Importance of Method Validation to Public Health

Method Validation Needed

You can’t escape the knowledge that the world is currently in the midst of a global pandemic of COVID-19, the disease caused by the novel SARS-CoV-2 strain of coronavirus.  Tracking and slowing the spread of disease have been on everyone’s mind for much of the year. We know that this will be difficult to do without rapid and accurate testing, which has been in short supply in the United States. The U.S. must produce or acquire accurate tests, quickly and in high volumes, which is why many are pushing to loosen regulations to get more tests into the hands of health care professionals. The laboratory informatics experts at CSols have a unique insight into laboratory testing and data analysis, and we have been discussing—remotely, of course—how our experience with successful LIMS implementations can help experts predict and prevent future pandemics.

The value of a well-implemented laboratory informatics system comes down to being confident in your data: Do you really have what you think you have? Our laboratory and computer scientists have broken this down into three questions concerning COVID-19 testing:

Question 1: How will you make sure your laboratory operations scale with your production operations when adding new methods in times of crisis?

Question 2: How can you be sure you developed an analytical method that reliably tells you if a patient has a particular disease, despite variances in testing conditions and the patient’s viral load?

Question 3: How will you retrieve and report that data reliably and in a meaningful way?

The short answer to all three questions is: trustworthy informatics systems. CSols specializes in helping clients select, implement, and validate laboratory informatics systems, so that their LIMS can become reliable for the lab and achieve trustworthiness.

Today’s blog post focuses on a detailed answer to question one, which is to use a LIMS to support high-quality method development and validation for new assay methods that are needed to generate cheaper, faster, and more reliable tests for the current COVID-19 crisis or future pandemics.

Why Method Validation Matters and How a LIMS Can Help

Currently, most of the approved SARS-CoV-2 tests are real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Laboratories have executed billions, if not trillions, of these assays across the globe since the 1985 invention of PCR. Testing reagents for these kits are commercially available and robust—meaning the technique itself is low-risk as a platform for new virus-specific assays.

Even with that in mind, there are infinite numbers of possible analytical methods—differences in the protocols, temperature cycles, and data analysis applied—in use for qRT-PCR, which allow limitless opportunities for error. For example, in February 2020, the CDC announced that reagents used in an initial shipment of SARS-CoV-2 test kits were faulty and would have to be re-manufactured, further delaying critical testing for patients around the country. These faulty qRT-PCR tests for SARS-CoV-2 resulted in multiple false negatives, apparently due to lack of robustness. It seems likely (though it could not be conclusively proven at the time of publication) that early SARS-CoV-2 tests required meticulous handling to be accurate, and may not have been handled correctly.

A rigorous method validation process ensures that assays are appropriately robust and hold up to less-than-fastidious handling. The lack of validation rigor might have contributed to the multiple false negative test results, like those that Chinese whistle-blower Dr. Li Wenliang received before his death. It is not uncommon for new assays to lack sensitivity or robustness, which is why strong, reliably enforced method development processes and accurate documentation are vital to public health. Properly executed and documented method development serves as the foundation upon which continual innovation grows.

How LIMS Supports Proper Method Development and Validation   

In ordinary times, method validation is an involved process that must stand up to rigorous regulatory scrutiny. Pharmaceutical and clinical assay developers must prove that an analytical procedure is suitable for its intended use and is acceptably robust within well-defined limits of the analysis (i.e., instrument detection limits). Method validation is an essential part of the approval process for new pharmaceutical products, new medical devices, and clinical tests, like the SARS-CoV-2 test.  

Proper method validation ensures that the analytical technique and protocol (in the case of COVID-19, the genetic test that identifies the presence of the novel coronavirus SARS-CoV-2) is fit-for-purpose, safe, effective, sensitive, and specific in the intended patient population. Without the safeguard of method validation, an ineffectual assay method could produce a lethal false negative. Laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) use rigorously validated methods and must substantiate that validation with thorough documentation.   

High-quality and high-integrity data collection driven by state-of-the-art laboratory informatics and rigorous method and computer system validation procedures can assure us that anyone who produces data can capture and report it reliably.    

How LIMS Speeds Time-to-Market

Although qualifying reagents for existing protocols is vital, we are still in desperate need of cheaper, faster tests to survey the population at the level required to slow and eventually halt the spread of COVID-19. Properly developed analytical methods—including any method that might outperform the existing qRT-PCR method—are critical to ensure that not only viral tests, but biotechnological products meet relevant acceptance criteria that ensure safety and efficacy. Method validation provides this assurance.

As of late March 2020, laboratories in the United States struggle to find SARS-CoV-2 test kit components and other vital qRT-PCR reagents. Millions of test kits are needed, however, and researchers continue to identify candidates for alternative testing platforms, including immunoassays and CRISPR-based techniques. 

But how can scientists avoid past mistakes during the discovery and validation process for these new—hopefully faster and cheaper—tests?

The answer, again, is high-quality, high integrity data. The process standardization inherent in a LIMS ensures that technicians follow procedures and document them correctly. Automatic process enforcement is one way to leverage a LIMS to improve and speed the method validation process. Also, GAMP 5 LIMS implementations lead to vast improvements in data quality and integrity as well as more transparent, accessible, and reportable data analytics.   

If You’d Like to Learn More…

If you’re curious about how CSols’s services can help your business, read on for some answers to questions two and three mentioned earlier.

Answer to question 2: Use properly validated LIMS and LIMS-instrument interfaces to systematically and reliably capture, store, and report results.

If your lab is seeking CLIA accreditation or adding regulated products to your catalog, a properly validated informatics solution can support your accreditation with less paper and faster turnaround times.

Answer to question 3: Leverage a properly configured, fit-for-purpose tool with reports and dashboards that can grow and expand with ever-changing businesses in a dynamic economy.

Implementing a LIMS will prepare your lab for the next pandemic and allow you to be more agile than your competitors and to meet the rising public need first. If your lab needs to ramp up operations to respond rapidly to a public health crisis while still meeting regulatory requirements, CSols can help you choose the best informatics system for your operation. If you already have a system, a qualified informatics consultant can provide the upgrade support you need to add value to your lab, regardless of how mature your current informatics system is.

Is your lab prepared to ramp up quickly in the face of the next public health emergency?

If the answer is no, or you aren’t sure, contact us now to get started with selecting an informatics system that works for your lab. Not only will you have a head start on your competitors when the next crisis arrives, but we can also help you reduce the costs and risks associated with a major application implementation, upgrade to a current system, or validation to make sure you stay compliant with CLIA and FDA regulations, now and in the future. 


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