Thorough cleaning is crucial to aseptic fill operations, but it must be validated as well as monitored. This article has presented some sampling, extraction and analysis options that have proved successful in their application.
Validation is a formalized demonstration of the capabilities of the processing.8 The US Food and Drug Administration (FDA) has stated: “In the end, the test of any validation process is whether scientific data shows that the system consistently does as expected and produces a result that consistently meets pre-determined specifications.”9 This Guide to Inspections, intended to cover equipment cleaning for chemical residues only, suggests:
- Written procedures are required that detail the cleaning processes and how these cleaning processes will be validated, addressing “who is responsible for performing and approving the validation study, the acceptance criteria and when revalidation will be required.”
- The sampling and analysis combination should be challenged to determine what fraction of the target material is actually sampled and then detected.
- Direct sampling (for example, with swabs) is “most desirable,” although rinse sampling may be satisfactory.
Sterilization validation is a specialty with its own extensive literature and is not covered in detail here. The broader topic of the validation of aseptic pharmaceutical processes has been
explored in detail by the book of that title.