22/23 May 2024
Inspection results often help with the interpretation of regulatory requirements. The FDA Warning Letters are a very good source for that purpose. A recent Warning Letter criticises deficiencies in process validation.
In the Warning Letter, the FDA criticised the fact that no microbiological tests were named in the validation protocol and that the active ingredient specification did not correspond to the current process. Process validation studies were also missing for other medicinal products with regard to different active ingredients and dosage forms.
In the company's response letter, the FDA lacked a detailed description of how the company will ensure in future that the manufacturing process consistently produces medicinal products of suitable quality. The FDA refers to the validation life cycle and specifically mentions the importance of developing the manufacturing process and monitoring after the actual validation. Each significant stage of a manufacturing process must be adequately developed and ensure the quality of the starting materials used, the in-process materials and the finished drug product. Process qualification studies include intensive monitoring and testing of all significant process steps to characterise within-batch variation and evaluate batches to determine whether an initial control state has been achieved.
Successful process qualification studies are required prior to commercial distribution, according to the FDA. Referring to its process validation guidance, the FDA writes that without adequate process validation that considers all production factors and parameters that may affect product quality, the company lacks the basic assurance that it can reproducibly deliver products that meet specifications.
Specifically, the FDA requires:
You can find the entire Warning Letter on the FDA website.