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 multipurpose 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 worstcase 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.:

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. (21 CFR 211.165(a)).


2. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates. (21 CFR 211.166(a)).


3. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment. (21 CFR 211.67(b))