What do Authorities expect from Cleaning in the GMP Area?

Cleaning is an important process step in the field of pharmaceutical production. So what are the requirements for GMP-compliant cleaning from the perspective of the authorities? A current FDA Warning Letter provides information on this.

In a pharmaceutical company, the production tanks filled with several different products were not cleaned and sanitised according to the approved cleaning and sanitising instructions. For example, temperatures and filling heights that had to be maintained were not observed. The management was aware that some employees did not know how the tanks needed to be cleaned. The lack of documentation within the cleaning programme was also criticised. It was specifically mentioned that a bucket of cleaning solution without any label was used. Furthermore, there was no documentation on the production of the cleaning solution with information on quantities of chemical to achieve the required concentration. There was also no indication in the cleaning instructions as to how/when areas that are difficult to clean can be assessed as clean.

The pharmaceutical manufacturer's response to re-training their personnel was far from sufficient for the FDA. In a Warning Letter the FDA requires:

  • A risk assessment of the "findings" regarding the potential for cross-contamination with regard to product quality
  • Evidence that the deficiencies have been remedied (including a CAPA plan)
  • A detailed summary of weaknesses in life-cycle management with regard to equipment cleaning and disinfection
  • A description of the improvements of the cleaning and disinfection programme (explicitly mentioned are the cleaning effectiveness and a continued verification of the cleaning itself)

The FDA also demands improvements to the cleaning programme, taking into account worst-case scenarios. These worst-cases should include:

  • Drugs with higher toxicities
  • Drugs with higher drug potencies
  • Drugs of lower solubility in their cleaning solvents
  • Drugs with characteristics that make them difficult to clean
  • Swabbing locations for areas that are most difficult to clean
  • Maximum holding time before cleaning

Finally, the FDA is awaiting a summary of the updated SOPs to ensure that an appropriate program is in place to verify and validate cleaning procedures with respect to products, processes and equipment.

Conclusion: A validated, well-documented cleaning and sanitization of the equipment, is important to the FDA. A "simple" repetitive training of personnel to remedy deficiencies was not sufficient in this case.

You can find the complete Warning Letter on the FDA website.

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