APR January/February 2022 - 12

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MICROBIOLOGY
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USP <1111> Microbial Contamination
Risk Factors Re-Visited
Tony Cundell, PhD
Principal Consultant
Microbiological Consulting, LLC
Scarsdale, New York
Abstract
This review article discusses the microbial contamination risk
factors presented in USP General Informational Chapter <1111>
Microbiological Examination of Non-sterile Products: Acceptance
Criteria for Pharmaceutical Preparations and Substances for
Pharmaceutical Use and other pertinent USP chapters when
evaluating non-sterile drug products for objectionable
microorganisms. Emphasis is given to the exclusion of members of
the Burkholderia cepacia complex.
Introduction
One of the challenges for microbiologists working in the
pharmaceutical industry is setting up policies and procedures to meet
their microbiological quality requirements and exclude objectionable
microorganisms from our non-sterile drugs as required by the U.S.
Federal Good Manufacturing Regulations 21 CFR 211.113 Control of
Microbiological Contamination. The current FDA thinking on microbial
release testing,
risk associated with Burkholderia cepacia complex
contamination of aqueous non-sterile drug products, exclusion of
objectionable microorganisms from non-sterile drug products and
devices, out-of-specification result investigations, process equipment
cleaning, and product recalls may be found in the November 30,
2021 FDA Warning Letter to Dental Technologies, Inc., Lincolnwood,
IL addressing their adulterated Paroex 0.12% chlorhexidine oral rinse.
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It is widely recognized that the risk of microbial contamination
varies amongst different dosage forms. Similarly, the presence of
microorganisms that are objectionable would vary by dosage form,
formulation, microbial quality of the ingredients, manufacturing
process, physicochemical attributes, route of administration, and
the intended recipient population. USP <1111> Microbiological
Examination of Non-sterile Products: Acceptance Criteria for
Pharmaceutical Preparations and Substances for Pharmaceutical
Use recommends microbiological quality requirements by site of
administration for microbial counts and a limited range of specified
microorganisms that must be absent from 1 g or mL of a product,
but does not list objectionable micro-organisms as this risk-based
decision is the responsibility of the drug manufacturer, not the FDA
as the regulator or the USP as the standard-setting organization.
Industry practices may be found in the 2014 PDA Technical Report
No. 67 Exclusion of Objectionable Microorganisms from Non-sterile
Pharmaceutical and OTC Drug Products, Medical Devices and Cosmetics
and more recent book chapters published by the author (Cundell,
2020a and b). However, in addition to the specified microorganisms
listed in Table 1 (see USP <1111>), the chapter recommends that the
significance of other microorganisms recovered should be evaluated
in terms of the following potential risks factors:
* The use of the product: hazard varies according to the route of
administration (eye, nose, respiratory tract).
* The nature of the product: Does the product support growth?
Does it have adequate antimicrobial preservation?
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