Cleaning in 6th Place in the FDA Warning Letter Statistics

Recommendation

4/5 October 2023

Advanced Level: Trending of Process Data for OPV/CPV - Live Online Training

The ECA regularly provides evaluations of the FDA Warning Letters per fiscal year. In 6th place in the fiscal year 2022 (Oct. 2021 - Sept. 2022) there are deficiencies regarding the topic of cleaning/cleaning validation. What was found? 

In the fiscal year 2022, a total of 42 Warning Letters were sent to pharmaceutical manufacturers, in which the GMP deficiencies are explicitly described in connection with the paragraphs of 21 CFR 211. In 6th place are deficiencies relating to 21 CFR 211.67 Equipment cleaning and maintenance (Subpart D - Equipment), cited in 13 Warning Letters.

Although the title 211.67 "only" refers to equipment cleaning and maintenance, almost all deficiencies are also always associated with inadequate cleaning validation. Interestingly, three of the 13 Warning Letters also criticize the manufacture of products that are not pharmaceuticals.

To remedy the deficiencies in cleaning validation, the FDA almost always wants to see worst-case scenarios evaluated. To be considered are:

• Medicinal products with higher toxicities 
• Medicinal products with higher active ingredient contents 
• Medicinal products with low solubility in the purification reagent 
• Medicinal products with properties that make them difficult to clean
• Swab sampling sites at locations that are most difficult to clean
• Standing 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.

Conclusion: When it comes to cleaning, always consider cleaning validation.