As former OGD Director Kathleen “Cook” Uhl, MD used to say, “Read the commitment letter.”  This certainly applies for GDUFA III and in spades.  Why?  Because a number of enhancements that were made in the GDUFA III negotiations are designed to make the review process more efficient and improve the number of first‑cycle approvals.

In GDFUA I and II, there was no penalty for submitting an original ANDA or supplement when one or more of the facilities listed were not ready for inspection.  That has changed in GDUFA III.  Actually, you are still getting a break because the FDA could have decided to refuse to receive the ANDA if a facility was not ready for inspection but it never did and it still seems that it won’t.  Under the new GDUFA III commitment letter (here), if a firm marks on FDA Form 356h that a facility is not ready for inspection, the FDA will assign a fifteen‑month goal date.  And should the ANDA applicant not submit an amendment at least thirty days prior to the original fifteen‑month goal date stating that the facility is now ready for inspection, the FDA will assign another fifteen‑month goal date for a total of thirty months to potentially receive the first CRL.  Note that the FDA will delay any substantive review of the ANDA until the amendment notifying it that the facility or facilities are ready for inspection, at which time it will assign a standard or priority review goal date.

This keeps the OGD from wasting time in reviewing an ANDA until it can be assured that all facilities listed in the ANDA and on FDA Form 356h are, indeed, ready for inspection.  The FDA has issued a draft guidance titled Facility Readiness: Goal Date Decisions Under GDUFA (here).  Make sure you read this draft guidance carefully; it will be important for assigning the appropriate GDUFA goal date.

There is a bit of a lack of clarity regarding what will happen if an applicant checks the box that says a facility is ready for inspection but, when compliance tries to schedule an inspection, the facility says it is not ready.  What is the penalty for an incorrect statement on the 356h?  Will the FDA just simply adjust the GDUFA goal date to fifteen months if it was originally a standard review?  The other question that needs to be answered is how the FDA will calculate approval times for applications that are submitted with facilities not ready for inspection.  It could be up to thirty months just for the initial review!  This could significantly skew approval‑time calculations to the detriment of the FDA.  I am sure there will be other takes on this guidance as well as the other guidances that seem to be popping up now that GDUFA III has been reauthorized.