Hayden Skalski - Lead Global Product Application Specialist, SUEZ – Water Technologies & Solutions
Hayden Skalski is the Life Sciences Product Application Specialist for the Sievers line of analytical instruments at SUEZ, specializing in bacterial endotoxins testing (BET). Hayden has over 8 years of experience in the pharmaceutical industry and Quality Control Microbiology and has presented on numerous topics surrounding endotoxin testing.Previously, Hayden held roles at Charles River Laboratories, Regeneron and Novartis, validating and executing method development protocols for endotoxin testing, providing customer support, troubleshooting and supporting high-volume product testing. Hayden has a B.S. from the University at Albany (SUNY) in Biology.
The bacterial endotoxins test (BET) is a critical quality control release test, which means that life changing products cannot be released to the public for use until they pass this test. For the past 30 years, the endotoxins test has used Limulus Amoebocyte Lysate (LAL) reagent, which is derived from the horseshoe crab to test pharmaceutical drug products and vaccines. There has been little change over this time period regarding endotoxin testing and techniques, with minimal improvements until recently. The industry has seen the pain points of traditional LAL testing and has expressed many reasons why improving LAL testing would be beneficial. The industry seeks to improve endotoxin testing by adopting new innovation that is now available to not only reduce time spent executing the test, but also improve data integrity in order to get the product out to patients more efficiently and safely.
With the traditional gel clot and 96-well plate methods come some caveats. These older techniques are extremely manual and require significant analyst hands-on time in the QC lab. The more human intervention needed, the more likely the LAL test is prone to errors. The gel clot method is a qualitative test, meaning that it is a pass or fail test. The 96-well plate kinetic methods are a step up from the gel clot method as these tests are quantitative and semi-automated. However, these methods still require significant time to set up and execute and are prone to a slew of errors.
The LAL test is a very sensitive test, detecting endotoxin down to one part per trillion (equivalent to one grain of sand in an Olympic-size pool). This sensitivity is remarkable, however it also means that any type of small contamination by the user will most likely be detected. Companies want to get their product out to market faster to help patients, so if there are failed or invalid LAL tests due to contamination, this results in retesting, investigations, and ultimately delayed product release to patients in need.
By adopting newer tools that are currently available, such as the microfluidic technology offered by the Sievers Eclipse microplate, QC labs can be assured that they will not only significantly reduce analyst hands-on time, but they will also reduce the percentage of potential invalid tests and time spent retesting and writing investigations. The ease of use for a product such as this helps labs produce results more successfully and in a timely manner, as the steps of loading of the microplate are drastically reduced compared to 96-well plates. The time saved when these two tasks are no longer needed will free up an analyst’s time to run additional LAL tests or focus on other lab priorities. Having a microplate with an embedded standard curve and positive product controls (PPCs) utilizing Reference Standard Endotoxin (RSE) also reduces significant variability within the test from analyst to analyst.
Another reason why the industry seeks to improve LAL testing is data integrity. This is tied back to human error and the fact that a lot of the processes associated with traditional LAL testing allow for error to occur. As labs use more dated methods such as gel clot, they are subjecting themselves to data integrity issues and human error due to the manual process of the test.
Gel clot is subjective because it is based on an analyst’s observations. The analyst must read test tubes after one hour of incubation and state whether the gel has clotted (positive result) or not clotted (negative result). This test often has a passenger, which would be a secondary analyst to review and verify the result. This is known as the ‘four eyes principle’ and is introduced as a data integrity check. However, this test now encompasses two analysts and pulls lab resources away from other activities.
As innovative kinetic methods are introduced, the subjective aspect goes away. The test no longer is a pass/fail, as endotoxin detection software is introduced and can provide actual quantitative data for the lab. The software that LAL companies produce must be 21 CFR Part 11 compliant and adhere to the guidelines specified for electronic data. Endotoxin data must be secure, unalterable, and easily attainable for audits. Newer endotoxin detection software allows QC labs to securely review and sign off on assays from any location, further reducing the time it takes to walk to the location where the assay was executed and check results. It is crucial that the data review process allows for security and efficiency. Quality control labs want to readily review and sign off on data and batch release information – and always in a secure manner – in order to release product or in-process materials to continue their manufacturing process. Moving from a more dated LAL method to a newer, innovative method shows auditors and regulatory agencies that your lab is looking to improve upon its current data integrity standpoint. By removing potential for human error and providing secure and streamlined data review, BET is now an assay that can be completed with ease and in a timely manner.
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