EXPIDITING THE PROCESS: METHODOLOGY DEVELOPMENT FOR ONSITE SPORICIDAL AGENT EFFICACY TESTING AND SCREENING IN COMMERCIAL PHARMACEUTICAL SETTINGS

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Melinda Victoria Plyler Axtman (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Effective facility cleaning and disinfectant practices are crucial to the safe manufacturing of pharmaceutical products. Without an effective plant wide cleaning strategy, risk of site contamination, product adulteration and regulatory action increase. One of the most crucial decisions in designing a facility cleaning strategy is the choice and validation of a sporicidal agent. Facilities do not currently have developed methodologies to complete onsite sporicidal agent testing due to the lack of well-defined and concise methodology, poorly crafted positive controls, lack of neutralization activity, and incorrect materials selection. By defining a methodology for commercial facilities, regulatory action such as a 483 letter from the FDA can be avoided and patients protected. When a 483 warning letter is received involving the incorrect use or failure to validate a sporicidal agent, it can lead to fines, legal action, and/or product seizure. Based on this, designing a robust methodology to be completed onsite in any standard commercial pharmaceutical facility would reduce the time, expense, and risk from validating a sporicidal agent for efficacy. In this study, a strategy was developed to demonstrate the efficacy of sporicidal agents for commercial use. The strategy was used to assess Stabilized Aqueous Ozone (Tersano), Spor-Klenz RTU (Steris) and Peridox RTU (Contec) for efficacy at Fujifilm Diosynth Biotechnologies in the Research Triangle Park. The method included the use of suspension and surface microorganism testing to evaluate the three sporicidal agents against a range of challenge organisms including: Aspergillus brasiliensis (A. brasiliensis), Bacillus subtilis (B. subtilis), Candida albicans (C. albicans), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). Four common facility surfaces were used for surface testing\; stainless steel 316L, stainless steel 304, epoxy-based flooring, and PVC wall covering. Surface testing involved seven test stages\; plate sterilization, initial suspension preparation, suspension enumeration (serial dilution), coupon inoculation, coupon plating, and plate counting. A successful replicate of the method had an inoculate concentration high enough to meet the required log reduction (varies per organism), successful neutralization, and quantifiable efficacy results. Stabilized aqueous ozone failed to prove efficacy during the suspension testing. Peridox and Spore-Klenz demonstrated efficacy in the suspension and surface testing. In the surface testing, out of 24 material and organism combinations, 22 had at least one successful method replicate (two replicates were completed per combination). Out of 48 total replicates 31 were successful. The 17 non-successful replicates had initial inoculation concentrations that were not high enough for the required log reduction to be achieved, even if the test plates had no growth. The methods used during this study were successful in proving the level of efficacy of two sporicidal agents. Testing was expanded to include facility isolates and additional materials to create an even stronger qualification claim for a sporicidal agent. This method demonstrated robust positive and negative controls, clear efficacy results, and is effective for multiple materials and organisms.

Additional Information

Publication

Thesis

Language: English

Date: 2023

Subjects

Cleaning;Validation;Sporicidal

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