FDA and Design Qualification

The term Design Qualification is not used in the current FDA Guidance on Process Validation. However, it is addressed that the design of a facility plays a role within the scope of a qualification. For example, design specifications are required:

"Selecting utilities and equipment construction materials, operating principles, and performance characteristics based on whether they are appropriate for their specific uses. Verifying that utility systems and equipment are built and installed in compliance with the design specifications (e.g., built as designed with proper materials, capacity, and functions, and properly connected and calibrated).

FDA's Guide to Inspection of High Purity Water Systems does indeed contain design instructions, including that water in a water system should be kept in motion as continuously as possible.

And this is exactly where the FDA found deficiencies at a Canadian manufacturer of non-sterile pharmaceuticals. The FDA investigator detected pipes and hoses with stagnant water when the system was not in use. Explicit reference was made to the danger of biofilm formation, as also mentioned in the Guide for Inspection of High Purity Water Systems. The FDA also criticized the lack of compliance with USP specification for the appropriate water quality and lack of microbiological monitoring.

The answers of the pharmaceutical manufacturer to these inspection deficiencies were insufficient for the FDA, so that they have now issued a Warning Letter. This letter demands:

  • A summary plan that lists corrective actions to be taken for the inadequate design, control and maintenance of the facility.
  • A validation report for the system after the identified design deficiencies have been fully corrected and each correction has been completed.
  • In addition, the FDA wants to see the system validation protocol, all test results and the final validation report.

Furthermore, the FDA requires additional documents and data to monitor the system.

Further details can be found in the Warning Letter.  

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