The race to develop and manufacture COVID-19 vaccines and treatments has put a spotlight on Bacterial Endotoxins Testing (BET) and the criticality of this assay for research and manufacturing. The BET assay has long been a tedious, time-consuming, error prone assay that has seen little to no innovation until recently. Industry leaders have repeatedly stated desires for BET that is fully compliant, easy to set up and train analysts, reduces opportunity for error, and increases overall throughput. Increasing overall throughput may be even more crucial now with a global pandemic and the need to find solutions quickly.
Software is another component of the assay that has become increasingly important over time and contributes to the efficiency (or inefficiency) of the overall endotoxin detection program. Analysts and managers have dealt with software that can be cumbersome to set up and can result in questionable data integrity. In today’s environment, software should be a component of the assay that is never in question. Data should be secure along each step, including a quick and easy signature process.
Combining software needs with needs for ease-of-use, reduced errors, and increased throughput provide ample opportunity for simplification in endotoxin testing. Now, more than ever, it is crucial to leverage innovative technology and optimized procedures to improve operational efficiency, while maintaining compliance and accuracy to support the needs of the industry.
Here are three ways to simplify endotoxin testing:
1. Automation through Microfluidics
One of the most common issues in BET today is the time required to set up a full 96-well plate. Not only is there the pipetting time required to perform a single assay, but there is also significant time invested to fully train and re-train an analyst before they even start testing. With over 200 pipetting steps in the traditional assay, one misstep can lead to significant and costly out-of-specification investigations and timely retests. Simply adding positive product controls (PPCs) to a plate can cost 44 pipetting steps!
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With the use of microfluidic technology, pre-deposited endotoxin standards, and pre-deposited PPCs, automation of the endotoxin assay is achieved. Rather than relying on the 200+ pipetting steps analysts are used to, microfluidic technology facilitates accurate and rapid dispersion of reagents and samples to automate the process and drastically reduce manual steps. The Sievers Eclipse BET Platform significantly reduces the assay setup time as well as the opportunity for error by having less than 30 total pipetting steps.
2. Ease-of-Use and Definitive Root Cause Analysis
The 96-well plate assay requires highly skilled and trained analysts for proper execution. Even with months of training and years of experience, errors can and do occur. Whether it’s a missed PPC well, incorrect sample, or improper dilutions, these all lead to timely retests and potentially costly out-of-specification investigations. Imagine a time when an analyst is trained and certified the same day! Not to mention, a time when retests are minimized and definitive root cause analysis is used to close out an investigation. That would certainly make things simpler.
Using the Sievers Eclipse, pipetting steps are drastically reduced with a precise liquid handling device, and there are automated controls to help mitigate any errors in technique. This makes it remarkably easy to train analysts. With less than 30 pipetting steps and a closed system, an analyst can be trained and certified with the Sievers Eclipse in a single day, saving time and allowing for more cross-training capabilities. In addition to easy training, easy troubleshooting is achieved as well.
Using dual barrel optics with the unique microfluidic technology, the Eclipse platform can provide definitive root cause analysis by determining if the appropriate amount of liquid did not make it to the final optical well for reading. This can then be researched further to determine if the well was missed during the setup process or if a microfluidic channel failed to deliver the liquid. Together, easy training and troubleshooting simplify the endotoxin testing process and provide peace of mind.
3. Secure and Streamlined Data Review
A final aspect of endotoxin testing that can be simplified is data review and sign off. This can be less than efficient, typically forcing those reviewing and signing off on results to stop what they are doing and physically move to the location of the assay results to sign off. Some options used today even involve having to sign off on each and every sample that is analyzed leading to a time-consuming process. Even reviewing audit trails can be a daunting task when trying to find one piece that was tied to an assay.
The Sievers Eclipse platform helps reduce the stress from the traditional assay. Having fully validated and compliant software enables users to feel at ease knowing that everything is being properly tracked and documented. Another helpful feature is a client and server software setup. This allows designated users with the proper permissions to log in using a client install from any location to check results. With this setup, those in charge of reviewing and signing off on results can log in from somewhere else in the building, or even at home, and electronically sign for up to 21 samples in an assay. Each electronic signature is fully tracked by computer and user login, allowing for a complete and secure audit trail. In addition to these features, each assay has a dedicated audit trail that is attached to the end of the results, which makes the required audit trail review and sign off process simple and efficient. Ensuring data integrity and streamlining the review process allows manufacturers to maximize their uptime and increase throughput.
With the use of microfluidics to simplify the training and setup process, integrated technology to assist with failure analysis, and secure and streamlined data review, BET is now an assay that can be completed with ease and in a timely manner. By simplifying endotoxin testing, manufacturers can ensure product safety while increasing throughput and reducing burden on analysts.
Author Biography
Sydney Jannetta is a Life Sciences Product Application Specialist for the Sievers line of analytical instruments at SUEZ – Water Technologies & Solutions, specializing in endotoxin testing and ultrapure water monitoring. Sydney has supported Sievers instrument customers for the last five years with expertise in TOC and endotoxin applications. She has provided method development services and feasibility testing to pharmaceutical manufacturers and has presented at over 20 national conferences. Sydney holds a Bachelor of Science degree in Chemistry from the University of Northern Colorado.