The ‘Proposal for a Regulation of the European Parliament and of the Council on Medical Devices’ in 2012 was prompted in part by a series of implant-related scandals. The most promiment of these concerned French company, Poly Implant Prothèse (PIP), when EU authorities discovered that it had been using industrial, rather than medical-grade, silicone in its CE-approved breast implants since 2001.

With EU action pending, the proposal, as amended, outlines new requirements for achieving and maintaining CE approval for ‘high-risk’ devices. The proposed amendments are shown as italics in this article.

The 2012 proposal can be downloaded, free of charge, from the website of the European Commission ( The 2013 amendments can also be found online (search for "amendments adopted by the European Parliament on 22 October 2013 on the proposal for a regulation of the European Parliament and of the Council on medical devices").

Identifying high-risk devices

The first question to address for manufacturers concerns the nature of ‘high-risk’ devices. The amendments refer to "special notified bodies in the conformity assessment procedures of high-risk devices", and state that "only special notified bodies (designated by the European Medicines Agency) shall be entitled to conduct conformity assessments" for the following devices:

  • those that are implantable
  • devices incorporating substances (that, if used separately, could be considered to be medicinal products, including medicinal products derived from human blood or human plasma)
  • class-IIb devices intended to administer and/or remove medicinal products
  • devices manufactured utilising tissues or cells of human or animal origin, or their (non-viable) derivatives
  • all other class-III devices. (Article 43a, under Amendment 161).

Manufacturers of high-risk devices can find out if their notified body will receive ‘special’ classification and, if not, seek assistance elsewhere.

Three new bodies

The proposal, as amended, defines three new bodies: the Medical Device Coordination Group (MDCG), the Medical Device Advisory Committee (MDAC) and the Assessment Committee for Medical Devices (MDAC) for the provision of expertise in medical devices, device regulation and medicine. It would also provide a more rigorous conformity assessment procedure: "Special notified bodies shall notify the Commission of applications for conformity assessments [for some high-risk devices] with the exception of applications to renew or supplement existing certificates and devices. The Commission shall immediately [ask] the MDCG for an opinion. The MDCG may seek a clinical assessment from the Assessment Committee for Medical Devices (ACMD)." (Article 44a, under Amendment 165).

Under Article 78, Amendment 238, each EU member state would appoint members providing expertise in device regulation to the MDCG. The multidisciplinary MDAC, meanwhile, will be composed of experts to provide "support, advice and expertise to the MDCG" (Article 78a, Amendment 240), while the ACMD, would provide the MDCG with expert clinical assessments (Article 78b, under Amendment 240).

If the amended proposal is adopted, the time necessary to gain CE approval for new medical devices will be increased by the time required to obtain the opinion of the MDCG, as advised by the MDAC, after possible clinical assessment from the ACMD.

"The proposal outlines new requirements for achieving and maintaining CE approval for ‘high-risk’ devices."

For class-III and implantable devices, other than those that are custom-made, or investigational, "The manufacturer shall draw up a summary of safety and clinical performance that is clear to the intended user (Article 26). For devices classified as class-III and implantable devices, (this) shall be updated at least annually." (Amendment 173).

The European databank on medical devices (Eudamed) exists, but is not yet publicly accessible. The European Commission would use it to inform the public about devices on the market, as well as ongoing clinical investigations (Article 27). Devices would be traceable via the unique device identification (UDI) system (Article 24).

Literature-based clinical evaluation

In annexe XIII to the proposal, ‘Clinical Evaluation and Post-Market Clinical Follow-up (PMCF)’, the proposed amendments have been adopted:

  • A2: Confirmation of conformity… shall be based on clinical data. Data from independent scientific institutions or medical societies based on their own collections of clinical data shall also be taken into account.(Amendment 328).
  • A4: Clinical data relating to another device may be relevant where equivalence is demonstrated of the device subject to clinical evaluation to the device to which the data relates. Equivalence can only be demonstrated when the device that is subject to clinical evaluation and the device to which the existing clinical data relates have the same intended purpose, and when the technical and biological characteristics of the devices and the medical procedures applied are similar to such an extent that there would be not a clinically significant difference in the safety and performance of the devices.
  • A5: For implantable devices and devices falling within Article 43a, with the exception of those used for a short term (60 minutes to 30 days) (Amendment 329) clinical investigations shall be performed unless it is duly justified to rely on existing clinical data alone. Demonstration of equivalence in accordance with Section A4 shall generally not be considered as sufficient justification within the meaning of the first sentence of this paragraph.

If demonstration of equivalence would not be sufficient to justify use of existing clinical data for high-risk devices, one wonders if a literature-based clinical evaluation could ever again be sufficient to gain CE approval for a high-risk device.

Post-market clinical follow-up Annexe XIII continues as below.

  • A5a: All clinical data collected by the manufacturer as part of a PMCF should be made accessible to health professionals. (Amendment 330).
  • B1: PMCF is a continuous process to update the clinical evaluation and shall be part of the manufacturer’s post-market surveillance plan. To this end, the manufacturer shall proactively collect, register in the electronic system on vigilance referred to in Article 622 (Amendment 331) and evaluate clinical data from the use in, or on, humans of a device.
  • B3: The manufacturer shall analyse the… PMCF and document the results in a PMCF evaluation report (for) the technical documentation and be sent periodically to the concerned member states. For class-III medical devices, the manufacturer’s PMCF evaluation report shall be reviewed by a third party or external expert under the principles of highest scientific competence and impartiality. In order to conduct its review, the manufacturer shall provide the relevant data to the third party, or external expert. Both the manufacturer’s PMCF evaluation report and its review by an independent body shall be part of the technical documentation for class-III medical devices. (Amendment 332).
  • B4: The conclusions of the PMCF evaluation report and where applicable its review by a third party or external experts as referred to in paragraph B3, shall be taken into account for the clinical evaluation. If, through the PMCF, the need for corrective measures has been identified, the manufacturer shall implement them and inform the concerned member states. (Amendment 333).

Clinical investigations

Another annexe to the proposal is XIV, ‘Clinical Investigations’. Within this, the following (italicised) amendments have been adopted.

  • I.2.1: Clinical investigations shall be (done) to confirm or refute the technical performance of the device, the clinical safety and efficacy of the device when used for the intended purpose in the target population and in accordance with the instructions of use, and (Amendment 335) the manufacturer’s claims for the device.
  • I.2.3: Clinical investigations shall be performed in circumstances similar to the normal conditions of use of the device for the intended purpose in the target population (Amendment 336).
  • I.2.7: The clinical investigation report shall contain all clinical data collected during the clinical investigation and a critical evaluation of such data, including negative findings (Amendment 337).
  • II.1.11: Summary of the clinical investigation plan. As randomised controlled investigations usually generate a higher level of evidence for clinical efficacy and safety, the use of any other design or study has to be justified. Also, the choice of the control intervention shall be justified. Both justifications shall be provided by independent experts with the necessary qualifications and expertise (Amendment 340).
  • II.3.1.3: The clinical investigation plan (CIP) must contain information on the principal investigator, coordinating investigator… and… investigation site(s), as well as information about the contract between the sponsor and the investigating establishment, together with details of the funding (Amendment 343).
  • II.3.15a: (And) a plan for the further treatment of subjects after the clinical investigation. (Amendment 347).

What it means for you

In summary, the proposal, as amended, would result in an increased need for randomised controlled clinical studies to gain and maintain CE approval for high-risk devices. Literature-based clinical evaluations would be much less likely to gain CE approval for high-risk devices (other than short-term ones), and clinical investigations would have to be performed to achieve CE approval, if relying on existing clinical data could not be justified.

Also, independent experts would be needed to justify clinical study design for studies other than randomised, controlled investigations. For PMCF review of class-III devices, third parties, or external experts would be required.

Would the industry be able to comply without sacrificing timeliness in bringing new medical devices to the European market? Could a start-up raise sufficient venture capital to run the requisite investigations? Might parts of the proposal adversely affect your business without providing adequate compensatory benefit by raising the safety and performance of medical devices on the European market?

If the answer to any of these is ‘yes’, you may wish to lobby members of the recently elected EU Parliament.