Bing Li of the FDA’s Division of Bioequivalence
At the recent Orlando Inhalation Conference, Bing Li of the FDA’s Division of Bioequivalence in the Office of Generic Drugs of the Center for Drug Evaluation and Research (CDER) offered practical advice for companies submitting Abbreviated New Drug Applications (ANDAs) for generic nasal sprays.
Between 1987 and December 2013, Li says, her office received 85 nasal spray ANDAs. A total of 27 of those ANDAs have been approved, and 22 are still awaiting review. The FDA refused to receive 4 of those 85 submissions, and 32 were withdrawn.
Reasons for refuse-to-file ANDAs include submissions for which the test formulation is not qualitatively (Q1) and quantitatively (Q2) the same as the reference drug formulation and studies with unacceptable clinical endpoints.
Li cites three common errors in conducting in vitro bioequivalence testing that can lead to the rejection of an application, along with the solution to each problem:
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Error: Averaging multiple actuations from spray pattern tests to conduct a population bioequivalence (PBE) analysis
Solution: Use only a single actuation for the spray pattern test as recommended in the Draft Nasal BA/BE Guidance -
Error: Using the test product to conduct the pre-study validations for bioequivalence in vitro tests
Solution: Use the reference drug product to conduct pre-study validations -
Error: Using only 2 batches of the reference product
Solution: Use 3 or more batches of the both the test product and the reference product.
With an average of 6 new nasal spray ANDAs submitted each year, the backlog is growing, and poorly organized applications that can take months to review have contributed to the problem.
On the next page: hints for reducing review times
