The FDA report Advancing Health Through Innovation: New Drug Therapy Approvals 2023 (here) outlines the progress that the Agency has made on the approval of novel drugs (those “which are for therapies that have not previously been approved in the U.S.”), and provides a number of interesting statistics, so I urge you to read the full report. I think the most interesting and relevant metric is that, of the 55 novel drug therapies approved in 2023, 49 or 84% were approved in the first review cycle.

This is no easy task as these novel drug products must present the most complex approvals since the Agency is dealing with drugs that either have different mechanisms of action, are new chemical entities, or treat diseases for which there may be no other therapies available, but still the FDA was able to approve 84% in the first review cycle. CDER describes the attributes that led to this success in the conclusion of the report:

“Reviewing a drug application — whether for a novel drug or a supplemental approval — is a collaborative, well-coordinated process that involves scientific, regulatory, and policy experts from throughout CDER and sometimes other parts of the agency. For each application, we perform a very careful and diligent analysis of safety and effectiveness data, including a benefit-risk analysis that factors in the severity of the disease or condition, the currently available treatment options, and the intended patient population. If the therapy meets the standard for approval, we must reach agreement on the indication, labeling, safety issues, and other considerations.

We often consult outside scientific experts, patients and patient advocates, industry representatives, academics, and other community members who are involved in drug development and review. Each of these parties has their unique expertise and perspective, and we consider their viewpoints. We take our regulatory decision-making seriously, because we know our decisions affect the health and well-being of patients and consumers nationwide.”

Remember, these are first-time approvals of drugs that have never been approved before, and yet CDER has an 84% first-cycle approval rate. This raises questions in my mind regarding the much lower first-cycle approval rate for generic drugs, which was 18.9% (148 of 782 applications) in FY 2023. Why is it that, for a duplicate copy of a drug that has been around for years, the first-cycle approval rate is so much lower? Is it because of the much larger staff in the new-drugs side of CDER? Is it due to the much larger volume of ANDAs submitted? Is it because the expectations are better understood by industry on the new-drugs side of the house? Is it because the applications are of lower quality on the generic side of the house? Or is it because there are different standards for approval of new drugs versus generic drugs? The issue may be better understood by reading the two paragraphs taken from the conclusion of the novel drug report reproduced above.

It’s funny that these questions are exactly the same ones that have been asked regarding the low rate of first-cycle approvals ever since I joined the Generic Drug Program in 1984, the start of the Generic program as we know it today. And while the first-cycle approvals have jumped from less than 1% in the years prior to GDUFA to 18.9% in 2023, the answers to the questions regarding the discrepancy between first-cycle approvals of new drugs and generic drugs are still not clear.

The report on novel drug approvals is quite enlightening, and the statistics provide a look at what PDUFA and its subsequent iterations over the years have done for improvement of new drug approvals since inception in 1992. While GDUFA is only in its third iteration since its first effective date on October 1, 2012, one might think that (by now) the requirements should be well known, but still abbreviated new drug applications typically undergo at least two cycles of review, with most experiencing three or more cycles prior to approval. Given that there are other unique regulatory and scientific questions with generics that must be answered (for instance, sameness of ANDA products, labeling issues regarding carve-outs, unique bioequivalence issues, etc.), it is still not entirely clear to me why the industry and the OGD cannot seem to increase the percentages of ANDA first-cycle approvals. Is it just me or do others have the same questions?