Genzyme scientists, John Duguid, Edward Balkovic and Gary C. du Moulin, recently provided a comprehensive review of where rapid microbiological methods are today (see American Pharmaceutical Review, 7(14), 18-25, 2011).
They explain that microbiological testing is slowly evolving as traditional methods with microorganism detection requiring days or weeks to yield new technologies, collectively known as rapid microbiological methods, or RMMs, which may detect the presence of a single organism within hours.
The authors discussed the advantages, limitations, encouragements and barriers associated with the implementation of RMMs. For example the limitations of conventional microbiological testing have been well known. These include small test sample volumes, prolonged incubation periods, incompatibilities with membrane filtration and ambiguity associated with the use of turbidity as a detection endpoint. The authors then discussed encouragement from the regulatory agencies. In fact, they explained that regulators have never discouraged the pharmaceutical industry from exploring rapid methods as an alternative to traditional methodologies. However, there continued to be barriers to change. For example, comments made by the FDA during the USP Science and Standard Symposium suggested that there was a general reluctance of the industry to develop new methods. Specifically, it is thought that management may not readily support changes to existing applications because the microbiology methods that have been submitted and approved by the FDA continue to work, so there is no incentive to implement new methods. Furthermore, there is fear of the unknown, including the fear that happens when RMMs with lower detection limits uncover microbiological issues that less robust methods cannot detect. There are also concerns that the cost of validation may be too high and there is little return on investment or the payback period is too long. Finally, the lack of microbiological expertise can hinder the development of appropriate comparability studies that can establish equivalency of the rapid method with the official or conventional method.
Next, the authors discussed a variety of rapid method technologies and how choosing the appropriate technology for the desired application is critical to success. An brief overview of currently available technologies included impedance microbiology, CO2 detection, headspace pressure measurement, nucleic acid technologies, flow cyometry, endotoxin detection, ATP bioluminescence, direct laser scanning, auto fluorescence, and genotypic, phenotypic and mass spectrometry for the rapid identification of microorganisms.
The authors finished their article with a review of what is needed to develop a robust validation strategy, and how to demonstrate that a rapid method is appropriately and scientifically qualified, and shown to be equivalent or better than what is currently being used. They also concluded that the evolution of microbiological testing from classical procedures to more rapid methods will place new and unprecedented amounts of data into the hands of the microbiologist. The industry can then apply this information to aid in prompt decision-making in support of real-time release or perform timely root cause analysis for failure investigations, thus improving the safety of pharmaceutical products.
The full article may be read by visiting American Pharmaceutical Review.