Through March 16, the Office of Generic Drugs has issued 30 full approval actions and 7 tentative approval actions. This appears to be about the average number of mid-month approval actions totals we have seen for this current fiscal year. With fewer ANDAs being submitted, it is not clear to me why the approval actions are not surging ahead.
We still see multiple rounds of complete response letters (CRLs), interim response letters (IRs) and discipline review letters (DRLs) that ask additional new questions that were not addressed in the previous iterations. This frustrates the industry and highlights that the concept of a “first-time complete review” of the ANDA is not all it is cracked up to be. Granted, a firm’s responses to a CRL might raise the need for additional clarification or response but the issue of new deficiencies that seem to come out of the blue in cycle 2 or 3 must be addressed as they continue to frustrate the ability of the Agency to approve generic drugs in one or two cycles. Until a “complete review” is actually a complete review, I don’t see the number of first or second cycle approvals increasing anytime soon.
Clearly there is more work that needs to be done on industry’s part but there is also more work that needs to be done on OGD’s part. With the number of reviewers and their different backgrounds, the recipients of these communications receive a different set of questions from different reviewers. Thus, even if a firm diligently categorizes its previously received deficiencies to address them in a new filing, they might still receive different questions, particularly when a new reviewer picks up one of their applications. This is not a new problem and, after 31 years of Hatch-Waxman submissions, there still does not appear to be an easy fix.
One other issue that is also not new has to do with the workflow stream, as ANDA reviews come from multiple reviewers on a team and flow through a single supervisor. The proposed deficiencies may look reasonable on their face (as stated in the proposed CRL, IR, or DRL), but the supervisor does not always have the time to go back into the source ANDA document to see the details that precipitated the deficiency and so the letter may move forward to the applicant without the supervisor being able to fully vet the deficiency. There are cases where the deficiency is either not appropriate, or where the reviewer just missed the relevant information that already was in the application. I tend to think that this is more the case in the eCTD than it was in the old paper ANDA format but that may be because I am a dinosaur raised on paper!
However, one would think that with the advances in AI and all of the talk that the administration has engaged in about its use in speeding up drug approvals, that the standard eCTD format would make for an easier, more complete and efficient review, but I don’t think that the review process and incorporation of AI into the review process is there yet. Anyway, I guess that means that sometimes I just need to vent and this appeared to be the day on which I get to blow off some steam. Let me know if you see the same issues in your reviews or if I am just hallucinating like AI does sometimes! You can send your thoughts directly to r.pollock@lachmanconsultants.com.
