BIOBATCH PACKAGING REQUIREMENTS WILL BE DOSAGE-FORM OR PRODUCT SPECIFIC

BIOBATCH PACKAGING REQUIREMENTS WILL BE DOSAGE-FORM OR PRODUCT SPECIFIC in stipulating whether 100% of the bioequivalence batch for an ANDA must be packaged, FDA Office of Generic Drugs Acting Director Douglas Sporn told the National Association of Pharmaceutical Manufacturers June 15. "There will be a [policy] guide coming out that...will be dosage-form specific or product specific, and I think it should minimize the number of protocols that we should see, and it will be a lot clearer to you when 100% packaging is required and when it is not." The OGD policy and procedure guide (PPG) could be issued by the end of the summer if it clears review by division directors in the office.

Current OGD policy always requires firms to package 100% of the exhibit biobatch. Sporn said the changes are motivated both by industry's dissatisfaction with current policy and by "concerns we have had internally" that the current requirements for 100% packaging "could potentially be discouraging firms" from making biobatches larger than the minimum required. The upcoming change in policy is relatively recent; last August the agency reaffirmed in a letter to industry that ANDAs must contain data supporting complete packaging of the test batch ("The Pink Sheet" Aug. 9, 1993, T&G-3).

The agency is also developing an annual report guide common to OGD and the Center for Drug Evaluation & Research "that will make much clearer to industry what we expect to see in reports," Sporn said. The guide will contain a section "that will request... not require...the information on who are suppliers for the active ingredients, chemical tests and specifications" for a drug product.

In addition, a "common review format" for NDAs and ANDAs is being developed to make application review "standard," Sporn said. This format would result in a review process "that is essentially the same" from the applicants' perspective, he said, but "the order of different things in the application could possibly change."

The agency's Generic Drugs Advisory Committee will meet jointly with the Dermatologic Drugs Advisory Committee "some time this fall" to help FDA finalize its interim guidance on bioequivalence standards for topical corticosteroids, the OGD director said.

The committees will review data developed since their last meeting on topical corticosteroids in March of 1992 ("The Pink Sheet" March 19, 1992, p. 19). An interim guidance was issued in July of that year ("The Pink Sheet" July 6, 1992, T&G-5). The guidance encouraged the use of a chromameter to evaluate skin blanching along with visual scores when conducting the vasoconstrictor assay bioequivalence studies.

A guide on "scale-up and post-approval changes" is being developed by an ad hoc working group that includes CDER Associate Director for Science and Medical Affairs Roger Williams, MD, and Associate Director for Research Lawrence Lesko, PhD. The PPG will "much more clearly lay out what is considered a major and what is considered a minor change in immediate-release dosage forms," thus making clear which changes could be put in an annual report and which would require filing of a manufacturing supplement.

A draft Federal Register proposal that FDA "stop accepting type I DMFs" (Drug Master Files) is also in the works, Spore said. "We don't think we need those," Sporn said of the documents; FDA has been moving towards requiring that firms incorporate the information currently contained in type I DMFs into each individual ANDA or AADA. The Pharmaceutical Research & Manufacturers of America objected to this change in April 8 comments to the agency ("The Pink Sheet" May 16, T&G-7).

OGD is also working on developing a "common review format" for type II DMFs, Sporn noted. This policy guide would "make it much clearer both to our chemists and to industry what chemistry to look at when they go into that type of drug master file for the drug substance." OGD and CDER are working to develop a guidance on "when chemists are to review a DMF in clearing applications," the FDAer said, adding that FDA's goal is to "come up with a policy that covers DMFs for both the new drug and generic side."

The upcoming changes in OGD's policies regarding DMFs are partially a response to the HI-IS Inspector General's 1991 report on FDA. That report found that the agency "had neither specific guidance for chemists on when...and how the reviews were to be performed." The IG is planning another review of FDA's DMF policies in FY 1995 to assess FDA's corrective actions.