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RMM »
material, in-process material, and finished product), a reduction in warehousing space, and a decrease in repeat testing, deviations, out-of-specification investigations, reprocessing or lot rejection.
Because many RMM technologies consist of a combination of instrumentation, software, consumables and reagents, in addition to specific detection, quantitative or identification analytical methodologies, it is important to develop a comprehensive and holistic approach to the validation process to ensure that the entire RMM system is suitable for its intended use. This is where PDA Technical Report No. 33 (TR33) comes into play.
The original version of TR33, Evaluation, Validation and Implementation of New Microbiological Testing Methods, was published in 2000. This best practice document provided the pharmaceutical industry with the very first guidance on how to select and validate novel and rapid microbiology systems. Since that time, many new technologies were introduced, validation strategies were improved and, most importantly, acceptance and encouragement for implementing rapid and alternative methods by worldwide regulatory agencies increased significantly. For these reasons, there was a need to update the original technical report.
In the beginning of 2008, a task force team comprising subject matter experts in rapid and alternative microbiology technologies,
validation, regulatory affairs, quality control, manufacturing and statistics was assembled for the purpose of revising TR33. Committee members represented industry, technology suppliers, consultants and regulators (see Table 1).
Michael J. Miller, Ph.D., Chairperson John Albright Claude Anger
Dilip Ashtekar, Ph.D. Peter Ball, Ph.D.
Joseph Chen, Ph.D. Steve Douglas
William Fleming, III., Ph.D. Ren-Yo Forng, Ph.D. Gary Gressett Jianping Jiang
Robert Johnson, Ph.D.
Table 1. TR33 Committee Members David Jones, Ph.D.
Richard Levy, Ph.D.
Daemon Lincoln, Ph.D. Patrick McCarthy
Patrick McCormick, Ph.D. Jeanne Moldenhauer Paul Newby, Ph.D. Bryan Riley, Ph.D. Miriam S. Rozo Heather Wilson Elizabeth Young Pascal Yvon
When the committee was closing in on a final draft, additional reviews and input were provided by end-users who had successfully validated and implemented RMMs in their own facilities as well as key global regulators and pharmacopoeia experts. As a last step, PDA’s Science Advisory Board, Biotech Advisory Board, and Board of Directors provided their approval. The new TR33, Evaluation, Validation and Implementation of Alternative and Rapid Microbiological Methods, was published in October 2013.
TR33’s front matter is composed of an introduction, scope, purpose and a glossary of terms. The first section provides an overview of the challenges associated with classical microbiological methods including long times for obtaining a quantitative or qualitative result, the potential inability to recover microorganisms (e.g., when they are stressed, dormant or VBNC) and an unmet need for linking microbiology to Quality by Design and quality risk management principles. This is followed by an introduction to alternative and rapid methods including a discussion of their advantages over traditional growth-based methods in terms of time to result, sensitivity, accuracy and precision.
Because regulatory expectations for the validation and implementation of rapid and alternative methods have appreciably evolved over the last 10 years, TR33 addresses the current positions and opinions of authorities such as the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), the Australian Therapeutic Goods Administration (TGA) and the Japanese Pharmaceuticals and Medicinal Devices Agency (PMDA). The section discusses industry guidance documents, changes in policy and regulations, validation expectations and instances when a formal regulatory submission may or may not be necessary. Additional considerations when working with other regulatory agencies and countries (i.e., Rest of World) are also provided.
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