An aspect of contamination control is the assurance that residual material is not carried over into successive batches by incomplete cleaning of equipment. Cleaning procedures (both the cleaning process and the analytical method to verify cleaning effectiveness) to provide this assurance should be validated.
Sampling of equipment for the purpose of cleaning validation or cleaning verification should include swabbing or rinsing as appropriate to detect both soluble and insoluble residues. The sampling methods must be capable of recovering any residues remaining on the equipment after cleaning for quantitative analysis. Swabbing is the preferred method for surface sampling, although rinsing may be appropriate for surfaces that can’t be accessed with swabbing tools or have irregular surfaces. If rinsing, it must be assured that the rinse process is capable of recovering residue (that is, that the contaminant is soluble in the rinsate and all surfaces are accessible to the rinsate).
When performing analytical method validation, coupons representing equipment material (stainless steel, plastic, etc.) are dosed with the specific residue (active and cleaning agent) at the maximum allowable carryover limit. Typically, the limit is expressed as mg/cm2. The coupon is usually 100 cm2. The material used for swabbing in the laboratory must be free of any ingredients that, when extracted, will interfere with the detection of the residue of interest. The swab material, the coupon surface area, and the swabbing technique used in the laboratory must exactly match the material and technique used in the manufacturing arena to sample the equipment, or the process of determining residue is not validated. To this end, companies should standardize swabbing technique so that the same sampling process is used every time, both by the laboratory and the manufacturing sampler. Training in this technique is critical. Not following the swabbing technique that was validated for the analytical method for a material makes the data collected for cleaning validation or verification unreliable.
References:
Food and Drug Administration, “Validation of Cleaning Processes (7/93) – Guide to Inspections Validation of Cleaning Processes”, August 26, 2014, https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-guides/validation-cleaning-processes-793, web accessed on December 18, 2024.
Food and Drug Administration, “Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients – Guidance for Industry”, September 2016 (ICH) Revision 1, https://www.fda.gov/media/71518/download, web accessed on December 18, 2024.
