Medical Device Link.

Originally Published IVDT September 2002

REGULATIONS AND STANDARDS

Andres Heuberger and Bill Morton

Nanci Dexter, director of quality and regulatory affairs at Corgenix Inc. (Denver), is glad that she started early on the road to complying with Europe's Directive on In Vitro Diagnostic Medical Devices. Eighteen months before these sweeping new regulations go into effect, she says, "I feel confident that we'll meet the IVD Directive deadline."

Dexter has reason to be relieved that Corgenix's CE marking project is in good shape, since Corgenix joins a distinct minority of other American companies that are well on their way to compliance. Meanwhile, with thousands of products among them, many diagnostic manufacturers have yet to begin tackling the process of complying with the complexities of the IVD Directive. Depending upon the number of products or product families, compiling the necessary technical files for attaining compliance with the directive may be a daunting task. With fewer than six business quarters now remaining until the gates of the multi-billion-dollar European marketplace begin to slam shut on noncompliant products, those companies that have not yet begun the process of becoming compliant with the directive need to take urgent action.

The Road to the IVD Directive

As the European single market has evolved, product directives—and the CE mark that indicates compliance with them—have been introduced to facilitate the movement of manufactured goods throughout the European Economic Area. This entity includes the 15 member states of the European Union (i.e., Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, and the United Kingdom) as well as Iceland, Liechtenstein, and Norway, which are members of the European Free Trade Association.

Three directives related to medical devices have been promulgated. The first directive dealt with active implantable devices, like pacemakers, and went into effect in 1993 (directive 90/385/ EEC). The second general directive covered all medical products except active implantable and in vitro diagnostic devices, and became effective in 1995 (93/42/ EEC).

The third and most recent directive is the IVD Directive (98/79/EC), which was approved in October 1998.¹ The transition period for complying with the directive began June 7, 2002, and ends December 7, 2003. After December 7, 2003, in vitro diagnostic products offered for sale in EU member countries must conform with IVD Directive requirements and be CE marked.

From the experiences of setting up compliance programs to conform with the requirements of the first two directives, device manufacturers have learned key lessons that could bear on how they approach complying with the IVD Directive.

One lesson that medical device manufacturers have learned is the importance of maintaining detailed technical documentation. Competent authorities may audit the technical documentation of low-risk products on which a manufacturer may affix a CE mark without a third-party assessment by a notified body. For such products, the manufacturer is essentially self-certifying that it is in conformity with the applicable medical device directive. Competent authorities may conduct "for cause" audits, which have resulted from complaints filed by a competitor, or they may conduct such audits at random. If the competent authority determines that the technical documentation for a product is incomplete, it has the authority to force a company to remove its product from the market until the documentation conforms with the directive's requirements and the competent authority has reviewed the revised documentation.

Therefore, manufacturers of self-certified IVD products should not postpone compiling technical documentation that demonstrates conformity with the IVD Directive's essential requirements.

Another lesson is that properly translating product labels and instructions for use is a critical step toward attaining a CE mark. A common view among manufacturers is that translation is one of the most difficult and time-consuming aspects of the IVD Directive compliance process. Many device manufacturers paid a high price for underestimating the negative impact of poorly translated labels and inserts. As a result, their CE mark applications were rejected, resulting in delayed product ship dates, loss of market share, and reduced revenue.

IVD manufacturers that are selling products in the European market face the possibility of losing market share if they delay the CE marking process. As they did with the earlier device directives, European purchasing groups have already been asking suppliers to provide CE-marked products, even though the IVD Directive is in a transition period. If hospitals and other purchasing groups in Europe have a choice between purchasing a CE-marked product versus a non-CE-marked product, they are likely to select a CE-marked product.

Survey of IVD Directive Preparedness

A tremendous amount of ambiguity remains surrounding the CE marking process generally and the formation of a successful multilingual labeling strategy specifically. A Web site (http://www.ivd-translation.com) has been investigating the current state of IVD companies' efforts toward becoming compliant with the directive by conducting a quarterly survey that focuses on translation issues. The survey intends to provide timely information and analysis to IVD manufacturers that are seeking a CE mark for their products.

Having been invited to take part through introductory e-mail messages and Web site links, participants complete a short on-line survey on the Web site. The survey responses are then automatically submitted to an off-line database for tabulation and analysis.

The anonymous surveys attempt to measure industry's progress toward complying with the IVD Directive, and on a quarterly basis, these results provide a situation overview and a trend analysis. While not conducted to be statistically representative of the entire industry (e.g., the survey employs non- probabilistic sampling, and participation is self-selected), the surveys do offer a snapshot of respondents' IVD Directive preparedness at a given point in time and give insight into longer-term trends.

The IVD Directive translation survey will continue to be carried out quarterly until the December 2003 deadline. There were 108 respondents to the first survey, which was conducted during the first quarter of 2002. That survey posed the five questions listed below.

Does your company have a CE marking team?

Figure 1. Does your company have a CE marking team? (click to enlarge)

More than half of the survey respondents indicated that their companies had established CE marking teams, indicating an improved awareness and preparedness on the part of IVD manufacturers (see Figure 1). Discussions with U.S. diagnostics firms confirmed that companies have seen a significant increase in the formation of such teams over the past 12 months.

At the same time, though, industry experts are concerned that almost half of all manufacturers still have not yet started down the road toward IVD Directive compliance. "It is important that manufacturers move quickly to conform to the CE marking requirements," says Stephanie Horn, IVD program manager at TÜV Rheinland of North America Inc. (Newtown, CT). "The compilation and auditing of technical files often take longer than anticipated."

Corgenix's Dexter agrees with this sense of urgency. Corgenix has had a cross-functional CE marking team in place since September 2001. And it's a good thing that the company had the foresight to start early. "The biggest challenge for us has been allocating resources to this effort," says Dexter. "Because we are a small company, team members take on CE marking responsibilities on top of their regular full-time jobs."

How familiar are you with the IVD Directive?

Figure 2. How familiar are you with the IVD Directive? (click to enlarge)

The survey found that awareness and familiarity with the directive is relatively high (see Figure 2). Industry associations, consultants, and industry publications have delivered numerous seminars, workshops, and articles in an effort to educate the industry about the IVD Directive.

However, a little more than a quarter of respondents expressed marginal or no familiarity with the IVD Directive. For these companies, time is of the essence. "The IVD Directive significantly raises the compliance bar for manufacturers," says Horn. "Particularly for companies with Annex A products, it is very urgent to get a solid understanding of these requirements quickly," she says.

Those companies with products that do not fall into the self-certifying category especially cannot afford to wait any longer. "Working through a notified body takes time, and there are no shortcuts available," says Dexter.

How many languages are you currently translating?

Figure 3. How many languages are you currently translating? (click to enlarge)

As manufacturers gear up their IVD Directive compliance efforts, 73% of respondents are currently translating their product labels and instructions for use into fewer than nine languages (see Figure 3). The more surprising finding is that one-third of respondents have not yet begun the translation process.

The majority of EU countries require the use of the country's national language on labels and in instructions for use, which places a considerable financial burden on IVD manufacturers. Despite the industry's growing awareness of the December 2003 deadline, many manufacturers appear to be postponing this significant task as long as possible. Due to a lack of financial resources, especially in the current economic climate, a number of manufacturers have been pushing back translation issues from quarter to quarter.

Corgenix's Dexter advises diagnostics companies to expect that translation will take longer than anticipated. In addition to the time required for translation, multilingual labeling places new demands on change order processes, production resources, print vendors, and document control procedures. Such added demands can create an internal bottleneck as the clock winds down toward the compliance deadline. "Adjusting processes from single-language publishing to multilingual publishing takes planning, organization, and, above all, time," says Dexter.

By December 2003, how many languages do you expect to be translating?

Figure 4. By December 2003, how many languages do you expect to be translating? (click to enlarge)

Most respondents expect to be able to support one or more languages by the time the IVD Directive goes into effect (see Figure 4). The survey found that the majority of manufacturers are planning to translate into 9 to 12 languages.

This finding significantly contrasts with the lack of translation currently underway. According to the survey results, one in five companies has identified the need for translation but has not yet begun working on this issue. An even larger percentage of firms need to ramp up their efforts in order to support between 9 and 12 languages. These efforts will likely involve redesigning packaging and labeling materials and may involve additional complexities such as ensuring software and hardware support for lesser-used languages such as Greek.

For many diagnostics manufacturers, delaying translation work could create a bottleneck in late 2003. Because these language requirements are a new element in the IVD industry, the number of qualified translation vendors and linguists is relatively small. If a large number of manufacturers attempt to achieve IVD Directive compliance at the last minute, these limited resources may not be able to handle the onslaught of translation work.

Such possibilities, combined with the expense of translating entire product lines, have led industry insiders to believe that diagnostic manufacturers may choose to withdraw products from or postpone introducing new products in smaller markets like Portugal or Greece. Corgenix, for example, is currently sticking to the five core languages (i.e., English, French, German, Italian, and Spanish) and is holding off on translating into additional languages until market demand increases in those countries that require translation in other languages.

What is the biggest CE marking challenge that you have experienced?

The two most frequent responses to this question were as follows.

• Coordinating the document approvals between different manufacturing facilities, for both document updates and translation reviews; and
• Convincing management that now is the time to start planning a CE marking strategy.

CE marking and translating product labels are new experiences for most IVD manufacturers and industry professionals. The industry is in the process of climbing a significant learning curve, and while some companies underestimate the difficulties involved in translation planning and execution, most companies have been investing time to build internal consensus and research suitable CE marking approaches.

Completing the multilingual labeling process provides significant challenges because delays in obtaining approval for any one language can risk holding up the approval of the other languages, and thus the product may not ship. Rather than being surprised by such delays, Dexter advises IVD manufacturers to expect these kinds of challenges. "Accept that you will waste some print runs, and that you will miss some ship dates," she says. "To overcome these kinds of challenges quickly and efficiently, foster strong senior management support for the CE marking initiative."

The Deadline Is in Sight

The IVD industry has been making good progress toward the December 7, 2003, deadline, but much remains to be done. A number of survey respondents indicated that they are mobilizing resources in preparation for the CE marking of their products. However, a significant number of companies have not yet created CE marking teams.

As such teams form and analyze where in Europe to sell their products, they will realize that translation and multilingual labeling are the primary challenges. The vast majority of companies expect to do some translation work by December of 2003, but many have not yet begun these activities. This last-minute approach is likely to cause bottlenecks in finding appropriately qualified translators, reviewing and approving translations, and preparing products with suitable multilingual labeling.

Manufacturers also need to start compiling the necessary technical documentation—another important IVD Directive requirement—and this process may take longer to complete than anticipated. Even though the directive includes a two-year transition period, experience from previous device directives indicates that this changeover will occur much faster. As CE mark requirements are being introduced into purchasing specifications and linked to reimbursement plans, IVD manufacturers might find themselves at a competitive disadvantage without the CE mark.

In trying to meet the IVD Directive deadline, large companies may have an advantage in that they can allocate substantial internal and external resources to the compliance effort. However, such large companies typically have many more products to CE mark than their smaller competitors, and no amount of resources may be sufficient to complete the necessary work in time.

As Corgenix's Dexter points out, regardless of company size, "the IVD Directive deadline is in sight, and time is running out."

Reference

1. "Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on In Vitro Diagnostic Medical Devices," Official Journal of the European Communities 331 (1998): 1–37.

Andres Heuberger is the founder of ForeignExchange Translations Inc. (Boston), which provides translation services to medical device and diagnostics manufacturers. He can be reached via andresh@fxtrans.com. Bill Morton is president of Medical Device Consultants Inc. (North Attleboro, MA), a regulatory consulting firm to the medical device and in vitro diagnostics industries. He can be reached via morton@mdci.com.