The competent national authorities have identified several common issues while implementing market surveillance activities (presented below) to ensure the compliance of IVDs with the applicable EU regulatory requirements.
As a result, the Medical Device Coordination Group (MDCG) published a new Notice to third country manufacturers located outside the EU, or the EEA who are placing their in vitro diagnostic medical devices (IVDs) meant to detect the presence of and/or exposure to SARS-CoV-2SARS-CoV-2 on the European Market.
- Designation of an authorised representative
According to Article 10(3) of Directive 98/79/EC, and Article 11(1) of Regulation (EU) 2017/746, to place IVDs on the EU market, a non-EU manufacturer is obliged to designate one and, sole EU authorised representative (known as E.A.R. or EC REP) which will be responsible for the notification of IVDs to the competent authority where the authorised representative is established.
- Involvement of a notified body for self-tests under Directive 98/79/EC
SARS-CoV-2 self-tests (used by lay users at home, for ex.) need to be assessed by a Notified Body and obtain a CE Certificate.
SARS-CoV-2 IVDs intended to be used by professionals do not need this assessment.
- Translations of the instructions for use and the label
According to Article 4(4) of Directive 98/79/EC and Article 10(10) of Regulation (EU) 2017/746, manufacturers need to be compliant with the language requirements of every Member State where the device is being sold. This to ensure not only proper use of the device but also its safety and reliable performance.
The quality of translation displayed in the instructions for use and the label must be the highest possible as it will help the user to understand and execute each step necessary to perform the SARS-CoV-2 test correctly. This is especially relevant for self-tests used by lay users.
- Guidance on performance evaluation of SARS-CoV-2 IVDs
The MDCG 2021-21 provides helpful guidance for devices placed on the market under Directive 98/79/EC and Regulation (EU) 2017/746 on the performance evaluation of different types of SARS-CoV-2 IVDs, including SARS-CoV-2 self-tests.
- Transition to Regulation (EU) 2017/746 – IVDR
According to the original text of Regulation (EU) 2017/746, all SARS-CoV-2 IVDs will need to be assessed by a Notified Body.
Both EU and non-EU manufacturers who want to:
- keep a device previously notified to the Competent Authorities under the Directive 98/79/EC on the market, or
- place a new device on the European Market under the Regulation (EU) 2017/746,
should apply for a conformity assessment to a Notified Body. Additionally, non-EU manufacturers shall designate a European Authorized Representative.
In line with the transitional provisions of the IVDR, SARS-CoV-2 self-tests covered by a valid certificate issued under Directive 98/79/EC (‘’legacy device’’) may continue to be placed on the market after the date of application of the Regulation (EU) 2017/746, if:
- They continue to comply with the requirements of the Directive,
- There are no significant changes in the design or intended purpose,
- They comply with the requirements of Regulation (EU) 2017/746 on post-market surveillance, vigilance, and registration of economic operators and of devices that replace the corresponding requirements of the Directive.
It is important to note that on 14 October 2021, the European Commission put forward a proposal for a Regulation of the European Parliament and of the Council amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnostic medical devices and deferred application of requirements for in-house devices to extend the ‘’legacy concept’’ under the IVDR. The Proposal was approved by the Council and the Parliament and is awaiting publication in the Official Journal of the EU. Click below for more information:
- The European Parliament and the Council of the EU adopt IVDR progressive roll-out!
- The European Commission is proposing to give more time to certain IVDs to reach IVDR compliance!
Moreover, new COVID variants, among which the highly contagious Omicron can alter the performance of SARS-CoV-2 diagnostic tests giving false negative, especially if a mutation occurs in the part of the virus genome assessed by that test.
It is essential that manufacturers of COVID tests constantly assess the impact of the newly identified genetic variants on the performance, risks, and safety claims not to compromise the safety of patients, healthcare professionals, or other individuals.
14/01/2022 update: View from the Expert panel on the performance evaluation of SARS Cov-2 IVD
A new opinion from the Expert panel on IVDs was issued for a Qualitative double-antigen sandwich assay for the detection of Antibodies to SARS-CoV-2 in serum/plasma. This is relevant for the manufacturers placing COVID tests on the EU market under the IVDR. In this specific case, the Expert panel (2022) concluded:
‘’The information provided by the manufacturer is a comprehensive summary covering the main aspects of the Performance Evaluation Report. The data provided gives an overview on the analytical sensitivity and specificity and the clinical value of the assay for the intended purpose. The technology is state-of-the art. The information provided by the manufacturer shows its principal compliance with the IVDR requirements. However, direct comparison of the assay with other state-of the-art assays is missing, potentially explained by development of the assay already at an early stage of the SARS-CoV-2 pandemic. It would be recommended to provide an update search of the literature, including publications on direct comparison of the assay with competitor assays. There are additional recommendations for the manufacturer to provide evidence for its use in plasma samples. The ability to detect antibodies raised against new variants of concern of SARS-CoV-2 should be continuously checked and updated information made available.’’
- European Commission. (2022). View in the context of the Performance Evaluation Consultation Procedure (PECP). Retrieved on 14/01/2022 from https://ec.europa.eu/health/md_expertpanels/list-opinions-pecp_en
- Medical Device Coordination Group. (2022). MDCG 2022-1 Notice to third country manufacturers of SARS-CoV-2 in vitro diagnostic medical devices. Retrieved on 13/01/2022 from https://ec.europa.eu/health/sites/default/files/md_sector/docs/mdcg_2022-1_en.pdf
- Official Journal of the European Union. (2017). Regulation (EU) 2017/746 of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Retrieved on 13/01/2022 from https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0746&from=EN
- Official Journal of the European Union. (1998) Directive 98/79/Ec Of The European Parliament And Of The Council of 27 October 1998 on in vitro diagnostic medical device. Retrieved on 13/01/2022 from https://eur-lex.europa.eu/legalcontent/EN/TXT/PDF/?uri=CELEX:31998L0079&from=EN
- Medical Device Coordination Group. (2021). MDCG 2021-7 Notice to manufacturers and authorised representatives on the impact of genetic variants on SARS-COV-2 in vitro diagnostic medical devices. Retrieved on 13/01/2022 from https://ec.europa.eu/health/sites/default/files/md_sector/docs/mdcg_2021-7_en.pdf
- Blythe Adamson, Robby Sikka, Anne L. Wyllie, Prem Premsrirut. (2022). Paper Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series. Retrieved on 13/01/2022 from https://www.medrxiv.org/content/10.1101/2022.01.04.22268770v1.full.pdf
- FDA – Food and Drugs Administration USA (2021). SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests. Retrieved on 13/01/2022 from https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests#omicronvariantimpact