European companies manufacturing medical devices have seen important changes in the regulatory area that will shape the industry environment for years to come. Amendments to the Medical Devices Directive (MDD) (93/42/EEC) and Active Implantable Medical Devices Directive (AIMDD) became effective in 2007 and will have far-reaching ramifications for member states' governments and manufacturers alike. These amendments cover aspects of regulation such as clinical evidence, essential requirements, alternative labelling, hazardous materials and single-use devices.
The AIMDD revision has been designed to ensure alignment with Medical Device Directives 93/42 and 90/385.
The most significant change has been to align the requirements for active implantable medical devices containing an ancillary medicinal substance with those contained in the MDD. The most direct implication of this revision is that during evaluation this category of products must now be submitted to a screening by the national competent authorities for medicinal products or the EMEA to assure the quality and safety of these substances.
Eucomed has played an important role in negotiating with the European Commission and the relevant national authorities (medical and medicines agencies across Europe) a 'grandfather clause', requiring the collection of safety and quality records of these products over the last 15 years.
It is fair to say that the directives 93/42 and 90/385 have not been radically changed. Nevertheless, a series of clarifications have been added to improve the consistency of interpretation of procedures for the evaluation of these products across Europe.
More recently, provisions to cover the delivery of instructions-for-use using means other than paper (so-called alternative labelling) have been added along with some clarifications around single-use products.
The obligation to identify the intended user identifies the need for medical devices manufacturers to tailor their devices and the relevant instructions-for-use to the expected skills and knowledge of the user. This requirement is particularly important for devices intended for non-professional use.
NEED FOR CLINICAL EVIDENCE
The new directive emphasises the need for clinical evidence for all devices and strongly suggests that higher regulatory class devices should undergo clinical investigations.
A consequence of this is that manufacturers should now analyse and review the clinical part of their design dossier to identify any possible evidence 'gaps' that need to be filled through post-marketing clinical follow-up. Devices used in clinical investigations will have to be submitted to an appropriate vigilance system which requires that any adverse event is notified in a timely manner through the relevant national authorities.
This requirement has implications for both manufacturers and national authorities as it will generate a considerable workload which might challenge existing mechanisms and lead to delays. Eucomed has proposed a pragmatic approach to dealing with this challenge. As a first step, the process will be piloted in three member states (Switzerland, France and the UK) but more national applications are to be expected in the near future.
In the previous version of the directive, it was already implied that Notified Bodies had the right to verify the appropriateness of manufacturers' design procedures. This was previously done through an informal sample evaluation of a design dossier. However, these procedures were inconsistently applied and it was clear that there was a necessity to align them.
Manufacturers should therefore be ready to present a representative sample of their design dossiers for Class IIa and IIb products. This amendment will also require guidance by the European Commission to avoid uneven treatment for manufacturers across Europe. Eucomed is currently working with the Commission in order to prepare the guidance document.
The text of the directive now contains a better definition of the central circulatory system in order to determine the time of contact of invasive products and an overall reclassification of products for the disinfection of invasive devices. Software is now considered an active medical device.
Eucomed recommends that manufacturers carefully evaluate these modifications and their impact on their products.
During the debate over the revisions in 2007, the European Parliament expressed concerns regarding the use of some phthalates, such as DEHP. Phthalates are used in the production of medical devices to render the products soft. These substances have already been banned in the production of toys because of the possible risks for children exposed to these materials.
There are currently no materials available which combine the performance characteristics of soft PVC and have the same substantial evidence base for safety and efficacy.
As no scientific evidence exists of adverse events with soft PVC and given its proven benefits, the European Commission has decided to require appropriate labelling of products containing phthalates classified as DMR I and II according to directive 67/548/EEC.
In order to address the implications of this requirement, the Commission has recently put together a working group that will gather expertise and guidance from various stakeholders, including Eucomed, regarding the practicalities of implementation. The first meeting of this group took place on 25 April 2008.
OVERLAP WITH OTHER DIRECTIVES
The revision of the machinery directive and the issues detected in the marketing of products has led the EC to specify that a medical device has to be assessed by the conformity assessment requirement of the MDD. This is true for products that are considered both medical devices and personal protective equipment.
However, manufacturers will have to analyse and cross-reference the essential requirements contained in both directives to evaluate whether any are more specific than those provided in the MDD. Should this be the case, the MDD conformity assessment procedure will overrule the conformity assessment procedures of the other directives.
REGISTRATION OF PLACING ON NATIONAL MARKETS
The European Commission has considered requests from European member states to be informed about the introduction of any medical device on their markets in order to carry out effective market surveillance.
Eucomed is concerned that the Commission has not provided any further guidance on the modalities for implementing these requirements resulting in a variety of local rules across Europe. The consequence of these for the manufacturers is an increase in administrative costs which provide no benefit to patients.
Following the revision of the MDD in 2007 the European Commission will further analyse the issue of reuse of single-use devices and generate a recommendation in three years' time. An outline of the issues relating to reuse of single-use devices was summarised and discussed in a previous issue (2008 Vol. 1, pp87–88). While reuse of single-use medical devices should clearly be prohibited, if this practice persists, the explicit consent of the patient should be required in every case.
Furthermore, the companies performing reprocessing should be able to guarantee that the single-use devices that they are making available will perform to their original standards, so that patients have access to the same level of quality of medical treatment, regardless of the willingness to pay by healthcare providers.
Eucomed has been very active in exploring opportunities for the use of alternative labelling. While the revision of the Medical Devices Directive does not directly allow the production and supply of instructions for use in any form other than paper, it is envisaged that electronic labelling could be allowed. This can only be done on the basis of a special measure to be agreed according the Article 7(3) procedure which includes scrutiny by the European Parliament.
This option will initially be restricted to a certain number of devices still to be defined. Eucomed has sent its proposal to the Commission. The proposal is currently being analysed by an ad-hoc European Commission working group. The final document will be distributed to the Parliament for scrutiny in April 2009.
In the past, the medical device industry and notified bodies had difficulties in conducting the so-called consultation procedure with the national medicinal product authorities. These difficulties arose due to a lack of clarity in the definition of the responsibilities in the text of previous directives and inadequate guidance on the documentation required.
In the revised text, the remit for Notified Bodies and medicinal product authorities across Europe has been clarified. The text also defines a new review time for new products of 210 days. However, the Commission is reviewing MEDDEV guidance document 2.1/3 to provide more detailed guidance on the documentation to be submitted. Eucomed is currently involved in active discussions with the Commission, member states and the EMEA.
The main areas where modifications have been introduced are:
- the need to consider the targeted intended user in designing the product, with the aim of reducing errors in usage
- the need for clinical evidence
- the requirement for Notified Bodies to review representative samples of the design dossier in Class IIa and Class IIb
- some small modifications in the classification rules
Some other modifications are significant and need to be noted:
- references to hazardous materials, in particular phthalates
- clarification of the overlap with other directives such as the machinery and personal protective equipment directives
- the need for registering products of all classes before placing them on the national markets
- role of Notified Bodies and medicinal product authorities in relation to device-drug combination products.
Throughout the revision of the MDD, member states have increasingly shared information to improve market surveillance of the medical device industry across Europe. In order to maintain an effective dialogue on the development of the regulatory environment the medical device industry needs to do the same and strengthen both its relationships and networking. An enhanced cooperation between National and European Associations is vital if the European medical device industry wants to be aligned and prepared for future challenges.