Ranica Arrowsmith, Associate Editor04.08.14
“What we are talking about today, when we talk about medical devices?” asked German Member of Parliament Dagmar Roth-Behrendt during a recent parliamentary debate on medical devices (her comments have been translated from German). “We are talking about products designed to ensure the safety of patients to help them with diseases and ailments, and doctors should help so that they can be sure that they have only the best products for their patients. We talk about the competitiveness of European industry. We are performing a balancing act with this legislation. How is it so far? If hundreds of hip joints were faulty and must be surgically removed at great cost to the health system and great suffering for the patients, then something must not be in order. And that’s why we need a new system for medical devices. The old [system]has become so antiquated… We need a better system.”
Roth-Behrendt has been at the forefront of efforts to change the European Union’s (EU) Medical Device Directive (MDD), a 1993 council directive created in order to harmonize medical device regulation across the EU states. The most recent changes to the MDD were made in 2007, but now, the European Commission (EC) has proposed major changes that has the medtech industry waiting in limbo until a decision is made. According to the EC, the executive body of the EU responsible for lawmaking and administration, “Existing EU rules—dating back to the 1990s—have not kept pace with the enormous technological and scientific progress in the past 20 years.” The commission noted in a document titled “Citizen’s Summary” that EU countries are not as harmonized as they should be, and they interpret the current rules in different ways; it is not easy to trace medical devices back to their supplier, so new traceability rules are needed; and patients, healthcare professionals and other stakeholders do not have adequate access to essential information on how medical devices have been assessed, and what clinical evidence there is to show they are safe and effective.
“The need for greater transparency has been highlighted by recent scandals about faulty silicone breast implants and problems with some metal-on-metal hip replacements,” the document stated.
Hips and breast implants. For proponents of change, these have been the go-to examples for why the EU medical device regulatory system needs a total refurbishment. Readers of Medical Product Outsourcing are well versed by now in the problem with all-metal hips. Over the past several years, devices including Smith & Nephew’s R3 metal liners of the R3 acetabular system, DePuy’s ASR XL acetabular system, and Zimmer’s Durom acetabular component have been recalled over concerns that they could be depositing metallic particles in tissue surrounding the implant area and into patients’ bloodstreams, causing toxicity and adverse events. While recalls—and many lawsuits—have sufficed in terms of response in the United States, the EU is starting to re-evaluate its medical device regulatory system altogether.
Hips aren’t the only culprit. A high-profile scandal involving French company Poly Implant Prothèse’s (PIP) breast implants erupted in 2011 about concerns that the implants were causing cancer in women. Although the actual cause-effect relationship of the implants to breast tumors has never been confirmed by either the French or EU regulatory authorities, PIP ultimately was forced to close in 2011. Last year, PIP founder Jean-Claude Mas was sentenced to four years in prison for fraud, and ordered to pay a fine of $103,000. According to CNN, Mas admitted “authorizing the use of two gel formulas at PIP: a high-end version for wealthier clients, using American-made medical silicone, and a ‘house’ formula for everyone else.” This home-brew implant material allegedly was made from non medical-grade, industrial silicone, and was used in order to boost profits.
“If it’s going in your body, if it’s a pill, if it’s a medical device, it should be regulated by the government,” Bioethicist Arthur Caplan told CNN. “The consumer can’t tell what’s safe, what isn’t safe, what’s made according to good manufacturing processes. I think you have to have government watching over anything that people put into their bodies for a medical or a health purpose—I don’t buy the idea that it’s just buyer beware.”
Industry advocacy organizations in Europe have been resistant to change, however. Organizations including MedTech Europe, the European Diagnostics Manufacturers Association and Eucomed have voiced their concerns regarding suggested changes, claiming that stricter regulation will cause Europe to lose its purported advantage over the United States in terms of getting devices to market more quickly.
The Waiting Game
The European Commission released its proposal for the revision of the MDD and In Vitro Diagnostics Directives (IVDD) in September 2012. The European Parliament weighed in on the file, voting on its final report in a plenary session last October. In December, representatives from the 28 EU health ministries voiced their views on key issues. Although there is no official word to confirm this, MedTech Europe’s CEO Serge Bernasconi said “the word on the street” is that the EU Council is set to reach its final position by June with trialogue discussions (where the commission, parliament and council negotiate a final text) pencilled in for the fourth quarter of 2014.
“The regulatory climate in the EU remains in flux,” said Rebecca Pine, senior regulatory consultant & training instructor of Noblitt & Rueland, a medical device consulting firm specializing in technical U.S. Food and Drug Administration (FDA) and international regulatory issues based in Irvine, Calif. “Although there was a parliamentary vote, the EU Council is still discussing and defining the details, which is anticipated to have a direct impact on market access for new device technology. Centralization of an approval system for higher risk devices is very worrisome, as the centralized approval of devices in the United States is largely complex, time consuming and very costly, compared to the more agile system currently utilized in the EU today.”
Although discussions to change the MDD have been underway for about three years now, the EU’s parliament is up for reelection on May 22. The upcoming election has halted any progress on the proposals for change put forth thus far by the EC or the Parliament Committee for the Environment and Public Health.
“Everybody is in a state of limbo to see what is going to come out of the changes,” said Alan Schwartz, executive vice president of MDI Consultants Inc., a medical device consultant company based in Great Neck, N.Y. “They do realize that the MDD and the technical files are going to be harder to comply with. As earning CE marks for any new clients, it hasn’t had any effect. It’s just a state of limbo for companies that have their technical files already approved, seeing what changes are going to be made to those technical file requirements. The files are going to be more difficult to be put together. Our clients’ main concern is making sure they have all the information—do they have to run a clinical trial now? If they’ve been selling the product for a certain amount of time, they’re concerned about what they’ll have to do to comply with making sure they can maintain the technical file to maintain the CE mark.”
Major Changes
One of the major changes proposed by the EC is unscheduled audits.
“In the EU, the way things are regulated is through independent notified bodies who are supposedly managed and controlled through the competent authorities—the local medical regulatory bodies,” Bernard Sweeney, senior vice president of medical devices for Reston, Va.-based contract research organization Aptiv Solutions Inc., explained to Medical Product Outsourcing.
“However, it was believed that the management of those bodies was not strong enough, and those bodies did not have enough skilled resources to be able to keep up with the development of medical devices, particularly at the evolving end of it. Because of the PIP situation, EU regulators are becoming aware that unlike with the FDA, there is no ability to check up on what medical device companies were doing without notice. This is what happened with the PIP issue. The company was able to substitute a non-regulated material because they know that if they were going to be audited, they would have a few months notice. This of course is different with the FDA, as it can pop in at any time.”
Sweeney, a United Kingdom national, is based in Switzerland.
The Commission Recommendation on the Audits and Assessment Performed by Notified Bodies in the Field of Medical Devices was released on Sept. 24, 2013. It states, “The proper functioning of notified bodies is crucial for ensuring a high level of health and safety protection, the free movement of medical devices in the internal market, and citizens’ confidence in the regulatory system.”
According to the document, interpretations of 1990, 1993 and 1998 EU directives regarding the audits, assessment and unannounced audits performed by notified bodies vary too greatly. Therefore, “The recommendation aims at ensuring that the notified body carries out a proper verification of the fulfillment of the legal requirements by the manufacturer. Subject to the respective conformity assessment procedure, notified bodies perform product assessments or quality system assessments.
Accordingly, it is important to differentiate between these two types of assessments. To verify the continuous compliance with legal obligations, notified bodies should perform unannounced audits in addition to product assessments and quality system assessments.”
Another concern for medical device companies operating in the EU is the changes to come for high-risk devices.
“Our clients concerns are with how high-risk products will be regulated in the future,” said Sweeney. “The major concern is whether or not the EU community will adopt a premarket approval (PMA)-style approach and whether or not the EU community will actually place the responsibility of those products under the European Medicines Agency. The latest version of the medical device regulations actually moved away from that and recommended a small number of the notified bodies be approved as specialist notified bodies, and high-risk products will have to go through those specific notified bodies in order to get approval. So the commission did step away from the suggestion of a PMA-style approach, but there is real concern from my clients about whether that will reappear back on the list again when the new European parliament sits again in the fall.”
FDA vs. EU
In the past, FDA has been highly critical of the EU’s approach to medical device regulation. In 2012, the agency released a scathing report titled “Unsafe and Ineffective Devices Approved in the EU that were Not Approved in the U.S.”
“The recent revelation that over 80,000 women in the European Union received dangerous breast implants containing industrial-grade silicone has drawn attention to weaknesses in the EU’s regulation of medical devices,” reads the report’s opening paragraph. “This report examines 12 additional high-risk devices that were approved in the EU and later found to be dangerous or ineffective. Most of these devices were ultimately withdrawn from the EU market, but only after thousands of patients were harmed. In many cases, the device’s risks or ineffectiveness were discovered only as a result of studies conducted for approval in the United States. None of the dangerous and ineffective devices described in this report were approved here, and U.S. patients were spared significant harm.”
EU authorities didn’t like that. Jeffrey Shuren, M.D., current director of the FDA’s Center for Devices and Radiological Health, didn’t help matters when, in the same year, he made a comment to reporters about the EU using patients as “guinea pigs.” Reuters reported that Paola Testori Coggi, head of the EC’s health and consumers department, objected to Shuren’s remarks in a letter to FDA Commissioner Margaret Hamburg. Both the U.S. and European regulatory systems, “though on different paths, seek to secure a high level of patient safety,” Coggi said. If the FDA has evidence of unsafe devices on sale in Europe, “I would appreciate if you could share this information with European regulators,” she added.
The foundational difference between FDA and EU regulations lies in the perception of risk and how risk should be managed. Now that the EU Medical Device Directive is in flux, industry players speculate whether the proposed changes are in fact an attempt to emulate the FDA system of regulation more closely.
“There’s a constant discussion about this,” said Sweeney. “There’s been a lot of talk and research on this. From what I understand as a whole, it’s shown that both the FDA and EU seem to produce similar results in terms of products that cause a problem or not. Certainly the issues such as the problem with hips are equal in EU as they are in America. This discussion goes back to 1992 when the Global Harmonization Task Force was formed. So there have been attempts to harmonize U.S./EU regulation, but there are some fundamental differences behind the regulations, which make it a little difficult, particularly in terms of how those regulations are managed by the lawmakers.”
The main difference, Sweeney said, is that the FDA prioritizes efficacy while the EU prioritizes safety when evaluating devices. However, once the relevant approval is earned, fewer differences exist between the processes needed to maintain compliance between the United States and the EU, said Noblitt & Rueland’s Pine.
“There is little to no difference in the maintenance process—e.g., keeping up with changes in the respective regulatory environments,” Pine told MPO. “Different but similar avenues are available to keep abreast of forthcoming changes and those which are implemented more immediately. The analytical process for review and identification of gaps is the same, as is the planning and implementation process. Some differences exist, such as maintenance of state-of-the-art procedures—e.g., clinical evaluations, harmonized standard compliance, etc.—for EU technical files. However, with typical product life cycles and anticipated device modifications requiring FDA review, these efforts can be synchronous.”
Sweeney predicts that no real movement will occur on the MDD until 2015, as the upcoming election will mean a new leadership that will have to review all the changes proposed up to now.
“Because a new parliament comes into play this year, no one is really sure what happens next,” Sweeney said. “The new parliament does not have to follow the previous set of rules and regulations. The new head of medical devices may have a different view and opinion. So we’re stuck between a situation of knowing what’s likely to happen and one of not knowing, which is very unusual.”
Roth-Behrendt has been at the forefront of efforts to change the European Union’s (EU) Medical Device Directive (MDD), a 1993 council directive created in order to harmonize medical device regulation across the EU states. The most recent changes to the MDD were made in 2007, but now, the European Commission (EC) has proposed major changes that has the medtech industry waiting in limbo until a decision is made. According to the EC, the executive body of the EU responsible for lawmaking and administration, “Existing EU rules—dating back to the 1990s—have not kept pace with the enormous technological and scientific progress in the past 20 years.” The commission noted in a document titled “Citizen’s Summary” that EU countries are not as harmonized as they should be, and they interpret the current rules in different ways; it is not easy to trace medical devices back to their supplier, so new traceability rules are needed; and patients, healthcare professionals and other stakeholders do not have adequate access to essential information on how medical devices have been assessed, and what clinical evidence there is to show they are safe and effective.
“The need for greater transparency has been highlighted by recent scandals about faulty silicone breast implants and problems with some metal-on-metal hip replacements,” the document stated.
Hips and breast implants. For proponents of change, these have been the go-to examples for why the EU medical device regulatory system needs a total refurbishment. Readers of Medical Product Outsourcing are well versed by now in the problem with all-metal hips. Over the past several years, devices including Smith & Nephew’s R3 metal liners of the R3 acetabular system, DePuy’s ASR XL acetabular system, and Zimmer’s Durom acetabular component have been recalled over concerns that they could be depositing metallic particles in tissue surrounding the implant area and into patients’ bloodstreams, causing toxicity and adverse events. While recalls—and many lawsuits—have sufficed in terms of response in the United States, the EU is starting to re-evaluate its medical device regulatory system altogether.
Hips aren’t the only culprit. A high-profile scandal involving French company Poly Implant Prothèse’s (PIP) breast implants erupted in 2011 about concerns that the implants were causing cancer in women. Although the actual cause-effect relationship of the implants to breast tumors has never been confirmed by either the French or EU regulatory authorities, PIP ultimately was forced to close in 2011. Last year, PIP founder Jean-Claude Mas was sentenced to four years in prison for fraud, and ordered to pay a fine of $103,000. According to CNN, Mas admitted “authorizing the use of two gel formulas at PIP: a high-end version for wealthier clients, using American-made medical silicone, and a ‘house’ formula for everyone else.” This home-brew implant material allegedly was made from non medical-grade, industrial silicone, and was used in order to boost profits.
“If it’s going in your body, if it’s a pill, if it’s a medical device, it should be regulated by the government,” Bioethicist Arthur Caplan told CNN. “The consumer can’t tell what’s safe, what isn’t safe, what’s made according to good manufacturing processes. I think you have to have government watching over anything that people put into their bodies for a medical or a health purpose—I don’t buy the idea that it’s just buyer beware.”
Industry advocacy organizations in Europe have been resistant to change, however. Organizations including MedTech Europe, the European Diagnostics Manufacturers Association and Eucomed have voiced their concerns regarding suggested changes, claiming that stricter regulation will cause Europe to lose its purported advantage over the United States in terms of getting devices to market more quickly.
The Waiting Game
The European Commission released its proposal for the revision of the MDD and In Vitro Diagnostics Directives (IVDD) in September 2012. The European Parliament weighed in on the file, voting on its final report in a plenary session last October. In December, representatives from the 28 EU health ministries voiced their views on key issues. Although there is no official word to confirm this, MedTech Europe’s CEO Serge Bernasconi said “the word on the street” is that the EU Council is set to reach its final position by June with trialogue discussions (where the commission, parliament and council negotiate a final text) pencilled in for the fourth quarter of 2014.
“The regulatory climate in the EU remains in flux,” said Rebecca Pine, senior regulatory consultant & training instructor of Noblitt & Rueland, a medical device consulting firm specializing in technical U.S. Food and Drug Administration (FDA) and international regulatory issues based in Irvine, Calif. “Although there was a parliamentary vote, the EU Council is still discussing and defining the details, which is anticipated to have a direct impact on market access for new device technology. Centralization of an approval system for higher risk devices is very worrisome, as the centralized approval of devices in the United States is largely complex, time consuming and very costly, compared to the more agile system currently utilized in the EU today.”
Although discussions to change the MDD have been underway for about three years now, the EU’s parliament is up for reelection on May 22. The upcoming election has halted any progress on the proposals for change put forth thus far by the EC or the Parliament Committee for the Environment and Public Health.
“Everybody is in a state of limbo to see what is going to come out of the changes,” said Alan Schwartz, executive vice president of MDI Consultants Inc., a medical device consultant company based in Great Neck, N.Y. “They do realize that the MDD and the technical files are going to be harder to comply with. As earning CE marks for any new clients, it hasn’t had any effect. It’s just a state of limbo for companies that have their technical files already approved, seeing what changes are going to be made to those technical file requirements. The files are going to be more difficult to be put together. Our clients’ main concern is making sure they have all the information—do they have to run a clinical trial now? If they’ve been selling the product for a certain amount of time, they’re concerned about what they’ll have to do to comply with making sure they can maintain the technical file to maintain the CE mark.”
Major Changes
One of the major changes proposed by the EC is unscheduled audits.
“In the EU, the way things are regulated is through independent notified bodies who are supposedly managed and controlled through the competent authorities—the local medical regulatory bodies,” Bernard Sweeney, senior vice president of medical devices for Reston, Va.-based contract research organization Aptiv Solutions Inc., explained to Medical Product Outsourcing.
“However, it was believed that the management of those bodies was not strong enough, and those bodies did not have enough skilled resources to be able to keep up with the development of medical devices, particularly at the evolving end of it. Because of the PIP situation, EU regulators are becoming aware that unlike with the FDA, there is no ability to check up on what medical device companies were doing without notice. This is what happened with the PIP issue. The company was able to substitute a non-regulated material because they know that if they were going to be audited, they would have a few months notice. This of course is different with the FDA, as it can pop in at any time.”
Sweeney, a United Kingdom national, is based in Switzerland.
The Commission Recommendation on the Audits and Assessment Performed by Notified Bodies in the Field of Medical Devices was released on Sept. 24, 2013. It states, “The proper functioning of notified bodies is crucial for ensuring a high level of health and safety protection, the free movement of medical devices in the internal market, and citizens’ confidence in the regulatory system.”
According to the document, interpretations of 1990, 1993 and 1998 EU directives regarding the audits, assessment and unannounced audits performed by notified bodies vary too greatly. Therefore, “The recommendation aims at ensuring that the notified body carries out a proper verification of the fulfillment of the legal requirements by the manufacturer. Subject to the respective conformity assessment procedure, notified bodies perform product assessments or quality system assessments.
Accordingly, it is important to differentiate between these two types of assessments. To verify the continuous compliance with legal obligations, notified bodies should perform unannounced audits in addition to product assessments and quality system assessments.”
Another concern for medical device companies operating in the EU is the changes to come for high-risk devices.
“Our clients concerns are with how high-risk products will be regulated in the future,” said Sweeney. “The major concern is whether or not the EU community will adopt a premarket approval (PMA)-style approach and whether or not the EU community will actually place the responsibility of those products under the European Medicines Agency. The latest version of the medical device regulations actually moved away from that and recommended a small number of the notified bodies be approved as specialist notified bodies, and high-risk products will have to go through those specific notified bodies in order to get approval. So the commission did step away from the suggestion of a PMA-style approach, but there is real concern from my clients about whether that will reappear back on the list again when the new European parliament sits again in the fall.”
FDA vs. EU
In the past, FDA has been highly critical of the EU’s approach to medical device regulation. In 2012, the agency released a scathing report titled “Unsafe and Ineffective Devices Approved in the EU that were Not Approved in the U.S.”
“The recent revelation that over 80,000 women in the European Union received dangerous breast implants containing industrial-grade silicone has drawn attention to weaknesses in the EU’s regulation of medical devices,” reads the report’s opening paragraph. “This report examines 12 additional high-risk devices that were approved in the EU and later found to be dangerous or ineffective. Most of these devices were ultimately withdrawn from the EU market, but only after thousands of patients were harmed. In many cases, the device’s risks or ineffectiveness were discovered only as a result of studies conducted for approval in the United States. None of the dangerous and ineffective devices described in this report were approved here, and U.S. patients were spared significant harm.”
EU authorities didn’t like that. Jeffrey Shuren, M.D., current director of the FDA’s Center for Devices and Radiological Health, didn’t help matters when, in the same year, he made a comment to reporters about the EU using patients as “guinea pigs.” Reuters reported that Paola Testori Coggi, head of the EC’s health and consumers department, objected to Shuren’s remarks in a letter to FDA Commissioner Margaret Hamburg. Both the U.S. and European regulatory systems, “though on different paths, seek to secure a high level of patient safety,” Coggi said. If the FDA has evidence of unsafe devices on sale in Europe, “I would appreciate if you could share this information with European regulators,” she added.
The foundational difference between FDA and EU regulations lies in the perception of risk and how risk should be managed. Now that the EU Medical Device Directive is in flux, industry players speculate whether the proposed changes are in fact an attempt to emulate the FDA system of regulation more closely.
“There’s a constant discussion about this,” said Sweeney. “There’s been a lot of talk and research on this. From what I understand as a whole, it’s shown that both the FDA and EU seem to produce similar results in terms of products that cause a problem or not. Certainly the issues such as the problem with hips are equal in EU as they are in America. This discussion goes back to 1992 when the Global Harmonization Task Force was formed. So there have been attempts to harmonize U.S./EU regulation, but there are some fundamental differences behind the regulations, which make it a little difficult, particularly in terms of how those regulations are managed by the lawmakers.”
The main difference, Sweeney said, is that the FDA prioritizes efficacy while the EU prioritizes safety when evaluating devices. However, once the relevant approval is earned, fewer differences exist between the processes needed to maintain compliance between the United States and the EU, said Noblitt & Rueland’s Pine.
“There is little to no difference in the maintenance process—e.g., keeping up with changes in the respective regulatory environments,” Pine told MPO. “Different but similar avenues are available to keep abreast of forthcoming changes and those which are implemented more immediately. The analytical process for review and identification of gaps is the same, as is the planning and implementation process. Some differences exist, such as maintenance of state-of-the-art procedures—e.g., clinical evaluations, harmonized standard compliance, etc.—for EU technical files. However, with typical product life cycles and anticipated device modifications requiring FDA review, these efforts can be synchronous.”
Sweeney predicts that no real movement will occur on the MDD until 2015, as the upcoming election will mean a new leadership that will have to review all the changes proposed up to now.
“Because a new parliament comes into play this year, no one is really sure what happens next,” Sweeney said. “The new parliament does not have to follow the previous set of rules and regulations. The new head of medical devices may have a different view and opinion. So we’re stuck between a situation of knowing what’s likely to happen and one of not knowing, which is very unusual.”
European Commission: The executive body responsible for proposing legislation, implementing decisions, upholding treaties and the day-to-day running of the European Union. EU Council: The council is comprises the heads of EU member states, along with the council president and president of the European Commission. The EU Council has no legislative power. However, under the Treaty of Lisbon, it acts as the EU’s strategic and crisis solving body, behaving as the collective presidency of the European Union. EU Parliament: The directly elected parliamentary institution of the European Union. European Medicines Agency: A decentralized agency of the European Union, located in London, United Kingdom. The agency is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union. It began operating in 1995. Global Harmonization Task Force: Formed in 1992, the GHTF was a voluntary group of representatives from national medical device regulatory authorities whose goal was to standardize global medical device regulation. The founding members were the European Union, the United States, Japan, Australia and Canada. Disbanded in 2012, its mission has been taken over by the International Medical Device Regulators Forum. Notified Body: An organization in the EU that has been accredited by a member state to assess whether a product meets certain preordained standards. Technical File: All CE marking directives require the manufacturer of the product to create a technical file, which should contain the information required to show that the product properly complies with the requirements of the directives that apply to it. |