By John Godshalk, JG BioConsult
Cleaning surfaces in pharma and the biologics industry is very much the same as cleaning anything else—first you clean the surface, then you rinse off the cleaning agent. This applies to cleaning validation where the surface is product-contact, but not to surfaces in the facility, where cleaning agents typically are not removed. Thus cleaning validation for product-contact surfaces and cleaning efficacy studies for surfaces that are cleaned in the facility are quite different. Although the term “cleaning validation” might sometimes be used for facility surfaces, it is not strictly correct; this is termed “cleaning efficacy studies,” whereby one shows that microbes are inactivated by the cleaning agents used in the facility. Sometimes cleaning efficacy studies also show that residual product can also be cleaned from facility surfaces, where the facility is multiproduct.
Cleaning validation (CV) for product contact surfaces is required where the surfaces are re-used for another lot or product. This is often found where stainless steel surfaces or tanks are used for product-contact parts, lines, tanks, etc. Another option is cleaning verification (CVf), if a sponsor/company wants to test a given surface after each lot, rather than do full CV. CVf is more often used for the clinical trial phase of production, because it becomes a lot of work to test each time for full production, whereas for clinical trial phase production, where lots are limited, it may be easier just to test each time. The tests used vary, but often the test is chosen to measure either the residual product or the residual cleaning chemical or both. A popular test is TOC, total organic carbon, which is often useful for a range of products. Either CV or CVf is acceptable to demonstrate a clean product-contact surface is being used between lots or products.
What about cleaning efficacy studies (CES)? These are studies which show that the surfaces in the facility don’t contribute to possible cross contamination between different products or lots, or general microbial contamination of any product. These studies are particularly important for multiproduct facilities that are either licensed or getting ready for licensure. CES are not required for early clinical phase production in multiproduct facilities, but should be in place during phase III production, because they are needed for licensure. Information from the sanitant manufacturer can be leveraged during early clinical trial phase to show these sanitants are effective. CES for phase III and licensure show that the sanitant that is being used in the facility effectively cleans the surface (stainless steel, vinyl flooring, glass, epoxy paint, etc.) and inactivates different types of microbes.
Whether cleaning validation (CV), cleaning verification (CVf), or cleaning efficacy studies (CES) is being considered, think about what phase the product is in, what type of cleaning data is phase appropriate, and what the study is meant to show/prove. These studies often require a protocol also, and this should be carefully reviewed. Remember that CV, CVf, and CES are all different, and have different objectives and requirements.