On 29 June 2016, the European Commission issued a much-awaited new version of the MEDDEV 2.7/1 entitled “Clinical Evaluation: A Guide for Manufacturers and Notified Bodies under Directive 93/42/EEC and 90/385/EEC“. This revision substantially amplifies the previous version of the MEDDEV which was published in September 2009. It also provides detailed guidance on the steps by steps process for preparing and updating a clinical evaluation report.

The new version of the MEDDEV 2.7/1 is anticipated to be the new “standard” against which notified bodies and competent authorities will review clinical evaluation reports prepared by medical devices manufacturers. Manufacturers may, therefore, have to take steps to ensure that the clinical evaluation of their medical devices reflects the rules and criteria defined in this new document.

Background

Annex I Section 6a to the Medical Devices Directive and Annex I Section 5a to the Active Implantable Medical Devices Directive require that demonstration of conformity of a medical device with the relevant Essential Requirements include collection of clinical data permitting conduct of a clinical evaluation of the medical device. Conduct of a clinical evaluation is mandatory for all classes of medical devices prior to affixing the CE mark.

In order to perform a clinical evaluation, a manufacturer may use data from any of the following sources:

  • clinical investigation(s) of the device concerned; or
  • clinical investigation(s), or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or
  • published and/or unpublished data on clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated;
  • or any combination of the above.

The clinical evaluation conducted by a medical devices manufacturer is documented in a clinical evaluation report which is an integral part of the Technical File for the relevant medical device. During conformity assessment procedures, notified bodies review the clinical evaluation report as part of their review of the Technical File. The purpose of the MEDDEV 2.7/1 is to provide guidance to manufacturers and notified bodies concerning the purpose, methodology and documentation of a clinical evaluation.

The on-going nature of clinical evaluations

The new MEDDEV 2.7/1, which is the result of long discussion between the European Commission, the competent authorities of the EU Member States and other interested parties such as the EU industry associations, provides a new definition of “clinical evaluation”. This definition underlines the on-going nature of a clinical evaluation. The new MEDDEV 2.7/1 defines a clinical evaluation as:

a methodologically sound ongoing procedure to collect, appraise and analyse clinical data pertaining to a medical device and to evaluate whether there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer’s Instructions for Use.”

Through this new definition, the MEDDEV 2.7/1 clearly underlines the need for medical device manufacturers to update their clinical evaluation related to devices on a regular basis. According to the MEDDEV, the manufacturer should define and justify the frequency at which the clinical evaluation should be actively updated based of the risks related to the use of the medical device, innovation, changes in sciences related to the medical device, design changes or changes in the manufacturing procedures for the device.

In all cases, the revised MEDDEV 2.7/1 provides that the clinical evaluation shall be actively updated:

  • When the manufacturer receives new information from post market surveillance (PMS) that has the potential to change the current evaluation;
  • If no such information is received, then
    • at least annually if the device carries significant risks or is not yet well established; or
    • every two to five years if the device is not expected to carry significant risks and is well established, a justification should be provided.

These recommendations illustrate that the new MEDDEV 2.7/1 underlines the necessary link between clinical evaluation, post market surveillance and risk management process. It is for this reason that the MEDDEV also clarifies that the purpose of a clinical evaluation is not only to document that there is sufficient clinical evidence to demonstrate conformity with the Essential Requirements covering clinical performance and clinical safety that are laid down in Annex I to the relevant Directive but also to identify aspects that need to be systematically addressed during post-market surveillance (PMS).

Updated methodology for clinical evaluation

In the version 3 of the MEDDEV 2.7/1 issued in September 2009, manufacturers were recommended to conduct a four stages procedure for the clinical evaluation of their medical devices:

  • Stage 1 identification of clinical data;
  • Stage 2 appraisal of the data;
  • Stage 3 Analysis of the relevant data;
  • Stage 4 drafting of the clinical evaluation report.

The newly revised version of the MEDDEV 2.7/1 adds a preliminary stage, referred as Stage 0, which is the “scoping” of the clinical evaluation. Before a clinical evaluation is undertaken the manufacturer should define its scope, based on the Essential Requirements that need to be addressed from a clinical perspective and the nature and history of the medical device.

This preliminary stage shall serve as a basis for the next stages in the clinical evaluation process. For this purpose, the new MEDDEV 2.7/1 requires manufacturers to prepare a description of the device under evaluation and to prepare a clinical evaluation plan.

The previous version of the MEDDEV 2.7/1 already provided some guidance concerning the different stages of a clinical evaluation. This guidance is substantially amplified in the new MEDDEV 2.7/1. Information concerning the criteria or elements which must be considered by medical devices manufacturers and notified bodies for each stage of the clinical evaluation is now provided.

Stricter rules for demonstration of equivalence with other medical devices

The new MEDDEV 2.7/1 includes new rules that must be respected by manufacturers when they wish to rely on clinical data related to equivalent medical devices in their clinical evaluation. Like in its previous version, the MEDDEV 2.7/1 provides that, to be considered equivalent to a manufacturer’s device, another device must be compared with respect to its clinical, technical and biological characteristics. The novelty is that the new MEDDEV 2.7/1 provides that additional rules must be considered before “assuming equivalence”. This includes the following rules:

  • equivalence can only be based on a single device. If several devices are claimed to be equivalent to the manufacturer’s medical device, equivalence of each single device should be fully investigated, demonstrated, and described in the clinical evaluation report;
  • the differences between the medical device under evaluation and the medical device presumed to be equivalent need to be identified, fully disclosed, and evaluated; explanations should be given why the differences are not expected to significantly affect the clinical performance and clinical safety of the device under evaluation;
  • if measurements are possible, clinically relevant specifications and properties should be measured both in the medical device under evaluation and the medical device presumed to be equivalent, and presented in comparative tabulations;
  • comparative drawings or pictures should be included in order to compare shapes and sizes of elements that are in contact with the body;
  • for the evaluation of the technical characteristics, devices that achieve the same therapeutic result by different means cannot be considered equivalent;
  • the only clinical data that are considered relevant are the data obtained when the equivalent device is a CE-marked medical device used in accordance with its intended purpose as documented in the IFU

These additional rules may complicate the tasks of medical devices manufacturers wishing to rely on clinical data for medical devices which might be considered as equivalent to their medical devices.

Detailed recommendations for the review of clinical evaluation by notified bodies

As underlined in the new MEDDEV 2.7/1, notified bodies play an important role in the assessment and verification of clinical evaluation reports and supporting documentation provided by medical device manufacturers to support demonstration of conformity of a device with the Essential Requirements of the relevant Directive. To ensure a more harmonised review of clinical evaluations reports among notified bodies, the new MEDDEV 2.7/1 provides detailed recommendations for notified bodies including:

  • guidance for notified bodies on the assessment of clinical evaluation reports provided by medical device manufacturers as part of technical documentation (including design dossiers); and
  • guidance for notified bodies in development of their internal procedures for assessment of clinical aspects relating to medical devices.

The new MEDDEV 2.7/1 also include a specific section which underlines that notified bodies should have suitable resources, sufficient expertise and clinical competence to conduct assessment of clinical evaluations.