Cleaning Validation. Microbiological Contamination.

Information & Training. | Product & Process Validation.

Any surface that contacts or would be in close proximity to process raw materials or finished product should be examined for potential microbiological contamination. Facilities must also be considered as potential sources of microbial contamination. Decisions regarding areas and surfaces to test will be dependent on the potential risk of product contamination and potential user risk.

For non-sterile production a microbial cleanliness of < 200 cfu / 100 cm2 is widely considered as acceptable. For non-sterile production, it is important to determine the type of organism present. It is necessary to demonstrate the absence of pollution indicator organisms such as, Salmonella spp (subspecies), Escherichia coli (E. coli), and Pseudomonas aeroginosa from all locations monitored. It is necessary, as well, to ensure that high levels of other microbial flora do not mask these organisms.

For sterile production, the level of microbiological contamination of rinse water would normally be of the order of 10 cfu / 100 ml. For sterile production, the number of organisms present needs to be considered versus a focus on the type of organism.

All cleaning validation sampling methods will normally include a visual check which will provide an immediate feedback on the cleaning process deficiencies. The sampling method will then be based on some or all of surface swabbing, sample fluid rinse, coupon sampling, placebo sampling.

Microbiological Contamination.

Cleaning Validation. Product and Process Validation. Information and Training presentation.   >>>

Swabbing involves using a wipe or swab that is moistened with high purity water (WFI – water for injection) that is typically wiped over a defined area in a systematic multi-pass way always going from clean to dirty areas to avoid recontamination – i.e. 10 side by side strokes vertically, 10 horizontally and 10 each with the flip side of the swab in each diagonal direction. For TOC analysis very clean low background swabs or wipes and sample vials such should be used.

Rinse water sampling involves taking a sample of an equilibrated post-final rinse that has been re-circulated over all surfaces. Rinse samples should be correlated to a direct measuring technique such as swabbing.

Coupon sampling involves the use of a coupons or an actual removable piece of pipe that is dipped into high purity water to extract residues for analysis.

Placebo testing involves using placebo product and analyzing for residues from the previous batch.

Product and Process Validation Full Details

Information & Training.

Product and Process Validation.

  • The Validation Master Plan. Performing a Gap Analysis. Validation in the Design Process. Etc..
  • How to ensure Validation efforts are aligned with potential Risks.
  • How to ensure that Validation activity is appropriately documented, reviewed and aligned with requirements.
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FDA. Validation of Cleaning Processes.