BBI Contributing Writer

LONDON – A conference on "Device Regulation – Tackling the Latest European Challenges," held here in late March, turned out to be a wide-ranging and hard-hitting review of major issues in the field. In many instances, contributions from the regulators were balanced with responses from industry.

The recently implemented Medical Devices Directives stipulate that, for all but the least-risk-posing devices, product manufacturing standards and in some cases, designs, must be scrutinized and attested by an appropriate "Notified Body." Theoretically, an NB is an independent, expert auditor, called in by a manufacturer to examine a device's credentials and, hopefully, give it an "approvable" stamp to be submitted to the regulatory authority.

It is not altogether surprising that there are ongoing problems with NBs; they are a very recent construct. In 1994, there were only two Notified Bodies – one in France and one in Germany. By 2001 their number has grown to 66, of which the great majority (28) are in Germany. It was obvious from comments made at the IBC-sponsored conference and cited from other sources that the performance of NBs is variable. Jean-Claude Ghislain, of the French medical devices association AFSSAPS, said in September 2000 that "Notified Body competence is one of the principal subjects on France's European presidential agenda." At about the same time, Ditte Norgaard-Anderson, of the Danish association DMDA, said that Notified Bodies are "too formalistic, too superficial and too difficult to change," while Mike Kreutzer of the UK association ABHI said, "There are too many Notified Bodies and it has long been felt that there is uneven performance among them."

The Notified Body perspective was given at the London conference by Alan Kirkwillian, director of Amtac Certification Services. Problems arise, he said, partly because NBs are businesses, funded by their clients – manufacturers – but with the objective of fulfilling the expectations of many stakeholders, including their shareholders and clients, but also the European Commission and national regulatory authorities.

To tackle the NB problem, it was agreed at a meeting of European regulators in Paris last July to set up the Notified Body Oversight Group (NBOG). Its first meeting was held in London in November 2000. It has been charged with putting forward practical proposals for the short and medium term, to improve the overall performance of NBs mainly by identifying and circulating principles of best practice. Already in the pipeline are measures to promote skill enhancement, including training events (important because of advancing technology) and accompanied audits so that the auditing Notified Body can profit from the experience of accompanying experts.

Update on the IVD directive

The directive on in vitro diagnostics was the last of the three main "new approach" directives (European Union laws) governing the medical devices sector. It was published in 1998 with a timetable for transposition into the national laws of EU member states. Devices conforming to the directive must have a CE mark attached. According to the timetable, the first CE-marked diagnostics would appear beginning June 7, 2000, followed by a transition period during which some IVDs could still be marketed under previous legislation. But as of Dec. 7, 2003, only CE-marked devices will be permitted to be placed on the market.

Christine Tarrajat, director of the European Diagnostics Manufacturers Association (EDMA), gave an update on national transposition of the IVD directive. The timetable date set for transposition was Dec. 7, 1999. Not surprisingly, there has been wide variation in the performance of different countries in seeking to get up to speed. First out of the starting blocks was Austria, which published an amendment to its Medical Device Act, to include the IVD, in July 1999; the specific IVD ordinance was published in December 2000. France lags behind the field, with an ordinance published this March and the requisite "Application Decrees" still awaited.

One of the aspects of the European marketplace that strikes American exporters most forcefully is the need to grapple with many national languages when producing labeling and instructions for use (IFU). The IFU issue is especially crucial in the field of in vitro diagnostics because of the importance of clarity and because, for some self-testing devices, it is necessary to provide both professional IFUs and non-professional user IFUs. The directive leaves it up to member states to determine which languages to stipulate, and Tarrajat gave a rundown on the requirements that have been laid down by the individual countries. The resulting situation is complex and may be nightmarish for a U.S. exporter seeking to market a new IVD product across the EU. However, some countries accept English as an alternative to the national language but with conditions which can be forbidding. For example, Switzerland specifies German and French and Italian. English is acceptable under several provisions, including that the manufacturer has confirmation that the user can understand it; the user has appropriate technical knowledge; the protection of patients, users and third parties is guaranteed; the safe and proper use of the device is not jeopardized the provision of information in three languages is too burdensome; and additional information in one of the official languages is available on request.

Another vital cog in the In Vitro Diagnostics Directive implementation gearbox is the existence of appropriately qualified and registered Notified Bodies. Things are lagging behind here: only four EU countries already have Notified Bodies – seven in Germany and one each in the Netherlands, Portugal and the UK. In nine other countries, the candidacy of proposed NB candidates is under evaluation.

The EDMA maintains a website,, which is the place to go for the latest situation on the IVD Directive.

Products containing human tissue

There is a new generation of products containing human tissue, including demineralized bone, engineered skin constructs (fibroblasts and/or keratinocytes on a scaffold or matrix), cultured chondrocytes for cartilage repair and endothelial cells grown on tubular scaffolds for vascular grafts. Alison Dale, regulatory affairs manager in Smith & Nephew's wound management division, discussed the new regulatory challenges presented by these products.

The current regulatory situation differs markedly from one country to another, and one of the main problems is the reluctance of some national regulatory authorities to make any decisions as to the regulation of these products in their countries. Certain categories of products come under pharmaceutical regulations in some countries, but are either unregulated or come under different regulations in others. Dale noted that there is an urgent need for European-level regulation of human tissue products. The current variability between countries means that companies are reluctant to launch in some markets, because they cannot be assured of a return on their investment. More crucially, the present confused situation is dangerous for patients because of the unique potential risks associated with human tissue products. Public confidence in biological products, currently fragile, must be safeguarded. The European confusion contrasts with the situation in the U.S., where a full body of legislation covering tissue products is being developed.

Concern about re-use of single use devices

It might seem – indeed, it is – a contradiction in terms to reuse a single-use device. But it has become a common practice in cash-strapped European hospitals, and there is an argument, however feeble, that such re-use benefits the environment. A survey by the UK Patients Association in April 2000 found that one in 10 of infection control trusts reuse single-use devices despite government guidelines that that they must never be reused.

Eucomed is the European association of medical device suppliers, and Peter Schroer, who chairs the association's reuse task force, discussed a document issued by Eucomed, "Patients in Danger: The Reuse of Single-Use Medical Devices in Europe."

One of the crucial danger areas is the contribution of such reuse to hospital-acquired infections. The figures on such infections are alarming. For example, in the UK, the National Audit Office reported in early 2000 that at any one time, about 9% of all hospital patients had a hospital-acquired infection. Thus, there are at least 100,000 ongoing hospital-acquired infections in England and Wales, and around 5,000 patients die in the UK each year as a direct result of acquiring an infection. The cost to the National Health Service may be $1.4 billion a year. In Germany, 450.000 to 900,000 such infections occur each year and lead to between 25,000 and 50,000 deaths. Reuse of single-use devices may be a significant factor.

Hepatitis B and C represent specific risks. Research has shown that the greater the difficulty in cleaning some devices such as modern laparoscopic devices for keyhole surgery, the greater the risk of non-compliance with cleaning protocols in avoiding hepatitis. The hard fact is that when a single-use device is reprocessed for reuse, it is not possible to guarantee that all blood, tissue and body residues have been removed nor that all microorganisms have been inactivated.

Some European regulatory authorities have banned the reuse of single-use devices. In France, a ministerial circular in 1994 advised against reuse, and the highest court in the land stated in July 1999 that reuse of single-use devices is a deception of the patient. In the UK, a Health Service Circular on contamination in 1999 said "never reuse medical devices designated for single use." The UK Medical Device Agency has issued a Bulletin on Reuse that points out legal implications and states, "Single-use devices should not be reused under any circumstances."

The situation in Germany is less hard-and-fast: reuse is neither regulated nor banned, but there is a list of conditions to be met that would certainly preclude casual reuse of single-use devices.

What of the EU in all this? The Eucomed paper points out that the supply of reprocessed medical devices may fall within the scope of the Medical Device Directives. If the reprocessor does not comply with these directives, he may be committing a criminal offense. However, the main legal implication seems to come under the heading of product liability. The reprocessor (rather than the original manufacturer) may be exposed to product liability claims under both negligence and strict liability theories if the reprocessed device causes injury. Also, a physician or surgeon who fails to inform a patient adequately about the risks inherent in the use of a reprocessed device may be guilty of criminal and civil assault.

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