Recently, the Medical Device Coordination Group (MDCG) has published a new document (MDCG 2021-21) to guide MedTech stakeholders in the performance evaluation of SARS-CoV-2 in vitro diagnostic medical devices (IVDs). The MDCG 2021-21 introduces additional requirements in the performance evaluation process, including, among others, changes in risk analysis, increased sample sizes and the specific testing of equivalent populations to that of the EU.
This article will provide you information on MDCG 2021-21 guidance document and let you know how you can place and keep your SARS-CoV-2 IVD products on the EU market.
Who is affected?
The scope of the MDCG 2021-21 covers those SARS-CoV-2 IVDs that aim to be placed in the EU market under either Directive 98/79/EC (IVDD) or Regulation (EU) 2017/746 (IVDR). Specifically, this document concerns IVDs used for the detection or quantification of SARS-CoV-2, including:
- SARS-CoV-2 nucleic acid also referred to as nucleic acid amplification techniques (NAT) assays
- SARS-CoV-2 antigens
- Antibodies against SARS-CoV-2 (IgG-only, IgG combined with IgM and/or IgA, only IgM and/or IgG, and total antibody)
SARS-CoV-2 IVDs used for confirmatory or supplementary assays and those for self-tests are also covered by this guidance.
In addition, though manufacturers are the most affected market operators, MDCG 2021-21 is directed to all interested parties, including notified bodies, competent authorities, authorised representatives, and healthcare professionals.
MDCG 2021-21 is a guidance document that concerns the Performance Evaluation of SARS-CoV-2 IVDs.
The content paves the way for the upcoming Common Specifications, expected for the following months. According to IVDR Article 1(74).
“Common Specifications means a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system”
Back to MDCG 2021-21, the guidance provides a set of definitions to complement those given by the IVDR, especially for the terms referred to in Annex I, 9.1 (a and b), which include both analytical performance (i.e., limit of detection, analytical specificity) and clinical performance elements (i.e., diagnostic sensitivity, specificity). Interestingly, this MDCG also defines terms not previously found in the IVDR (i.e., robustness, whole-system failure), harmonising novel performance characteristics required for SARS-CoV-2 IVDs.
As a general consideration included in this guidance, manufacturers are now asked to conduct the performance evaluation by comparing their devices with state-of-the-art and CE-marked IVDs with equivalent performance characteristics.
Equivalent to the European population
One of the most challenging requirements introduced by the guidance is the necessity for manufacturers to perform the SARS-CoV-2 IVDs Performance Evaluation on a population equivalent to the European population. In other words, manufacturers who used non-equivalent samples for performance studies are asked to address it now with samples equivalent to those of the EU members.
Batch Verification and self-tests
MDCG 2021-21 sets the expectation that the manufacturer’s batch testing criteria should ensure that every batch identifies the antigens, epitopes, and antibodies for which the IVD is suitable.
On the other hand, the guidance also establishes that self-testing IVDs should meet the same sensitivity and specificity requirements as those IVDs for professional use. In addition, usability testing should include laypersons to ensure that the device is safe for the final user and that the instructions for use (IFU) are clear.
Specific requirements for each type of test
Seven tables of specific considerations to determine the analytical and clinical performance of each type of SARS-CoV-2 IVD test are introduced in MDCG 2021-21. We encourage manufacturers to go through the guidance document and check which requirement applies to their IVDs. For certain IVD types, additional requirements such as seroconversion panels or whole system failure rates from low-positive specimens within the risk analysis of the device apply. In addition, the guidance establishes a notable increase in sample sizes for determining performance characteristics.
Work with the experts
AKRN specialize EU IVDR 2017/746. As part of our regulatory services, AKRN can assist with all requirements needed to achieve the CE mark under the IVDR and perform a complete transition from IVDD to IVDR.
In addition, the introduction of MDCG 2021-21 and the new Commons Specifications expected for the nexts months, manufacturers must adapt to the significant shifts in the European regulatory landscape, something that global COVID-19 pandemic has accelerated even more.