FDA Requirements for Cleaning Validation

Official GMP inspection reports deliver helpful answers to the question what do authorities require regarding cleaning validation. Through the Freedom of Information Act, the FDA is required to publish inspection results. This is particularly the case with Warning Letters. Here, even details of deficiencies regarding cleaning validation are included in the Warning Letter.

As almost always, the FDA quotes 21 CFR 211.67 when it comes to cleaning validation deficiencies. What did the FDA criticize? It was criticized that the company could not demonstrate that contaminants could be removed with the cleaning/disinfection procedures used. The only measure applied was visual inspection of surfaces.

In its response, the company provided an overview of its cleaning validation strategy and timelines for implementation. The FDA objected that the company’s answer contained too little specifics and no rationale for its cleaning validation approach.

Specifically, the FDA requested:

• an extensive plan evaluating cleaning/disinfection procedures and activities (cleaning/disinfection techniques, agents, application times, testing methods and criteria)
• scientific rationale for the cleaning/disinfection validation strategy
• a summary of cleaning/disinfection validation protocols updates including worst-case scenarios

Worst cases should include:
– Evaluation of the medicinal products with the highest toxicity
– Consideration of the lowest solubility of drugs in cleaning solvents
– Evaluation of medicinal products with characteristics that make them difficult to clean
– Swabbing equipment places the most difficult to clean
Moreover, a summary of updated SOPs to ensure that an appropriate programme for verification and validation of cleaning/disinfection procedures is in place was requested.

This Warning Letter gives a very nice insight into the state of the art regarding cleaning validation from the point of view of the FDA.

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