Rapid Microbiological Methods - improve the detection, quantification and identification of microorganisms in the product

• By: Admin
• Date: December 09, 2009

Introduction

Rapid Microbiological Methods (RMMs) are methods designed to provide performance equivalent to the sterility testing methods described in 21 CFR 610.12, while providing results in significantly less time. In general, RMMs are based on technologies which can be growth-based, viability-based, or surrogate-based cellular markers for a microorganism (i.e., nucleic acid-based, fatty acid-based). RMMs are frequently automated, and many have been utilized in clinical laboratories to detect viable microorganisms in patient specimens. These methods reportedly possess increased sensitivity in detecting changes in the sample matrix (e.g., by-products of microbial metabolism), under conditions that favor the growth of microorganisms.

Benefits

The major premise on which Rapid Microbiological Methods are said to be beneficial is that it provides reliable and accurate test results in less time and with less operator intervention. Traditional methods though are effective in isolation of microorganism in manufacturing setting, they are limited by low production volumes, limited manufacturing time, and short dating periods which are becoming more of a concern with the emergence of new class of biological products. Requirements for large sample volumes, manual examination of cultures, and growth detection based on visual observation are some of the limitations intrinsic to traditional methods. Therefor the use of RMMs might prove beneficial for cell-based products by providing rapid results that could be used for product releases.

Validation is important

Effective monitoring of our manufacturing processes can help to ensure that a state of control is maintained, areas for continual improvement are identified, process and product understanding is enhanced, and manufacturing agility and efficiencies are realized. From a microbiology perspective, we can design processes to prevent contamination, investigate ways to correct a contamination event, and assess the potential impact of failing results on the patient. Unfortunately, our microbiology procedures are trapped in the 19th Century, using conventional methods that have not changed since the discovery of the agar plate!  Therefore, the modern microbiological laboratory should look towards developing innovative approaches to the detection, quantification and identification of microorganisms in our products, processes and manufacturing environments, and recent advances in Rapid Microbiological Methods now provide the analytical tools necessary to accomplish these tasks.

Proper validation of critical methods, including RMMs, demonstrates that the methods are suitable for their intended purpose and provides assurance that the results obtained are accurate and reproducible. Though RMMs are limited to few settings like clinical testing, they have not been subjected to comprehensive validation tests. Especially in settings like that of cell-based products where they are faced with challenging manufacturing issues because of the introduction of a additional product or process variables which will impact the test outcome. So it becomes necessary to account for these variables for the validation study so that the method is proved to be suitable for the intended product and application.

Additional Resources:

Webinar training package: Best-selling cGMP/Regulatory/Compliance Training CDs for the Microbiology Lab

Further reading
FDA Draft Guidance link: http://www.complianceonline.com/ecommerce/control/article?contentId=10364&catId=10902