FDA Warning Letters Dipped, But Don't Get Cozy

By Douglas B. Farquhar, Hyman, Phelps & McNamara

At the GMP by the Sea Conference in Cambridge, Maryland, a representative of FDA’s Center for Drug Evaluation and Research (CDER) presented some interesting trends in enforcement showing a heightened level of discretion from regulators when it comes to inspections where official action is recommended.

During the conference, which happened in August, Jennifer Maguire, the director of the office of quality surveillance within the Office of Pharmaceutical Quality at CDER, told attendees that there were 163 FDA inspections from the beginning of October 2022 to the end of March 2023 conducted at drug manufacturing facilities (excluding drug compounding facilities) that were classified as official action indicated (OAI). OAI is FDA’s classification for facilities it deems to be in an unacceptable state of compliance.

Of those, only about a quarter (26%) resulted in warning letters, fewer than a quarter (19%) resulted in the imposition of import alerts (restricting or prohibiting imports into the United States of drugs from a specified facility), slightly more (24%) resulted in regulatory meetings with the agency, and the plurality (29%) resulted in FDA exercising “regulatory discretion,” which means a decision not to take enforcement action. One inspection resulted in FDA’s securing a consent decree to restrict or shut down operations, and two resulted in an “untitled letter,” which is not available to the public on FDA’s website.

The large percentage of OAI inspections resulting in the exercise of regulatory discretion is unusually high. Lest we grow too optimistic, though, industry should be aware that this larger-than-historical number of what is a favorable disposition may not be a trend that will continue. It is believed that many of the inspections conducted during this period were of facilities producing essential medicines, such as COVID-related medications, for which FDA did not want to create or exacerbate product shortages.

Other Interesting Datapoints From The Presentation

For the period from fiscal year 2000 to May of 2023, the percentages of drug manufacturing inspections with OAI classifications were lower in China (about 5% of inspections) than in the United States (8%). Again, this is a trend that may not continue: not many FDA inspections were conducted in China during this period due to COVID travel restrictions, whereas U.S. facility inspections are approaching traditional levels.

FDA has created a list of essential medicines, and provided calculations of how many of the drugs were totally or partially manufactured in countries other than the United States. FDA also looked at how many of the active pharmaceutical ingredients for those drugs were manufactured overseas.

• Remarkably, only 11% of the finished drug products were totally manufactured overseas, although 92% of the API for those drugs was either totally or partially manufactured in foreign countries.
• Of those facilities manufacturing essential medicines deemed to be the product of complex manufacturing processes, 68% were in the U.S., the European Union, or the United Kingdom. For those facilities manufacturing essential medicines deemed to be non-complex, 60% were in these countries.

These figures confirm that, although the vast percentage of active ingredients of important pharmaceuticals come from overseas, the actual manufacturing of finished dosage form drugs occurs in the United States or Europe.

A version of this article was published first on Hyman, Phelps & McNamara’s FDA Law Blog. It is republished here with permission.

About the Author:

Douglas Farquhar is a director at Hyman, Phelps & McNamara. Since joining the firm in 1997, he has advised pharmaceutical and medical device manufacturers and wholesalers, compounding pharmacies, and individuals on a wide range of enforcement activities, including consent decrees, criminal investigations, debarment issues, arbitration proceedings, civil seizures, FDA inspection issues, and injunctions. He has a broad understanding of the investigatory process and has negotiated settlements and resolutions for both industry and government.