Monday, 8 January 2018

Microbiological Aspects of Cleaning Validation

Cleaning validation refers to the methodology applied to give the assurance that a cleaning process has removed residues and contaminants from a piece of equipment or machinery. Residues may be microorganisms; active pharmaceutical ingredients; other process chemicals, such as buffers; cleaning agents themselves (such as detergents); or microbiological culture media (in relation to aseptic process simulations). Assurance relating to cleaning validation refers to both the effectiveness of the cleaning process and the consistency at which cleaning is applied. As with any other type of validation, the ‘validation’ aspect refers to providing documented evidence that that the acceptance criteria have been met.

Tim Sandle has written a new paper. Here is an extract:

Cleaning is assessed based on the level of residues that remain, either those directly found on the equipment or those indirectly contained within the final rinse after water has passed through or over the equipment. Whether the residues remaining have been reduced to a satisfactory low level is based on predetermined acceptance criteria (2). The levels need to be sufficient low to ensure that the next product manufactured is not compromised by waste or contamination from the previous product (that is in ensuring that cross-contamination does not occur). An additional concern is with the microbial bioburden.

With equipment cleaning, this can be undertaken using an automated process (such as CIP - Clean-in-Place technologies) or manually (which often involves the physical removal of the equipment and its transport to a wash-bay; sometimes called COP - Clean-Out-of-Place). In general manual cleaning should be avoided due to process and operator variability. Where manual cleaning cannot be avoided, due to technical limitations, robust controls need to be in place to ensure consistency.

The chemical verification of cleaning validation is relatively well described. What is often less clear, and some contentious in terms of whether it needs to always be included, is the microbiological aspect. Important to the microbiological aspect are microorganisms themselves (a direct hazard) and the presence of residues that potentially provide a microbial growth source, should contamination be present or contamination occur during the hold period (an indirect hazard).

To evaluate these microbiological risks a sound microbiological sampling plan is required. The emphasis on sampling is important since microorganisms cannot be introduced into the process. This is unlike a chemical assessment where equipment can be deliberately soiled with a residue to test out cleaning efficacy. Microbial controls should not be introduced into the cleaning process. This article assesses the risks from microorganisms and the cleaning requirements necessary to achieve microbial control.

The reference is:

Sandle, T. (2017) Microbiological Aspects of Cleaning Validation, Journal of GxP Compliance, 21 (5): 1-12, at:

To find out more please contact Tim Sandle at:  

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