2020 Barsan Emergency Medicine Research Day

1. Developing a test for COVID-19 at MM
Duane W. Newton, PhD
Director, Clinical Microbiology Laboratory

2. Building a test
• FDA approved
– Manufacturer-developed
– Multi center clinical trial; 1000s of specimens (ideally); 6-12 months
– Defined system, reagents, parameters
• Laboratory performs verification (verify manufacturer’s claims)
• Laboratory developed tests
– In house development; 100s of specimens; 6-12 months
– Analyte-specific reagents; user-specific systems and parameters
– Not regulated by FDA
• Laboratory performs validation (establish performance characteristics)
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3. Tests for emerging pathogens
• Typically, CDC develops novel test, shares protocols
and reagents with state/local public health labs
– SARS (2003)
– Pandemic influenza (2009)
– MERS (2012)
– Ebola virus (2015)
– Zika virus (2016)
• No gold standard, no time for clinical trials
• Commercial vendors develop test on their own if situation
warrants/justifies
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4. Emergency Use Authorization
– “the FDA Commissioner may allow unapproved medical products or
unapproved uses of approved medical products to be used in an
emergency to diagnose, treat, or prevent serious or life-threatening
diseases or conditions caused by [certain] agents when there are no
adequate, approved, and available alternatives.”
– Utilized in 2009 for swine flu pandemic
• CDC gained EUA for their test
• Several commercial manufacturers developed EUA tests
• Limited assessment of performance
– Analytical performance only; no clinical trials
– Not structured for clinical laboratory test development
• Zika virus experience
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5. “Name that Outbreak”
• COVID-19
• Novel coronavirus (nCoV)-19
• SARS-CoV-2
• Testing slow to develop
– CDC rollout was not smooth
– FDA exerted tight control over testing
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6. 6
Letter sent to Congress and various news outlets
Signed by 107 US-based Clin Micro lab directors

7. Testing for COVID-19
• EUA structure changed on Feb. 29; guidance received from FDA
on Mar. 2
– Laboratories allowed to develop tests; EUA submission within 15 days
• Initiated acquisition of testing components based on CDC EUA
assay
– Positive control material was very difficult to come by
• Applied CDC assay to our platforms, followed FDA template for
validation
– Used simulated specimens spiked with quantified virus controls
• Limit of detection, cross-reactivity, specimen type
– Tested positive patient specimens that had been tested at Viracor or
MDHHS
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8. Timeline of testing*
• Mar. 5, 2020 First tests sent to LabCorp
• Mar. 10, 2020 First positive results; first tests sent to MDHHS
• Mar. 13, 2020 First tests sent to Viracor
• Mar. 17, 2020 MM live with LDT
– 21 samples/run; 6 hr analytical time; 24 hr TAT; ER/inpatient
• Mar. 21, 2020 Reagents received for high throughput assay
• Mar. 23, 2020 MM live with high throughput assay; reagents
received for rapid TAT assay
– 94 samples/run; 6 hr analytical time; 24 hr TAT; ER/inpt -> ambulatory/outpatient
• Mar. 26, 2020 MM live with rapid TAT assay
– 6-24 samples/run; 2 hr analytical time; 6 hr TAT; ER/inpt
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*best estimates

9. Moving forward
• Expansion of testing
– Drive-up specimen collection sites
– Employee testing
– Testing for partners/affiliates (VA, St. Joe-Chelsea, MidMI,
MetroHealth)
– Broadening of clinical criteria
– Pre-surgical, pre-transplant screening
– Removal of ID approval
– Skilled nursing facilities, home testing by MI VNA
– Discharge screening (in development)
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10. Moving forward
• Challenges
– Overuse of testing
– Specimen collection kits in short supply
– Discharge screening
• Role of serology
– Multiple assays currently being evaluated; timeline similar to
molecular but no FDA EUA process
• Diagnosis -> NO
• Proof of immunity -> ?
• Epidemiologic surveillance -> long term
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11. Lessons learned (the hard way)
• Lab medicine is a mystery to most (clinicians and lay-people)
• Regulatory landscape is complex and restrictive
– CLIA-certified labs are highly skilled and have large capacity
– Support/encouragement/incentives for commercial manufacturers is
limited
• CDC’s role is not well understood
– Can’t support testing load for the entire nation
• Better integration is needed between hospitals, public health,
government, and industry
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12. Thanks!
dnewton@med.umich.edu