COVID-19 rapid antigen testing devices that use serial testing for individuals without symptoms: Notice to industry

We have updated our policy position on COVID-19 rapid antigen self-testing devices used for serial testing.

New policy and updated submission requirements

Date: July 9, 2021

On this page

• Background and purpose
• New policy position
• New policy details and submission requirements
• How to apply

Background and purpose

Rapid antigen tests are easy to use and provide results in 15 minutes on average. However, their sensitivity is lower than that of molecular RT-PCR tests.

On September 29, 2020, Health Canada published a notice on the minimum value for sensitivity of rapid antigen testing devices.

Tests with sensitivity below 80% will not be authorized. This position aligns with the minimum value required by other regulatory agencies (for example, U.S. FDA, WHO, U.K. MHRA, Germany's PEI).

Recent scientific and medical studies show that serial testing may:

• increase the overall sensitivity of an antigen test and
• make it possible for less sensitive tests to meet the established 80% sensitivity requirement

As such, Health Canada is introducing more flexibility during the review process of antigen tests that use serial testing for individuals without symptoms.

The purpose of this notice is to communicate to industry this new policy and submission requirements.

New policy position

Health Canada may authorize an antigen test that uses serial testing for asymptomatic individuals without the support of pre-market clinical evidence.

This new policy is based on:

• early reports on the possible similarity of viral loads between people with and without symptoms
• technical reports and key messages on the use of rapid antigen tests
• strategies implemented by our international regulatory partners
• recent U.S. FDA recommendations to allow for more flexibility during pre-market evaluation of COVID-19 testing devices during the pandemic

New policy details and submission requirements

Manufacturers may consider a claim for serial testing of patients without symptoms and where there's no pre-market clinical evidence if the test:

• has undergone clinical evaluation with symptomatic individuals in a laboratory or a point-of-care (POC) setting and
• has a sensitivity of at least 80%, with 70% at the lower bound of the 2-sided 95% confidence interval

If these requirements are met, a screening claim for an asymptomatic population intended for use as part of a testing program may be granted. This is achieved by imposing an agreed-upon condition to the interim order (IO) authorization.

The condition will require a clinical study establishing the performance of the assay in an asymptomatic population. The clinical study should include at least 20 positive asymptomatic patients and the clinical data will need to be submitted within a specified timeframe.

Study samples must represent the viral loads expected, with 10% to 20% of the samples falling in the low positive category stratification. Analysis of the results by PCR Ct values should also be provided.

If manufacturers are unable to obtain the required 20 positive samples from asymptomatic individuals to support their clinical claims, they may present the results from 10 positive samples from asymptomatic individuals if:

• the data from symptomatic individuals are also submitted
• the analysis of cycle threshold (Ct) values demonstrates reasonably similar distribution of viral loads

Authorization is conditional on Health Canada receiving data from the remaining 10 positive clinical specimens.

As part of the conditional IO authorization for antigen tests, manufacturers will be required to submit a quarterly post-market report. This report must include:

• the number of devices sold in and outside Canada
• a summary of problem reports on the performance of the assay, number of false positive, false negative, invalid results and major complaints on the robustness of the assay
• published peer-reviewed articles on the performance of your device

The test labelling must include the following statement in the intended use:

"Individuals without symptoms or other epidemiological reasons to suspect COVID-19 infection, when tested twice over 2 (or 3) days with at least 24 hours (and no more than 36 hours) between tests."

In both the limitations and clinical performance sections of the Instructions for Use (IFU), manufacturers must clearly state that:

• clinical studies in asymptomatic patients using serial testing are ongoing to establish clinical performance
• the performance of this test has not yet been clinically validated for use in patients without signs and symptoms of respiratory infection or for serial screening applications
• note that performance may differ in these populations

How to apply

If manufacturers are applying for a new authorization, all requirements outlined in the following antigen guidance documents published by Health Canada and the FDA apply:

• Antigen testing overview (June 16, 2021)
• Antigen template for test developers (October 26, 2020)
• Template for manufacturers of molecular and antigen diagnostic COVID-19 tests for non-laboratory use (July 29, 2020)
• Supplemental template for developers of molecular and antigen diagnostic COVID-19 tests for screening with serial testing (October 25, 2021, Word document)

For an application that is currently under evaluation by Health Canada and meets the requirement of the new policy:

• email Device Licensing at devicelicensing-homologationinstruments@hc-sc.gc.ca
• ask Health Canada to consider your application (include the application number) for a serial testing claim in asymptomatic patients

If you have not submitted an application and you believe your device meets these criteria, you may include the claim in your indications for use along with the required labelling.