Global Regulatory Pulse

New Pre-Market Scrutiny Process for High-Risk Products in Europe

In European Market, Regulatory by Stephan Buttron

Existing European Medical Device regulations date back to the mid-1990s and have not kept pace with the enormous technical and scientific progress in the past 20 years. Patients, health care professionals and economic operators do not have appropriate access to essential information on how medical devices have been assessed and what clinical evidence there is to demonstrate they meet safety and performance requirements for its intended use.

The need for greater transparency and European collaboration escalated by scandals about faulty silicone breast implants (PIP) and safety problems with some metal-on-metal (MoM) hip replacement implant devices.

When reviewing the publicly available reports on field safety notices issued by manufacturers in the UK from 2006 to 2010 issued by the UK Competent Authority Medicines and Healthcare products Regulatory Agency (MHRA), there is a more than a tenfold increase over this 5-year reporting period as depicted in Figure 1 below.1

5 year reporting on field safety notices

These numbers may be an indication of a lacking scrutiny level in the pre-approval conformity assessment of medical devices including high-risk devices.

Perhaps what is even more concerning than the reported field safety notices and high profile cases (such as the MoM hips and PIP implants), is that many medical device problems go unnoticed. A substantial number of these devices may have caused serious adverse effects in patients and contributed to rising healthcare costs.

Among other problems, the controversial issue is the use of ‘equivalency arguments’ in clinical evaluation reports to substantiate credible evidence on patient safety and clinical performance, enabling commercial distribution for these devices in the European Economic Area.

Under the current Medical Device Directive (MDD), national medical device laws and ordinances, the scrutiny process to ensure robust evidence on patient safety and performance characteristics prior to market approval is subject to accredited Notified Bodies. However, many Notified Bodies lacked the expertise and experience to adequately evaluate the provided clinical evidence in view of patient safety and clinically relevant risk/benefit ratio.

In many cases, clinical data for market approval scrutiny was limited to a critical evaluation of the published relevant scientific literature for similar other (predicate) devices relating to the safety and performance of design characteristics and intended use when compared to the device under evaluation. However, the interpretation and utilization of the term ‘equivalence’ is left to the device manufacturer and the Notified Bodies to determine.

The potential problems with using the ‘equivalency’ concept in lieu of medical data from clinical investigations is well known. In 1976, US FDA introduced a less burdensome alternative to a Pre-Market Approval process known as the 510(k) provision under the Medical Device Regulation Act. The 510(k) pathway did not require clinical data from clinical investigations. Instead, the manufacturer was only required to demonstrate a device was ‘substantially equivalent’ as compared to another (predicate) device already on the market. The problem now is that the definition of equivalence is interpreted so loosely that US FDA admits they need to ‘clarify the meaning of “substantial equivalence.”2

The maze of national laws, decrees and ordinances of Member States led to differences in levels of regulatory pre-market scrutiny; in some cases, to different approaches between EU Member States. As a consequence, a variety of interpretations could be observed across the European Union for safety and performance requirements for clinical investigations, reporting requirements during clinical investigations and opinion on the classification of high-risk and borderline products.

All stakeholders agree the current fragmented regulatory system needs a major overhaul. Though not final, the Medical Device Regulation (MDR) is expected to change the pre-market approval process. The bar on demonstrating patient safety, clinical performance and usability will be significantly higher.

The equivalency argument will no longer be an option for class III and implants. High-risk devices will have to demonstrate patient safety and clinical performance for its intended use(s) with robust data from clinical investigations with a scientifically valid clinical trial design.

The following graphic may illustrate a scenario of the anticipated scrutiny process for high-risk class III and implant devices.3

Proposed Scrutiny Procedure

The proposed scrutiny process may recognize new decision makers with different expectations and timelines on evaluating on patient safety and clinical performance including usability at the time of initial approval.

In addition, mandatory post-market clinical trials and Periodic Safety Update Reports (PSUR) with public access will ensure an early warning if and when safety issues become visible during commercial distribution.

The goals are to evaluate more data (clinical and nonclinical), to coordinate communication among European member states and improve harmonization of Notified Bodies for more competent and timely reviews. To some extent, manufacturers will benefit from clearer rules and a level playing field that benefits innovative small and medium-sized manufacturers.4

It is in the best interests of device manufacturers to start preparing for the regulatory changes ahead as soon as possible.


  1. BMJ Open. 2011 May 15;1(1):e000155. doi: 10.1136/bmjopen-2011-000155. Medical-device recalls in the UK and the device-regulation process: retrospective review of safety notices and alerts. Heneghan C1, Thompson M, Billingsley M, Cohen D.
  2. US Food and Drug Administration 510(k) Working Group preliminary report and recommendations. August 2010. (last accessed 2 April 2012)
  3. MedTech Europe. (2013). Proposed Scrutiny Procedure. Retrieved May 4, 2016, from
  4. Safer, more effective and innovative medical devices [Press release] Brussels, 26 September 2012

Stephan Buttron currently serves as NAMSA’s Senior Product Development Strategist. Mr. Buttron has over 20 years’ experience in achieving EU, U.S. FDA and other international regulatory medical device approvals and registrations. He has provided global consulting services on regulatory strategy development to medical device manufacturers regarding least burdensome pathways for 510(k)/PMA and MMD-CE mark applications. He has successfully managed FDA pre-submission meetings for Investigational Device Exemption (IDE) pathways with multiple FDA specialty branches. Stephan is considered a key industry thought leader on risk management, and has provided multiple training sessions to medical device manufacturers on structured risk management process per EN ISO 14971 & EU MDD 93/42 as amended with directive 2007/ 47. Mr. Buttron has also provided countless educational opportunities to international organizations regarding medical device design and development issues related to ISO 13485 & EU MDD 2007/47 compliance.