The Harmonization of the Microbial Limits Test - Absence of Specified Organisms

The last issue of the PMF Newsletter (vol 12, no. 3) contained a review of the harmonization status of the Microbial Limits Tests – Enumeration. In addition, the article provided a brief overview of the compendial harmonization process as agreed to by the Pharmacopeial Discussion Group (PDG). In this article, I would like to focus on the other side of the Microbial Limits Tests – the “Absence of Specified Microorganisms” component.
USP
EP
<61> Microbiological Examination Of Nonsterile Products: Microbial Enumeration Tests
2.6.12 Microbiological Examination Of Nonsterile Products: Microbial Enumeration Tests
<62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms
2.6.13 Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms
<1111> Microbiological Quality of Nonsterile Pharmaceutical Products
5.1.4 Microbiological Quality of Nonsterile Pharmaceutical Products
Table 1: Harmonized Chapter Numbering Scheme
There is a significant controversy in the United States over the intent of this evaluation. The FDA is bound by the concern expressed in the Code of Federal Regulations (21CFR 211.113 and 21CFR 211.165) relating to the importance of “objectionable microorganisms.” This is not the concern of the compendial chapters. The controversy is worthy of discussion, but not the topic of this review – it will be discussed in length in the final of three articles on the harmonization of the microbial limits tests to be published in next month’s newsletter.
What follows is a tabular presentation of the existing “Microbial Limits – Absence of Specified Microorganisms” tests from the current USP and Pharm Eur, as well as the draft harmonized document (the finalized document is extremely close to this version, but not release to the industry). It is provided as an aid to evaluation, and may assist in determining whether revalidation of method suitability studies is needed. It should be noted that this harmonization draft represents a true compromise by all parties, with (at least in the author’s opinion) significant changes from the current USP, Pharm Eur and JP chapters.