If It Isn't Broken, Still Consider Fixing It: The Time for Rapid Microbial Methods is Now!
Despite innovative technologies and strategies, myths persist about rapid microbiological methods
The hesitancy surrounding the use of rapid microbiological methods (RMMs) for quality control testing dates back decades. Regulatory agencies have approved RMMs and some of the most renowned drug and consumer care product manufacturing companies have implemented a rapid method for contamination detection and seen success. So, why are microbiologists and quality control laboratories still having doubts?
Michael Miller, Ph.D., President of Microbiology Consultants, LLC. presented at the 2021 Parenteral Drug Association Pharmaceutical Microbiology Conference. He looked back at a presentation he gave in 2011 based around “debunking” the myths of RMMs and how a lot of these questions are still asked in recent conversations with microbiologists. We can deduce that most industry professionals’ thoughts and questions have not changed with the times, regardless of the innovative technologies and strategies that have been tried, tested, and ultimately proven beneficial.
A big one is the question of “Are RMMs approved by regulatory authorities?” The answer is yes, and have been for years. The issue is that agencies don’t necessarily promote these ideas and innovations, especially if the method is not compendial. Aside from the standardized reports that are published, it’s not like they have big flashing lights on billboards that say, “You Should Probably Be Using an RMM By Now”. This, unfortunately, leads many to believe that automated testing is not being widely utilized or validated by agencies.
Another common trend we see is the “If it isn’t broken, don’t fix it” mentality in the industry. Traditional methods relying on visual confirmation of turbidity or colony enumeration continue to be used because they have been considered compendial, and therefore safe. However, over recent years, deficiencies in these methods, resulting in many FDA 483’s, have begun to emerge. Shortcomings stemming from the idea of human error, whether in the detection of contamination and subsequent reporting, have been identified by many regulators. The risk of staying the same is growing.
Rapid detection methods are best for short shelf-life drugs
Moreover, the risk of switching methods has obscured the benefits of change. From protecting patient safety to reducing contamination response time and reducing costs, the technical shortcomings of traditional methods preclude the advantages of rapid methods. If a company doesn’t know about the time, money, and resources they could be saving, then they won’t understand the benefits of implementing one in the first place.
As new medicinal methods are sprouting worldwide, a new approach to contamination testing should be adopted. For example, the emergence of ATMPs, cell and gene therapies, and other short shelf-life products are developing faster than anticipated. The 2018 European Guidelines for ATMPs stated that the compendial Ph. Eur. 2.6.1. sterility test, taking 14 days to incubate, may not be appropriate for short shelf-life drugs. Not only are these drugs time-sensitive to administer, but the compendial method of testing for contamination typically requires more sample to be used. Rapid detection methods, such as Celsis® adenosine trisphosphate bioluminescence, require only 50 µl per replicate - a fraction of the amount, saving more product for patients in need.
With the new 2021 revisions to Annex 1, regulatory authorities are pushing for the adoption of rapid, automated monitoring systems. They argue that it will expedite the detection of contamination and reduce the risk of product release, especially in the case of short-shelf-life drugs. Also, USP <1071> provides guidance when the compendial method is not suitable for short-shelf-life sterility testing, which recommends the use of rapid sterility tests to be used as in-process controls prior to final release. It’s anticipated that additional USP general chapters will be released after June 2022 as well.
So, if you needed a sign to implement an RMM into your manufacturing processes, this is a great indicator to begin moving forward. While compendial methods may not be broken, it’s about time to fix them.
Kate Shannon is a Marketing and Client Engagement Specialist for Microbial Solutions, focusing on rapid microbiological methods and contamination detection. She is located in Wilmington, MA, and is responsible for monitoring pharmaceutical industry trends and market patterns.