FDA official discusses common shortcomings derailing ANDAs

Posted on April 27, 2022 | By Joanne S. Eglovitch

The U.S. Food and Drug Administration (FDA) rejected a lower number of abbreviated new drug applications (ANDAs) in fiscal year 2021 through its Rejection of Receipt (RTR) mechanism compared to previous years, said Peter Enos, a reviewer with the agency’s office. of Generic Medicines. He attributed the improvement to increased transparency with industry, better filing practices and better communication with claimants.

Enos also shared how the industry can improve its submissions to avoid RTRs on day two of the FDA’s Generic Drug Forum on April 27. The forum was sponsored by the FDA’s Small Business and Industry Assistance (SBIA) program.

FDA figures show that in fiscal year 2021, 4.7% of the 808 ANDA applications were deemed RTR, which is lower than the rejection rate of 8.33% of the 1,057 applications submitted in FY2021. the 2018 financial year.

The major deficiencies in FY2021 triggering an RTR included inadequate stability data and insufficient Q1/Q2 similarity studies to the reference drug (RLD). Other major issues were inadequate dissolution studies, insufficient identification of impurities and inadequate bioequivalence studies, and lax justification for the use of certain inactive ingredients.

To ensure the acceptability of the stability data, Enos stated that “it is imperative to provide at least three test batches using two [active pharmaceutical ingredient] API lots of each strength, and data must include at least six months of accelerated, long-term study data with three time points.

Interim studies should be performed if there is a stability failure at any time in the accelerated studies.

Stability studies should also be studied for the most pessimistic and non-pessimistic scenarios.

To avoid inadequate Q1/Q2 comparisons, sponsors should ensure that parenteral pharmaceuticals contain the same inactive ingredients and at the same concentration as the RLD. He pointed out that exception excipients that diverge from the RLD are permitted if used in buffers, thickeners or antioxidants. Exception excipients are not permitted in ophthalmic products.

To ensure that dissolution studies are adequate, sponsors have been advised to consult the FDA’s Product Specific Guidelines (PSGs), which include dissolution study recommendations and other guidance for developing products. specific generics.

These dissolution studies must include a minimum of 12 dosage units for each concentration of the test product and the RLD. PSG’s latest guidelines were released in February. (RELATED: FDA releases 43 new and revised product-specific guidelinesRegulatory guidance February 17, 2022)

In other logistics areas, Enos said ANDAs should be in English. In addition, submissions in the Electronic Common Technical Document (eCTD) must be legible, pages must be oriented correctly, and submissions must include adequate and descriptive bookmarks or hyperlinks.


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