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Policy for Diagnostics Testing in Laboratories Certified to Perform High 

Complexity Testing under CLIA prior to Emergency Use Authorization 

for Coronavirus Disease-2019 during the Public Health Emergency: 

Immediately in Effect Guidance

Timothy Stenzel, MD, PhD

Director, OHT7: Office of In Vitro Diagnostics and Radiological Health

Office of Product Evaluation and Quality

Center for Devices and Radiological Health

March 2, 2020
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• Background

• Summary of Immediately In Effect Guidance

• Questions and Answers

Agenda
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Objective

• Explain policy for molecular diagnostics testing in high-complexity Clinical 

Laboratory Improvement Amendments (CLIA)-certified laboratories prior to 

emergency use authorization for coronavirus disease-2019 (COVID-19) 

during the public health emergency.
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• Guidance issued February 29, 2020 describes a policy regarding certain 

laboratories immediately using tests they developed and validated in order 

to achieve more rapid testing capacity in the U.S.

• To address the COVID-19 public health emergency, the FDA has 

determined that prior public participation for this guidance is not feasible or 

appropriate and issued this guidance without prior public comment.

• This guidance document is immediately in effect, but it remains subject to 

comment in accordance with the FDA's good guidance practices. 

Background
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• The new policy is limited to:

– Laboratories certified to perform high complexity testing, consistent with 

the requirements under the Clinical Laboratory Improvement Amendments 

(CLIA)

– Molecular diagnostics for SARS-CoV-2

• The new policy does NOT impact:

– Requirements under the Clinical Laboratory Improvement Amendments

– CDC recommendations for who should be tested

Scope
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The guidance includes recommendations regarding: 

• Validating newly developed SARS-CoV-2 tests prior to clinical use

• Notifying FDA when clinical use of a validated test begins 

• Confirming the first 5 positive and negative samples with an EUA authorized test

• Indicating in test reports that the test has been validated but independent review 

by FDA is not yet complete

• Submitting an EUA within 15 days of initiating testing

• Steps to take if any specimens fail confirmatory testing or if FDA is unable to 

authorize the EUA

Policy
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• The guidance includes recommendations regarding the minimal testing to be 

performed for validation:

– Limit of Detection (LoD)

– Clinical Evaluation

– Inclusivity

– Cross-Reactivity

• Limited viral materials are available

– FDA, BARDA, and CDC prioritize and coordinate shipments to labs when 

ready to validate 

Test Validation
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• Defined as the lowest concentration at which 19/20 replicates are positive

• Methods: 

– Recommend testing dilution series with 3 replicates per concentration 

(range finding) and

– confirming final concentration with 20 replicates (around initially identified 

LoD only)

• Samples:

– pooled negative clinical samples or artificial matrix 

– if multiple specimen types are intended, most challenging should be 

evaluated (e.g., sputum)

Limit of Detection
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• Recommend testing at least 30 contrived reactive specimens and 30 nonreactive specimens 

– Contrived reactive specimens can be created by spiking viral RNA or 

inactivated virus into leftover clinical specimens

– Twenty (20) of the contrived specimens should be spiked at a 

concentration of 1x-2x LoD, with the remainder of specimens spanning 

the assay testing range. 

• Acceptable performance: 

– 95% agreement at 1x-2x LoD and 

– 100% agreement at all other concentrations and for negative specimens 

Clinical Evaluation
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• Recommend conducting an in silico analysis of the percent identity 

matches against publicly available SARS-CoV-2 sequences that can be 

detected by the proposed molecular assay. 

• 100% of published SARS-CoV-2 sequences should be detectable with 

the selected primers and probes 

Inclusivity
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• Recommend conducting an in silico analysis of the assay primer and 

probes compared to common respiratory flora and other viral pathogens

• There should be >80% homology between one of the primers/probes 

and any sequence present in the targeted microorganism 

• Recommend following recognized laboratory procedures for any 

additional cross-reactivity testing in the context of the sample types 

intended for testing

Cross-Reactivity
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• CDC EUA authorization Feb 4, 2020

– Covers CDC-qualified IDT 2019-nCoV Kit Lot#0000500383

– Additional IDT lots undergoing qualification by CDC

• NYS Wadsworth Center EUA Authorization Feb 29, 2020

• CDC, FDA and BARDA are working with multiple IVD manufacturers and 

laboratories to enable additional EUA authorizations as soon as possible; 

monitor at: 

https://www.fda.gov/medical-devices/emergency-situations-medicaldevices/emergency-use-authorizations#coronavirus2019

Status of EUA Tests
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• Notification of clinical use of a validated test should be directed to 

CDRH-EUA-Templates@fda.hhs.gov and should include:

– name of the laboratory

– name of the lab director

– address

– contact person

• EUA should be submitted within 15 days of initiating clinical testing to 

OIR-Operations@fda.hhs.gov and should include:

– Form 3514 available at: 

https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM080872.pdf

– Completed EUA template available at: https://www.fda.gov/media/135658/download

Submissions to FDA
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• COVID-19 Guidance Document: https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/policy-diagnostics-testinglaboratories-certified-perform-high-complexity-testing-under-clia-prior

• General EUA Guidance Document: 

https://www.fda.gov/media/97321/download

• FDA’s Novel Coronavirus (COVID – 19) webpage: 

https://www.fda.gov/emergency-preparedness-and-response/mcmissues/novel-coronavirus-covid-19

Resources
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Questions?

For questions on the guidance and accelerated EUA template, or if you wish to 

consider use an alternative specimen type, contact the Division of Microbiology 

devices at (301) 348-1778 or: CDRH-EUA-Templates@fda.hhs.gov.

Slide Presentation, Transcript and Webinar Recording will be available at:

http://www.fda.gov/training/cdrhlearn

Under Heading: Special Technical Topics; Subheading: In Vitro Diagnostics