FDA Warning Letter: Distribution of OOS Batches and Lack of Stability Data

On 18 April 2023, the U.S. Food and Drug Administration (FDA) has published a Warning Letter dated 06 April 2023 to a drug manufacturer in Mexico. The letter goes back to an inspection in October 2022, during which significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals were found.

The company's response to the Form FDA 483 that preceded the Warning Letter did not convince the FDA, "because it did not provide sufficient detail or evidence of corrective actions to bring [the] operations into compliance with CGMP."

Investigation of Out-of-Specification (OOS) Results

According to the FDA, the company did not adequately investigate out-of-specification (OOS) results. Even more serious than the fact that the firm had to admit that no procedure to handle OOS results was in place, is that batches of over-the-counter (OTC) drug product with OOS results were released and distributed.

So far, the firm did not provide a retrospective review to ensure that all former OOS results were thoroughly investigated. Furthermore, no OOS procedure or an implementation date for such a document was provided.

Stability Testing

Obviously, there was a lack of stability data to confirm the expiration dates of the drug products. The authority also writes that the temperature storage conditions were not monitored throughout the study, and there are no protocols for humidity.

Process Validation

Another finding mentioned in the Warning Letter is that the manufacturing processes was not adequately validated. According to the FDA, the company also has not implemented an ongoing program "for monitoring process control to ensure stable manufacturing operations and consistent drug quality."

Annual Product Review and Complaint Handling

The FDA writes that no adequate written procedures for annual product review and a for complaint handling were in place. The FDA concludes that the quality unit (QU) did not provide adequate oversight for the manufacture of the firm's OTC drug products.

In the overall view, the FDA considers the firm's quality systems as inadequate and strongly recommends engaging a qualified consultant. The FDA is awaiting a detailed response to the Warning Letter and has also called for a number of specific actions.

For more details, see the full Warning Letter to Zermat International S.A. de C.V. published on the FDA website.