COVID-19, caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization in March 2020. Since then, various diagnostic tests have been introduced to the EU market, including direct detection tests (such as NAT and antigen tests) and indirect tests designed to detect antibodies, whether neutralizing or not.
Under the In Vitro Diagnostic Directive (IVDD), SARS-CoV-2 IVDs were placed on the EU market as “other products.” However, under the In Vitro Diagnostic Regulation (IVDR), they are classified as Class D, reflecting the initial high risk posed by the virus. Given the evolving epidemiological landscape, in July 2024 the Medical Device Coordination Group (MDCG) has requested the European Medicines Agency (EMA) to review whether this classification remains appropriate.
1. Regulatory Background
1.1 IVDD ((EU) 98/79/EC)
Classification: Under the IVDD, SARS-CoV-2 IVDs were classified as non-List A and B devices, meaning they were considered lower-risk devices. This classification did not require the same stringent regulatory oversight as higher-risk devices.
Market Access: Manufacturers could self-certify their compliance with the IVDD, and notified body involvement was not mandatory for non-List A and B devices.
Pandemic Response: During the COVID-19 pandemic, the European Commission issued guidelines to expedite the availability of SARS-CoV-2 IVDs, allowing for rapid market entry under emergency use provisions.
1.2 IVDR ((EU) 2017/746)
Classification: Under the IVDR, SARS-CoV-2 IVDs are classified as Class D, the highest risk category for IVDs. This classification is based on Rule 1, 2nd indent of Annex VIII, which states that devices intended to detect transmissible agents causing life-threatening diseases with a high risk of propagation are Class D.
Regulatory Requirements: Class D devices are subject to the most stringent regulatory requirements, including:
Notified Body Involvement for conformity assessment.
Performance Evaluation: Extensive clinical evidence and performance studies are required.
PMS: Enhanced post-market monitoring and reporting obligations.
Rationale for Class D: The initial classification was based on the high transmissibility and life-threatening nature of SARS-CoV-2 during the early stages of the pandemic.
2. Scientific Advice from EMA
In December 2024, the EMA delivered scientific advice to the MDCG regarding whether the classification of SARS-CoV-2 IVDs should be revised in light of the evolving epidemiological situation.
2.1 Key Consideration:
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Life-Threatening Disease: SARS-CoV-2 was initially considered a life-threatening disease due to its high mortality rate and severe clinical outcomes. However, with the emergence of less virulent variants (e.g., Omicron) and widespread immunity from vaccination and prior infections, the severity of the disease has decreased.
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Risk of Propagation: SARS-CoV-2 remains highly transmissible, but the risk of severe outcomes has diminished for the general population. Vulnerable groups (e.g., elderly, immunocompromised) remain at higher risk.
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Erroneous Results: The impact of false negatives or false positives in SARS-CoV-2 testing is generally low for the general population but may have more significant consequences for vulnerable groups, such as pregnant individuals or those with underlying health conditions.
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Neutralizing Antibody Tests: Devices detecting neutralizing antibodies are not used for diagnosing active infections or guiding patient management decisions. Erroneous results from these tests are unlikely to lead to life-threatening situations.
2.2 Expert Panel Recommendations:
- Reclassification Considerations: The classification of SARS-CoV-2 IVDs as Class D under the IVDR reflects the initial high risk posed by the virus. However, with the changing epidemiological landscape, the expert panel suggests that SARS-CoV-2 may no longer meet the criteria for a life-threatening disease with a high risk of propagation for the general population. In this context,
- IVDs could potentially be reclassified under Rule 3(c) or Rule 3(e) as Class C devices, depending on their intended use.
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- Alternatively, if the criteria for Class D or C are no longer met, some IVDs could fall under Rule 6 as Class B devices.
However, the expert panel also emphysizes that the virus remains a significant risk for vulnerable populations, and its high transmissibility warrants continued monitoring. Any decision to down-classify SARS-CoV-2 IVDs will require careful consideration of the epidemiological data, the intended use of the devices, and the potential impact on public health.
4. Implications for Manufacturers
Manufacturers of SARS-CoV-2 IVDs must comply with the IVDR requirements, including performance evaluations, clinical evidence, and post-market surveillance. The development of common specifications and experience gained during the pandemic will facilitate regulatory preparedness for future variants or emerging infectious agents.
If SARS-CoV-2 IVDs are down-classified, the regulatory burden may be reduced, but manufacturers must still ensure compliance with the applicable classification rules under the IVDR.