The recent vote in the European Parliament’s Committee for Environment, Public Health and Food Safety (ENVI) has created a lot of concerns for the medical device industry in Europe. The main fear is that the proposed amendments will do little to improve patient safety and that we are now witnessing a grotesque political compromise in the making that will only add more layers of regulation and bureaucracy. The chief executive officer of Eucomed, Serge Bernasconi, stated in a press release 1,
“Let it be clear that this is a [premarket approval] PMA in disguise carried out on a case-by-case basis and will deal a blow to patient access and medical device innovation in Europe.“
Others, like Antoine Papiernik, managing director of venture capital (VC) firm Sofinnova has gone even further, being quoted saying,
“An FDA-like system would kill patients and kill innovative companies.“
On the other side of the battleground, ENVI’s rapporteur Dagmar Roth-Behrendt proclaims that,
“We have achieved our main objective: patients will be better protected from defective products. We were able to enforce our goals and to be more ambitious than the Commission proposal. We really needed to put patient safety first and to bring transparency to an industry that is quite unregulated 2.“
For those not directly involved in medical devices regulation, it might be difficult to understand what’s happening and why the industry finds ENVI’s amendments unacceptable. So, let’s take a step back and look at the big picture.
The regulatory framework that applies to medical devices differs greatly from that used for drug development. For one, the medical device legislation is more recent: Mature laws were born only in the 1990s, and they are harmonized across the world to a lesser degree than in the pharmaceutical industry. Since 1993, the Global Harmonization Task Force (GHTF) – representing Australia, Canada, the EU, Japan and the USA – has made some progress, but a unified approach to quality monitoring, marketing approval and market vigilance is still at an early stage 3. European device regulations are currently under revision, and all sides recognize a need for necessary and effective improvements to strengthen the system 4,5.
Risk management is the principle governing device approval and monitoring. The manufacturer has the responsibility of guaranteeing (and declaring) the conformity of a product, based on its safety, performance, quality control and labeling assessment. The extent of the assessment needed for each device is dependent on the classification of risk, and is usually divided in three to four classes, depending on the region. Devices with more potential risks must undergo an extensive pre- and post-marketing evaluation 3.
Overview of European and FDA regulations
In Europe there are three directives concerning medical devices 6-8:
- 90/385/EEC on Active Implantable Medical Devices (AIMD), which covers powered devices left in the human body;
- 93/42/EEC, the main Medical Device Directive (MDD), which covers a vast range of devices; and
- 98/79/EC, the In Vitro Diagnosis Directive (IVDD).
The new regulations consist of only two directives: the MDD and IVDD. The former MDD and AIMD are now merged into one directive 4,5.
The European Medicines Agency (EMA) and national authorities are not always involved in the process of assessing and authorizing medical devices. This task may be carried out a Notified Body (NB), a private and certified institution, based on a contract with the manufacturer. NBs are certified by the member state’s national health authority and may test all devices, or specific classes of devices. When a device makes use of a drug, the NB must request advice from the national authority 6-8.
The approval landscape in the USA is different from that in the EU. US Food and Drug Administration (FDA) regulations concerning informed consent, institutional review boards, and financial disclosure (21 CRF 50, 56 and 54, respectively) apply both to pharmaceuticals and medical devices. Specific device regulations (21 CRF 800) have been developed since 1976, with the introduction of risk classifications and premarket notification. Post-marketing monitoring and a streamlined notification process were introduced between 1990 and 2002 9. Unlike European authorities, the FDA is directly involved in the approval of new devices, regulating their manufacture, labeling and marketing. The FDA system is often criticized for delivering no additional safety benefits for patients and that it causes unnecessary delays of 3 to 5 years in lifesaving medical devices reaching patients compared to the current European approval system.
Three major steps to approve a medical device – current system in the EU and US
What is changing in Europe?
The revision of medical devices directives were triggered by the Poly Implant Prothèse (PIP) silicone implants scandal. Consequently, new directives have been drawn up to ensure transparency and traceability over medical devices approval and market surveillance 4,5.
The main proposed changes are:
- NB accreditation and supervision: NB quality control reinforced by new measures; e.g., by restricting the outsourcing of auditing work.
- Qualified Person: manufacturer required to have ‘qualified person’ within the organization (similar role to that defined in pharmacovigilance legislation).
- Clinical studies: clinical evaluations and investigations submitted to central registry database (EUDRAMED). Manufacturers to publicly disclose safety and efficacy clinical data summaries for high-risk devices.
- Device/drug combinations: EMA (or the national authority) power to refuse a certificate issued by an NB.
- Software: new section added to revised directives, including requirements for integration with mobile platforms.
- Unique Device Identification: manufacturers to gradually implement (depending on risk classification) a system allowing device traceability.
These new regulations, which will be applicable up to 3 years after coming into force, are currently under discussion. The ENVI Committee voted on the new legislative proposal on 25 September 2013 and passed it on to the EU Parliament who will have a plenary vote during the 21 to 24 October session in Strasbourg. The timeline for application currently ranges from 4–6 years 4.
Risk – seek and ye shall find
Medical devices regulations are less harmonized than pharmaceutical regulations. They are also more prone to major revisions: the new European regulations, which are currently under discussion, include more than 900 proposed amendments 10. Since medical device definition includes a wide range of devices, the regulatory requirements can go from simple labeling and technical specifications to extensive clinical studies.
The main difference between pharmaceutical and medical device legislation is in its philosophy towards risk. Pharmaceutical development aims to prove that a new drug is safe before approval (via phases of intense clinical research). Medical device development is based on an effectiveness assessment—the burden of proof for safety is handed over to real-life assessment, with a focus on post-marketing studies. The consequences of that difference in approach, both for EU legislation and for patient safety, are still being played out.
A liger in the EU legislative jungle?
Chances are high, however, that we will see some kind of a hybrid with an added requirement for pre-market authorisation process for high-risk devices. Currently, 400 – 600 Class III devices enter the European market each year. A new pre-market authorisation scheme will no doubt require a lot of extra bureaucracy. It is proposed that the EMA will not only start managing and controlling the Notified Bodies; the ENVI Committee would also like to set up an additional conglomerate of up to 600 clinical experts who will do a second assessment of all high risk devices. Nobody knows yet how the new EU medical devices directives will look like, but it is likely to be a blend of many political compromises. In the animal kingdom hybrids are very rare and most often a result of human intervention. A fascinating creature is the liger. A liger is the result of breeding a male lion to a tigress. Unfortunately, the liger suffers from many birth defects and usually dies young. Because ligers are usually larger than either parent, it puts the tigress at great risk in carrying the young and may require C-section deliveries or kill her in the process 11. For the sake of patient safety, fast access to new technology and the competitiveness of the medical device industry in Europe, we must hope that the EU Council votes through workable rules and that the EMA will have the necessary strength to cope with the added regulatory burden.
- EUCOMED Press Release: Rushed deal leaves patients and jobs in second place, http://www.eucomed.org/pressreleases/12/150/Rushed-deal-leaves-patients-and-jobs-in-second-place [Accessed: 26 Sept 2013].
- ENVI Press Release: Health MEPs call for stricter controls on medical devices http://www.europarl.europa.eu/news/en/news-room/content/20130923IPR20607/html/Health-MEPs-call-for-stricter-controls-on-medical-devices [Accessed: 27 Sept 2013].
- World Health Organization. Medical device reglations: global overview and guiding principles. Geneva: WHO, 2003. 43.
- European Commission. Proposal for a Regulation of the European Parliament and of the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009. Brussels: EC, 2012.
- European Commission. Proposal for a Regulation of the European Parliament and of the Council on in vitro diagnostic medical devices. Brussels: EC, 2012.
- European Council. Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices. OJ L 1990;189:0017-36.
- European Council. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. OJ L 1993;169:1.
- European Council. Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices. OJ L 1998;331:1.
- Liu MB, Davis K. A Clinical Trials Manual from the Duke Clinical Research Institute: Lessons From A Horse Named Jim, Second Edition. Oxford: Wiley-Blackwell, 2010.
- European Parliament. Parliamentary Committees – Environment, Public Health and Food Safety. 2013. http://www.europarl.europa.eu/committees/en/envi/amendments.html?linkedDocument=true&ufolderComCode=ENVI&ufolderLegId=7&ufolderId=10806&urefProcYear=&urefProcNum=&urefProcCode=# [Accessed: 26 Sept 2013].
- Liger Facts. http://bigcatrescue.org/liger-facts/ [Accessed: 26 Sept 2013].