The TGA has reviewed all COVID-19-specific laboratory antigen tests and rapid antigen tests (RATs), including point-of-care and self-tests, included in the Australian Register of Therapeutic Goods (ARTG). The purpose of the review was to determine if tests have been impacted by the current known variants of SARS-CoV-2, and to ensure the manufacturer has implemented ongoing post-market surveillance to assess their ability to detect emerging variants.
As part of the review, laboratory testing of all point of care (PoCT) and self-test RATs included in the ARTG was undertaken to validate their performance in detecting the Delta and Omicron variants.
A variant of the virus arises from mutations in the SARS-CoV-2 virus of the genome and may alter the structure of the expressed viral protein. As a result, test kits may no longer be able to sensitively detect the virus, leading to false negative results.
Manufacturers of these kinds of tests have provided the TGA with study data to validate the performance of their test kits, including recombinant protein studies, live virus studies, inactivated virus studies, and clinical studies.
Note: Manufacturers are required to undertake proactive monitoring to ensure their tests are not impacted by the variants of the virus.
TGA testing of RATs
As each Variant of Concern (VoC) emerges, the manufacturer is expected to undertake an analysis, in line with their risk management plans, to verify that their tests continue to perform as intended, and that any adverse impacts are identified and communicated to users and regulatory authorities. The TGA expects manufacturers to continue this analysis even though the post-market review by the TGA has been completed.
As an additional measure, the TGA commissioned the Peter Doherty Institute for Infection and Immunity (the Doherty Institute), in collaboration with the National (Serology) Reference Laboratory (NRL), an operating division of St Vincent’s Institute of Medical Research, to undertake laboratory testing. This was to verify the manufacturer’s claims regarding the analytical sensitivity (Limit of Detection – the lowest concentration at which an analyte can be detected (LoD)) for SARS-CoV-2 (wild-type – original SARS-CoV-2 strain) and the Delta and Omicron variants.
In order to demonstrate compliance with the Essential Principles, the test kits must meet the sensitivity requirements as set out in the World Health Organisation (WHO) guidelines. The TGA has published guidance COVID-19 Rapid antigen tests - Performance on requirements and risk mitigation strategies outlining the expectation that all test kits included in the ARTG meet this requirement. The review is on-going and information about the performance of each RAT against the variants will be published on this webpage as it becomes available.
Testing details
The WHO published guidance about the minimum sensitivity requirements, where the LoD of all RATs must be no higher than 100 to 1,000 TCID50/mL (tissue culture infectious dose – TCID). The TCID50/mL is a measure used to quantify and assess viral levels, which allows the sensitivity of a kit to be evaluated.
The TGA, in conjunction with the Doherty Institute and the NRL, developed a protocol to assess the performance of RATs against the Delta and Omicron variants when compared to the sensitivity of the kit to the original strain of the SARS-CoV-2 virus.
The Doherty Institute and the NRL reported the LoD for each of the kits, in units of TCID50/mL and viral copies/mL.
Combination rapid antigen self-tests, capable of detecting multiple viruses (e.g. COVID-19, influenza A, and influenza B), have been approved to be included in the ARTG. These devices were included in the testing done by the Doherty Institute and NRL. Only the COVID-19 component of the devices were evaluated.
Review Status and Test Results
As of 6 March 2023, the manufacturers of the following test kits have provided analytical and clinical evidence, to support their performance with the variants specified below. The analytical evidence provided can be any combination of recombinant protein studies, inactivated virus studies, and live virus studies. Evidence provided by clinical studies is identified separately.
Please note, the table below includes results from the Doherty Institute and NRL testing, and the manufacturer’s data.
Testing was conducted on 92 batches of RATs (including self-tests and PoCT), all results are outlined in the below table.
To be found compliant during testing, RATs were required to have acceptable sensitivity (less than 1,000 TCID50/mL) for the Wild-type, Delta, and Omicron variants of SARS-CoV-2. They were also required to have acceptable product quality, with all components of the RATs being present and in working order, an acceptable number of invalid results (less than 5%), not falsely reacting to negative samples (false positives), and having appropriate labelling and instructions.
In total, 79 RATs were found compliant with all of the TGAs requirements, as they had acceptable product quality and met the requirements for analytical sensitivity for the Wild-type, Delta, and Omicron variants.
In the first round of testing, 72 RATs were found to meet requirements. Seven (7) RATs were initially found to be non-compliant and were re-tested. During a second round of testing, all 7 RATs were found to be compliant for analytical sensitivity and quality requirements.
Six (6) RATs were found non-compliant and were not re-tested. All of these self-test RATs found to be non-compliant were cancelled from the ARTG, initiated either by the sponsor or the TGA, and are no longer supplied in Australia.
The post-market review is now complete. However, the TGA will continue to monitor the performance of all RATs included in the ARTG and may re-open the review or commence additional testing if required.
Assessed RATs included in the ARTG
The TGA carefully reviewed the data submitted by manufacturers at the time of their application for inclusion in the ARTG. As a condition of inclusion, the TGA has required all manufacturers to continue providing data after approval, to demonstrate performance against variants of concern, and to show that they continue to meet safety and performance requirements. The data provided by manufacturers has included recombinant protein studies, inactivated virus studies, live virus studies, and clinical studies. Recombinant protein studies are considered to be acceptable preliminary evidence to support the performance and are considered initially acceptable evidence for variants of interest. However, to demonstrate performance for variants of concern such as delta and omicron, additional studies including inactivated or live virus studies, and clinical studies are required.
The TGA has also undertaken additional validation testing to confirm the manufacturers’ analysis. This involved third-party laboratory testing, where the TGA staff have worked alongside the Doherty Institute and the NRL. The results of the LoD testing are presented as either:
Tick - compliant with the WHO guidelines (estimate LOD within the WHO guidelines of 100-1000 TCID50/mL) or
Cross - non-compliant (estimate LOD does not fall within the WHO guidelines of 100-1000 TCID50/mL).
As part of this testing, the RATs were also assessed for compliance with labelling requirements, and any potential design and quality defects were also identified. Any non-conformances identified are specified below under 'Device quality'.
The test results have been certified by a responsible analyst under the Therapeutic Goods Regulations 1990.
Where a test is identified as not performing as intended, or has a decrease in sensitivity, with a particular variant of concern, the TGA will specify this below.
If the results are 'non-compliant', the TGA will investigate further to determine whether the deficiencies are related to an impact due to a variant, overall performance issue, or a batch-related issue. This result may suggest reduced sensitivity or inability to pick up positive results for patients in earlier stages of their infectious period for a particular variant, and not that the test is completely ineffective.
Note about symbols used in the table
* Variants that have only been tested with recombinant protein studies.
† Where multiple RATs are included under the one (1) ARTG number and have the same product composition, they have only been assessed once in the TGA testing. For example, if a product has a self-test and POCT version, only one was tested.