Introduction to the New MDCG Guidance
A new MDCG guidance document has been published today, providing welcome clarification regarding the practical application of EU MDR Articles 61(4) – (6). This new guidance, "MDCG 2023-7: Guidance on exemptions from the requirement to perform clinical investigations pursuant to Article 61(4)-(6) MDR and on ‘sufficient levels of access’ to data needed to justify claims of equivalence" opens up strategies and pathways that many assumed were blocked off under EU MDR, and sheds new light on the following:
- when contracts are or are not required to claim equivalence to (and therefore use the associated clinical data from) another manufacturer’s device;
- when implantable and class III devices can be exempted from the statutory requirements for clinical investigations (per Article 61(4));
- what “sufficient levels of access” to the data required to justify claims of equivalence (per Annex XIV Section 3) looks like.
Understanding Contract Requirements and Equivalence Claims
On the first point above, what will be surprising to many is the confirmation that contracts are never required to claim equivalence with another manufacturer’s device. However, caveats apply: for implantable and class III devices, a manufacturer may still be required to undertake clinical investigation(s), regardless of the strength of their clinical evidence package, unless one of the four exemption cases described in Articles 61(4) – (6) applies.
In short, the key clarification the guidance makes is that Articles 61(4)-(6) are not defining when equivalence may or may not be used, but rather when implantable and class III devices may be exempted from the requirement for premarket clinical investigations. This may sound like the beginning of a semantic argument, but there are important ramifications to this clarification which should significantly reduce barriers to market for many implantable and class III devices.
Practical Implications for Implantable and Class III Devices
What it means in practical terms for implantable and class III device is:
- For the legacy MDD and AIMDD devices described in Article 61(6)(a), and the listed WET devices in Article 61(6)(b), the clinical evaluation can include data from another manufacturer’s demonstrated equivalent device, without a contract, in the clinical evaluation of their own device. If all of the conditions of these Articles are met, the manufacturer can place these devices on the EU market without undertaking pre-market clinical investigations.
- The guidance also clears up a frequent point of confusion: Both Article 61(6)(a) and 61(6)(b) include a requirement that the clinical evaluation is “based on sufficient clinical data”. Some have assumed that this means “clinical data on the subject device, not from equivalent devices” – but the guidance very clearly explains that any clinical data within the definition of clinical data in Article 2(48), including equivalence data, is acceptable. Equivalence data could therefore form part, or all, of the clinical evidence package submitted to demonstrate conformity with the relevant safety and performance requirements per Article 61(1).
- Similarly, for devices which are modifications of (a) device(s) already marketed by the same manufacturer, and meet the other conditions described in Article 61(4) bullets one to three, clinical data from another manufacturer’s device can be included in the clinical evidence package. Although Article 61(4) bullet two requires that “the clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements”, the guidance explains that “The MDR does not prohibit the use of data from another manufacturer’s [equivalent device] in the clinical evaluation of the manufacturer’s already marketed device.”
- Data from another manufacturer’s equivalent device can even be used without a contract in what is described as exemption CASE 4, where the manufacturer has a contract with at least one manufacturer. The utility of this is somewhat limited however, as data from additional manufacturers’ devices can only be used to support the same indications covered by the contract.
- Finally, in the case where the device is class III or implantable and none of the exemption cases apply, and therefore premarket clinical investigations are mandatory, the guidance indicates that here too, clinical data from another manufacturer’s equivalent device can be used, without a contract, alongside clinical data gained from the clinical investigation(s).
Analyzing the Exemption Cases and Their Impact
This flexibility reflects the lower risk associated with each of these cases, that justifies the exemption from the requirement for clinical investigations that is applied to implantable and class III devices by default. In other words, with respect to the CASEs described in the guidance:
- CASE 2: if your device has been previously certified under the Directives, it will have several years’ market experience, and likely data from PMCF, during which safety or performance issues should have been identified. In addition, the majority of these devices (with the exception of some up-classified devices previously placed on the market under quality systems certification only) will have had a design examination or renewal within the last five years. Within this period, requirements for clinical data and post-market surveillance had become significantly stricter, and application of guidance such as MedDev 2.7/1 rev 4 means that the conformity assessment would have been similar in rigour to current requirements under the Regulation;
- CASE 4: if you are relying on equivalence but have a contract with the manufacturer of that device providing full access to the technical documentation as per Article 61(5), it lessens the risk of unknowns related to device design, clinical results and adverse events, product changes, etc.;
- CASE 1: similarly, if your device is a design variant of one of your own devices, and you can demonstrate equivalence (as per bullets 1-3 of Article 61(4)) the risk of such unknowns is largely eliminated;
- CASE 3: finally, if your device is one of the listed WET of Article 61(6)(b), these devices are by their nature comparatively low risk, being standard of care and generally having a well-known safety and performance profile.
Emphasizing the Role of Clinical Data in Device Safety and Performance
This flexibility will be welcome to device manufacturers who may have been at risk of refusal or reduction of indications, with the clarity provided that they can use all forms of clinical data within the definition of Article 2(48) to demonstrate the safety and performance of their devices, including equivalence with another manufacturer’s device. It may also be useful for future product development, by expanding the pool of clinical evidence available to manufacturers. Note, however, two points regarding PMCF:
- the guidance explicitly states that, where PMCF studies were a condition of prior certification, these exemption cases cannot be used to justify failure to complete such studies;
- typically, when clinical evaluation is based in whole or in part on equivalence, there is an expectation that PMCF studies will be undertaken to ensure that clinical data of an appropriate quality will be collected on the subject device.
Navigating 'Sufficient Levels of Access' to Data
With respect to “sufficient levels of access” to the data required to justify claims of equivalence per Annex XIV Section 3, the guidance also clarifies that a contract is not the only means by which a manufacturer can demonstrate this. Appendix II of the guidance provides examples of other means, and suggests a hierarchy with respect to the completeness of access (and by extension, the likely strength of the justification that the level of access is sufficient).
A few important points to note here:
- the guidance reinforces what is already clearly stated in Annex XIV section 3, but which has sometimes been a source of confusion: namely, access is required to the data needed to justify claims of equivalence (i.e, the clinical, technical and biological parameters of the claimed equivalent) and NOT to the totality of the technical documentation. (The occasional confusion may arise because Article 61(5) does require access to the full technical documentation, but as the guidance confirms, the requirements of Article 61(5) do not apply outside of that Article);
- a “level of access” is considered insufficient only if there are gaps in the completeness or expected accuracy of associated clinical, biological and technical data which would be considered to invalidate claims of equivalence;
- the table in Appendix II is provided for illustrative purposes only, and is not intended to be exhaustive or prescriptive. This point is made explicitly in Section 5 of the guidance, as well as in the footnotes to the table in Appendix II. This reminder should hopefully provide some flexibility to notified bodies to apply a risk-based approach when assessing the adequacy of access to data.
Strategic Next Steps for MDR Conformity and Clinical Development
If your technical documentation has not yet been submitted for MDR conformity assessment, or if it is still in the queue and awaiting notified body feedback, you may wish to review your clinical evidence package to determine if this could be strengthened through use of equivalence. If such is the case, it would also be advisable to review and update associated documentation such as risk or PMCF plans.
For products still in development, review clinical development plans to determine if this new understanding could affect clinical investigation strategy or accelerate product launch timelines.
Embracing these steps will position your organization at the forefront of compliance, ready to navigate the evolving landscape of medical device regulations with confidence and clarity.
More EU MDR resources at your fingertips:
- Watch RQM+ Live! #75 Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers
- Watch RQM+ Live! #72 EU MDR Timelines and Fine Lines: Unraveling Critical Transition Nuances to Gain Compliance
- Read our two recent guides:
- Follow #MedTechVoices on LinkedIn and get insights from our team as they analyze each of the opinions published by the Expert Panels as part of the Clinical Evaluation Consultation Process.
- Follow RQM+ on LinkedIn for all of our updates!