Meghan Swanson, Senior Regulatory Specialist
The interplay of MDR and MEDDEV is complex
The release of the revised guidance regarding Clinical Evaluations (MEDDEV 2.7/1 Rev. 4) in 2016 introduced some significant changes to the process of clinical evaluation. Now, as the dust has just settled following the update to the MEDDEV, and two years short of the implementation date of the MDR, it may seem premature to consider the impact of the MDR on your Clinical Evaluation Reports, but there are changes on the horizon that will require careful thought and planning to ensure your products can remain in the European market. It’s not too early to start thinking about them; in fact, it may soon be too late.
The good news is that the MEDDEV update took significant strides in bridging the gap between CERs that had been written according to the MDD and MEDDEV Rev. 3 and what will be required for CERs written according to the MDR. However, the implementation of the MDR will bring with it further changes and while some may be relatively minor (e.g. the change in terminology from Essential Requirements to General Safety and Performance Requirements), others may have significant impact on the clinical data available and required to support your product.
The following list is not exhaustive, but does explore three of the most significant changes.
Clinical Evaluation Plan (CER):
Although the MEDDEV introduces the idea of a Clinical Evaluation Plan (CEP), the MDR is much more explicit regarding the required elements of this plan. Most of the defined elements outline information that was likely already gathered as part of the clinical evaluation process (e.g. intended purpose, target groups, methods and parameters used to determine the acceptability of the benefit-risk profile and residual risks and side-effects). However, some of the items listed in Annex XIV may require more detail for the Clinical Evaluation Plan than had previously been included in the CER. In addition to these existing elements, the MDR also requires that a clinical development plan be included as a part of the CEP. The clinical development plan requires a long-term view of the planned clinical investigations related to the product, spanning from feasibility studies all the way through to post-market clinical follow-up studies.
The MDR contains a few more specifics than were included in the MDD or MEDDEV in regard to when clinical investigations are required for class III products and implants. Essentially, all class III products and implants require a clinical investigation, unless they:
1. are a line extension of an existing CE marked product;
2. are equivalent to a device already CE marked where there is a contract in place to allow the manufacturer full and ongoing access to the technical documentation (see below);
3. were lawfully placed on the market under the MDD/AIMDD, there is sufficient clinical data, and where device-specific common specifications have been adopted to which the device complies; or
4. have been explicitly exempted (e.g. sutures, staples, etc.) and meet the applicable common specifications.
Product-specific common specifications are a bit of a mystery at the moment. They are defined as “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.” The MDR allows the commission to adopt such specifications, but other than for those products without an intended medical purpose (e.g. non-corrective contact lenses) does not direct the commission to do so. It’s not clear at this time what, if any, product groups will be subject to such specifications, nor is it clear that every product group subject to product-specific common specifications could be exempted from the clinical investigation requirements, as the reference to “clinical requirements” seems to leave open the possibility that such specification could actually increase clinical investigation requirements.
For classes I, IIa, and IIb, the MDR is relatively silent on when clinical investigations will be required. The MEDDEV provides more guidance on this than is present in the MDR and the increasingly stringent requirements on “sufficient clinical evidence” seen since the implementation of Rev. 4 is likely to continue.
Although the MDR still allows for the use of equivalents, and even provides definitions of the qualifying characteristics that are essentially the same as those provided in the MEDDEV, there are additional requirements, particularly for class III devices, which are likely to make the establishment and defense of an equivalence claim more difficult and therefore more rare.
In order to establish any equivalent device, regardless of device class, the manufacturer will be required to clearly demonstrate that they have “sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.” Exactly what constitutes “sufficient levels of access” is not explicitly defined, but taken into context with the MEDDEV requirements for measurements, pre-clinical study reports, and knowledge of special manufacturing treatments, the general consensus so far is that Notified Bodies are likely to insist that manufacturers either have access to the technical documentation for any claimed equivalent, regardless of class, or be able to perform their own comparative testing on the two devices.
Requirements for equivalence claims for class III devices are more explicitly stringent. The MDR requires that “the two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis” in order to rely on any clinical investigation performed for the equivalent device. Although individual circumstances will vary, it’s hard to imagine that such agreements will be anything other than exceedingly rare, meaning that successful equivalence claims for class III devices, outside of the context of a product line extension or similar situation, are likely to all but disappear.
If you have questions about writing or updating CERs, contact Samantha Spence at firstname.lastname@example.org or 952-224-2260 to be put in touch with an RCRI expert.