The fundamentals of EU regulations are evolving rapidly....
In this whitepaper I want to discuss the fundamentals of medical device regulations in the European Union with the goal of determining whether or not a clinical study is necessary in order to obtain certification and CE Mark. This is an introductory discussion intended for those who are new to the medical device industry.
The fundamentals of medical device regulations in the United States are discussed in a companion whitepaper and workshop. The companion US workshop is available Wednesday, 30 June 2010, 11 AM Central and on OnDemand soon after.
The European Union
Europe was not always a union, and most would argue that it isn't one yet today. It is a collection of individual states (countries) whose integration is driven by economic aims, not political ones. The upshot is that industry and regulators are often at odds with each other: industry pushing for a common regulatory system across the union while regulators strive to retain opacity and independence.
An economic union is a collection of peoples and geographic areas that share a common market through the free movement of goods, services, jobs, and people; and who present a common economic face to the world: they share a common currency, have common import and export tariffs, a common tax rate, and common fiscal and economic policies. If you've shopped in Europe you know that they are not quite there yet. The price tag on a sweater lists the price in Euros, true, but there is a different price for France, Germany, Italy, and every other country.
In 1992 there were 15 member states in the union, consisting of Western, economically developed countries. Today there are 27 member states. In 2004, the EU saw its biggest single enlargement when Malta, Cyprus, Slovenia, Estonia, Latvia, Lithuania, Poland, the Czech Republic, Slovak Republic, and Hungary were admitted as members.
The government, located in Brussels, consists of a Parliament, Council, and Commission. The Council sets the general direction and priorities of the Union. The Commission proposes laws (i.e. directives) consistent with the priorities set by the Council. The Parliament and Council jointly approve the directives, which are then issued as law by the Council.
The New Approach
When Europe sought to set up a review and approval system for medical devices, they wanted to take advantage of existing governmental institutions. Since the 'old' way to set up a government was to create a entirely new infrastructure, the idea of using what was already there was called the New Approach.
In the New Approach, the European Council issues directives (laws) to govern the sale of medical devices. There are three directives of particular concern to us:
 Active Implantable Medical Device Directive (AIMD) 1990-385-EEC.
 Medical Device Directive (MDD) 1993-42-EEC.
 In Vitro Diagnostic Directive (IVD) 1998-79-EC.
The Standards Body (ISO or CEN), using a committee of experts from industry, investigative sites, and regulators, publishes new standards that are incorporated into directives and become de facto regulation. The standard of concern for medical device trials is ISO/FDIS 14155 "Clinical investigation of medical devices for human subjects—good clinical practice" (2010) and it will be incorporated into Annex 7 and Annex X of the AIMD and MDD, respectively. The standard does not apply to in vitro diagnostic devices.
The Regulatory Body or Competent Authority, usually the department of health and welfare for that country, is responsible to implement directives, regulate clinical research, appoint Ethics Committees and Notified Bodies, and approve the initiation of medical device trials. Most countries have only one Competent Authority, but Germany has more than 40, one from each county.
The various Ethics Committees located within a member state are often appointed regionally and may be structured in a tiered approach. Some Ethics Committees give only opinions, but not approval, regarding a clinical trial. The Ethics Committees in Germany have a close association with the professional medical society.
Finally, the Notified Body, an independent accredited body of experts, is authorized by the Regulatory Body to enforce regulations, review clinical trial results, and inspect a manufacturer's quality management system in application for certification, CE Marking, and approval for sale of a medical device. A country may have as many Notified Bodies as it wants; Germany has sixteen.
Devices are as diverse as toothbrushes to heart valves, or sunlamps to breast implants. It would be unreasonable to regulate all devices the same way. Wrapping your mind around a country's approach to device regulation is challenging. The point of entry is to first learn how that country classifies devices. All countries classify devices by history or risk, and then regulate the devices differently depending on its classification. In Europe, devices are AIMD, MDD Class I, MDD Class IIa, MDD Class IIb, MDD Class III, or IVD.
 Active implantable medical devices: are both implanted and energy requiring.
 MDD Class I: non-invasive devices that do not contact blood or body tissues.
 MDD Class IIa: short-term use devices that channel blood or body liquids or connect to higher-class devices, also dental devices.
 MDD Class IIb: long-term use devices which contact breached skin, supply energy, deliver drugs, monitor vital processes, contraceptives, disinfectants, or blood bags.
 MDD Class III: long-term invasive devices which are heart or central circulatory system contacting, central nervous system contacting, biodegradable, drug-device combinations, implantables, or based on animal tissues.
You can consult the European Commission medical devices guidance document MEDDEV 2.4/1 Rev.8 July 2001 for details of classification. Europe is fundamentally different than the States in its classification strategy: there are a series of eighteen rules to follow, which allow you to determine the classification by process of elimination. It is a tidier and simpler approach than the States, but then Europe had the benefit of studying the strengths and weaknesses of our system before developing their own.
The BIG question—do you need a clinical trial?
The question we've been trying to answer with all of this is whether or not you need to do a clinical trial in order to get Notified Body certification of your quality management system, which gives you authority to affix a CE Mark to our device. But you have a few more variables to work out first, before you can be sure.
The next step is to determine which of eight possible pathways you want to follow in order to assess conformity of your manufacturing process to the specifications set forth in your quality management system. Putting it simply, you:  select a Notified Body,  have the Notified Body inspect your quality management system and issue you a certificate,  design a device and complete a technical file,  give yourself a CE Mark, sign your Declaration of Conformity, and start selling, and then  the Notified Body reviews your Technical Files at their next visit to see if they agree with your decision.
Clinical Evaluation Reports have the answer
Finally, you prepare a clinical evaluation report for the device. The clinical evaluation report consists of three modules:
 review of published literature to assess safety and performance.
 review of any related clinical studies you may have sponsored to assess safety and performance.
 review of any related complaints to determine if the quality management system is adequate to support an argument of safety and performance.
The results of the clinical evaluation report should lead you to a decision as to whether existing data are sufficient to support an argument of safety and performance for the device's intended use, or if new, additional clinical data are necessary. I discussed the details of how to perform a clinical evaluation report in a whitepaper published last April.
If you liked the whitepaper, take the workshop
The objective of the workshop is to learn the basics of European regulations and how to determine if you need a clinical study in order to get market your device. Sign up at registration.
This is an introductory workshop and focuses on European regulations. A complimentary workshop focusing on US regulations is also available.
You will receive, we will discuss
[x] PowerPoint slides.
[x] A two-hour presentation.
[x] Discussion of the Directives.
[x] Meaning of Essential Requirements.
[x] Medical device classification in Europe.
[x] Relationship between standards and regulations.
[x] Supporting handouts, flowcharts, and graphic presentations.
[x] A complimentary US/ISO Adverse Event mousepad/notepad (by mail).
[x] A 30-minute quiz to reinforce your learning experience.
[x] CEUs and certificate of attendance.
Who should attend
[x] Anyone new to medical devices.
[x] Anyone new to medical device clinical trials.
[x] Anyone needing to know about medical device regulations.
Dr. Nancy J Stark is President and Founder of Clinical Device Group, a CRO and consulting firm that has been in business since 1990. Her curriculum vitae can be found at www.nancystark.com.
[x] Personal computer.
[x] Internet Access.
Date, time, registration for US Workshop
The three-hour workshop will be presented on Wednesday, 30 June 2010, at 11:00 Central Time. Event materials will be distributed the day before the workshop. Sign up at registration.
Date, time, registration for EU Workshop
The two-hour workshop will be presented on Wednesday, 1 July 2010, at 11:00 Central Time. Event materials will be distributed the day before the workshop. Sign up at registration.
Learn the world discount
Register for both workshops and get $100 off! Enter the coupon code SUMMER at check-out.
Nancy J Stark, PhD
President, Clinical Device Group Inc