1111 MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: ACCEPTANCE CRITERIA FOR PHARMACEUTICAL PREPARATIONS AND SUBSTANCES FOR PHARMACEUTICAL USE
The presence of certain microorganisms in nonsterile preparations may have the potential to reduce or even inactivate the therapeutic activity of the product and has a potential to adversely affect the health of the patient. Manufacturers have therefore to ensure a low bioburden of finished dosage forms by implementing current guidelines on Good Manufacturing Practice during the manufacture, storage, and distribution of pharmaceutical preparations.
Microbial examination of nonsterile products is performed according to the methods given in the texts on Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62. Acceptance criteria for nonsterile pharmaceutical products based upon the total aerobic microbial count (TAMC) and the total combined yeasts and molds count (TYMC) are given in Tables 1 and 2. Acceptance criteria are based on individual results or on the average of replicate counts when replicate counts are performed (e.g., direct plating methods).
When an acceptance criterion for microbiological quality is prescribed, it is interpreted as follows:
101 cfu: maximum acceptable count = 20;
102 cfu: maximum acceptable count = 200;
103 cfu: maximum acceptable count = 2000; and so forth.
Table 1. Acceptance Criteria for Microbiological Quality of Nonsterile Dosage Forms
Table 1 includes a list of specified microorganisms for which acceptance criteria are set. The list is not necessarily exhaustive, and for a given preparation it may be necessary to test for other microorganisms depending on the nature of the starting materials and the manufacturing process.
If it has been shown that none of the prescribed tests will allow valid enumeration of microorganisms at the level prescribed, a validated method with a limit of detection as close as possible to the indicated acceptance criterion is used.
Table 2. Acceptance Criteria for Microbiological Quality of Nonsterile Substances for Pharmaceutical Use
In addition to the microorganisms listed in Table 1, the significance of other microorganisms recovered should be evaluated in terms of the following:
Where warranted, a risk-based assessment of the relevant factors is conducted by personnel with specialized training in microbiology and in the interpretation of microbiological data. For raw materials, the assessment takes account of the processing to which the product is subjected, the current technology of testing, and the availability of materials of the desired quality.
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USP35NF30 Page 691Pharmacopeial Forum: Volume No. 29(5) Page 1733