RAPID METHODS SUPPLEMENT


CHALLENGES AND STRATEGIES FOR THE APPLICATION OF


RAPID MICROBIOLOGICAL METHODS IN THE PHARMACEUTICAL INDUSTRY


Youwen Pan Technology Resources / Sterility Assurance, Baxter Healthcare Corporation


With the advances of science and technology and innovations in pharmaceutical manufacturing, the development and application of rapid microbiological methods (RMMs) have generated considerable interest. Multiple technologies, including those based on the detection and measurement of cell reproduction, ATP, polysaccharides, pH, metabolites (e.g. CO2


), enzyme activity, membrane integrity, membrane


potential, redox potential, and nucleic acids have been developed and applied in RMMs over the past several years. Unfortunately, many challenges exist in method selection, evaluation and validation, which prevent pharmaceutical manufacturers from implementing RMMs. To help understand some of the primary issues involved in the implementation of RMMs in the pharmaceutical industry, the major challenges are presented and corresponding strategies are proposed.


The primary decision faced by the pharma - ceutical microbiologist is the choice of precisely which technology to implement, ensuring it fits the purpose of its desired or intended use. Many RMM technologies have been developed and are readily available in the market. Almost all RMMs rely on complex technology platforms including but not limited to optical devices, spectroscopy, chemical/biochemical reactions and enzyme-mediated and inevitably


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European Pharmaceutical Review Volume 16 | Issue 5 | 2011


supported with novel software. Each system or instrument available for rapid microbial analysis has its own particular set of features which may favour a particular application or use. Primary selection of an appropriate system should be driven by the technology’s intended use. Choice of technology solely based on its technical merits may not be appropriate because many available systems simply do not have sufficiently broad functional capability for a wide array of


microbiological tests. For instance, to examine the presence of specific microorganisms in non- sterile sample items or mycoplasma in sterile biological products, real-time polymerase chain reaction (qPCR) method is applicable and can be considered as a RMM for this particular purpose, however, it would be inappropriate to use PCR method as an alternative to the sterility test due to several uncontrollable factors that may have negative impact on the test results. In addition to the intended use, many other important factors involved in RMM implementation should be carefully considered before making a final decision to adopt a system for performance evaluation and qualification. These factors can fall into two categories: technical reliability and business benefit. The key factors in technical reliability


involve equivalence of sensitivity (limit of detection (LOD)), specificity, accuracy and precision to corresponding conventional methods, risks in generating false positive


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