FDA Complete Response Letters Reveal Compliance Gaps: Identifying Opportunities for Technology Vendors

Pharmaceutical manufacturers are subject to Current Good Manufacturing Practices (cGMP) that look to ensure safety for patients and the quality levels of the drugs and vaccines produced. Adherence to the practices are enforced by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The FDA published over 200 Complete Response Letters (CRLs) in response to approved New Drug Applications (NDAs) and Biologics License Applications (BLAs) between 2020 and 2024. The letters are issued to manufacturers that have, on inspection, failed to meet the cGMP at their facilities, but have since that time rectified the situation. Contents of the letters shine a light on working practices that don’t meet standards and provide opportunities for technology vendors to help rectify.

The issues are wide ranging and include glass containers being incompatible with alkaline solutions (Gilead Sciences), the overall control strategy for the manufacturing process for lebrikizumab (Eli Lilly), and cGMP violations that include falsification of manufacturing data, inadequate cleaning procedures, and failure to properly test incoming raw materials (Tyche Industries).

A couple of notable innovations in suppliers’ offerings can support (cGMP) compliance. These include MasterControl now including human-in-the-loop oversight as part of the solution’s content generation and documentation summarization capabilities. Veeva Vault Quality Management System (QMS) from Veeva Systems enables customers to align quality related information, clinical data with regulatory data. Finally, Dot Compliance launched Dottie AI, which is an Artificial Intelligence (AI) assistant for quality engineers that can be utilized to support cGMP.

The fact that even well-known manufacturers such as Eli Lilly can fall foul of regulators should encourage technology vendors to go through the CRL database and endeavor to showcase that their solutions can support cGMP.

ABI Insight “Regulators Issue Good AI Practices for the Pharmaceutical Industry” outlines that the FDA and EMA have published joint principles around AI. AI can help notify production staff that glass containers are incompatible or that manufacturing processes are about to veer outside of guidelines. But AI isn’t going to solve issues if manufacturers continue to collect data electronically with paper. 

Pharmaceutical manufacturers will continue to be required to improve their data governance both in terms of processes and data that support decision-making such as AI systems. Transparency will be critical both internally and throughout the process from drug discovery to consumption by the patient, in fact the Drug Supply Chain Security Act (DSCSA) in the United States, mandates end-to-end traceability.

Pfizer is one example of a manufacturer that is utilizing digital technologies as part of its processes to ensure GMP compliance. These include not only QMSs, but also the use of data analytics to identify risks that processes won’t meet inspectors’ expectations. The overarching culture is Quality by Design (QbD) principles, as well as proactively rectifying issues such as missing information and robust Corrective and Preventive Actions (CAPA) processes to get to the root cause of issues.

Pfizer was identified as best of breed for utilizing technologies to ensure compliance in ABI Research’s Digital Transformation Benchmarking Index for Pharmaceutical Manufacturers Best of Breed presentation (PT-3443), which showcases ABI Research’s evaluation of 15 large pharmaceutical manufacturers on topics such as digital leadership and utilization of AI on the factory floor.