Cleaning Validation from the FDA's Point of View

The requirements for cleaning validation are not very clearly defined in the US GMP regulations 21 CFR 210/211. Even a Guide to Inspection of the 1990s on this topic does not represent the current interpretation of the FDA. Current Warning Letters on the subject of cleaning validation can help - like the one issued to a Korean drug manufacturer of over-the-counter products. 

FDA Requirements in terms of cleaning validation

The FDA criticised a complete lack of a cleaning validation, even though multi-purpose equipment is used on which non-pharmaceutical products are also manufactured. The FDA explicitly points out that chemical and microbiological residues can lead to problems with the medicinal products manufactured in these facilities. A corresponding cleaning validation programme is now demanded for all products exported to the USA, naming "worst case" conditions. The following are to be considered as "worst cases

  • Medicinal products with higher toxicities 
  • Medicinal products with higher active ingredient contents 
  • Medicinal products with low solubility in the cleaning reagent 
  • Medicinal products with properties that make them difficult to clean 
  • Swab sampling sites at locations that are most difficult to clean 
  • Hold time before cleaning 
  • Overview of updated SOPs to ensure that an adequate cleaning process verification and validation programme is in place for products, processes and equipment.

In addition, the FDA requires the necessary steps to be taken in the change management system before a new manufacturing equipment or product can be introduced.

Further information can also be found in the FDA Warning Letter to Cosmo Bio Co. Ltd.

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