Medical Devices In Vitro Diagnostics Combination Products

A key working group at the European Commission has approved major changes to the current guideline on clinical evaluation of medical devices (MEDDEV 2.7/1, Rev 3), including stricter requirements for demonstrating equivalency between a device under evaluation and an approved product.

 The changes aim to minimize –but does not eliminate – the use of the "equivalency route" (also called the "literature route") by device sponsors, under which they are currently able to rely on clinical data from other similar products to show that the new product for which a CE-mark is being sought is at least as safe and performs as well as the approved device. The revised guideline (MEDDEV 2.7/1, Rev 4), when in effect, would force more companies to generate fresh clinical data to support the approval, and also the renewal, of their devices.

The changes to the MEDDEV appear to be a prelude to the forthcoming EU Medical Device Regulation, which contains even stricter requirements on clinical evaluation of devices.

Specifically, the revised MEDDEV states that sponsors may use only a single device against which to demonstrate equivalency and that when demonstrating equivalency, all three characteristics of a device – ie, clinical, technical and biological – should be critically discussed. Also, it clarifies that devices being compared should have "the same material and [should be] for the same intended use and medical indication. The differences between the device under evaluation and the device presumed to be equivalent need to be identified, fully disclosed, and evaluated".

This is in sharp contrast to the current practice, wherein device sponsors typically refer to "several equivalent products", and are mostly able to make a case that the new device (for which a CE-mark is being sought) raises no new safety or performance concerns and that there is, therefore, no need to undertake fresh clinical evaluation with the new product, and that they can rely on post-market surveillance and/or post-market clinical follow-up.

The revised MEDDEV requires notified bodies to challenge the ability of a device sponsor to access information relevant for demonstrating equivalence. With the introduction of these changes, demonstration of equivalence might be difficult or impossible for some devices, especially in cases where sponsors have limited access to technical documentation of the comparator device.

As a result of these changes, device manufacturers would have to update the clinical evaluation reports (CERs) for their respective products, and might therefore have to employ additional resources. Also, they would have to decide which devices in their portfolio can follow the literature route.

The revised MEDDEV was adopted by the EU working group on Clinical Investigation and Evaluation (CIE) on April 13. It was then submitted to the Medical Devices Expert Group (MDEG) for approval via a written procedure, and this process is still ongoing. After finalization, the revised guideline will be published on the commission's website.

If things go as planned, the revised MEDDEV would likely be published on the commission's website later June 2016.

Some notified bodies have already started to slowly push device sponsors, whose files are currently under active review, to start adjusting to the principles outlined in the revised MEDDEV as these principles also form the basis of the joint assessments of notified bodies that are carried out by the commission and national competent authorities.

However, some of the crucial questions that need answering are: when will notified bodies start enforcing the new MEDDEV? Will they apply it for new certificates and renewals only or also for reviewing change requests, or for all products currently on the market that have their CER based on equivalence?

For each of these scenarios, the real impact of the revised MEDDEV will be determined by how much time manufacturers would be allowed to re-work their data set. Also – and most importantly – it remains to be seen whether there would be any cases where the underlying certificates will be put under suspension until the revised CERs have been reviewed and approved.

Some of the other changes made to the MEDDEV include:

  • clarifying that the clinical evaluation requirement applies to all classes of medical devices and that it is the responsibility of the device manufacturer;
  • clarifying that the clinical evaluation process is mandatory for obtaining the initial CE mark and that it must be updated thereafter;
  • improvements to the various stages of the clinical evaluation process to reflect a clearer picture;
  • new examples of the types of studies deemed inadequate to demonstrate clinical performance and/or clinical safety of a device;
  • the introduction of a special interpretation for devices for unmet medical needs;
  • the introduction of specific requirements regarding the clinical evaluation team at the manufacturer and the clinical assessment team at the notified body site; and
  • specifying minimum expectations regarding the clinical evaluation assessment report (CEAR) of the notified body's assessment of the manufacturer's application.