It's back to business as usual in Europe for medical device regulations with nothing but confusion on the horizon as far as any expert can see.
Last summer, the European Commission sparked a very un-Brussels controversy with a sudden and startling proposal to consolidate its complex set of medical device regulations and create a super agency to oversee both medical devices and pharmaceuticals.
Three prominent players in the debate updated their positions in presentations during the MedTec 2009 gathering in Stuttgart, Germany, last month, agreeing that the soonest any recast of European Medical Device Directives could be put in place would be 2015, if then.
John Brennan, director for regulatory affairs at Europe's leading med-tech trade association, Eucomed (Brussels, Belgium), exuded a zen-like calm as he reminded the audience the term for the current European Commission expires this year and a new commission with new faces and a new agenda will come to power in 2010.
"We have entered a period of reflection and discussion with the current Commission," he said in eloquent Brussel-ese.
Peter Bischoff-Everding from the European Commission's Medical Devices and Cosmetics Division of the Directorate-General for Enterprises and Industry said that a lot of attention has been given to the proposed recast of Medical Device Directives and people may have forgotten there is a major revision to existing directives on the table.
"The clock is ticking," he said, referring to the March 2010 deadline when Directive 2007/47/EC will become a mandatory requirement for the 27 member states.
A sweeping revision of regulations adopted in 1990 that are ill-suited to today's technology and applications of medical devices, the transposition of the European directive into national law has been roundly ignored by most member states.
Despite the formidable sound of a European directive, the European Union (EU) has no mandate in its treaty to regulate health affairs and directives are only guidance for national legislation.
The result is a rich opportunity for consultants to guide medical device manufacturers through a bewildering landscape marked by towering European directives with fragmented and shifting national rules.
Meanwhile, Mika Reinikainen, managing director of the consulting firm Abnovo (Weybridge, UK), who organized and chaired the session at MedTec, offered a fresh perspective, saying that by 2020 legislative systems will be overwhelmed trying to regulate emerging technologies in any event and that cost, not laws, will more likely be the controlling factor for utilization.
A proposed revision of EU Medical Device Directives dating back to the 1990s is long overdue. As guidance to national laws they could be simplified as there are currently three directives covering active implantable devices, medical devices and in vitro diagnostic devices, as well as the six subsets of directives that either modified or implemented the three principal directives.
Brennan agreed the scope is too narrow as many newer technologies are not covered, including especially the recent combination of drugs and devices.
Market surveillance is not coordinated and vigilance in Europe amounts to 27 different reactions to any problems.
The EC's Bischoff-Everding said surveillance and vigilance is essentially an email alert system in Europe with sometimes disastrous results for manufacturers who have seen Europe-wide markets destroyed by claims of a single regional distributor.
Brennan also said Eucomed agrees the system of notified bodies, which grant CE-mark approval, should be revisited to improve performance.
"We have 80 notified bodies among 27 member states, with so many designated as competent for reviewing all medical devices, which is something I have trouble believing," he said.
But Brennan said the EU proposal to recast directives put at risk the New Approach principles underlying the three current Directives that has become a passport to Europe's internal market, fast-tracking the introduction of novel technologies with a CE mark for safety compared to the "more burdensome systems in Japan or the United States."
"The current system fosters a high level of innovation and competitiveness," he said. "Europe's citizens are consistently two years ahead of the patients in the United States for access to new treatments and 10 years ahead of Japan."
"What could be lost with the proposed recast are the benefits this has brought to Europe," Brennan said. "There is a proven high level of safety in Europe's methods. There are not bodies in the streets, so we are not talking about legislation to react to widespread adverse events.
"If we take this away, the whole system of benefits to patients and industry collapses," he said, adding the current system encouraging novel devices creates jobs in Europe.
Brennan added that the involvement of a super agency in regulating medical devices would increase the current level of approval costs for a device from an estimated average of E20,000 ($25,000) to between E160,000 ($188,000) and E330,000 ($414,000).
Eucomed proposes going forward with a merger of the Active Implantable Medical Device Directive with the Medical Device Directive, and then to use the time afforded with the change of the Commission in 2009 to create a high-level think tank to solve the remaining challenges.
Brennan also urged the Commission to take time to analyze the impact of Directive 2007/47/EC as it moves toward implementation in March of next year.
Meanwhile Bischoff-Everding said the EC is currently contemplating "infringement procedures" for member states that have failed to transpose the guidance of Directive 2007/47/EC and that he hopes that the coming months will se more states adopting the guidance into national law "to assure a level playing field in Europe."
He said that the Commission is planning a follow-up on a December workshop on reprocessing of medical devices, with an eye to issuing a report, though he could not say "if it would be the case that it is issued September 5, 2010, as targeted in the directive."
The most light-hearted moment for the audience in a morning filled with regulatory affairs and untranslated official-speak was a discussion of the Eudamed database that seeks to register medical devices with a goal of strengthening market surveillance and transparency.
Introduced by a 1998 directive but not given a deadline until the proposed 2007/47/EC Directive, Eudamed "for some is essential, while for some it is the epitome of the failure of the internal market effort," Bischoff-Everding said.
The database is operational, "but only some nations use it," he admitted, adding that "other nations have invested significantly in establishing their own databases for surveillance and it would not be easy to convince them to abandon their systems for Eudamed that they consider too simple."
In his look to the future, Reinikainen elicited the only laughter from the audience when he observed, "Who knows? Eudamed may happen!"
CorMatrix expands in Europe
CorMatrix Cardiovascular (Marietta, Georgia), which is focused on developing extracellular matrix (ECM technology) biomaterial devices that harness the body's ability to repair damaged cardiovascular tissue, said it has begun its expansion in Europe following the first use of the CorMatrix ECM technology in a patient undergoing cardiac surgery.
Following implantation by a surgeon, the CorMatrix ECM technology acts as a scaffold into which the patient's own cells migrate and integrate, stimulating the body's innate wound-healing mechanisms to repair tissue at the site of implantation.
As the patient's cells populate the matrix, they lay down their own collagen, which matures over time to form a functional tissue repair. The implanted ECM material is gradually replaced and reabsorbed by the body as the patient's tissue is remodeled.
The first procedure in Europe was completed by Stephan Jacobs, MD, and Volkmar Falk, MD, both of University Hospital Zurich in Switzerland, who used the CorMatrix ECM technology to close the pericardium of a 70-year-old patient following triple coronary artery bypass graft surgery.
"Our European launch further validates the increasing interest and acceptance that our ECM Technology continues to receive among the clinical community," said CorMatrix President/COO Beecher Lewis. "Because our ECM Technology supports native tissue repair, it represents a significant advancement over currently available materials."
The company's chief scientific officer, Robert Matheny, MD, said, "Closure of the pericardium is beneficial as it restores the natural barrier between the heart and the chest wall; it protects the heart, underlying grafts that were applied to the heart, and makes it easier and safer to re-access the heart if a subsequent procedure is required."
Since the launch of the CorMatrix ECM for pericardial closure, the technology has been used at more than 220 hospitals across the U.S. and has been implanted during more than 10,000 cardiac procedures.
CorMatrix Cardiovascular holds an exclusive license from Purdue University (West Lafayette, Indiana) to research, develop, manufacture and market naturally occurring ECM products for cardiovascular applications.
The company currently has U.S. clearance and European CE-mark approval for ECM as an implant for pericardial closure, and clearance in the U.S. for use in cardiac tissue repair.
New textiles for wound care in Germany
In partnership with Germany's Society for the Promotion of Medical, Biological and Environmental Technologies, the Hohenstein Institute (Boennigheim, Germany/Elon, North Carolina) has developed textile technologies that it says will improve the future of wound treatment.
According to the institute, which is a leading global textile research and testing laboratory, the new textile technology will be used in wound compresses to deliver active ingredients that encourage healing.
The technology, called Nanosol, can be adapted for different types of medicines to ensure appropriate release rates and shelf life. The Nanosol technology currently has been applied to deliver antibiotics to prevent infection, proteins to promote healing, and vitamins to encourage skin regeneration. Additional therapeutic applications are in development.
Hohenstein scientist Dr. Dirk Hoefer and his research team have developed a method to coat individual cellulose fibers with inert silicon (SiO2) and then to bind active ingredients to the silicon coating. When incorporated into a wound compress and applied, the moisture from the wound activates release of the medicine continually and directly into the wound site.
Testing conducted at the institute confirmed the delivery effectiveness of the new technology.
NeoMatrix gets OK for HALO
NeoMatrix (Irvine, California) said it has received CE-mark approval for European commercial sales of its HALO Pap Test for the Breast. The company also has received regulatory approval in Brazil to commercialize HALO, and the first order was shipped to that country recently.
The HALO test is a 5-minute, noninvasive test performed with a device that delivers a combination of warmth, massage, and vacuum in order to collect nipple aspirate fluid – which can then be examined to identify women who are at high risk of developing breast cancer.
The company said the HALO Breast Pap Test is the first fully automated, noninvasive breast disease-screening device designed for use in the primary care setting.
"We are pleased to receive the CE mark and are excited about our business prospects in Europe where, as in the U.S., breast cancer remains a major health problem. In fact, breast cancer is the primary cause of cancer deaths in women worldwide," said COO Matt Heindel.
He said the company is "evaluating" several distribution opportunities and expects to initiate European sales later this year.
Regarding the beginning of sales in Brazil, Heindel said, "There has been excellent local organization preparing for the launch of HALO in Brazil, [which] has a great reputation for healthcare. There has been significant interest in screening and prevention of breast cancer, both of which rely on identifying the high-risk population."
He added that several other countries are in various stages of the registration process and "we look forward to bringing HALO to women all over the world in the near future."
Many breast cancer experts believe that identifying high-risk women is the key to reducing the incidence and death rate from the disease. "Currently, most women diagnosed with breast cancer have no known risk factors," NeoMatrix said. "The previous inability to identify those most likely to develop the disease has made it difficult to apply proven preventative treatments, and may result in late detection of the disease, reducing a woman's chance of a cure and making treatment options more invasive."
The company said that over the past 18 months since HALO was launched in the U.S., about 35,000 tests have been performed. "In addition to the many women identified as high risk who were previously unaware of this fact, HALO testing has also led to discovery of early-stage breast cancer in patients who had been routinely screened by other methods," NeoMatrix said.
HALO is not a replacement for routine screening with breast exams and mammograms, which are designed to identify lesions and typically find tumors after they have been growing for eight to 10 years, according to the company. "Rather, HALO is an adjunct to these methods with a different objective: to find women at high risk in order to facilitate prevention and/or early detection when the disease is still 100% curable."
Swiss trial planned for Oxycyte
Oxygen Biotherapeutics (Costa Mesa, California) said it has hired PFC Pharma Focus AG (Volketswil, Switzerland), a contract research organization, to supervise the planned Phase II, dose escalation, clinical trial in that country for use of Oxycyte in traumatic brain injury (TBI).
Oxycyte is the company's perfluorocarbon therapeutic oxygen carrier.
The company has initiated the filing process for its protocol in Switzerland with the relevant cantonal ethic committees and Swissmedic, the Swiss counterpart to the U.S. FDA. The protocol is the same as the one the company plans to submit to the FDA.
Principal investigator will be Michael Reinert, MD, of University Hospital Berne. The company said trial sites and further trial details will be reported after they are finalized.
"We have interest from what I consider to be some of the best neurosurgeons in Switzerland who want to be clinical investigators in these trials and from leading Swiss hospitals interested in being study sites," said Chairman/CEO Chris Stern. "Depending on the timing of the review process in Switzerland, we could begin enrolling patients in the second quarter."