|This is an excerpt of a 2,375-word article in the March 9, 2020 issue of THE DARK REPORT (TDR). The full article is available to members of The Dark Intelligence Group.
CEO SUMMARY: Clinical labs are working with haste to develop a novel coronavirus test. In this rare behind-the scenes look, laboratorians can learn about Northwell Health’s efforts to prepare for high capacity testing for viral respiratory illness include validating molecular tests for the newly-identified virus and making those tests available for testing patients who may have the COVID-19 illness. At Northwell, the lab team has been validating the CDC’s manual test and a multi-test panel for respiratory diseases that will include the novel coronavirus.
Following the outbreak of a novel coronavirus in China at the end of December, clinical laboratories have faced multiple significant challenges.
Among the challenges they face are validating a diagnostic novel coronavirus test that has the sensitivity and specificity to make it useful for physicians treating patients and working with public health officials to manage a rapidly evolving epidemic.
Another of these challenges is to develop the ability to perform these novel coronavirus tests at high volume levels and with a fast turnaround time for results. While seeking to meet all of these challenges, clinical labs also must comply with federal and state regulations that govern the use of these assays.
In mid-January, scientists in China released the genetic information for this novel virus. At that time, the leaders and staff in the clinical laboratories of Northwell Health in Lake Success, N.Y., recognized the need to be able to validate a novel coronavirus test that the federal Centers for Disease Control and Prevention (CDC) would release, and then be able to run that test in enough numbers to meet an unknown level of demand.
As one of the nation’s biggest health systems, Northwell has 23 hospitals and a central reference laboratory serving both Northwell and other hospitals in the greater New York metropolitan area, making Northwell’s lab one of the largest in-system clinical laboratories in the United States, according to Stefan Juretschko, PhD, D(ABMM), Northwell’s Senior Director of the Division of Infectious Disease Diagnostics. Juretschko is leading the systemwide efforts to increase the labs’ capacity for testing for the novel coronavirus that causes the coronavirus disease (COVID-19).
As soon as the test kits arrived from the CDC and from the New York State Department of Health (NYSDOH), Juretschko, other lab directors, and the lab staff began the steps required to validate and run the novel coronavirus test in Northwell’s labs. Also, the lab began acquiring new analyzers, testing supplies, and reagents from vendors nationwide to support their efforts to run large volumes of tests for patients and their physicians.
Working Day and Night
During an interview with The Dark Report on March 4, Juretschko outlined those processes and said he was confident that Northwell Laboratories would be capable of testing patients in large numbers by the end of March. Since the middle of January, Juretschko and other lab staff have worked night and day to scale up testing for the virus, he said. During this time, events in other countries and in the United States began to unfold quickly.
For example, on Jan. 21, officials from WHO conducted a field visit to Wuhan, when Chinese scientists released the primers and probes for novel coronavirus test kits that labs in other countries would use to detect the virus.
On Feb. 4, Alex Azar, the Secretary of the federal Department of Health and Human Services, issued an emergency use authorization (EUA) saying that the coronavirus created a significant potential for a public health emergency that could affect national security or the health and security of U.S. citizens. That same day, the FDA issued an EUA allowing the emergency use of the CDC’s 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel.
Under this EUA, testing was limited to qualified, CDC-designated, and CLIA-certified laboratories to perform high-complexity tests. The clinical labs at Northwell Health meet these criteria.
Emergency Use Tests
The FDA then issued two EUAs on Feb. 29. One outlined the policy-specific guidance that public health laboratories needed to follow to contain the public health emergency. The second EUA allowed two public health laboratories in New York to expedite the availability of diagnostic testing.
“The EUA required labs to follow specific procedures when seeking to produce assays and test kits for identifying the virus, a process that slowed Northwell’s efforts,” Juretschko said. For individuals who meet the CDC’s criteria for such testing, the FDA’s instructions called for collecting upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate).
Since then, Northwell’s lab staff has made significant progress in drafting plans for the novel coronavirus tests, and to have the equipment and supplies in place to test an unknown, but presumably large number of patients.
By March 7, lab leaders were deep into validating the test kits received from the CDC and preparing to validate novel coronavirus test platforms from commercial companies such as GenMark Diagnostics in Carlsbad, Calif., and Cepheid in Sunnyvale, Calif., Juretschko explained. He expected the lab to complete validating multiple platforms for identifying the virus by March 15 or so.
“We learned recently that we will shortly get some quality control material from NYSDOH that is not infectious. It is contrived material that we will use for quantitative analysis.”
Testing at Scale
“We are developing a three-pronged approach to do testing on a large scale,” Juretschko reported. “The first approach is to implement the original assay that the CDC and all public health laboratories use, along with controls and detailed directions.
“The second approach is to use a device, similar to a commercially-available respiratory pathogen panel to test for the novel coronavirus,” he added. “This panel allows for more mobility and flexibility in testing because we can provide the assay directly to the hospital laboratories.
“The ability to apply for an EUA opened up opportunities for labs like ours to do research on how to get these tests running on a larger scale,” Juretschko explained. “For example, we used the EUA to have conversations with three vendors to get the tests and the equipment we need to serve our health system.
“The approach would entail an even more automated process for testing on several big-footprint instruments,” he continued. “These analyzers are already placed at the core laboratory and can be ‘fed’ with the original patient samples, processed internally by robot arms, and thus allow for extremely high throughput testing of 1,000 to 2,000 patients per day. The actual assays and reagents have yet to be designed and validated, but we expect to launch those assays and reagents within the next several weeks.”
Before going into detail about the second approach (using the respiratory pathogen panel), Juretschko outlined the first approach: validating and running the novel coronavirus test from the CDC. “The CDC has its own validated assay,” he explained. “It’s distributing this assay to all departments of public health across the United States. That assay includes all details about probes and primers and the entire standard operating procedure for the test.”
During the interview on March 4, Juretschko said the lab team was at the end stage of the validation process to run that novel coronavirus test in the lab. Via email, he con-firmed that the process was completed on March 7.
While CDC validated the test itself, the Northwell lab staff needed to validate the CDC assay on its own equipment and in the laboratories in which it will run, he said. That validation includes ensuring that physicians can order the tests electronically, and also that the results can go back to ordering physicians.
“Plus, we want to make sure that physicians can read and understand what the results mean,” Juretschko added.
The lab team’s multi-pronged strategy, as Juretschko described, is to scale up the novel coronavirus testing by first using the assay from the CDC. In a parallel effort, the lab will use an automated respiratory pathogen panel from GenMark and other vendors. As Juretschko explained, the work the Northwell lab team is doing to prepare to do high-volume novel coronavirus testing provides an excellent example for other labs in hospitals and health systems of the benefits of having a highly-integrated in-system laboratory network.
“Our core lab serves our very large health system and an additional 11 area hospitals as the reference lab,” he said. “And in our own system hospitals, the clinical labs are already equipped with the Respiratory Pathogen (RP) Panel from GenMark. This means that, if we successfully validate the GenMark platform, we can deploy such testing throughout the health system, not just at the core lab.
Is your lab working on novel coronavirus testing? Please share your thoughts with us in the comments below.