The Harmonization of the Microbial Limits Tests - Pharmaceutical Technology

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The Harmonization of the Microbial Limits Tests

Pharmaceutical Technology

The introduction of these three harmonized chapters is likely to require some revalidation of existing methodologies. Companies should put plans in place immediately for this work and show consistent progress toward this goal.

The National Formulary monograph requirements for the absence of specific organisms is a minimal requirement and should not be taken as proof that the product is suitable for sale from a microbiological perspective. Harmonized Chapter ‹1111› recommends the determination of the risk associated with "other organisms," which is in agreement with the FDA expectation for absence of "objectionable" organisms. The manufacturer is responsible for the quality and safety of the product marketed, and it is FDA's clear expectation (as described in CFR) that this will include a determination of the microbial safety (i.e., the "absence of objectionable microorganisms") from the product. These positions have been publicly stated for decades and should not come as a surprise. The harmonized microbial limits tests only address the "absence of specified microorganisms" and leave the determination of the "absence of objectionable microorganisms" in the capable hands of each company's appropriately educated and well-trained microbiology group.

Scott Sutton, PhD, is a consultant with emphasis on microbiology and GMP issues at Vectech Pharmaceutical Consultants, Inc., tel. 585.594.8273,
He also operates the PMFList, a microbiology e-mail list (http:// and the PSDG e-mail list (pharmaceutical stability topics).

Submitted: Aug. 30, 2006. Accepted: Sept. 26, 2006.

Keywords: European Pharmacopoeia, Japanese Pharmacopoeia,limits, microbial testing, US Pharmacopeia,


1. USP Chapter ‹1196›, "Pharmacopeial Harmonization," US Pharmacopeia (USP) 29–National Formulary (NF) 24 (US Pharmacopeial Convention [USP], Rockville, MD, 2006), pp. 3031–3035.

2. USP, Chapter ‹61›, "Microbiological Examination Of Nonsterile Products: Microbial Enumeration Tests," Pharm Forum. 29 (5), 1714–1722 (2003).

3. USP, Chapter ‹62›, "Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms," Pharm Forum. 29 (5), 1722–1733 (2003).

4. USP, Chapter ‹1111›, "Microbiological Quality of Nonsterile Pharmaceutical Products," Pharm Forum. 29 (5), 1733–1735 (2003).

5. Chapter ‹61›, "Microbial Limits Tests," USP 29–NF 24 (US Pharmacopeial Convention, Rockville, MD, 2006), pp. 2503–2508.

6. Chapter ‹1111›, "Microbiological Attributes of Nonsterile Pharmaceutical Products," USP 29–NF 24 (USP, Rockville, MD, 2006), p. 2969.

7. European Directorate for the Quality of Medicines, http://, accessed Oct. 23, 2006.

8. US Food and Drug Administration, Bacterial Analytical Manual Online, http:// The second appendix with tutorial on most probable number methods: http://, accessed Oct. 20, 2006.

9. Chapter ‹1227›, "Validation of Microbial Recovery from Pharmacopeial Articles," USP 29–NF 24 (USP, Rockville, MD, 2006), pp. 3053–3055.

10. USP, Chapter ‹1117›, "Microbiological Best Laboratory Practices," Pharm Forum. 30 (5), 1713–1721 (2004).

11. US Food and Drug Administration, "Guide to Inspections of Microbiological Pharmaceutical Quality Control Laboratories,", accessed Oct. 20, 2006.

12. Chapter "Bacteriological Examination of Gelatin," USP XII (USP, Rockville, MD, 1942), pp. 556–559.

13. Chapter, "Microbial Limit Tests," USP XVIII (USP, Rockville, MD, 1970), p. 846.

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22. USP, "Microbial Contamination of Sterile and Non-Sterile Articles, with Special Reference to Pseudomonas cepacia," Pharm. Forum. 8 (4), 2239 (1982).


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