Wednesday, 4 October 2023 13.00 - 17.00 h
The handling of out-of-specification analytical results should follow strict rules in the GMP-required quality control laboratory. FDA inspectors are sensitive when they find that a laboratory deviates in its approach from the procedure that corresponds to the FDA's common GMP understanding of OOS results and retesting, as described in the guidance "Investigaton Out-of-Specification (OOS) Test Results for Pharmaceutical Production."
This was precisely the experience Missouri Analytical Laboratories had when it received a Warning Letter for not invalidating OOS results in accordance with GMP after multiple testing. In addition, the FDA inspectors also found massive violations of the data integrity requirement and circumstantial evidence of intentional falsification or "disposal" of disagreeable data at this contract laboratory.
Citing Section 211.192 of the Code of Federal Regulations (CFR), the Warning Letter describes GMP violations that can be summarized as follows:
This was apparently standard practice in this company's laboratory, as the Warning Letter describes this procedure for both finished product content determination and testing of the API. In any case, the invalidation of analytical results that do not comply with the specification without a well-founded scientific justification is completely unacceptable for FDA inspectors.
Section 211.68 of the CFR regulates the handling of electronic data in the GMP area and specifies the measures that must be taken to preserve the integrity of such data. Inspectors found the following violations of these regulations at Missouri Analytical Laboratories:
The standards that were violated here form the tough core of the GMP regulations that an analytical laboratory subject to GMP must comply with by all means. Accordingly, the FDA's requests for additional documents, which it usually requires within 15 days, are quite extensive.