Facility Issues Sink Minor Amendment Designation

Historically, the Office of Generic Drugs (OGD) has classified major/minor amendments on the time necessary for review.  Minor amendments required minimal review, while major amendments required extensive review.  If there was an issue with a facility (e.g., cGMP), the old Deficiency Letters (DLs) and Complete Response Letters (CRLs) used to state that the firm should not respond to the letter until the facility issues have been resolved.  Now, the industry is dealing with a revised final guidance, ANDA Submissions – Amendments to Abbreviated New Drug Applications Under GDUFA, July 2018 (here), that puts the kibosh on that principle and places an added penalty on the GDUFA goal date.

We have heard grumbles from industry representatives regarding this seeming change in policy and are trying to speculate why such a change was made, given that it seems to fly in the face of the Commissioner’s stated objective to try to get generic products to the market as soon as possible.  So, now, even if the OGD or Office of Product Quality (OPQ) remaining deficiencies are minor in nature, if there are any issues related to a facility that are unresolved at the time of the review, then the resubmission is classified as a major amendment, placing the response into a longer queue.  This seems somewhat arbitrary; especially if the facility issues are resolved quickly, why should the timeline for the ANDA response review be penalized?

Is it a communication issue between ORA, Office of Compliance, and OGD/OPQ that necessitated the change?  Is “kicking the review can down the road” happening because of workload issues and pressure to meet GDUFA II goal dates?  We don’t know, but the difference in review time for a minor and major amendment certainly can make a financial difference to a firm, and potentially a difference to patients if a faster review and approval could impact prices at pharmacies.

I can see no rationale for this change.  The old system seemed to work well and delayed a firm’s response to a CRL until the firm could certify that facility issues had been resolved.  Why, then, should the OGD/OPQ review goal date be longer as a firm must still wait until all issues are addressed until it submits its response?  This seems to be a double penalty on the applicant.

Check out the one sentence regarding what constitutes a major amendment in Appendix A of the Amendment Guidance referenced above; it seems to be causing great angst in the generic industry and reads, “Deficiencies that indicate one or more facilities were found inadequate at the time of action.”  This seems to be something that needs to be revisited.