What is the Sievers Eclipse platform and how does it work?
The Eclipse platform uses highly innovative technology and automation to make endotoxin testing easier and more efficient without changing the biochemistry or reagents used in the assay. This is accomplished with full compliance and decreased strain on natural resources.
The Eclipse platform consists of a microplate, an analyzer, and enterprise software that bring advanced microfluidics, automation, and ease-of-use together to greatly increase efficiency in QC labs. The heart of the Eclipse is the microplate, a precision-crafted microfluidic liquid handling device that facilitates accurate and rapid dispersion of reagents and samples to significantly streamline kinetic chromogenic assays without the complexity of robotics. Assay setup is simplified in several ways:
- Use of pre-loaded standards and positive product controls (PPCs).
- Reduction in pipetting. With the unique liquid handling abilities of the microplate, you substantially decrease the number of pipetting steps needed – in less than 30 pipetting steps, you’re ready to run 21 samples.
- Minimizing use of Limulus Amoebocyte Lysate (LAL). Just 1 mL of LAL reagent is used to run a 21-sample assay on the Eclipse, an up to 90% reduction compared to traditional assays.
- Automation. The Eclipse microplate uses centrifugal force and pneumatic chambers to measure and evenly distribute precise amounts of LAL reagent water, samples, and LAL across 104 optical wells.
How does the Eclipse platform address common challenges related to endotoxin testing, such as time, throughput, and analyst training?
One of my favorite parts of developing this product has been the intricate involvement of customers throughout the journey—sharing their challenges, testing early versions of the product, and giving feedback—all of which allowed for a collaborative and iterative process. I’ve also been able to bring my own experiences to the table, as I’m all too familiar with the pains of running 96-well plate assays!
Along with compliance, we know QC labs are focused on productivity and accuracy. Yes, we want to make the test faster and less cumbersome to set up, but we also need to make sure data integrity, compliance, and other aspects are considered that contribute to the overall burden of endotoxin testing. Like other Sievers products, compliance, efficiency, and ease-of-use are hallmarks of the Eclipse. Here are some highlights:
- Simplifying assay setup. Often highly trained analysts take 45-60 minutes for assay setup. With Eclipse, setup can be completed in as little as 9 minutes.
- Streamlining training. Endotoxin assays are known to require highly trained analysts. With Eclipse, anyone can run a valid and effective assay, and there is substantially less opportunity for error and contamination.
- Increasing sample throughput and efficiency. With reduced assay setup time, analysts gain valuable time in their days, and labs reduce time-to-results – allowing them to release samples faster, increase productivity, and contribute to greater overall operational efficiency.
- Providing highly secure data management and compliant enterprise software.
How is the platform different than other products on the market?
There are similarities and differences between Eclipse and what is currently on the market. First, Eclipse uses commercially available LAL and embedded standards derived from the reference standard endotoxin produced by the USP. This is critically important because the biochemistry of the assay remains consistent. What we have changed is how reagents and samples are moved into their reaction wells—to summarize it simply, the Eclipse does a lot of the pipetting work for you with precise microfluidic liquid handling, plus mixing and high definition visualization of reaction kinetics. The Eclipse technology provides speed, accuracy, and ease-of-use to enable faster time-to-results with confidence. It’s hard to imagine setting up an assay in under 10 minutes with less than 30 pipetting steps, not to mention the substantial reduction in LAL usage, but the innovation achieved with Eclipse delivers remarkable efficiency. Together with software designed by former analysts, you have a solution that will really take QC labs into the future!
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What are common considerations around validation and method transfer? How do you validate the Eclipse platform?
The first consideration is how the system is validated in the laboratory. Endotoxin detection systems typically include an incubating instrument, software, and a PC. These components are involved in system validation, together with qualified reagents and consumables. Because kinetic endotoxin assays require the use of software to interpolate data against a generated standard curve, test cases are required during operational qualification (OQ) that focus on data integrity and 21 CFR Part 11 compliance. The physical installation of the system must also be qualified (IQ), which shows that the instrument and software themselves were successfully and securely installed. Lastly, a performance qualification (PQ) must be performed, which completes the validation by demonstrating that all components of the system are working together to detect endotoxins.
Eclipse is validated through a full IQ/OQ/PQ protocol that includes all the above and is also supplemented by robust validation testing completed by SUEZ. The Eclipse platform is not an alternative method, but by performing validation testing similar to requirements of USP <1225>, full confidence is instilled for the validation. A report summarizing this testing is provided to customers to supplement the validation work performed at each site.
How would I switch from my current testing routine to using the Eclipse?
Determining how to switch to the Eclipse platform for routine testing depends on the current state of testing. Once SUEZ understands the method or technique currently used for each sample type, we can help customers formulate a transition plan. Here are the most common scenarios:
Kinetic Chromogenic - Kinetic Chromogenic on Eclipse
This is the most direct transition because the kinetic chromogenic technique is the same within the Eclipse platform. In this scenario, the biochemistry, or the reaction between samples, standards, and LAL, will remain the same due to the consistency of the 1:1 sample to lysate ratio. That ratio verification is part of the Eclipse system validation process, part of routine maintenance, and is a hard-coded protocol within the Eclipse software. Once the system is validated, a brief bridge study can be completed to finalize the transition, which consists of side-by-side testing with the existing sample preparation remaining consistent. With the simplicity and efficiency of assay setup on the Eclipse, running a bridge study requires little additional effort.
Kinetic Turbidimetric - Kinetic Chromogenic
From my experience and feedback collected, most customers have chosen to work with the turbidimetric formulation because they want a quantitative endotoxin assay and the turb option is more economical for routine testing. Typically, this decision is not made because there is an incompatibility with the chromogenic method and sample type(s). The simplicity and efficiency gains now achieved with the Eclipse provide an economical and sustainable option for quantitative results. First, a customer should perform method suitability testing to compare inhibition/enhancement to the turb technique and demonstrate that they can adequately recover endotoxin with the chromogenic method. Generally, when switching method or technique it is recommended to perform a three-lot revalidation for final product release testing. Once the dilution required to overcome interference is identified, the customer can leverage the validation feature in Eclipse software to test the required number of lots (customizable setting) at their pace when samples are available. When complete, a clean validation summary report is provided for each sample that meets the established criteria, and the customer can begin testing those samples routinely with the kinetic chromogenic technique on the Eclipse platform.
Gel-clot - Kinetic Chromogenic
The gel-clot technique is commonly leveraged for difficult sample matrices and for legacy product final release. However, many labs still use the gel-clot technique for sample types such as water and are eager to implement a simpler quantitative technique. As with the scenario above, users should first perform method suitability testing to confirm that the samples they wish to convert are compatible with the kinetic chromogenic technique by performing inhibition/enhancement testing. For samples that do not require dilution to overcome interfering factors, such as ultrapure water, the process is further simplified. For product samples, this testing can be followed by a three-lot revalidation.
Regardless of the current state of testing, the Eclipse makes the transition to an optimized endotoxin testing platform simple. The SUEZ team is available to thoroughly support this process with applications testing to optimize the test method, on-site support of a bridge study, and a bridge study protocol.
How does the Eclipse platform address current needs related to compliance, data management, and data integrity?
The Eclipse platform meets the requirements outlined in the harmonized pharmacopoeias:
- Minimum 3-point standard curve in duplicate
- Samples and PPCs in duplicate
- Standardized endotoxin
- Negative controls in duplicate
- Analyst and lysate lot qualification in triplicate
- FDA licensed LAL
Regarding data management and integrity, Eclipse software was designed with ALCOA+ principles at the forefront. Data are complete, consistent, enduring, and available and are attributable, legible, contemporaneously recorded, original copies, and accurate (ALCOA). Any changes to metadata are thoroughly tracked in system and assay audit trails with pre- and post-change information recorded. Each assay’s audit trail can be reviewed and electronically signed, and each report that is generated is version controlled to maintain complete visibility through final signature. SUEZ ensured these critical needs were met through customer feedback and rigorous testing.
David Wadsworth is the Global Product Manager, Bio-Detection at SUEZ – Water Technologies & Solutions, focusing on next-generation endotoxin detection. Dave has a Bachelor of Science degree in Biology from Wheaton College Massachusetts and has over 14 years of experience in the endotoxin industry. His first introduction to endotoxin detection was as a seasonal employee responsible for collecting and processing amebocytes for a LAL manufacturer, and he’s been enthusiastic about bacterial endotoxins testing ever since!