USP Updates <61> and <62> for Microbial Testing of Non-Steriles

June 4, 2009
The United States Pharmacopeia (USP) has significantly changed the USP XXXI Microbial Limits Test, updating it and dividing it into two parts
  • USP <61> Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests
  • USP <62> Microbiological Examination of Non-Sterile Products: Tests for Specified Microorganisms

The effective date of the changes was May 1, 2009. The new USP <61> and <62> provide harmonization to existing European Pharmacopeia method for testing non-sterile pharmaceuticals, says Francis McAteer, VP of Quality at Microbiology Research Associates, Inc. (Acton, Mass.). The methods are now more inclusive for more organisms.

“These are major impact changes for microbial limits testing,” he says. “In the upcoming months, many companies will have to evaluate their non-sterile products to these updated methods.”

Below is a brief summary of changes, courtesy of McAteer:

  • USP <61> Microbial Enumeration Tests includes changes in pass/fail criteria and includes longer incubation durations than in previous editions.
  • The Preparatory Test is replaced by the Method Suitability for product inhibition.  The growth promotion organisms and the methodology had been significantly updated to include more types of organisms and different growth medias.
  • The tests for specified microorganisms are included in USP <62>; the modifications change many microbiological medias utilized in testing for specific pathogens.  Critical changes have also been made to incubation temperatures and duration.
  • More organisms have been specified in the new USP <62> chapter than in previous USP editions. Organisms such as Candida albicans, Clostridia species, and Bile-Tolerant Gram-Negative Bacteria may be required to be tested depending on specifications regarding product formulation.
  • No retests are allowed.

McAteer is advising clients to review the status of their non-sterile product testing in light of the changes to USP <61>, <62> Microbial Limits Testing. She is also recommending that these products be revalidated to conform to the new USP <61> and <62> Suitability Test. Clients must now specify which microorganisms are required to be absent. This requirement is based on the unique characteristics of the product based on formulation process, raw materials, etc.

Table 1 is a summary of the new medias and organism that are required for <61> and <62>, courtesy of McAteer’s firm.

Table 1. Typical Morphology Characteristics on Selective Agar Media and Biochemical Assays

The Suitability of the Test Method demonstrates that the test specimen to which the testing is applied does not, of itself, inhibit the recovery of the microorganisms that may be present, says McAteer. The performance of the Suitability Test ensures that any antimicrobial activity inherent in the sample to be tested does not adversely affect the reliability of the test and that the test procedure to be routinely utilized is otherwise suitable for use with the sample.

Acceptance Criteria include the following:

(a) The average plate counts obtained from the test plates, for the total aerobic count and the total yeast and mold count, must be > 50% and < 200% of those obtained from the positive control inoculum verification plates.

(b) For verification of specified organisms typical growth in the presence of the sample must be received for all test organisms on selective medias as described in USPXXXI <62>  Supplement.

(c) Positive control inoculums must be performed for each organism preparation and have an average value of (NMT) 100 CFU per total inoculated volume for the specified organism.