Few raw materials used in making pharmaceutical products are sterile as received, and special treatment may be required to render them microbiologically acceptable for use. Strict adherence to effective environmental control and sanitation, equipment cleaning practices, and good personal hygiene practices in pharmaceutical manufacture is vital in minimizing both the type and the number of microorganisms.

Monitoring, in the form of regular surveillance, should include an examination of the microbiological attributes of Pharmacopeial articles and a determination of compliance with such microbiological standards as are set forth in the individual monographs. It may be necessary also to monitor the early and intermediate stages of production, with emphasis being placed on raw materials, especially those of animal or botanical origin, or from natural mineral sources, which may harbor objectionable microorganisms not destroyed during subsequent processing. It is essential that ingredients and components be stored under conditions designed to deter microbial proliferation.

The nature and frequency of testing vary according to the product. Monographs for some articles require freedom from one or more species of selected indicator microorganisms such as Salmonella species, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. For some articles, a specific limit on the total aerobic count of viable microorganisms and/or the total combined molds and yeasts count is set forth in the individual monograph; in these cases a requirement for freedom from specified indicator microorganisms may also be included. The significance of microorganisms in nonsterile pharmaceutical products should be evaluated in terms of the use of the product, the nature of the product, and the potential hazard to the user. Also taken into account is the processing of the product in relation to an acceptable quality for pharmaceutical purposes.

It is suggested that certain categories of products should be tested routinely for total microbial count and for specified indicator microbial contaminants, e.g., natural plant, animal, and some mineral products for Salmonella species; oral solutions and suspensions for E. coli; articles applied topically for P. aeruginosa and S. aureus; and articles intended for rectal, urethral, or vaginal administration for yeasts and molds.

Definitive microbial limits (stipulated microorganisms and/or counts) are incorporated into specific monographs on the basis of a major criterion, i.e., the potential of the stipulated microorganisms and/or counts, and of any others that they may reflect, to constitute a hazard in the end product. Such considerations also take into account the processing to which the product components are subjected, the current technology for testing, and the availability of desired quality material. Any of these may preclude the items from specific requirements under Microbial Limit Tests 61. Regardless of such preclusion, it remains essential to apply strict good manufacturing practices to assure a lowest possible load of microorganisms.

The relevant tests for determining the total count of viable aerobic microorganisms and the total combined molds and yeasts count, and for detection and identification of designated species are given under Microbial Limit Tests 61. For reliable results, the personnel responsible for the conduct of the test should have specialized training in microbiology and in the interpretation of microbiological data.

Expert Committee : (MSA05) Microbiology and Sterility Assurance

USP29–NF24 Page 2969

Phone Number : 1-301-816-8339