1/2 December 2021
The FDA has recently added three new questions to its Q&A section on cGMP in the Quality Control Laboratory - "Questions and Answers on Current Good manufacturing Practices - Laboratory Controls" - that relate to chromatography systems and describe FDA's perception of basic cGMP principles in chromatographic procedures.
The following is a brief summary of the FDA's questions and answers:
Only highly purified and well characterized materials should be used that can be accurately weighed, e.g. pharmacopoeia standards or standards of other origin (e.g. NIST). Substances from a supplier or in-house standards should be purified and characterized using validated procedures. The purification process should remove impurities as far as possible to avoid interferences with the analysis (no finished drugs should be used as calibration standards).
Highly pure and qualified primary or secondary standards must be used. Each new secondary standard batch must be qualified against the primary standard. Finished dosage forms or APIs that are not qualified may not be used for the system suitability test. This also applies if they are qualified but are from the same batch as samples being tested.
No. An analytical "test run" of a sample aiming at obtaining an "unofficial" result (pass or fail) does not meet the GMP-compliant procedure prescribed for a QC laboratory. All analytical data of a product sample must be stored and reviewed. No samples of a product batch may be used for conditioning the chromatography column.
The problems presented here in the form of questions originate from numerous observations of FDA inspections in the QC laboratory area and appear repeatedly in various Warning Letters. FDA's clear position on these procedures is certainly helpful in preparing for an inspection.