Pest Activity, Water Leaks, and Misuse of QC Laboratory in U.S. Drug Manufacturing Facility

On 29 October 2024, the U.S. Food and Drug Administration (FDA) has published a Warning Letter dated 21 October 2024. The document goes back to an inspection performed earlier this year at a manufacturer of over-the-counter (OTC) topical drug products in North Carolina.

The Warning Letter summarizes a couple of significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals

Condition of the Laboratory

The initial observation already says a lot about the condition of the buildings and facilities, especially the laboratory. The authority writes: "Our investigator observed pest activity in your raw material storage area, and evidence of water leaks and missing ceiling tiles in your drug manufacturing area. In addition, our investigator observed that your quality control (QC) laboratory was used by employees for meal preparation, dishwashing, and storage of soiled employee garments."

This misuse of the laboratory environment poses a high risk of contamination and compromises the reliability of product testing and quality control procedures. As the company failed to maintain clean and sanitary conditions in their manufacturing areas and was unable to provide sufficient measures to improve the condition in its response to the inspection report, the FDA is now demanding a series of measures, including:

A detailled corrective action and preventive action (CAPA) plan

Creation of detailed procedures

A risk assessment for all drug products distributed to the U.S. market

Laboratory Testing and Stability Testing Program

The company did not conduct appropriate laboratory tests for each batch of drug product to ensure conformance to specifications, including the identity and strength of active ingredients and microbial contamination. This oversight meant that products were released into the U.S. market without sufficient proof of their safety and effectiveness.

Furthermore, the firm failed to establish and maintain an ongoing stability testing program to support the labeled expiry of the distributed drug products. The FDA concludes: "There is no assurance that [the] drug products will remain acceptable throughout their labeled expiry period without an ongoing stability program."

Unapproved New Drug Violations and Misbranded Drug Violations

Another focus of the FDA's Warning Letter was the violation concerning the marketing of unapproved new drugs. Some of the company's products were found to be unapproved new drugs, violating various sections of the Federal Food, Drug, and Cosmetic Act. The Warning Letter also addressed issues related to misbranding under section 502 of the FD&C Act. The FDA explains in detail why the products did not meet the “generally recognized as safe and effective” (GRASE) standard required for OTC drugs

Conclusion 

The FDA warned that failure to promptly address these issues could result in severe regulatory actions, including product seizures, injunctions, and restrictions on new application approvals. The letter emphasized that the company's executive management must oversee and ensure compliance with CGMP requirements.

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FDA announces Experiential Learning Site Visit Program

The U.S. Food and Drug Administration (FDA) is announcing the Fiscal Year 2025 CDER Office of Pharmaceutical Quality (OPQ) Experiential Learning Site Visit Program (ELSVP). ELSVP is an educational initiative aimed at enhancing FDA staff's understanding of pharmaceutical manufacturing processes, innovations, and industry challenges. The program provides FDA staff with the opportunity to engage directly with pharmaceutical industry sites, gaining hands-on experience and insights into contemporary manufacturing and quality practices.

Background

The OPQ is responsible for ensuring the quality of medicines produced for the U.S. market. To better align regulatory oversight with the current industry practices and innovations, the FDA established the ELSVP as a mechanism for improving staff knowledge of pharmaceutical processes. This initiative supports FDA's mission to apply a science- and risk-based approach to pharmaceutical regulation.

How it works

The ELSVP is a site-based learning initiative where FDA staff visit pharmaceutical manufacturing facilities. These visits provide FDA reviewers, inspectors, and scientists with the opportunity to observe real-world manufacturing technologies and quality control systems. Key areas of focus include continuous manufacturing, advanced analytical tools, and comprehensive quality management systems. The program relies on voluntary participation from pharmaceutical manufacturers who apply to host FDA staff at their facilities. Participants from the FDA are then matched with the appropriate facilities for immersive, practical learning experiences.