Investigating and addressing deviations in the manufacturing process is a critical requirement for compliance with Good Manufacturing Practices (GMP). A Warning Letter (WL) issued to Sanofi’s drug manufacturing facility in Paris highlights the procedural deficiencies that all manufacturing facilities should address to stay GMP compliant.
Deviations from the process could happen for various reasons. Per the GMP requirements, the facility must investigate all deviations, take corrective and preventive actions (CAPA), and ensure the minimization of future repeat occurrences. All deviations and associated CAPA must be conducted promptly and adequately documented. Facilities are also required to have appropriately designed equipment for each product being manufactured and have appropriate quality control and quality assurance (QC and QA) processes. From this WL, it seems that the Sanofi facility was deficient in all these requirements.
The FDA inspectors observed that about 20% of the total manufacturing runs conducted over 2 and half years were rejected for contamination or other quality failures. Obviously, one out of five manufacturing runs failing because of quality issues is unacceptable as it demonstrates a lack of process control. The site’s investigations “failed to identify all potential contributing causes, did not consider the conclusions of an engineering study that contradicted the assigned root cause for the OOS appearance events, and did not document all investigational activities.” The deviation investigations were also not conducted on time with some investigations more than 180 days behind schedule. The FDA inspectors also found multiple deviations and repeated out-of-specification (OOS) events that were not even reported or recorded. The CAPA activities were inadequate as well and the incidents kept repeating. The FDA concluded that the facility’s QA unit lacked appropriate authority and sufficient resources to conduct its job.
The above observations appear to be scathing criticism of the site’s operations as some fundamental compliance requirements were not met over an extended period. For us, the intent of highlighting this WL is not to further beat up a major global organization already likely going through major internal reviews and trouble-shooting but to highlight for all other GMP facilities the critical importance of dealing with deviations, CAPA, and OOS events in a timely manner. We can learn from someone else’s mistakes which is why WLs are made publicly available by the FDA.
