Alerts and Updates

OIG Reports on FDA Generic Drug Review Process

June 23, 2008

Pharmaceutical Manufacturers and Sponsors Be Aware

On June 13, 2008, the Office of Inspector General for the U.S. Department of Health and Human Services (the "OIG") released its report entitled "The Food and Drug Administration's Generic Drug Review Process." The report outlined the evaluation process for Abbreviated New Drug Applications ("ANDAs") as well as how long the evaluations took from start to finish in 2006. Additionally, the OIG used the report to offer recommendations to the Food and Drug Administration's Office of Generic Drugs ("OGD") regarding how it could increase efficiency and expedite generic drug release. Manufacturers should be aware of procedural changes likely to affect FDA new drug approvals.

Prior to marketing and selling or marketing generic drugs, manufacturers must submit ANDAs to the FDA for approval. New generic drugs may be either approved, tentatively approved, or disapproved. Every ANDA submission is reviewed by Division of Chemistry, Division of Bioequivalence and Division of Labeling and Program Support. Each Division reviews the ANDAs separately, and all must complete their respective reviews despite prior outright disapproval by another Division, which more often than not comes from the Chemistry Division. The OIG assessed the review process for 989 original ANDAs under review during 2006.

Federal law requires that submissions receive a status determination (i.e., approval or disapproval) within 180 days of filing. However, nearly all evaluations required substantially longer to reach completion. Prior to even entering the queue for the various Divisions to evaluate, the OGD spends nearly 60 days simply assessing the completeness of the ANDA. Of 535 ANDAs approved in 2006, the median approval time was 17 months, nearly three times longer than mandated by federal law.

Of all ANDAs in 2006 with review times exceeding 180 days, nearly 70% of the reviews were not begun prior to the 180-day review period expiration. According to information from OGD reviewers, queue time ranged from two to 10 times as long as actual review time.

Approval status appeared dependent upon chemistry deficiencies or valid patents or exclusivities existing for the brand name drug. The Division of Labeling permits informal application amendments prior to determination to remedy minor deficiencies, thus avoiding a disapproval, which ultimately requires formal amendments. A vast majority of applications disapproved in 2006 suffered chemistry deficiencies, while all 3% of the 2006 ANDAs given tentative approval were not granted outright approval due to existing valid patents or exclusivities.

Prioritization practices have a great impact on total review time, and the Center for Drug Evaluation and Research ("CDER") has a policy of evaluating ANDAs based on the order in which they are received. Current policy dictates that ANDAs closest to ultimate approval as well as those previously disapproved and supplemented with minor amendments are bumped to the front of the queue, thus greatly increasing queue time for newly submitted ANDAs and those with major amendments. For example, if an ANDA has no chemistry deficiencies, the other Divisions are expected to bypass the standard priority protocol and expedite their portion of the ANDA evaluation. However, this prioritization practice is not implemented uniformly across OGD Divisions, and the various Divisions have no system in place for consistent classification and prioritization of consults. The priority policy is intended to promote application review efficiency, yet in practice seems to do little to actually accelerate ANDA approval.

The OIG offered recommendations to improve efficiency at the FDA. First, the OGD is urged to identify common ANDA deficiencies and offer more guidance to the generic drug industry to decrease the percentage of applications disapproved. If implemented, this practice would likely reduce the volume of amendments filed for disapproved ANDAs. In turn, that would reduce time spent in queues for other ANDAs. The OIG also encouraged the FDA to increase the percentage of original ANDAs reviewed by all Divisions within 180 days.

Lastly, the OIG urged the FDA to identify new prioritization practices to reduce review times for abbreviated new drug applications close to approval. Specifically, the OIG recommended evaluating and modifying the consultation process to meet review timeframes specified by FDA policy, and identifying and assigning high priority to ANDAs closest to receiving approval.

The FDA agreed with the need to identify and inform the industry of common deficiencies ultimately preventing approval, yet made no clear indication of whether it concurs with the other recommendations. The FDA has considered modifying its processes and has developed a focused staffing scheme that includes increasing the reviewer workforce. More staff requires more funding; and the FDA's 2009 proposed budget is reflective of the increased demand.

The industry may see a significant increase in filing fees for generic drug applications. However, increased efficiency within the OGD may significantly accelerate new generic drug market entry.

For Further Information

If you have any questions about this Alert or would like more information, please contact Frederick R. Ball, any of the other lawyers in the Pharmaceutical, Medical Device, Pharmacy & Food industry group, any of the attorneys in the Intellectual Property: Generic Pharmaceuticals Practice Group or the attorney in the firm with whom you are regularly in contact.

Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.