Medical Device Link.

Originally Published IVD Technology April 2003

Regulations & Standards

Maurizio Suppo

Maurizio Suppo, PhD, is vice president of regulatory affairs and quality systems for  Dade Behring International (Caselle, Italy). He can be reached via maurizio_ suppo@dadebehring.com.

The European Union’s IVD Directive first originated in 1991 as a proposal in a white paper that was written by the European Diagnostic Manufacturers Association (EDMA; Brussels) and presented to the European Commission (EC). Working in conjunction with EDMA, a group of IVD manufacturers wanted to make sure one of the directives the EC had undertaken would also take into account in vitro diagnostic products.

Looking back, it was a very ambitious proposal on the part of the IVD industry, considering that the European regulatory environment for IVDs was not particularly stringent. The following list offers some examples of IVD regulations in Europe at that time:

• In France, all IVD reagents needed to be registered at the Laboratoire Nationale de la Santé, which later became the Agence du Medicament and then the Agence Francaise de Securité Sanitaire des Produits de Sante (AFSSaPS).
• In Germany, only seven categories of IVD products needed to be registered at the Paul Ehrlich Institute.
• In Italy, only HIV and hepatitis B and C products had to be registered at the Instituto Superiore di Sanita and the Ministero della Sanita.
• In Spain, HIV products had to be registered at the Ministerio da Salud and the Instituto Carlos III.
• There were also registration requirements in Switzerland for IVDs related to infectious diseases transmitted between humans, and in Austria for HIV products.

Despite these regulatory requirements, a large portion of the European IVD market was left essentially unregulated.

Good Timing

The initial registration requirements for IVDs in Europe were not particularly rigorous and had been in place for quite some time. In addition, these requirements were enforced only in certain countries. However, the IVD industry was concerned about a proliferation of national IVD-related legislation that would spread to all of the European countries, thereby creating significant barriers to the IVD market and posing a heavy burden on the industry. The industry realized early on that a single set of rules and regulations encompassing all of Europe was the ideal solution. Under such circumstances, companies could reap the benefits of a single European market without having to deal with national trade barriers.

The IVD industry’s timing could not have been any better from a social and political point of view. Europe was still continuing to tear down all of its technical, scientific, logistical, and legal barriers in order to give the European economy a boost and to help it compete with the other major world markets, in particular the United States. For this reason, the European Parliament and the Council of Ministers, the two highest institutions in the European Union, favored any new legislation that would contribute to the creation of a single European market. 

The order in which select EC member states transposed the IVD Directive into national law.

Getting the Ball Rolling
During the mid-1980s, the EC had been mandated to create several regulatory directives in all commercial areas, such as transportation, telecommunications, construction, and healthcare. In the healthcare arena, two directives had already been identified and were listed in the EC’s working projects. The first one dealt with active implantable medical devices, which later became the AIMD Directive (90/385/EEC). The second dealt with medical devices in general, which later became the MD Directive (93/42/EEC).

However, the EC’s initial work project list did not include a project to create a directive dealing with in vitro diagnostic products. As stated above, this project came about somewhat later, due primarily to the demands made by the IVD industry. The industry not only requested a directive for IVDs, but it also prepared a first draft on its own in order to get discussions started.

This was a good move by the IVD industry because it was unlikely that the two other key stakeholders in the process, the professional organizations and the various national health authorities, would have produced a starting document. The professional organizations were too fragmented at the time and thus could not speak easily as a single voice. At the same time, for political reasons, the various national authorities were reluctant to propose their own drafts as the text for the directive for IVDs. In addition, the various national health authorities involved in IVD regulations were unaccustomed to working together in an international context.

The Review Process

The drafting and approval process for the IVD Directive took approximately seven years to complete, much longer than it took for the AIMD and the MDD directives. Being the third healthcare-related directive to be drafted had its advantages and disadvantages. 

One advantage was that since the whole directive drafting-and-approval process had been already well established, the IVD industry could approach the process with relative confidence, knowing what was going to happen next. However, one disadvantage was that the various national health authorities, being much more experienced about the directive process, already had identified some perceived weaknesses in the previous two medical device directives, so they were more strict and demanding than they had been with these prior directives.

Once the EC was able to put together a first draft that already contained some comments from the various national health authorities, the draft IVD Directive was sent to the Economic and Social Committee (ECOSOC) for a first review. 
ECOSOC reviews all directives and other documents, and its main task is to assess their impact on the economic and social life of all European citizens. The draft IVD Directive passed through the ECOSOC review without any significant change.

The draft directive was then sent to the European Parliament and the European Council of Ministers. While there is only one European Parliament, there are several European councils of ministers. Depending on the nature of the directive or other legislation being discussed, various ministers may become involved: ministers of defense, human rights, health, internal affairs, economic affairs, etc. In the case of the IVD Directive, as was the case with the previous two medical directives, the ministers of health did not get involved in the process. Rather, the ministers of internal affairs were interested due to the economic reason these directives were being drafted, which was to create a single European market.

Every time a draft directive needs to be discussed in the European Parliament, the first step is to select the various committees that need to be involved in the discussion and review process. For the IVD Directive, two parliament committees were involved: the environmental, public health, and consumer protection committee (ENVI), and the economic and monetary affairs and industrial policy committee (EMAC). For the same reason that the ministers of internal affairs got involved, EMAC was responsible for being the lead committee.

Once this responsibility has been assigned to one of the European Parliament committees, that committee then nominates a person who is primarily responsible for drafting the committee’s comments on the draft directive being discussed and presenting them, both within the committee and later to the European Parliament plenary session. This person is traditionally known as the rapporteur, a French word meaning the person who drafts and presents a report on a specific subject.
Although the whole process foresees involving all of the committee members and getting their formal vote, it is clear that the rapporteur has much influence over the whole process. Especially for highly critical issues—which the IVD Directive was not—the various political parties represented within the European Parliament fight in order to have the role of the rapporteur, which is assigned to a member of their own party.

For the IVD Directive, the role of the rapporteur was assigned to Alain Pompidou of France, who has professional experience in in vitro diagnostic products. Throughout the whole process, Pompidou acted in a balanced and professional manner. However, some people in the IVD industry felt that he kept close contacts with the AFSSaPS, which further facilitated the French health authorities’ influence on the IVD Directive.

Gaining Approval

Timeline of events leading to the creation and enactment of the European Union’s In Vitro Diagnostics Directive (Click to Enlarge).

Toward the end of the long drafting and approval cycle, the IVD Directive was heavily commented on and modified not only by the French but also by several other health authorities from other countries, such as Spain, Germany, Austria, and Portugal. The numerous comments, or amendments, from these health authorities and their very critical and controversial nature were debated both by the European Parliament and the Council of Ministers. These actions accounted for the long time it took for the directive to clear its two readings before finally being published.

During the many years in which the IVD Directive was drafted and commented on, it was mostly possible for all interested parties to express their points of view and argue in favor of or against certain paragraphs or modifications. However, this became less and less possible during the final stages of debate, in particular when the directive was proposed for debate and approval at the European Parliament plenary session.

For example, despite being already debated and then rejected in the past, the proposal that premarket notification should be made to competent authorities was put forward again at the eleventh hour, a day before the European Parliament plenary session was to vote on the two committees’ proposals. It was reproposed by the European Radical Alliance Group, a group with a heavy influence from French parliamentarians, which also demanded an extensive expansion of Annex II to include all biological tests for genetic diseases, all tumor markers, and hormone tests.

With less than a day between the presentation of these amendments and the plenary session vote, it was impossible for the interested parties to present their views to the European Parliament members. Nonetheless, on the day of the plenary session, parliament rejected the proposal for premarket involvement of the competent authorities. However, it did approve a significant expansion of Annex II, adding those tests proposed by the European Radical Alliance Group, as well as HLA, rubella, toxoplasmosis, and all self-tests.

The composition of Annex II in particular fluctuated during those years as unpredictably as the Dow Jones index. It started to stabilize only when the Council of Ministers Working Party (COMWP) found an acceptable compromise by defining Annex II as it looks now. The French delegation at the COMWP tried again to give competent authorities the opportunity to make a premarket intervention for Annex II products after being approved by a notified body. This proposal finally got rejected by the COMWP, thus clearing the way for the final publication on December 7, 1998, of what is now the European IVD Directive.

Conclusion

It took a considerable amount of hard work and the combined efforts of many people to get the IVD Directive drafted, reviewed, revised, and finally approved. By the end, the final product was well worth their efforts, and the directive will prove to be beneficial for the entire IVD market. 

Copyright ©2003 IVD Technology