Some medical devices are set to face more stringent clinical trials as European directive 2007/47/EC works its way into the laws of the member states. This document brings around 150 changes to the Medical Devices Directive and aims to harmonise the differences in the directive between the three classes of medical devices.
From 2010, when the directive should have passed into the laws of most member states, the rules for medical devices and active implantable medical devices should be in line with each other. An important part of this will be clinical evaluation.
The most recent EN/ISO14155 standard comes in two parts – one covers general considerations and the other how to conduct a clinical trial. Under the new directive, these will be brought together.
One of the problems the changes are looking to address is how to deal with products that fall under both the pharmaceutical rules for clinical trials and those that are medical devices. Take, for example, a tube that is inserted into an artery and coated with a coagulant. This could be classed as both a device (tube) and pharmaceutical (coagulant), according to medical device consultant Duncan Fatz.
"Putting such a device through a clinical trial was difficult in terms of classification," says Fatz. "Is it a device or is it a drug? There are many more examples where the classification was not clear, such as an insulin pump."
A number of real problems have brought these issues into focus. A good example concerned breast implants, when one design using soya bean oil had to be withdrawn because of toxicity problems, says Jeremy Tinkler, a director with professional services company Medpass International.
"This shouldn't have been on the market, so how did it get on the market?" he asks. "Yet there was a big fuss with silicone gel and there were no problems with that at all."
With the new directive, the trials for devices and pharmaceuticals will be similar, taking away much of this classification headache.
What is not clear though is exactly how this will be implemented by device manufacturers. It may mean more stringent quality procedures.
"Companies are still discussing how this might affect them," says Fatz.
"But this had to happen because we were finding companies doing pharmaceuticals moving over to the device side and discovering there were huge differences on how to do things."
What all companies will have to do is carry out a clinical risk assessment. Though there will be some products that will not need a full clinical trial, the risk assessment will force companies to justify this.
The process today is that the manufacturer will usually contact a third party, known as a Notified Body, and have this company come in and work through the requirements to give the device a CE marking. This gives the product access to all EU countries.
The Notified Body would have to decide on the classification. Low-risk products include things such as bedpans. Medium-risk devices are those that are usually not implanted or, if they are, for only a short time. And high-risk devices are the invasive products such as a pacemaker.
"The first thing they do is decide the classification and then that sets down the rules of what they have to comply with," says Robert Russell, president of RJR Consulting, a company running seminars on this topic for online training company Benastrum.
For high-risk medical devices, the changes will make little – if any – difference but the requirements will be stated more clearly. But for low-risk devices, the manufacturer will have to decide whether clinical data will be needed. If not, then they have to give their reasons.
"For low-risk devices, they can sometimes self-certify themselves," says Russell. "But if some measurement is involved or it is a sterile product, the Notified Body will have to check this."
Tinkler adds: "there is an intermediate area where it has never been clear whether clinical trials are needed or not". The justification part of the directive will push some of these into an area where they do need clinical trials whereas in the past they didn't."
INCREASING MANUFACTURER RESPONSIBILITIES
In the past, some products in this area have relied on information from other sources, such as white papers and design data, but now many will have to go to clinical trial. They must also consider before a product goes to market what post-market surveillance will be needed, whether active where more clinical trials are carried out as the product is being used in earnest or passive where the product is used and nothing is done further unless problems arise.
"Whether you can rely on passive surveillance or need active surveillance is now enshrined in the directive," says Tinkler. "It was there in the past on the risk management side but it has been made clearer because people did not understand it. Putting it on a legal footing draws attention to it and makes sure people do it. Before it was muddled up as to what was voluntary and what wasn't. This does tighten things up in terms of responsibilities and people justifying their actions."
This will mean more work for some manufacturers, and this will almost certainly be passed on in the price of products. The number of patients involved in a clinical trial will be lower than, say, for a new drug, but could still involve 100 to 150 people. This is smaller than the thousands in a drug trial but still expensive to carry out.
"It won't slow things up drastically," says Russell. "But they will have to put this into their product development cycles; it could add two to five months. It will also affect manufacturers who have devices on sale outside the EU and want to bring them in. They will be required to do a relatively small trial somewhere in the EU."
There are also contract research organisations that will take much of the headache of organising the trials away from the manufacturers. These are already used extensively for drug trials.
"The EU felt uncomfortable that the device world was not as regulated as the pharmaceutical world," said Russell. "They were also worried because devices were becoming more sophisticated and thus brought new elements of risk. The system was not as tight as they would have liked."