Cleaning validation -Failure

Hope you could help on a scenario question in the output of annual revalidation.
The annual cleaning validation has been completed and it fails. You get a peak OOS.
OOS confirmed.
It’s a multiproduct facility making high Therapeutic index products, low therapeutic index products and you have identified your worst-case product which you do your cleaning validation on.

There could be several reasons for the failure of cleaning validation such as,

  • The lack of a well-defined procedure that consistently cleaned the equipment surface which could be identified as the major contributor

  • The lack of consistency in cleaning the equipment surfaces due to manual cleaning operations. Clean-in-place (CIP) operations are always reproducible as compared to manual cleaning operations.

  • Change of surface characteristics of the equipment under cleaning due to its frequent use over a long time ( The surface of the equipment may be modified due to the deposition of a thin film of material on the surface or due to a change in the oxidation state of one or more of the elements in stainless steel (e.g. Fe, Cr, and Ni).

Therefore, you will have to investigate the root cause of getting an extra peak (OOS Lab result) in chromatographic analysis. Based on the root cause(s), modify the cleaning method or maybe if it is due to rough equipment surface/dents/scratches over a period of time then there is a need to the re-polish surface of the equipment before you revalidate the cleaning procedure.

As the annual cleaning validation has failed you will have to perform a Risk assessment to determine and assess the impact of using inadequate cleaning procedures/conditions to clean the equipment since the last successful cleaning validation was done. All the batches manufactured using equipment which were inadequately cleaned are questionable. (Generally first batch in a product campaign).

The following points are very important to be considered before initiating the cleaning validation exercise as these influence effectiveness and reproducibility of equipment cleaning operations.

  • Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner, and these procedures should be validated according to the U.S. Food and Drug Administration (FDA) requirements or other regulatory agencies.

  • The analyst or manufacturing operator conducting the swabbing must follow a structured procedure to ensure that recoveries are reproducible regardless of who performs the swabbing. The procedure should explicitly detail the swab type, the number of swabs used, the diluent, the amount of solvent used, the exact sweeping pattern, the number of strokes applied to the sampling surface, the amount of time spent swabbing/extracting the samples, the method of detection (ultra-violet, fluorescence, mass spectrometry, total organic carbon, etc. ), the extraction technique of the material from the swab head, etc.