The second day of the Generic Drugs Forum provided a significant amount of new and rehashed data, including explanations and suggestions regarding certain application submission issues, including but certainly not limited to DMFs, data integrity and the ongoing nitrosamine saga. Here are a few of the helpful hints presented:

    1. When providing amendments to DMF, the DMF holder should summarize the changes in tabular format and clearly focus on the changes.
    2. If a change to a DMF requires an applicant to supplement its ANDA, the ANDA applicant should identify the changes that require supplementation and clearly identify changes that are subject to the DMF and identify the DMF number in the cover letter to the supplement.
    3. Be certain that letters of Authorization are included and updated. And be certain to cite secondary DMFs. All DMF submissions should contain a completed FDA Form 3938
    4. FDA teams went over common deficiencies for various complex API and drug products. You can and should review this information once the slides are available on the Small Business and Industry Assistance web site.
    5. A session on Data Integrity (DI) identified problems found with certain CROs. The FDA identified six (6) different CROs over a fifteen (15) year period (2011-2025) that had significant DI issues which lead to ANDA sponsors having to have studies repeated at different CROs. These DI findings caused delay in approvals, changes in therapeutic equivalence codes for approved products and significant expense to sponsors that had to have the BE studies repeated. Please be certain to carefully evaluate your CROs and look for data that just does not make sense or data with “unusually similar pharmacokinetic profiles or unusual PK trends. Also look for questionable repeat analysis or be suspicious of switching test and references standards or making dilutions to make the study pass BE criteria”.
    6. FDA presenters discussed in detail the current state of control of nitrosamines and offered an alternative bioequivalence approach (see table below) for product reformulations with an FDA researched antioxidant. Please note that this alternative approach is not applicable to narrow therapeutic index drugs, buccal dosage forms, orally disintegrating tablets or chewable tablets. In addition, FDA will entertain additional alternative approaches on a case-by-case basis.

The items identified in this blog post are simply highlights of some of the presentation topics. Please use FDA’s other available resources and guidances that may be instructive relative to your individual issue or scenario, or contact Lachman Consultants for additional assistance.