FAQs: Microbiology

1. How are microbial limits and specified microorganisms determined?

In determining the appropriate microbial limit, the USP Microbiology Expert Committee considers such matters as the route of administration, the form of the product, and the source material. For example, it is never appropriate to have any microorganisms in a product intended for injection intravenously. Therefore, you will never see a microbial limit listed for such products. Instead, those products must meet the test for Sterility General Chapter <71>. Other products may be in a form possessing extremely low water activity, such that microbial growth could not occur. You may not see microbial limits provided for some of those products. Many other products, such as those intended for oral administration, will have limits provided. Those limits are selected such that the risk of harm to the consumer is extremely low, while being reasonable from a manufacturing and quality control perspective. Products from botanical sources may have higher limits due to the larger bioburden associated with the raw materials. Again, the limits are set such that consumer risk is minimized without creating an untenable situation for the manufacturer. Consideration is also given to the likelihood of product spoilage. Since some products are more prone to spoilage due to microbial contamination, limits may be set lower for these. The issues discussed above also influence which, if any, specific organisms must be tested.

2. What are you supposed to do when it is not possible to neutralize the antimicrobial properties of a product during method suitability demonstration of Sterility Tests despite the use of all suitable methods (dilution, chemical / enzymatic neutralization, membrane filtration)?

If no suitable neutralizing method can be found, it can be assumed that the failure to isolate the inoculated organism/s is attributable to the antimicrobial activity of the product. This information serves to indicate that the article is not likely to be contaminated with the given species of the non-recovered microorganism(s). However, it is possible that the product inhibits only some of the microorganisms specified, but does not inhibit others not included among the test. Then, perform the test under the conditions compatible with microbial growth or recovery of most of the challenge microorganisms.”