Overview of Rapid Microbiological Methods Evaluated, validated and Implemented for Microbiological Quality Control.
Gordon O, Gray JC, Anders HJ, Staerk A, Schlaefli O, Neuhaus G, (2011). European Pharmaceutical Review, vol. 16(2), pp. 9-13.
The risk for patients through spoiled or otherwise adulterated pharmaceuticals has been acknowledged for many centuries and led to the establishment of Good Manufacturing Practice (GMP) and pharmacopoeial guidelines. Besides chemical purity, pharmaceuticals also have to
meet microbiological standards, the latter primarily depending on the administration route. Drug products which are injected directly into blood vessels or tissues or that are applied directly into eyes and ears represent a greater infection risk than products which are administered orally or
onto intact healthy skin. While parenteral drug products are required to be free from any viable microorganism (USP <71>, Ph. Eur. 2.6.1), oral and topical products are not required to be sterile, but are subject to strict guidelines limiting the number and types of acceptable microorganisms (USP <61> and <62>, Ph. Eur. 2.6.12 and 2.6.13).
It is the responsibility of the pharmaceutical industry that these microbiological standards are maintained until secondary packaging of the drug product. Knowledge of the microbiological quality of the used excipients and active ingredients, microbiological monitoring of the environment in which the pharmaceuticals are produced, as well as release-testing of the final drug product contribute to maximising patient safety. Testing for microbiological quality requirements relies on traditional methods based on visual detection of a large enough population of microorganisms, either as a colony on solid nutrient medium or as turbidity in liquid nutrient medium. The duration until microbial growth can be detected visually is dictated by the generation time of the microorganisms present; whilst fast-growing microorganisms like E. coli can be seen within hours, visual detection of slow-growing microorganisms can take days or even weeks. Therefore, microbiological quality control often represents the bottleneck for release of drug products after manufacturing. In addition, the late detection of a microbiological quality issue complicates subsequent investigations for the root cause of the contamination. Accordingly, there is high interest throughout the pharmaceutical industry to
replace traditional test methods by faster alternative methods. The encouragement by several health authorities to implement such alternative microbiological test methods, as well as official validation guidance documents for the pharmaceutical industry (USP <1223>, Ph. Eur 5.1.6,1)
heralded a start to the transition to the use of alternative, faster test methods. In this article, several Rapid Microbiological Methods which were evaluated or validated by Novartis will be presented.