Microbial Disinfectant Cleaning Challenge Studies
James Zellner, ARL Bio Pharma Technical Sales
How do you know your staff is doing a thorough job disinfecting surfaces and equipment at your facility? Do you have proof that your cleaning procedure is effective in removing potential contaminants from surface areas?
An important part of a complete quality program is generating data that the standard operating procedures (SOPs) in place are achieving their intended goals. Specific to cleaning SOPs, pharmacies must demonstrate that cleaning agents, combined with instructions and procedures for their use, remove microbial contamination from surface areas where sterile drug products are compounded. USP <1072> Disinfectants and Antiseptics states explicitly in its first line,” A sound cleaning and sanitization program is needed for controlled environments used in the manufacture of Pharmacopeial articles to prevent the microbial contamination of these articles”. This USP directive is met by performing Microbial Disinfectant Challenge studies.
There are two parts to consider when designing a disinfectant challenge study to generate data that demonstrates the efficacy of a facility’s cleaning SOP and choice of agents for removing microbial contamination. Use-Dilution testing ensures that agents at their in-use concentrations, whether premixed or mixed on-site, can decontaminate a surface in the contact time specified. Once the efficacy of the cleaners is established, Surface Challenge testing determines the effectiveness of procedures to remove contamination from appropriate surfaces. The agent’s individual efficacy is demonstrated with Use-Dilution testing, followed by combined usage by SOP instruction in the Surface Challenge test.
Cleaning studies should have sound and realistic acceptance criteria based on the cleaner’s method of action, surface cleaned, organism(s), and contact time. A well planned microbial disinfectant cleaning study provides a facility the information to confidently continue using their selected methods of decontamination, or data that indicates a modification to SOPs is necessary to improve the state of control.
While the specifics of a microbial cleaning challenge study may vary, a general framework is recommended. Three lists are the driving factors behind the study design. The examples below are not exhaustive, but provide the cleaners, surfaces, and organisms to use. First, make a list of the cleaners used in your facility. The cleaning agents should complement each other’s method of action and fall into several groups:
Generally, a combination of disinfectants with germicidal and sporicidal properties are used in sequence with a final sterile alcohol step during cleaning.
Once the cleaners and procedures for their use are specified, list the surfaces to clean. Commonly cleaned surfaces in the compounding pharmacy are:
- Stainless Steel (the grade should be specified)
- Clear lighting panels
- Epoxied floor
- Ceiling tiles
- Wall surfaces
- Flooring surfaces
Facilities should acquire coupons (small samples) of each of the surfaces from the manufacturer or another source for submission to a laboratory for surface challenge testing. The lab uses the facility’s cleaning SOPs and mimics the surfaces cleaned at the compounding facility.
Next, select microorganisms to verify the cleaners and procedures. In USP <1072>, Table 5 provides a guide for organism selection. Like many of the microbiological chapters in USP, the organisms chosen should be representative of a class of potential contaminants. Suggested bacteria and fungi that serve as challenge organisms are:
- Staphylococcus aureus (Gram-positive cocci)
- Pseudomonas aeruginosa (Gram-negative rod)
- Escherichia coli (Gram-negative rod)
- Bacillus subtilis (Spore-forming bacteria)
- Candida albicans (Yeast)
- Aspergillus brasiliensis (Mold)
A facility may also use bacterial and fungal organisms recovered during environmental monitoring as challenge organisms. This is important if an environmental recovery is of a class not covered by the traditional representative organisms mentioned above.
Finally, acceptance criteria needs to be clearly stated. USP <1072> gives an example of a 2-log reduction in bacterial spores and a 3-log reduction in vegetative bacteria on the coupons used in the Surface Challenge test. This example expectation can be further expanded based on the cleaning agent’s efficacy and the organisms tested. Ultimately, the facility and lab should work together to establish acceptance criteria for the cleaning agents and methods. If changes are made to the SOP, as part of a continuous effort to maintain the optimal compounding environment, an additional study should be performed to ensure that the new procedure meets the criteria of the tests.
Microbial cleaning studies are essential to validating a facility’s cleaning SOP. This is an important component to ensure quality drug products reach your patients. It demonstrates that the disinfecting steps and agents a compounder is taking to maintain controlled areas are adequate to produce a sterile product.
For more information, contact ARL at 800-393-1595 or email@example.com.