The Generic Drugs Forum for 2026 got off to a great start this morning.  The two-day session is covering the “soup to nuts” of interest to generic drug sponsors.

Here are just a few tidbits from this morning’s session:

 

    1. The Refuse-to-Receive (RTR) rate for original ANDA submissions dropped from a high of 10.9% in FY 2017 to 3% in FY 2025. This signals better understanding of the OGD’s requirements by industry.  The goal of the OGD is to get the rate down even further, and this is why the FDA holds these informational forums.
    2. In the last quarter, only two ANDAs were reviewed sixty days past the goal date. In the second quarter of FY 2025, there were about seventy.
    3. The OGD hit > 90% performance for meeting GDUFA on-time performance metrics for ANDAs in 2025 and > 90% performance for meeting Controlled Correspondence (CC) response goals.
    4. When submitting a CC for a Maximum Daily Dose (MDD), only three requests may be included in each CC.
    5. As of March 8, 2026, the OGD has issued 2,407 Product-Specific Guidances (PSGs).
    6. 61% of PSGs have an in vivo bioequivalence requirement.
    7. Don’t forget to use two lots of Active Pharmaceutical Ingredient (API) for each strength of drug product in an ANDA filing.
    8. The number of minor deficiencies found in an ANDA filing review for completeness and acceptability are very important. If there are ten or more, the ANDA will receive an RTR letter.
    9. Prior to 2003, the Inactive Ingredient Guide was in a paper, non-searchable form. The electronic, searchable Inactive Ingredient Database (IID) began in 2003 and has evolved significantly over time.  The searchable database now provides currently approved levels for most inactive ingredients as well as a number of Maximum Daily Exposure (MDE) levels.  Currently, for the most part, if an inactive ingredient/excipient is used in an FDA-approved NDA drug product, use in a generic product is considered safe if it does not exceed the level previously approved.  However, the concept of calculation of the MDD for a drug product could play into a final determination of the safe level of the inactive ingredient/excipient.  Be careful!
    10. Inactive ingredients in biologic products or Over-the-Counter (OTC) products marketed under the OTC monographs are not included in the IID.
    11. The IID currently lists MDE limits for about 44% of inactive ingredients. The FDA says that it hopes to raise this number up to 70%.  There are also ongoing discussions during the Generic Drug User Fee Amendments (GDUFA) negotiations that could see up to 500 MDEs per year added to the IID after the start of GDUFA IV.
    12. Calculation of MDD for an API is, in many instances, straightforward; for instance, the number of tablets per day times the amount of API in each dosage unit. However, based on the specific disease state and/or dosage forms (e.g., topical product), a direct calculation using common key standardization, such as an average body weight of 60 kg or average surface area of 1.62 m2, might not always be possible.  The OGD does permit standardized calculations; however, there are so many potential exceptions that FDA toxicologists advise you to use a CC to affirm your position if there is any doubt.

 

One question posed by the audience had to do with non-proportional dosage strengths.  Say there is a 5-mg tablet and a 100-mg tablet where a single, highest strength tablet might provide the maximum exposure to an inactive ingredient at an acceptable level, but use of the lower strength would require twenty tablets to reach the same 100-mg dose.  The use of twenty tablets of the 5-mg strength might result in exceeding the MDE of one or more of the inactive ingredients.  The question being, is it unreasonable to assume that a patient would take twenty 5-mg tablets instead of one 100-mg tablet?  Melanie Mueller, Pharm.D., Ph.D., Master Toxicologist in the Division of Pharmacology/Toxicology Review (DPTR), Office of Safety and Clinical Evaluation (OSCE) in the OGD, says that there are no FDA-established limits on the number of tablets that would be considered for use of a lower strength before it might be unreasonable to assume that scenario.  Each scenario may need to be evaluated on a case-by-case basis.  She advises that the firm submit a CC to ensure that its view comports with the OGD’s current thinking for anything that may be a bit out of the ordinary.  It should be noted that she answered most questions for which the answer was not based on a definitive standard calculation of MDD by saying that the best avenue would be to submit a CC.  I take that to mean that you are taking a big risk if you don’t get the OGD’s agreement on your position before proceeding with the development of a formulation that may be impacted by a MDD issue unless there is unambiguous clarity.

Well, that’s it for the time I was able to spend this morning.  You still have time to register for Thursday’s sessions and, if you do, you’ll have immediate access to all of the presentations for both days.  You can register here.