Microbial Tests for Non-Sterile Products
USP <795> states that pharmacists performing non-sterile compounding must ensure that the finished preparation has its accepted potency, purity, quality, and characteristics. This article discusses the tests described in USP <61> and USP <62> that are used to determine if non-sterile products meet quality requirements. These tests can also be used by sterile compounders for qualifying raw materials and performing in-process quality control testing.
The general considerations for testing non-sterile products are much like USP <71> Sterility testing. Growth promotion is required to demonstrate that every lot of media will grow the microorganisms required for each test. Method suitability is also performed prior to product testing to establish the ability of the test to detect microorganisms in the presence of the specific formulation to be tested. All testing must be completed under aseptic conditions to avoid extrinsic microbial contamination of the product tested and must include proper positive and negative controls.
USP<61> Microbial Enumeration Tests
USP <61> is often called “Bioburden” or “Microbial Limits” because the test determines how many microorganisms are present in the sample. To perform the test, the sample is plated onto two types of growth media (Soybean-Casein Digest Agar and Sabouraud Dextrose Agar). The plates are incubated at a defined temperature and duration. At the conclusion of the test, the number of colonies present on the plates are counted and the results calculated. The results can then be compared to the acceptance criteria. USP <1111> can be referenced for acceptable amounts of microorganisms present based on whether the sample is a raw material or finished drug product. If the sample is a finished drug product, the acceptance criteria depends on the route of administration.
USP<62> Tests for Specified Organisms
USP <62> provides instructions on how to perform tests that demonstrate particular microorganisms are not present in non-sterile substances and products. These tests are performed similarly to USP <61> tests, but with microorganism specific growth media. At the conclusion of incubation, a result of “Pass” or “Fail” is generated. A passing result indicates the absence of the tested specified microorganism. USP monographs and <1111> define which organisms to test based on the route of administration of the raw material or finished drug product. For example, USP <1111> recommends that cutaneous (topical) products be tested for the absence of both Pseudomonas aeruginosa and Staphylococcus aureus, versus an oral preparation where the recommendation is to test for the presence of Escherichia coli.
Please contact ARL (800) 393-1595 or firstname.lastname@example.org with questions.
Andrew Taylor, Microbiology Supervisor
United States Pharmacopeia <61>