In March 2010, the medical device regulatory landscape in Europe will change significantly as EU Directive 2007/47/EC, which amends aspects of the Medical Devices Directive (93/42/EEC) and other medical device directives, comes fully into force. While the directive introduces changes in a number of areas, some of the most significant changes relate to the need for clinical evaluation and the update of clinical information from post-market surveillance data.
"I suppose the biggest changes in the medical devices world from a regulatory perspective are the recent changes made by the amending directive to the medical device legislation which, I suppose, is trying to put an end to an age-old myth that medical technology or medical devices don't require clinical trials, clinical investigation or clinical evidence," says John Brennan, director of regulatory affairs at Eucomed, the European medical technology industry association.
"Directive 2007/47/EC, amending the Medical Devices Directive, is really clarifying the fact that you need clinical evidence for medical devices and, in particular, for implantable and higher risk category medical devices."
At the same time, notes Brennan, the technical annex of the directive details some particular requirements in terms of verification, whether it is via investigations, literature or a combination of both, as well as how any investigation should take place, the reporting of incidents, and so on. There is a lot more detail to support existing Commission guidance on what is required to conform to the regulatory framework.
While the directive is intended to clarify the regulatory framework for medical devices, many stakeholders, including manufacturers, have criticised the new directive for complicating matters. Others complain that it seems onerous to have to provide clinical evaluation data for devices that have been on the market for some time, and some say that the regulatory environment is now impeding technological progress to the detriment of the patient.
"I think any criticism is probably due to the fact that science and technology has moved on," Brennan adds. "Often, in the absence of something more appropriate, many member states default to the clinical trials directive, which was geared towards pharmaceutical industry and medicinal products – it was implemented in the UK as the Medicines for Human Use (Clinical Trials) Regulations 2004 – and choose to apply it to medical devices, but this does not really work.
"The problem on both sides, whether it's a drug or device, is that the thinking and the approach we have to clinical trials and clinical evidence needs to change and needs to be more appropriate to the technology, and to the science of the present, let alone the future."
It is clear that application of the directive and its amendments create problems in some areas.
"On the device side, for example, you get a situation with people wanting to have double-blind trials with hips – you can't implant a hip and pretend you have a hip being implanted," says Brennan. "I think we're all frustrated with the inappropriate application of the current rules. I wouldn't be an advocate for deregulation or less regulation, however, I would advocate smarter and better rules. I think we're all advocates for smart regulation."
It may be argued that it is appropriate to adopt the clinical trials approach as applied to pharmaceuticals just to deal with the ethical rather than the technical elements. However, says Brennan, people inevitably get into the technical detail, the technical details contain references to the pharma guidance, and the technical guidances refer to factors such as trial sizes and trial powers.
"When a drug is going to be applied to millions of people, an appropriate clinical trial would require tens and thousands of patients," he explains. "With a medical device technology like stenting, when you talk of tens and thousands of patients, that's the actual total population size to be treated in Europe. So the numbers don't add up."
Equally, says Brennan, when you implant or use a medical device you do not have a systemic effect. The concept of applying a medical device to a healthy volunteer, giving a hip replacement or stent to someone who does not require one, is not appropriate. There are several concepts present in the pharma legislation for clinical investigations which do not easily apply to medical devices. But Brennan does not favour less regulation. What is required, he says, is more effective regulation.
"It's wrong to send out the message that we're going to deregulate this," he explains. "It needs to be regulated in the best possible way, in the best interests of the patients, and in the best interests of the quality of the products that will be given to the physician. And that is in the best interests of the manufacturer because then they have a good, clear scientifically solid pathway for clinical trials and clinical investigation that makes sense."
Some suggest that the current regulatory situation stifles innovation, or at least prevents beneficial technology for patients reaching the market in a timely fashion.
"While it is in the patient's best interests to have a safe and effective product, it is also in their interest to have that the latest and best possible treatment in due time," says Brennan. "So it is important that you not only control and ensure patient safety, but that the system allows the latest possible techniques to be used in a relatively short time on patients, which is not the case with pharma."
Brennan believes that the way medical device product safety is approached may have to undergo a fundamental reappraisal if the benefits of new technology are to be reaped in such a rapidly changing medical field. "With a new or different technology you're often in the unknown, as are the authorities," says Brennan. "When you're dealing with the unknown the default response is to ask for more data, making the barriers higher, without any particular benefit to the patient or knock-on improvement in the product design.
"We need to have a better understanding of how, within these unknown areas, we can release products to the market in a very controlled way. We need to get away from this idea that products have to be 110% understood before they enter the market; that's not the scientific reality of medical technology or of life. So maybe we need a paradigm shift in terms of how we think about clinical evidence and what it's telling us, the product entering into use and the continued gathering of clinical evidence about the product throughout its lifetime."
The good news is that the European Commission intends to make the medical devices directives more robust and has already announced its intention to produce a proposal in 2010. One welcome change, says Brennan, would be some reduction of discrepancies among member states when applying guidance. There needs to be a more consistent application of the directive and regulations.
Other areas that are likely to be addressed are issues such as the clarification of certain terms, such as what constitutes severe adverse events. Severe adverse events need to be notified to member states, but the term is interpreted in different ways. So there are a number of areas where definitions need to be clarified so that they are applied uniformly.
"I think we need to be careful with the changes that the Commission is talking about in the current legislation, particularly in the area of clinical evaluation," says Brennan "But, if we can get that right, then we can deal with the future properly and in the best interests of the patients, the member states and the manufacturers."