EU Update: New Guidance on Exemptions to Clinical Investigations for High-Risk Medical Devices

By Heather Crawford and Evangeline Loh

Medical device makers doing business in the EU will want to take note of new guidance regarding exemptions to clinical investigation requirements for high-risk medical devices.

In December 2023, the Medical Device Coordination Group (MDCG) published guidance (MDCG 2023-7)  to clarify when Class III and implantable medical devices are exempt from clinical investigation requirements according to MDR Article 61 paragraphs (4)-(6).

The Medical Devices Regulation (MDR) (EU) 2017/74, Article 61, paragraphs (4)-(6), describes the requirement for clinical investigations for Class III and implantable medical devices. While the provision for clinical investigations was also included in the Medical Devices Directive (MDD) 93/42/EEC, Annex X, 1.1a (the predecessor to MDR (EU) 2017/74) it permitted exclusions based on existing clinical data. This was often leveraged and documented in Clinical Evaluation Reports (CER) by manufacturers and had seemingly been accepted by notified bodies. There has been much discussion about the interpretation of this Article in the MDR.

Criteria for exemption

The guidance (MDCG 2023-7) is organized into four independent cases which provide exemptions from the requirement to perform a clinical investigation. 

Emergo by UL has summarized the criteria for each case: Article 61(4) indents 1-3, Article 61(6)(a), Article 61(6)(b), and Article 61(5).

The guidance also introduces the acronym for the device under evaluation as DUE and the equivalent device as ED.

Case 1: Article 61(4), Indents 1-3

For a modified DUE to be exempt from clinical investigations, the following criteria must be met:

• DUE has been designed by modifications of a device already marketed by the same manufacturer.
• Equivalence demonstrated between DUE and manufacturer’s ED per Annex XIV Section 3 and demonstration of equivalence endorsed by the notified body.
• Clinical evaluation of already marketed device sufficiently demonstrates conformity of modified device with relevant safety and performance requirements.
• PMCF plan is appropriate, including post-market studies to demonstrate the safety and performance of the DUE.

Case 2: Article 61(6)(a)

There is a clarification that legacy DUEs would be exempt from clinical investigations, provided the DUE was compliant with the following:

• DUE lawfully placed on the market or put into service in accordance with AIMDD or MDD.
• Clinical evaluation is based on sufficient clinical data (defined per Art. 2(48)).
• Clinical evaluation complies with the relevant product-specific common specification (CS) for the clinical evaluation of that kind of device, where such a CS is available.

Case 3: Article 61(6)(b)

Exemptions from clinical investigations for devices that are on the exempted implant list in Article 52(4) are:

• DUE is a listed device type, i.e., “sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors”.
• Clinical evaluation is based on sufficient clinical data (defined per Art. 2(48)).
• Clinical evaluation complies with the relevant product-specific CS for the clinical evaluation of that kind of device, where such a CS is available.

Case 4: Article 61(5)

In cases where a DUE is equivalent to another manufacturer’s ED and there is a contract between the two manufacturers, the following conditions exist:

• Equivalence demonstrated between DUE and another manufacturer’s ED per Annex XIV Section 3 and demonstration of equivalence endorsed by the notified body (via Art. 61(4)).
• Clinical data from the ED clinical evaluation sufficiently supports the intended purpose(s) of the DUE (via Art. 61(4)).
• The two manufacturers have a contract in place explicitly allowing full access to the technical documentation of the other manufacturer’s ED on an ongoing basis.
• Clinical evaluation of other manufacturer’s ED complies with MDR requirements.
• PMCF plan is appropriate, including post-market studies to demonstrate the safety and performance of the DUE (via Art. 61(4)).

Concluding remarks

The MDR requires clinical investigation to be performed for implantable and Class III medical devices.  MDCG 2023-7 provides clarification on circumstances in Article 61(4)-(6) by which such devices may be exempted from the requirement for clinical investigation.

Exemption case 4 which applies Article 61(5) requires a contract between manufacturers to provide full access to the technical documentation for the demonstration of equivalence on an ongoing basis, whereas the other exemption cases do not require a contract. Note that MEDDEV 2.7/1, Revision 4, expected the notified body to “challenge” the manufacturer’s ability to access data on another manufacturer’s ED, though never formally stipulated there was a contract between the parties.

Lastly, it is expected that this exemption from clinical investigations, if relevant, be documented in the manufacturer’s Clinical Evaluation Plan as well as the CER.