26/27 May 2021
In a recent warning letter issued to "Wuxi Medical Instrument Factory", the FDA criticised deficiencies concerning process validation, amongst other things.
Interestingly, there is no particular article on process validation in the FDA's cGMP rules (21 CFR 210/211). Merely the validation of aseptic and sterile procedures as per 21 CFR 211.113 is mandatory. In the present case, the FDA cites article 21 CFR 211.100 (a), which addresses the topic of process control.
In describing the deficiencies, the FDA uses the new terminology of their process validation guidance of 2011. The authority criticises that Wuxi was neither able to provide a batch record on process qualification runs nor quality control test documentation. Only a protocol and a summary report were submitted, both of which had been insufficient. The production records of commercial products lacked the documentation of significant process parameters, as well. Times, the sequence of ingredient addition and sampling frequency and size were listed exemplarily.
With reference to the FDA Process Validation Guidance, the FDA clarified the meaning of validation: a scientifically sound, data-driven program which identifies and controls sources of variability in order to ensure that the process consistently meets the appropriate parameters. This includes an assessment of equipment for suitability, assuring the quality of input materials and the reliable determination of the capability of each manufacturing process step and control.
Furthermore, the FDA demanded the revision of the operating instructions describing the program for process monitoring. The program's objective is to discover variabilities in the product lifecycle. This relates to step 3 (Continued Process Verification) of the process validation lifecycle.
Further deficiencies involved lab control (21 CFR 211.160(b)) and cleaning/sanitisation/sterilisation (21 CFR 211.67(a)).
Conclusion: the FDA considered the deficiencies listed above as so grave as to suggest the company employ a cGMP consultant who meets the requirements of 21 CFR 211.34.
More details on the authority's findings can be found in the FDA Warning Letter to Wuxi Medical Instruments Factory.