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Proposal for stricter regulations in approval of medical devices in Europe sparks controversy
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With an implementing act issued in September 2013 by the European Commission, the European Union seems to be moving toward more centralized, uniform and transparent regulations concerning the approval of medical devices across member states. The legislative proposal is aimed at ironing out inconsistencies in the current regulatory system to better protect patients from defective products such as PIP breast implants and metal-on-metal hip implants.
Keith Barton, MD, FRCP, FRCS, FRCOphth, said that although not everything should necessarily be uniform in Europe, common rules shared by the Notified Bodies of individual countries “would make sense for medical devices.” More stringent premarket investigation for glaucoma devices, which he has been using for many years, would make him feel “less concerned about the possibility that potential problems might arise many years after implantation.”
However, he expressed concern about the increased amount of bureaucracy and barriers to innovation that a more centralized system might introduce. Increasing barriers will not necessarily result in improved safety, he said.
Aiming at more consistent, transparent rules
The European CE regulatory approach and device marking process is a decentralized system. Manufacturers submit their application for approval to one of the 75 Notified Bodies designated by the competent authorities of member states to carry out conformity assessment. The Declaration of Conformity obtained from one Notified Body in one country allows the product to be sold within the whole European community.
Image: Barton K
“Many of us thought that this was an unsatisfactory situation because it leaves a lot of room for different interpretations of the rules,” John Wilkinson, Director of Medical Devices at the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom, said. “Potentially it meant that Notified Bodies in different countries were operating with slightly different standards.”
The implementing act established the basis for new legislation that, once issued by the European Parliament, would compel Notified Bodies to go through a full re-designation process by a joint audit including the European Commission and the competent authorities of the member state and two other member states.
“The end result will be, we hope, a much more consistent performance both by member states and Notified Bodies. The idea is to bring this into one system operating consistently via a very clear set of rules,” Wilkinson said.
The current legislation on the assessment process for medical devices was introduced in the early 1990s, and it was time it was reviewed and brought up to date, he said. In addition, as stated in the implementing act, “the need for investigation by the Commission is exacerbated since technical progress has increased the risk that Notified Bodies do not possess the necessary competence with regard to new technologies or products falling under their scope of designation.”
The legislation would also fill in the gap that currently exists between the assessment process of medical devices and medicinal products, according to Bernard Chang, BSc, MBChB, FRCSEd, FRCOphth, Ophthalmic Adviser at MHRA.
“With medicines, there is a more established way of conducting premarket trials, and postmarket surveillance is much better,” he said. Devices would benefit from a similar system, he said.
Is innovation under threat?
The relatively rapid approval times for innovative technologies in Europe have offered significant benefits to patients and companies. Concern exists among ophthalmologists that more stringent regulations might cause delays in accessing new technologies, Barton said. Small device companies with limited resources may face approval delays and be unable to withstand the costs of long regulatory protocols.
“The effect on small- to medium-size companies is going to be dramatic,” Guy Van de Weyer, independent medical consultant at MCI, said. “Nowadays companies have difficulties in raising money to get started, and once they have started, they need more money for the following stages. Lengthy premarket approval (PMA) procedures discourage investors. Innovative ideas with even good results may be stopped because regulatory demands are too high.”
Most of the innovation currently stems from small enterprises, but more stringent regulatory requirements may discourage research and development, according to Juliette E. Cook, PhD, Director of Quality and Regulatory Affairs at Rayner Intraocular Lenses.
“Providing premarket clinical data through randomized controlled trials will be challenging, especially for innovative devices where there may not be another similar device for comparison. Small to medium companies may not pursue approval for innovative devices due to the costs and resources required,” she said.
Nobody could be against provisions that enhance patient safety, Van de Weyer said. However, patients could be damaged by unnecessary delays in the access to innovative treatment.
“A good approval study basis is important, but I have rarely seen that long study times improved anything. What was shown after 1 year was usually still the same after 3 years. PMA procedures are going to require an additional 3 or 4 years. An example is cross-linking, approved and well established in Europe and still not available in the U.S. Those who can, come to Europe to have it performed,” he said.
He is also concerned that the new regulatory approach will call for “an enormous amount of additional bureaucracy.”
“Bureaucracy is a self-feeding monster, and every time you give it a chance to get bigger, it does,” Van de Weyer said.
Wilkinson said there is no reason to be concerned that the new proposal will create hurdles, excess bureaucracy and barriers to innovation.
“Our proposals are designed to make the approval process more precise and more transparent, not unduly burdensome. They retain the fundamentals of the system that has been around for the last 20 years,” he said. “There have been voices in the Parliament that have proposed a move towards a more centralized premarket approval, similar to the FDA process, but that’s not the direction that we think would be wise or helpful.”
According to Chang, the new legislation will promote competition and good manufacturers will grow.
“Only bad companies will be stopped. Patients will benefit from it,” he said. “European competitiveness will be retained, but not at the expense of patient safety.”
Taoufiq Jellal, Senior Training Manager for Europe at Alcon Laboratories, thinks the new regulations “are a very positive move towards promoting quality and safety.”
“I strongly believe that all manufacturers should be in favor of any process that enhances patient safety,” he said.
He also said that approval should be based on clinical evidence rather than manufacturing standards and advocated an approach more like the U.S. Food and Drug Administration for medical devices in Europe.
“The timeline for obtaining FDA clearance may be longer and regulations stricter, products may be rejected or withdrawn from the market, but there is still a lot of innovation, a lot of new technology coming from U.S. companies,” Jellal said.
Small companies, however, may not be able to withstand the competition from larger companies, according to Cook.
“The potential delays, combined with the increased regulatory and financial burden associated with unique device identification, implant card, input of data into central databases and so on, are likely to prove disproportionately large for small to medium enterprises. It is probable that some smaller companies will find it difficult to compete in such an environment,” she said.
A long negotiation process
In order to become a law, the proposal will have to go through a long negotiation process between the EU Parliament and individual member states, Wilkinson said.
“This process is taking a long time and should be finalized this summer, before the end of this particular Parliament. It is by no means certain that there will be agreement. It would be improper of me to predict, but given the time available, the chance of completing this negotiation looks challenging,” he said.
Prolonged negotiations may have positive implications because they will give time for stakeholders to get involved and influence the legislation, according to Chang. In particular, clinicians and ophthalmological societies should be more involved.
“In the U.K., the Royal College helped to set national standards through having representatives working with the regulatory agency. Not in all countries are ophthalmologists so directly involved,” he said.
Companies play the key role, according to Barton. Scientific societies should have more of a voice, but they are made of “busy clinicians who have not much time to dedicate to politics,” he said.
“As regulators, we need to work with the clinical community on a consistent basis. Clinicians have the best informed understanding of the balance of risk and benefits that is inherent in any regulatory system, and that reflects the thoughts and decisions clinicians make on a daily basis,” Wilkinson said.
The key role of Europe
Europe has played a key role in the progress of ophthalmology, as it has been an ideal ground for the development and growth of innovation.
“It has the demographics, the clinical quality and the regulatory framework to set up the lighter study formats required by companies investing in innovation. U.S. companies come to Europe to build up data and get something tangible for potential investors,” Van de Weyer said.
Other areas of the world do not offer comparable advantages. Established countries such as Japan and China have challenging systems that are often difficult to approach by foreign enterprises, he said.
“It might take years before your file gets in motion,” he said.
Singapore has a good level of science, an accessible regulatory system and a high level for studies, but data are usually not accepted in the U.S. because of the small demographic representation. There are also countries with few regulatory limitations, “but no company respecting itself would use that as a basis for product development,” Van de Weyer said.
“There is no true alternative to Europe,” Barton said. “The FDA has lengthy procedures, and American physicians complain to be behind with devices. Asian countries have even bigger hurdles and problems. Europe is still the leader, but tighter rules will make it vulnerable.” – by Michela Cimberle
- References:
- Commission implementing regulation (EU) No 920/2013 of 24 September 2013. Official Journal of the European Union. eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2013:253:0008:0019:EN:PDF.
- Health MEPs call for stricter controls on medical devices. Press release. European Parliament website. www.europarl.europa.eu/news/en/news-room/content/20130923IPR20607/html/Health-MEPs-call-for-stricter-controls-on-medical-devices. Published Sept. 25, 2013.
- Medical devices: European Parliament’s ENVI committee vote. European Public Health Alliance website. www.epha.org/5826. Published Sept. 27, 2013.
- MHRA Director of Devices concerned with proposed regulations. Healio website. www.healio.com/ophthalmology/regulatory-legislative/news/online/%7Bf7554262-1c68-4bc1-ad3d-0c5ee2cda6a5%7D/mhra-director-of-devices-concerned-with-proposed-regulations. Published Oct. 4, 2013.
- Ophthalmology Futures European Forum puts Euro device advisory in perspective. Healio website. video.healio.com/video/Ophthalmology-Futures-European;Ophthalmology-Futures-European. Published Oct. 3, 2013.
- For more information:
- Keith Barton, MD, FRCP, FRCS, FRCOphth, can be reached at Moorfields Eye Hospital, 162 City Rd, London EC1V 2PD, United Kingdom; +44-20-7253-3411; email: keith@keithbarton.co.uk.
- Bernard Chang, BSc, MBChB, FRCSEd, FRCOphth, can be reached at Spire Leeds Hospital, Jackson Avenue, Roundhay, Leeds, LS8 1NT, United Kingdom; +44-845-456-2021; email: bypchang@doctors.org.uk.
- Juliette E. Cook, PhD, can be reached at +44-1273-205-401; email: juliettecook@rayner.com.
- Taoufiq Jellal can be reached at +41-79-927-68-25; email: taoufiq.jellal@alcon.com.
- Guy Van de Weyer can be reached at email: gvdw@mci.be.
- John Wilkinson can be reached at MHRA, 151 Buckingham Palace Road, Victoria, London, SW1W 9SZ, United Kingdom; +44-20-3080-7900; email: nicholas.spears@mhra.gsi.gov.uk.
Disclosures: Barton has no relevant financial disclosures. Chang is a consultant ophthalmologist and Ophthalmic Adviser at MHRA. Cook is Director of Quality and Regulatory Affairs at Rayner Intraocular Lenses. Jellal is Senior Training Manager for Europe at Alcon Laboratories. Van de Weyer is an independent medical consultant at MCI. Wilkinson is the Director of Medical Devices at the MHRA.
Is it desirable for Europe to have a centralized regulatory approval process based on scientific evidence, similar to the FDA process, or is speed of approval valued over risk?
Science, manufacturing standards should be considered
The essential tenet of approval by regulatory authorities of a medical device is that it should be safe and effective. At present, the rules for such approval are somewhat different in the United States and Europe. The authority in the United States is the U.S. Food and Drug Administration (FDA), and it is seen by many as a drag on the early ability of doctors to use new devices because of the cumbersome requirements to obtain approval.
In the FDA system, there are two basic types of approval before a product can enter the market. If there is substantial equivalence to a product already available, a 510(k) needs to be obtained. So, for example, a new knife for cataract surgery would be able to show equivalence. However, new devices for which there is no equivalence already in the market need to go through a much more extensive and rigorous process called premarket approval (PMA). This is described by the FDA as follows: “There are administrative elements of a PMA application, but good science and scientific writing is a key to the approval of a PMA application.” Herein lies the fundamental difference between the U.S. and European systems. The system of CE marking, which allows medical devices to be sold in the European Union, is predicated on the following: “Devices need to be designed and manufactured in such a way that, when used under the conditions and purposes intended, they will not compromise the clinical condition or the safety of patients.”
Although there is mention of a clinical evaluation, the science is not highlighted in the same way as the FDA. Europe should have a system in which both science and manufacturing standards are taken into consideration, providing it can act in a timely manner to bring innovation to us and our patients.
Richard B. Packard, MD, DO, FRCS, FRCOphth, is OSN Europe Edition Chairperson of the Editorial Board and a senior consultant surgeon at Prince Charles Eye Unit, Windsor, England. Disclosure: Packard is a consultant to Alcon, Core Surgical, Excellens and Shire Pharmaceutical.
European system offers fewer ‘speed bumps’
The European Medicines Agency (EMEA) is the closest thing in Europe to the FDA in the United States. It functions for medical devices, diagnostics and therapeutics. A pharmaceutical company can apply to the EMEA for approval, which, if obtained, covers all EU member states. Alternatively, it can apply to the relevant licensing authority in a single EU country and, if successful, applications to other EU countries become progressively easier. For example, Thea Pharmaceuticals (France) used this method to obtain approval for Aprokam (cefuroxime) for intracameral use after cataract surgery. Approval was granted initially in Sweden based on its lengthy experience with intracameral cefuroxime, the Swedish National Cataract Register and the published reports of the ESCRS Endophthalmitis Study. It has subsequently been approved in more than 10 EU member states.
For medical devices, the EMEA is considered to be a smoother and more rapid process than the FDA. A recent international conference in Dublin encouraged and actually secured the set-up of Dublin offices for several American medical device manufacturers to enable them to apply from here to the EMEA for approval rather than to the FDA. An example is a collaboration between Enterprise Ireland and the Mayo Clinic.
In summary, I think the advantage of the European system is not speed of approval over risk, but rather a process that offers fewer “speed bumps” than its American equivalent.
Peter Barry, MD, FRCS, is the head of the department of ophthalmology at St. Vincent’s University Hospital, Dublin, Ireland. Disclosure: Barry has no relevant financial disclosures.