GENERICS
FDA Aims to Approve Record Number of Generics

WARNING LETTER

The US Food and Drug Administration launched a new program on Oct. 4 to increase the number and variety of generic drugs available to the public, beginning in fiscal year 2008. The Generic Initiative for Value and Efficiency (GIVE) will use existing resources to help the agency "modernize and streamline the generic drug approval process," according to FDA.

"To keep pace with the increasing number of generic drug applications, FDA will implement some changes to the generic drug approval process," said Gary Buehler, director of FDA's Office of Generic Drugs (OGD), in an agency release. "The GIVE plan outlines ways to maximize the use of our resources so that FDA can review and approve even more high-quality generic drugs during the upcoming fiscal year than it did in 2007."

More than 600 generic drugs, which cost 30–80% less than brand-name drugs, were approved by FDA in fiscal year 2007. This number represented a 33% increase over fiscal year 2006. Although generic drugs undergo FDA review before approval, generic drugmakers are not required to repeat the extensive clinical trials that have already been used to develop the original drug, Buehler pointed out. "But they must scientifically demonstrate that their product is bioequivalent" or performs in the same manner as the brand-name product. Generic manufacturers must also demonstrate that the generic version delivers the same amount of its active ingredient over the same amount of time, and uses the same administration route as the brand-name drug.

Under the GIVE initiative, FDA intends to increase the number of applications it reviews and facilitate the review of applications to make more generic drugs available to the public more quickly. These efforts should cut down on the backlog (approximately 1300) of abbreviated new drug applications (ANDAs) within OGD. As a review-oriented program, FDA says that GIVE will focus on:

• Mobilizing staff efforts to increase review productivity
• Optimizing the capacity and capability of all assets within OGD and leveraging resources from other FDA components wherever possible
• Using every avenue possible to recruit, hire, and train reviewers for critical need areas
• Using new application review procedures to increase the number of low-cost-generic products available to consumers.

Specific GIVE improvements in the OGD review process, according to FDA information, will include:

• Revising the review order for certain applications. First generic products, for which there are no blocking patents or exclusivity protections on the reference listed drug, are identified at the time of submission for expedited review.
• Using a new review process for the chemistry, manufacturing, and controls information in the ANDA called "Question-based Review." The process is based on the Quality Overall Summary and other components of the common technical document and uses the principles of quality by design.
• Completing team reviews in the Divisions of Chemistry of multiple applications for the same drug product, including early review of drug master files to ensure timely resolution of any issues
• Encouraging sponsors to submit bioequivalence data in summary table format to enable a more rapid review of data
• Concluding the review of changes being effected (CBE) supplements with an approval, if appropriate, at the same time it is determined the proposed change qualifies as a CBE supplement
• Capitalizing on the capabilities of regulatory project managers in the divisions of chemistry and bioequivalence, including acting on administrative supplements and responding to requests for information
• Developing mechanisms to leverage the power of the Internet to provide dissolution and bioequivalence information, quality overall summary templates, bioequivalence data table formats, and microbiology review templates to the industry to ensure submission of full documentation of the quality of the products
• Increasing direct communication with individual sponsors and industry as a whole through communication about application-specific matters and providing training to the industry in meetings and webcasts.