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Heeding the emergency call by federal regulators to rapidly develop and distribute tests for 2019-novel-coronavirus SARS-CoV-2, diagnostic manufacturers and clinical labs have taken unprecedented steps, surmounting delays and challenges to meet the demands of a global outbreak modern history has never seen.

In January, Clinical Chemistry reported on two new rapid tests developed by Hong Kong researchers that could produce results in about an hour. The assays use real-time reverse transcription polymerase chain reaction to detect two gene regions found only in SARS-CoV-2 and in closely related coronaviruses such as SARS. “Diagnostic tests specific for this infection are urgently needed for confirming suspected cases, screening patients, and conducting virus surveillance,” said Leo L.M. Poon, DPhil, of the University of Hong Kong, who led the research.

At the time of Poon’s report, a limited number of cases of COVID-19—the illness caused by SARS-CoV-2—had been diagnosed in the United States. Since then, cases and deaths have mounted daily, spurring the need for an accelerated ramp-up of testing.

In vitro diagnostics (IVD) manufacturers and private labs began working behind the scenes to develop tests and meet Food and Drug Administration (FDA) emergency use authority requirements, which the agency issued initially in February and modified twice in March.

Mayo Clinic and UNC Medical Center in Chapel Hill, North Carolina, were two private labs that hit the ground running to fast-track a SARS-CoV-2 test following FDA’s policy change. Sharing their experiences with Clinical Laboratory News (CLN), lab directors at Mayo and UNC discussed the challenges of crafting an accurate test that met FDA standards. 

These tests must do three key things: show accuracy, determine the limit of detection, and not produce false positives in the presence of another kind of infection, Matthew Binnicker, PhD, a professor of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minnesota, told CLN. Developing, validating, and seeking an emergency use authorization (EUA) for a SARS-CoV-2 test is an intense process, he added. Even with Mayo’s plentiful resources, “it’s still taken a lot of time and energy,” said Binnicker.

In mid-March, FDA granted an EUA to Hologic for its Panther Fusion SARS-CoV-2 assay. The system can upload patient samples upon arrival to the lab, a “random access” process that improves efficiency and workflow, the company said in a statement. The plan is to produce at least 600,000 tests per month. “Demand for testing is much higher than what any of us at companies can make right now, so we are ramping up production 12-fold,” Kevin Thornal, president of Hologic’s diagnostics solutions division, said in an interview. “Our team is so proud to step up in situations like this to play a part.”

That said, Hologic doesn’t want to overpromise on capacity and delivery. “We’ve been on calls with government officials and have been very honest about this. You have to balance public and private sector needs. All companies are partnering together. Not one company can support it all.” Like the rest of the healthcare system, IVD manufacturers face their own supply chain challenges. Hologic makes all of its own material for reagents, primers, and probes, “so we are less reliant on others for general reagents,” Thornal said.

In the meantime, a German lab was able to leverage the Panther Fusion’s open channel to develop and validate a molecular assay for detecting SARS-CoV-2.

Roche’s fully automated cobas® 6800 and cobas® 8800 systems can process up to 384 results and 1,056 results, respectively, in an 8-hour shift. Results are available in about 3.5 hours. On March 13, the company began to ship its first weekly allotment of 400,000 cobas SARS-CoV-2 Tests to hospitals and reference laboratories across the United States. The goal is to ship an additional 400,000 tests weekly to a network of more than 60 lab testing sites across the nation with the capacity to immediately run this assay.

“At our current rate, we can supply approximately 3.5 million tests/month on the cobas 6800/8800 instruments globally. We are working around the clock to increase that quantity as we recognize the critical need for patients to have access to these tests,” a Roche spokesperson told CLN Stat. Collaborating with government agencies, “we have aligned on our current U.S. approach of targeting our limited supply to large, national reference labs as well as regional hospitals in the most highly impacted areas.”

Roche will continue to assess its strategy as the situation develops, the spokesperson added. In other business plans, the company said it will be supporting use of SARS-CoV-2-related assays and other patient-critical products, as well as new-system installations for adding the SARS-CoV-2 assay capability.

Another big player, Thermo Fisher Scientific, has a goal to ramp up to 2 million TaqPath COVID-19 tests in production a week, eventually reaching 5 million in production in April, CEO Marc Casper said in an interview. “We’ve started shipping to labs across the country,” he said. Producing results in about 4 hours, “the labs know this test is high quality and reliable, and it simplifies workflow tremendously.”

The TaqPath COVID-19 test runs on Thermo Fisher’s Applied Biosystems 7500 Fast Dx Real-time PCR instrument and is used by clinical laboratories world-wide.

The list of FDA EUA approvals is expected to grow. As CLN Stat went to publication, 34 tests developed by test kit manufacturers and commercial labs and 12 laboratory-developed tests had received this designation.

Among the various tests, there’s really only one competitor out there: the virus, Casper said. Whether it’s a test from Abbott, Roche, Thermo Fisher, or a lab-developed test, “expanding capacity is super important in addressing the virus.”

As manufacturers continue to roll out tests, labs across the country are scrambling to expand hours and testing bandwidth as well as optimize their personnel to amp up COVID-19 testing.

Spectrum Health Advanced Technology Laboratories in Grand Rapids, Michigan, has been using the Abbott m2000 test (RealTime SARS-COV-2 test) as well as the CDC 2019-nCoV Real-Time RT-PCR test. Both tests were launched in March, Spectrum’s laboratory director Kim Collison, MSA, MT(ASCP), told CLN Stat. For the m2000, “we decided to bring this test up on two different platforms because each platform had advantages and disadvantages,” said Collison. “However, the biggest reason was our fear that we would not be able to obtain reagents in a timely manner. This proved to be our immediate and current issue.” At CLN Stat’s deadline, Spectrum was preparing to launch another test, the Abbott ID NOW COVID-19 test.

The lab has the capacity to run more than 900 tests a day. At the moment, it’s only running 300 tests daily. “Our health system opened this testing up to all hospital inpatients in West Michigan, critical healthcare workers, and prescreened individuals. We have limited testing to these people due to challenges in obtaining the necessary reagents and consumables,” Collison said.

Her team has been able to turn around COVID testing in less than 18 hours from collection.

Spectrum has staggered its molecular lab staffing to be open 22 hours per day (from 4 a.m. to 2 a.m.), up from the normal 12 hours per day Monday through Friday, and 6 hours per day on weekends. “This is challenging because we only have nine technologists in this department,” Collison said. The lab staff devised its schedule to reach maximum capacity and still provide critical testing needed to support its cancer center and health system. Flow cytometry staff has cross-trained into molecular to offer additional support, and specimen processing has also increased its hours to mimic those of the technologists.

“The entire team at the Advanced Technology Labs has risen to the challenge and are totally focused on patient care,” said Collison.

Looking forward and beyond the pandemic, Melissa B. Miller, PhD, D(ABMM), F(AAM), UNC’s director of the clinical microbiology and the clinical molecular microbiology labs, offered some key perspectives to CLN. “Lab testing needed to be available earlier,” she said. “Capacity needed to be built earlier. When the dust settles from this pandemic, we really need as a nation to go back and look at the process. How can we more effectively enable CLIA labs to have widespread testing of a new infectious agent available more quickly but still safely?”