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InPrint: Validation Requirements for Cleaning and Sanitization Practices

by Rebecca Stauffer, PDA | Aug 26, 2019

The following is excerpted from the chapter, “Cleaning and Sanitization Practices,” in the book, Contamination Prevention for Nonsterile Manufacturing, by Andrew Dick. The book can be purchased at the PDA Bookstore.

Validation Requirements

  • Include identification and classification of equipment (by type) in the validation.
  • Identify the strategy by which product(s) and/or equipment are grouped in the validation. Use the hardest-to-clean products and hardest-to-clean equipment for the validation study and supply a rationale (e.g., why one piece of equipment is used rather than another).
  • Be prepared to demonstrate reproducibility of the resultant cleaning; in most cases, three executions are sufficient to demonstrate reproducibility.
  • Identify or define the specific cleaning procedure that will be used to clean the equipment (i.e., in an SOP), including reference to a change control document, as well as validation frequency.
  • Ensure the results meet the “reasonable” industry standard of 1/1000 of the active ingredient level dose or no more than 10 ppm of any previous product.
  • Conduct residue studies to ensure elimination of product, detergent, and chemical sanitizer. The detergent manufacturer should list the specific composition of the chemical so that the site can test for the composition recovery after cleaning. Two methods are commonly used:
    • Direct Surface Sampling: Measures the actual equipment surface being cleaned. Determine the type of sampling material used and its impact on the test data as the sampling material may interfere with the test. For example, the adhesive used in swabs has been found to interfere with analysis of samples. Therefore, early in the validation program, ensure that the sampling medium and solvent (used for extraction from the medium) are satisfactory and can be used readily.
    • Rinse Samples: Tests for contaminants remaining in rinse water. There are two advantages of using rinse samples: a larger surface area can be sampled and inaccessible systems, or those that cannot be routinely disassembled, can be sampled and evaluated. One disadvantage of rinse samples is that the residue or contaminant may not be soluble or may be physically occluded in the equipment, giving a false negative result. (Rinse water samples taken may pass; however, when opened, residue is evident indicating that water did not rinse the surface.)
    • An analogy that can be used for rinse samples is the “dirty pot.” In evaluating the cleaning of a dirty pot, particularly one with dried-out residue, observe the interior of the pot to see that it is clean, rather than observing the rinse water.
  • Check to see that a direct measurement of the residue or contaminant has been made for the rinse water when it is used to validate the cleaning process. In other words, the rinse water cannot simply be tested to see that its quality meets pharmacopeial standards; it must also be tested for potential contaminates and TOC.
  • Identify the times, locations, and number of replications for equipment sampling, including “worst-case” scenarios. Include which equipment must be dismantled for sampling and inspection.
  • Identify the people responsible for cleaning and sanitizing equipment.
  • Provide validation activity summaries as indicated in the validation protocol. Testing should demonstrate the ability of the cleaning procedure to adequately meet the criteria for success. Any test results exceeding the criteria for success must be addressed, the risk assessed, and corrective action implemented.
  • Include digital photographs of the equipment that requires cleaning and sanitizing in the master validation report and validation implementation. Take photos both before cleaning and after sanitization to demonstrate what is expected.