In our last update, we discussed the FDA’s new pathway for streamlining the submission and review of antibody tests through their umbrella EUA and updates to their EUA policy to provide EUA templates for serology assays. On May 11, 2020 FDA again updated their EUA policy to remove the serology templates from the appendices and add a new section VI to point to all EUA templates on their website. They now also have an EUA template for antigen tests provided by manufacturers. But the biggest news is the updates FDA made to their molecular diagnostic EUA templates.
A quick comparison between the previous molecular diagnostic EUA template (last updated March 12, 2020) and the newly released template (May 11, 2020) reveals the following updates:
- Intended use - Updated recommended intended use statement to:
- Clarify that detection is of RNA from SARS-CoV-2 from individuals “suspected of COVID-19 by their healthcare provider” (removing “with signs and symptoms of infection”), and
- Clarify what a positive result indicates.
- Special conditions for use statements - Added “For Emergency Use Authorization (EUA) only.”
- Reagent stability - Updated reagent stability testing requirements to recommend testing with a known positive diluted patient sample rather than positive control material to establish reagent stability.
- Limit of Detection - Clarified material to use for LoD studies by providing additional examples of sample types and as well as examples of “most challenging sample types” when the assay is intended to be used with multiple common upper or lower respiratory tract specimens.
- Cross-reactivity - Updated the requirements to require wet testing at concentrations of 10^6 CFU/ml or higher for bacteria and 10^5 pfu/ml or higher for viruses, while clarifying that in silico analysis may still be used for organisms difficult to obtain. There was also a correction to one of the listed organisms.
- Microbial interference – Clarified for tests employing multiplex panels and updated to allow for pooled testing of organisms.
- Clinical evaluation:
- Rewritten to prefer testing of natural samples.
- The natural samples may be prospective, retrospective, or leftover.
- It is also acceptable to use frozen samples.
- There is now allowance for mixing specimen types to achieve an upper respiratory claim as well as some additional exceptions for a sputum claim or claims for multiple specimen types.
- Since natural samples are now required, FDA now provides guidance for comparator analysis with other EUA RT-PCR methods as well as for discordant analysis and how to present these results.
- Acceptance criteria were also updated based on the use of natural samples to 95% positive and negative agreement for clinical performance.
- Clarified that clinical evaluation testing should be blinded to the tester.
- Sample stability – Sample stability information is now required, including where necessary, shipping stability information.
To stay current with FDA’s thinking on SARS-CoV-2 diagnostic tests, follow FDA’s COVID-19 IVD-specific FAQ page and tune into their weekly town hall series for which they also post past transcripts.
FDA Guidance for COVID-19 IVDs
Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency
FAQs on Diagnostic Testing for SARS-CoV-2
Emergency Use Authorizations
Molecular Diagnostic Template for Manufacturers (Updated May 11, 2020)
Molecular Diagnostic Template for Laboratories (Updated May 11, 2020)
Serology Template for Manufacturers (unchanged from May 4, 2020)
Serology Template for Laboratories (unchanged from May 4, 2020)
Antigen Template for Manufacturers (new May 11, 2020)
Virtual Town Hall Series - Immediately in Effect Guidance on Coronavirus (COVID-19) Diagnostic Tests
The comparison between the previous molecular diagnostic EUA template (last updated March 12, 2020) and the newly released template (May 11, 2020) is provided below for download.