When Watchdog began thinking about this week’s column, the plan had been to discuss the US Food and Drug Administration’s approach to releasing complete response letters (CRLs), what the agency’s decision to pause public disclosure meant for the future of the policy, and what the last letter released before the pause could tell us in particular about the state of drug development.
Then the Pink Sheet scooped that CRL releases have been unpaused, and we have a few more lessons for you.
The FDA had begun posting CRLs, the formal notices telling a company its application cannot be approved in its current form, for unapproved products in September 2025, part of a “radical transparency” push under then-Commissioner Martin Makary. But in April, a law firm filed a citizen petition on behalf of an unnamed manufacturer, arguing the disclosures broke several laws at once, and the flow of letters simply dried up.
Agency officials continued to say that CRL posting would continue, but the legal cloud over the program was evident in the development of a proposed reg that would formally end the “longstanding presumption” that an application’s very existence is confidential and the FDA’s request to Congress for explicit statutory authority.
So it seemed we wouldn’t be seeing any fresh CRLs for a while, and an HHS spokesperson even acknowledged there was a pause. However, the floodgates opened shortly after that, and 16 previously unpublished letters were posted.
The Surprising Challenge of Pharmaceutical Manufacturing
Nearly all of the new batch of letters cited facility inspection or product quality issues that are heavily redacted. (If you, dear reader, can divine particular application deficiencies based on the size and shape of these vast gray boxes, please share your dark magic with me!)
Manufacturing is, of course, a critical element of the pharmaceutical universe, but it receives surprisingly little policy attention outside the geopolitical “we should do more of it here” context, even though GMP issues often are responsible for approval delays, as the most recent batch of letters illustrates.