The new article covers the matters related to antigen diagnostic tests and explains the approach to be applied by the test developers in order to ensure the continued effectiveness of their devices. 

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the policy for evaluating the impact of viral mutations on tests intended to be used in the context of the outbreak of Coronavirus Disease 2019 (COVID-19) caused by the virus SARS-CoV-2 or the “novel coronavirus”. In particular, the document describes the approach to be applied by test developers to address the impact of viral mutations on the accuracy and reliability of test results. The document provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered by medical device manufacturers (test developers) in order to ensure compliance thereto. At the same time, the authority explicitly states that provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed with the authority in advance. 


Antigen Diagnostic and Serology Tests: Key Points 

The scope of the guidance covers, inter alia, the aspects related to antigen diagnostic tests and serology tests based on the specific nature of such devices. According to the guidance, developers of such tests should also take into account the potential impact of viral mutations on the accuracy and reliability of test results. The authority acknowledges that in the case of antigen and serology tests, the general monitoring of the impact of genetic variants is not as straightforward as it is in the case of molecular tests (the aspects related to the latter are described in detail in the previous article). As it is stated in the document, FDA is considering how to best assess the impact on antigen and serology test performance, such as obtaining samples of novel variants to characterize their impact on the analytical performance of the test, using in silico and/or in vitro models to characterize the impact of certain mutations on the proteins responsible for eliciting an antibody response, and/or evaluating the clinical performance using clinical specimens obtained from individuals with the novel viral variants. 

The authority also encourages test developers to get in touch in advance at the early stages of test development since the authority continuously analyses the information becoming available and develops recommendations to be considered in order to ensure proper performance and effectiveness of COVID-19 tests. The said recommendations apply to both tests already placed on the market and the ones being currently reviewed under the respective authorization request. 

According to the guidance, test developers should pay attention to the matters related to the genetic mutations and potential impact thereof. In this respect, they should develop a plan to:

  • Routinely monitor for new genetic mutations and viral variants; and 
  • Assess the impact of the mutations or viral variants on their test’s performance, as needed, considering the potential of a given mutation or viral variant to impact their test.  


The authority also mentions that any reduction in the test’s performance by more than 5% would be considered significant and would require special attention to be paid. The same approach applies in case if due to the impact of viral mutations, the actual test’s performance drops below the recommendations provided in the respective Emergency Use Authorization (EUA) template. As previously described, EUA stands for a special framework introduced in order to facilitate and streamline the approval process for vitally important medical devices making them available to healthcare professionals and patients within the shortest timeframe possible. It is also important to mention that the authority reviews the applicable EUA templates on a regular basis in order to make sure the new information becoming available to the authority is duly reflected there.

Additional Resources

Apart from the aspects described hereabove, the document also provides a list of resources to be used by medical device manufacturers (COVID-19 test developers) to obtain additional information and data they may find useful. The links provided by the authority include, inter alia, the ones to:

  • GISAID – a global science initiative and primary source that provides open access to genomic data of influenza viruses and the novel coronavirus responsible for COVID-19;
  • FDA COVID-19 Test Policy Guidance;
  • FDA EUA Templates that developers may choose to use to facilitate the preparation, submission, and authorization of an EUA for various types of COVID-19 tests;
  • FDA FAQs on Testing for SARS-CoV-2;
  • CDC Summary of Variant Surveillance;
  • CDC SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance; and 
  • WHO SARS-CoV-2 Variants. 


In summary, the present FDA guidance outlines the key points to be taken into consideration by COVID-19 test developers with respect to antigen diagnostic and serology tests based on the specific nature of these products. Apart from that, the document also provides a list of additional resources the parties involved may find useful in terms of additional information and recommendations to be followed. 

The main purpose of the guidance is to describe the approach to be applied by medical device manufacturers in order to ensure COVID-19 tests they develop remain efficient notwithstanding the impact of viral mutations the virus could be subject to from time to time, and the results provided by such tests remain to be accurate and reliable. 



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