/audiences/iact/forum/200704_sherwood.pdf. Accesssed on 

June 26, 2007. 

72 We confirmed this OGD practice by examining COMIS data. A COMIS data field 

tracks major and minor amendments for Chemistry. Codes in other divisions do not 

designate amendments as major or minor. 

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FINDINGS 

ANDAs in the queue, regardless of the significance of the data 

contained in the amendment. 

Not classifying amendments as major or minor may place ANDAs 

with more deficiencies ahead of those with fewer. This may dilute the 

effectiveness of the amendment prioritization process by delaying 

reviews of amendments that are truly minor and original ANDAs. 

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Δ RECOMMENDATIONS 

Generic drugs are generally thought of as one way to rein in increasing 

health costs. FDA’s timeliness in approving generic drugs has recently 

been a topic of scrutiny by both Congress and the media. Federal law 

requires that FDA approve or disapprove original ANDAs within 

180 days of receipt. 

We found that FDA disapproved most original ANDAs under review in 

2006 because they did not meet FDA review standards. Nearly half of 

Chemistry review times exceeded the 180 days required by Federal law. 

Moreover, many review times in other OGD divisions exceeded 

180 days. In addition, for a sample of ANDA reviews exceeding 

180 days, most reviews did not begin before the 180-day periods expired. 

Finally, we found that FDA prioritization practices affect ANDA review 

times. 

The ANDA submissions have increased at more than double the rate of 

review resources in the last 5 years. To better manage OGD’s current 

ANDA reviews and to potentially increase the number of ANDAs 

reviewed and approved within 180 days, we recommend that FDA: 

Identify Common Original Abbreviated New Drug Application Deficiencies 

and Offer More Guidance to Industry To Decrease the Percentage 

Disapproved 

Without lowering review standards, FDA should identify ways to decrease 

the percentage of disapproved original ANDAs. Disapproving fewer 

original ANDAs would reduce the number of amendments that FDA’s 

OGD receives and reviews. If OGD received fewer amendments, the queue 

would become smaller, and OGD could allocate more resources to review 

original ANDAs within 180 days. 

To decrease the percentage of ANDAs originally disapproved, we suggest 

that OGD examine deficiency letters to identify common deficiencies in 

original ANDAs. The types of deficiencies that occur most frequently 

indicate the areas in which applicants need more guidance. FDA should 

create or revise guidance to address these problem areas. Expanded 

guidance may improve the quality of the ANDAs submitted to OGD and 

increase the percentage of original ANDAs approved within 180 days. 

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RECOMMENDATIONS 

Increase the Percentage of Original Abbreviated New Drug Applications 

Reviewed by All Divisions Within 180 Days 

Federal regulation requires that FDA approve or disapprove original 

ANDAs within 180 days of receipt. In addition, FDA’s proposed rule 

would require that all divisions review ANDAs within the 180-day 

regulatory requirement, regardless of whether Chemistry identifies 

deficiencies in the original ANDAs. 

In light of the current regulation and proposed rule, FDA should 

continue to revise the ANDA review process to reduce review times in 

all divisions. Because queue times in our sample of ANDAs were longer 

than division review times and the 180-day period passed while most of 

our sample waited in the queue, FDA should focus on reducing queue 

times. 

Identify New Prioritization Practices To Reduce Review Times for 

Abbreviated New Drug Applications Close to Approval 

ANDAs that are close to approval include those that have high-priority 

consults, have no valid patents or exclusivities (or have patents or 

exclusivities that expire soon), are deemed approvable in multiple 

divisions, or contain only minor deficiencies. 

We recommend that FDA assign priority to and meet review timeframes 

for consults based on whether the ANDAs are close to approval, 

according to CDER’s consult policy. In addition, FDA should identify 

ANDAs close to approval and improve the prioritization process to 

reduce review times for these ANDAs. These new prioritization 

processes would generate exceptions to CDER’s first-in, first-reviewed 

policy for reviewing ANDAs. If implemented, OGD would need to 

uniformly apply and properly document these exceptions. 

Evaluate the consultation process to meet review timeframes specified by 

Food and Drug Administration policy. FDA’s CDER policy defines high- and 

low-priority consults based, in part, on whether the ANDA is close to 

approval. The policy also establishes review timeframes based on the 

consult’s priority. However, we found that, in practice, consult results 

generally are not returned to OGD within specified timeframes, regardless 

of the consult’s priority. 

FDA should examine the ANDA consultation process to determine how 

consults can be returned to OGD within the timeframes specified in CDER 

policy, particularly consults for ANDAs close to approval. Obtaining 

consults within designated priority timeframes may reduce the number of 

ANDAs exceeding the 180-day regulatory requirement. 

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R E C O MMENDA T I O N S 

Identify and assign high priority to Abbreviated New Drug Applications close to 

approval. Assigning high priority to some ANDAs will reduce review times 

for these ANDAs but will also delay reviews for lower-priority ANDAs. In 

light of this, we offer the following options to FDA’s OGD for identifying 

ANDAs that are close to approval and improving the ANDA prioritization 

process. We also recognize that there may be additional options to 

improve the prioritization process. 

•	 Prioritize Abbreviated New Drug Applications based on potential market 

entry date. OGD could review ANDAs for generic drugs without 

valid patents or exclusivities ahead of those with them. OGD could 

assign high priority to and reduce review times for ANDAs that can 

be approved and marketed immediately (i.e., ANDAs without valid 

patents or exclusivities) or in the near future (i.e., ANDAs with 

valid patents or exclusivities expiring soon). However, OGD should 

not delay ANDA reviews if the delay violates current FDA policy 

(e.g., ANDAs expedited under the PEPFAR program or expedited 

first generic drugs). 

•	 Assign high priority to Abbreviated New Drug Applications with 

approvable reviews in multiple divisions. OGD could prioritize 

ANDAs based on the number of divisions with approvable reviews. 

As a result, ANDAs with few deficiencies across divisions (i.e., 

ANDAs approvable by multiple divisions and, thus, close to 

approval) would be reviewed more quickly. 

•	 Classify amendments according to Food and Drug Administration policy 

and assign high priority to Abbreviated New Drug Applications with only 

minor deficiencies. OGD could follow or revise amendment policies 

so that divisions classify and prioritize amendments similarly. In 

all divisions, OGD could assign high priority to ANDAs with minor 

deficiencies (i.e., ANDAs close to approval) and review them before 

ANDAs with major deficiencies. 

AGENCY COMMENTS 

In its comments to the draft report, FDA noted that OGD and CDER 

staff have already identified portions of the primary recommendations, 

and FDA is implementing process improvements that are the same as or 

similar to the recommendations. Specifically, FDA agreed with our first 

recommendation but did not indicate whether it concurred with the two 

additional recommendations. 

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RECOMMENDATIONS 

FDA agreed that increasing the number of original ANDAs approved 

(i.e., in the first review cycle) would help streamline the review process 

by decreasing the number of amendments and subsequent review 

cycles. FDA has provided guidance to assist industry in submitting 

more easily reviewed applications and indicated that the development of 

guidance is a continually evolving process. 

Although FDA did not indicate whether it concurred with the second 

recommendation, FDA noted that it continues to alter its review process 

with the goals of reducing queue times and reviewing original ANDAs 

within 180 days. FDA has developed a focused hiring program to 

increase staff and anticipates that additional reviewers will eventually 

decrease review times. In addition, FDA is developing other approaches 

to increase review efficiency, including shifting responsibilities to the 

Project Management staff. 

FDA also did not indicate whether it concurred with the last 

recommendation. FDA stated that a variety of external forces can affect 

an application’s review and approval, which makes determining 

whether an ANDA is “close to approval” difficult. FDA also expressed 

some concerns about the options presented in our recommendation. 

However, it appears that FDA has taken some actions to address this 

recommendation. FDA noted that it prioritizes some ANDAs based on 

potential market entry date and may consider further revisions to this 

process. In particular, FDA indicated that a possible consideration 

would be to delay reviews for ANDAs with patents that expire far into 

the future. However, FDA noted that such a process would require a 

thorough examination of all related issues and policy changes within 

OGD. 

FDA also provided several technical comments to the report. We have 

incorporated these comments into the report, as appropriate. 

We ask that, in its final management decision, FDA more clearly 

indicate whether it concurs with each of our recommendations. For the 

full text of FDA’s comments, see Appendix E. 

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Δ APPENDIX~A 

ADDITIONAL INFORMATION ON METHODOLOGY 

Below we provide additional information about the methodology used to 

accomplish our objectives. 

Food and Drug Administration Policies, Procedures, and Guidance 

We reviewed the Food and Drug Administration’s (FDA) Center for 

Drug Evaluation and Research (CDER) policies, procedures, and 

guidance on the: 

• issuance and tracking of consults in the Office of Generic Drugs 

(OGD), 

• review order of original Abbreviated New Drug Applications 

(ANDAs) and amendments, and 

• classification of major and minor amendments. 

We compared these documents to information gathered about ANDA 

review practices from OGD officials as well as data obtained from FDA’s 

Centerwide Oracle Management Information System (COMIS), surveys of 

OGD reviewers, and structured interviews with OGD officials. We 

identified generic drug review practices that deviated from CDER policies, 

procedures, or guidance. We also identified policies and practices that 

affected ANDA review times (e.g., OGD does not prioritize ANDAs based 

on potential market entry date). 

Centerwide Oracle Management Information System Data 

We obtained COMIS data from FDA to assess each division’s review 

times for ANDAs under review in 2006. We defined ANDAs as “under 

review” if they contained a date between January 1 and 

December 31, 2006, in any of the following COMIS fields: 

• the date on which the ANDA was addressed to OGD, 

• the date on which at least one division completed its review of the 

ANDA, or 

• the date on which Chemistry acted on the ANDA. 

We obtained COMIS data for all ANDAs meeting at least one of the 

above criteria. Although we received data from FDA for 1,619 original 

ANDAs, we analyzed review times for 989 original ANDAs. 

We removed data for 37 ANDAs because they did not meet our criteria 

of being submitted, in the review queue, under review, or reviewed by at 

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APPENDIX~A 

least one division in 2006. Additional records were removed from the 

data set if at least one of the following criteria was met: 

• The ANDA was closed administratively or not assigned to divisions 

based on the results of the filing review (116 ANDAs), 

• COMIS did not contain data for the ANDA in all three divisions 

that review each ANDA (Bioequivalence, Chemistry, and Labeling; 

393 ANDAs), and 

• The ANDA had been pending fewer than 180 days and Chemistry 

had not completed its review (84 ANDAs). 

The COMIS data were analyzed using SAS,® a statistical analysis 

program. ANDA review times were calculated for each of the four 

divisions by subtracting the date on which OGD received the ANDA 

from the date on which each division completed its review. If an 

ANDA was currently pending in a division for more than 180 days, we 

entered the date on which we obtained the COMIS data from FDA 

(April 2, 2007) as the review completion date and assigned a pending 

code to the record. 

In some cases, an ANDA contained multiple records for a division 

(e.g., Bioequivalence has multiple COMIS division codes that all 

reflect the Bioequivalence review). To capture the total time for a 

division to complete the ANDA review, the last date on which a 

review was completed in the division was used as the review stop 

date. 

For cases in which one record for an ANDA within a division 

contained a review stop date but another record within the same 

division and ANDA contained no stop date, the last stop date was 

used. A review stop date indicates that the review is complete, and 

we did not classify these cases as pending. 

Office of Generic Drugs Reviewers 

From the COMIS data, we identified ANDAs with review times greater 

than 180 days and selected a sample of 105 ANDA reviews. To obtain 

this sample, we identified reviewers assigned to a subset of recently 

submitted ANDAs within each division. We sampled from ANDAs in 

which the 180-day review clock would have expired in the 4 months 

prior to the date on which we requested the data from FDA. These 

ANDAs were submitted from June through September 2006. 

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APPENDIX~A 

We randomly selected 25 tentatively approved, disapproved, or pending 

ANDAs within each division. In each division, we randomly selected 

one ANDA review per reviewer until each reviewer was sampled once or 

until 25 ANDA reviews were selected. If we did not obtain 25 ANDA 

reviews within a division after each reviewer was sampled once, we 

randomly selected additional ANDA reviews in the division, 1 per 

reviewer, until we obtained 25 ANDAs within the division. 

We also selected all ANDAs that were approved but had review times 

greater than 180 days. This added five ANDA reviews to Chemistry 

and one ANDA review to Labeling for our sample. 

Therefore, we collected data from reviewers for a total of 106 ANDA 

reviews: 30 Chemistry, 25 Bioequivalence, 26 Labeling, and 

25 Microbiology. However, one Labeling reviewer indicated that the 

COMIS data for his review were wrong and the ANDA was reviewed 

within 180 days. We removed this ANDA review from our sample. 

Thus, our analysis of reviewer data was based on 105 ANDA reviews. 

Reviewers’ survey responses indicated the date on which their review of 

each ANDA began as well as the factors that contributed to the ANDA 

reviews’ exceeding 180 days within their division. 

Office of Generic Drugs Officials 

We conducted structured interviews with a division director (in all 

divisions except Microbiology), team leader, and project manager from 

each of the divisions as well as the Director of OGD. We asked these 

12 individuals open-ended questions concerning factors that contribute 

to longer review times throughout the generic drug review process. 

We used reviewers’ and officials’ responses to understand ANDA review 

practices and to identify factors that contribute to ANDA review times 

exceeding 180 days. In addition, data from reviewers and officials 

provided the basis for collecting and analyzing additional FDA data. 

For example, reviewers’ and officials’ responses prompted us to examine 

the OGD consult data and to compare review times for ANDAs affected 

by valid patents or exclusivities with those that could enter the market 

immediately. 

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Δ APPENDIX~B 

2006 Chemistry Review Time Ranges 

ANDA Approval Status Review Time Range for ANDAs With Review Time > 180 Days 

Approved 246–306 days 

Tentatively Approved 187–667 days 

Disapproved 181–816 days 

All 181–816 days 

Source: Office of Inspector General analysis of FDA COMIS data, 2007. 

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Δ APPENDIX~C 

2006 Microbiology, Bioequivalence, and Labeling Review Time Ranges 

OGD Division Review Time Range for ANDAs With Review Time > 180 Days* 

Microbiology 181–651 days 

Bioequivalence 181–610 days 

Labeling 181–627 days 

* Review time ranges may be underestimated because review times for pending ANDAs in these divisions were 

accruing when we obtained the data. For ANDAs with review times greater than 180 days, the percentages that 

were pending at the time we obtained the data were: 73 percent for Microbiology (127 of 175 ANDAs), 3 percent 

for Bioequivalence (16 of 576 ANDAs), and 32 percent for Labeling (178 of 556 ANDAs). 

Source: Office of Inspector General analysis of FDA COMIS data, 2007. 

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0–90 

91–180 

181–270 271–360 361–450 451–540 541–630 631–720 721–810 8 11–900 

Δ APPENDIX~D 

25 

Frequency 

Distribution of
 

Office of Generic 20

Drugs Consults 

Pending as of 

June 2007 

Number of Consults 15 

10 

5 

0 

Number of Days Pending 

Source: Office of Inspector General analysis of FDA’s consult data, 2007. 

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Δ APPENDIX~E 

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APPENDIX~E 

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APPENDIX~E 

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APPENDIX~E 

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APPENDIX~E 

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Δ ACKNOWLEDGMENTS 

This report was prepared under the direction of Robert A. Vito, Acting 

Regional Inspector General for Evaluation and Inspections in the 

Atlanta regional office, and Dwayne F. Grant, Deputy Regional 

Inspector General. 

Jaime Durley served as the lead analyst for this study. Other principal 

Office of Evaluation and Inspections staff from the Atlanta regional 

office who contributed to this report include Sarah Ambrose and Mina 

Zadeh; central office staff who contributed include Ayana Everett, Kevin 

Farber, Rob Gibbons, and Mark Richardson; Joyce Greenleaf from the 

Boston regional office also contributed. 

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