Discussing developments in RMM with Dr Tim Sandle, Bio Products Laboratory

In March 2021, European Pharmaceutical Review’s Hannah Balfour interviewed Dr Tim Sandle, Head of Microbiology, Risk Management and Sterility Assurance at Bio Products Laboratory Limited, to find out more about rapid microbial methods (RMM). In the discussion they explored a range of topics, from the differences and primary benefits of RMMs compared to traditional microbiological methods, to some of the latest developments in the field and his suggestions of what to consider when implementing RMMs.

Dr Sandle explained that the primary benefits of RMM include their rapidity, improved detection and greater sensitivity. “They also have elements like automation and the ability to capture data digitally,” he said, adding later that it is these capabilities that make RMM suited for use in process analytical technologies (PAT), which the US Food and Drug Administration (FDA) is encouraging as it allows for real-time risk-based decision making.

Dr Sandle also discussed some of the key RMMs currently being used in the industry, he divided them into three categories: qualitative rapid methods, quantitative rapid methods and identification-based methods. “Some of these methods are growth-based, so we’re looking for… some kind of signal as the micro-organism is growing. Some are viability-based… here the micro-organism does not need to be growing, it just needs to be present and the other category is looking for some kind of cellular marker,” he explained.

 In terms of recent advancements in the field, Dr Sandle gave four examples:

• optical spectrophotometry, using light scattering to determine how many of the particles in the air may be biological and therefore potentially micro-organisms, in cleanroom and aseptic filling environments;
• head space analysis, looking at the amount of carbon dioxide in bottles from aseptic media filling to ascertain if bacteria is growing;
• using blue light laser excitation to determine if there are microbes present using micro-colonies; and
• lab on a chip technologies for mass screenings of antibiotics.

Additionally, he explained that the COVID-19 pandemic has shown the importance of having RMM: “because some of the ways the COVID-19 vaccines have been really, really fast and that has shown that the faster we can get laboratory results out, the better.” One of the key areas for RMM with regards to the vaccines, stated Dr Sandle, is with regards to endotoxin testing, such as using recombinant lysates, automation and rapid endotoxin test kits.

Dr Sandle also gave his recommendations for what to consider when looking to implement RMM: “it is important not to get too wowed by the technology and the sales rep, a lot of rapid methods are in earlier stages of development so it’s important to say: ‘is this technology mature?’ and ‘is there good supporting literature?’ And then it is important to follow the guidance.” He added that you must always start with a risk assessment, follow the classic validation steps (design, installation and operational performance qualifications) and be careful when looking to compare classic microbial methods with RMM, since they could be assessing very different things.

His final point was the opinion that regulators are a brick wall to rapid methods, is actually a myth and they are in fact trying to encourage the industry to look at RMM. Dr Sandle said this is evident in the revision to Annex 1, for example, as it has adopted no growth, instead of 1 cfu, as the new limit for Grade A environmental monitoring, is “a nudge that some rapid methods can be used”.