16/17 November 2021
What are the authorities' requirements regarding process validation? Regulatory GMP inspection reports are useful in answering that question. The "Freedom of Information Act" obliges the US FDA to publish inspection results. The FDA does that particularly when it comes to warning letters.
As is customary when it comes to deficiencies regarding process validation, the FDA cites 21 CFR 211.100. The FDA criticised the insufficient process validation and the inadequately qualified equipment. They particularly took issue with the process qualification studies and the ongoing monitoring program, which shows process stability and ensures constant product quality. Although the drug manufacturer pledged that they would improve their process validation program and qualify all current and future equipment, the FDA wasn't satisfied.
They stated that the manufacturer could not show the process to be reproducible and functional regarding all quality attributes. They demand a validation plan guaranteeing a state of control throughout the whole product life cycle. This includes a process performance qualification as well as monitoring of batch to batch variations. They further asked for the process performance protocols and corresponding studies.
Conclusion: in the recent past, mentions of the process validation life cycle in FDA warning letters have increased. Especially defects connected with Step 3 "Continued/Ongoing Process Verification" are criticised more often. And this time, a European manufacturer is involved.
Please also see the FDA's Warning Letter to Laboratoires Clarins for further details.