Cutting QC Time: The Future of Microbial Testing

Ensuring pharmaceutical safety and efficacy hinges on rigorous quality control (QC). By identifying potential microbial contaminants early in drug development and production, microbial QC tests safeguard research outcomes and patient health. However, traditional workflows are often labor intensive, time consuming, and prone to variability.

In this Innovation Spotlight, Nilay Chakraborty, the BioNexus Foundation principal scientist and head of cryobiology for ATCC, discusses the importance of microbial QC testing and highlights MicroQuant™, a new solution made in response to the typical workflow challenges.

Why is microbial QC testing so essential during drug development?

Microbial QC testing is a critical step in drug development and production that ultimately ensures patient safety and appropriate control. These tests are designed to detect microbial contaminants that have entered drug stocks or are present in model systems. In the latter case, they can lead to abnormal, inconsistent results; false conclusions; and wasted resources. Failure to detect these contaminants in drug stocks can significantly increase the risk of serious unintended side effects when given to patients. It is therefore vital that drug developers monitor for microbial contamination using QC tests. The tests associated with microbial QC are essential tools that provide crucial gatekeeping standards by which the sterility of the product and production environment can be monitored. Such monitoring enables traceability and the identification of potential problem areas that may impact drug safety and efficacy.

What is the traditional microbial QC workflow, and what common pain points do scientists experience during this process?

The most important aspect to understand about the conventional microbial QC workflow is the time and effort required to culture reference microbes. Researchers start a culture based on the relevant compendial guidance by inoculating recommended controls from an authenticated source, such as the biological resource and standards organization ATCC. This is followed by growing and maintaining the culture until stationary phase, after which the organisms are collected, serially diluted, and then plated for colony growth—a process that can take up to two weeks depending on the organism used. In most cases, the cultures are incubated at least overnight, and sometimes longer. The colonies are then counted and adjusted for appropriate dilution before they are used for QC testing.

This process is resource intensive with multiple points for significant user-to-user variation that can result in errors, making it challenging to accommodate fast turnaround times. There are also concerns related to genetic drift in the stock microorganisms following continual culture maintenance. This is usually mitigated using rigorous genomic characterization.

How can scientists improve their QC workflow?

The best way for scientists to improve their microbial QC workflows is to utilize new technologies and products that can reduce the time and resources required to generate authenticated, ready-to-use microbial reference strains. The conventional workflow requires dedicated personnel and equipment to maintain microbial cultures for QC assays. ATCC’s MicroQuant™ product line provides end-users access to passage zero, authenticated reference strains of the most commonly used organisms for microbial QC testing in a precisely quantitated format, eliminating the need for maintaining in-house cultures and removing major sources of variance. MicroQuant can reliably reduce two weeks of workflow involving the growth, monitoring, and quantification of microbes into the simple act of dissolving a pellet in less than a minute.

What inspired you to innovate microbial QC testing?

The driving force behind developing this innovative technology was recognizing that saving QC time benefits everyone in pharmaceutical development, from producer to end user. Streamlining QC testing allows scientists to focus on other more innovative and demanding tasks. This time savings translates directly into cost savings, which everyone in the development chain can benefit from. Reducing variance in cultures can also improve confidence in outcomes, ensuring product and patient safety. Finally, MicroQuant provides end-users with access to the authenticated ATCC organisms recommended in the compendial guidance for QC testing without the need for continuous culture maintenance and associated potential risk of genetic drift.

What is the main technological advancement behind the MicroQuant line?

The key innovation in the MicroQuant product line is the process employed for preserving the microbes in a quantified format. Using the innovative preservation process developed at ATCC, we can accurately predict, and subsequently verify, the number of colony-forming units (CFU) that will be present after creation of the product. This format can help alleviate the major pain points associated with traditional workflows, minimizing microbial QC testing time and accelerating the acquisition of reliable results. The near instant dissolution of the quantitated MicroQuant pellets with our specially formulated rehydration buffer allows end users to have a usable suspension of microbes within minutes of taking the box out of the refrigerator.

What does the future hold for innovation in microbial QC testing?

I expect that the future of microbial QC testing will continue to trend towards developing more technologically advanced instrument platforms driven by machine learning and artificial intelligence (AI) to further expedite testing. As new technologies and methods are developed, microbial QC testing may become a simple routine task that takes up minimal personnel bandwidth. I also see more automation taking hold in this space; when that happens, it will be even more critical to utilize pre-quantified products. MicroQuant provides the microbial QC testing community with a product that is ready for the future of automation in pharmaceutical development. The innovation here also provides a reliable and easy translatory avenue for automated detection of microbial colonies through enhanced automation and AI and machine learning.