Typically, microbial testing is a labour-intensive process that involves filtering samples from almost every stage of the production process onto culture plates, and waiting several days for any contaminating microorganisms to grow into colonies that can be observed by eye. Rapid Micro Biosystems' approach is based on this tried, tested and validated approach, but with one key difference. It uses the existing quality control laboratory approach to harvesting samples, but then relies on advanced imaging technologies and automation to identify and warn of microorganism growth, sometimes in as little as a day. "Visual plate counting can only detect colonies of around a million cells; our system can do the same with as few as 100 cells," said Steve Delity, Rapid Micro Biosystems' president and CEO. The company has placed the first system, called Growth Direct, into a pharmaceutical company for evaluation. Pharmaceutical manufacturing is 'in crisis', according to Delity, and outdated testing methods are a part of the that problem. The industry has a manufacturing efficiency of 90 to 95 per cent, which means that 5 to 10 per cent of batches do not meet acceptable standards. This may seem good at first glance, but it does not reach the heights achieved in other industries, such as semiconductors, which boast 99.9999 per cent efficiency rates. For high-value products such as pharmaceutical that equates to an expensive waste, and is one reason why pharma spends more than twice the amount on manufacturing as it does on R&D (36 per cents versus 17 per cent, respectively, of revenues). "A typical pharmaceutical facility will carry out 50,000 microbial contamination tests a year, and this can rise to hundreds of thousands a year at large facilities," noted Delity. The cumulative time and cost saving from automating that process and getting results back quicker is hard to quantify, but is likely to be significant, he said in an interview. The delay in getting the results back from testing - typically up to seven days for in-process product testing - puts pharmaceutical manufacturers in a real dilemma. Either they put the batch on hold until the results come back, which is a waste of resources, or they press ahead and accept the risk that a batch may have to be ditched for being out-of-specification. Rival systems Other automated technologies have been developed to speed up the microbial testing process, but have a number of drawbacks. Unlike growth-based approaches they may lack the sensitivity to detect a single cell, or are destructive. This is a particular drawback as regulators will often ask for identification of a contaminant once discovered, says Delity. ATP bioluminescence can give a rapid readout on whether contamination has occurred but it destroys the microorganism in the process, and because it requires reagents to be added can create validation issues. Laser cytometry is also being used, but is a manual process that has a low throughput (40 samples per day, versus 100 samples per day for culture systems) and can give false positives - picking up what are known as viable but not culturable (VBNC) cells. There are also nucleic acid-based approaches that are great for identification of organisms, but are held back by small sample sizes. Typically they max out at around 0.5ml, while production scales samples can be several hundred millilitres in volume. But perhaps the greatest advantage of the Growth Direct system is its simplicity, and the fact that it is based on culturing samples - exactly the same way this type of testing has been carried out for decades. That means regulators should have fewer questions about the validity of the results, and the system fits in perfectly with existing quality processes. Delity said that the current version of the Growth Direct unit costs in the region of $475,000, and has a throughout of 40-50,000 samples a year. A larger unit with a throughput of several hundred thousand samples per year is also in development.
