Tightening the Reins on the Regulation of Medical Devices: An Overview of the New European Commission Regulations

Introduction

Proposals for new rules governing the regulation of medical devices were published by the European Commission on Sept. 26 (6 MELR 594, 10/3/12). Substantial changes have been proposed to the regulation of in vitro diagnostic medical devices (IVDs), which bring regulation of IVDs more in line with that for other medical devices. The general structure of regulation for all other medical devices is broadly unaltered, but significant amendments have been made to the detailed requirements and several measures have been proposed to increase transparency. There is no doubt that the new rules will increase the regulatory hurdles for the medical devices industry.

The positive news for companies operating in the medical devices industry is that the existing Directives are to be replaced with Regulations¹Directives merely set down a framework of minimum requirements which are then implemented into national law by each Member State. By contrast, Regulations are directly effective in each Member State and so one set of rules applies throughout the EU.. Whereas Directives have to be implemented nationally leading to national variations, once the proposed Regulations are in force there will only be one set of rules that a pan-European company needs to consider, and accordingly more cohesion and harmony in the regulation of medical devices across the European Union.

In this, the first article of a series, we set out the current position, briefly outline the proposed changes and note the initial reaction to the proposals.

The Current Position

Currently, there are three main European Union Directives²Council Directive 90/385/EEC on active implantable medical devices; Council Directive 93/42/EEC on medical devices; and Directive 98/79/EC of the European Parliament and of the Council covering in vitro diagnostic medical devices. regulating the circulation of medical devices in the EU (and the European Free Trade Association (EFTA) countries and Turkey). These Directives were introduced with the main objectives of the safety of medical devices and their ensuring free movement throughout the EU. The basis of the legislation is that manufacturers of medical devices must apply a CE-marking to their products and to do so they must satisfy certain “Essential Requirements” as set out in the Directive and can demonstrate such compliance either on a self-declaration basis for the lowest risk (Class I) devices or to a “notified body” in other cases. Since the first Directive appeared in 1990 not only has the medical devices industry developed rapidly, there have been growing differences in the way the Directives are interpreted and applied. That the Directives no longer fulfil their initial goals and that regulation of medical devices across Europe is not “fit for purpose” has been an increasingly widely-held belief.

Efforts to change the rules to tighten up regulation while increasing harmonisation and promoting the free movement of medical devices across Europe have been in progress since at least 2008 (when the European Commission held the first of two consultations on amending the Medical Devices Directives). The perceived need for change was increased by the PIP breast implants scandal and the issues surrounding metal-on-metal hip replacements, both of which are reported to have caused the public to question the adequacy of regulation of medical devices. On June 14, the European Parliament adopted a resolution calling on the Commission to develop a sufficient legal framework to guarantee the safety of medical technology.

The result is the two Regulations³Proposal for a Regulation of the European Parliament and of the Council on medical devices and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009, 26 September 2012 and Proposal for a Regulation of the European Parliament and of the Council on in vitro diagnostic medical devices, 26 September 2012. proposed by the European Commission to replace the existing three Directives—one for IVDs and the other for all other medical devices (including active implantable medical devices). The Council and the European Parliament will now consider the proposals and may seek to amend aspects of the new Regulations during this process. The final versions of the Regulations are expected to be adopted in 2014, with the Medical Devices Regulation becoming applicable three years after it comes into force and the IVD Regulation five years after that regulation comes into force.

Key Changes

Scope

The Medical Devices Regulation will cover most medical devices, including active implantable medical devices. Its scope will be extended to include products that are manufactured using non-viable human tissue cells, or their by-products that have undergone substantial manipulation, unless they are already covered by the Regulation on advanced therapy medicinal products.

The Medical Devices Regulation will also encompass some implantable or other invasive products without a medical purpose, e.g. non-corrective contact lenses and implants for aesthetic purposes.

Products containing living micro-organisms and food covered by Regulation (EC) No 178/2002 on the general principles and requirements of food law are not included in the Medical Devices Regulation.

The scope of the IVD Regulation will be clarified to cover high-risk devices created and used within a single health institution. Where they are to be used as IVDs, tests supplying information about the predisposition to a medical condition or a disease and tests providing information to predict a response or reaction to a treatment are dealt with by the IVD Regulation. The IVD Regulation also encompasses medical software.

Classification and conformity assessment

The classification rules have been tailored to take account of technical progress. Under the Medical Devices Regulation, medical devices are still divided into four classes based on the possible risks associated with the technical design and manufacture. Manufacturers will continue to conduct the conformity assessments of class I devices unless the device has a measuring function or is sold sterile. A notified body will be involved in approvals in relation to classes IIa, IIb and III, and for class III devices, prior approval of the device and the quality management system (QMS) will be required. Products at the boundary between medical devices and medicinal products which fall within the definition of a medical device are classified in the highest risk class.

New applications for conformity assessment for high risk devices will be made subject to a “scrutiny procedure” whereby notified bodies will be obliged to alert an expert committee of the application. The expert committee will have the power to request a preliminary assessment from the notified body on which they will have 60 days to issue comments. Use of the procedure is intended to be exceptional.

Custom-made devices are subject to a different procedure which does not involve a notified body.

Conformity assessment is the aspect for IVDs where the changes are most significant. The existing lists of IVDs will be replaced by a new risk-rule based system similar to that currently used for other medical devices. Under the new system IVDs will be divided into four classes of risk which allow for the potential risks associated with the technical design and manufacture. They will be classified A (lowest risk), B, C, and D (highest risk).

For class A IVDs, manufacturers will conduct the conformity assessments unless the product will be used for near patient testing, has a measuring function, or is sold sterile. The notified body will be involved with the assessment of classes B, C, and D. Solely for class D, prior approval of the device and the QMS will be needed. As for other medical devices, high risk IVDs may also be subject to the “scrutiny procedure”.

Devices for performance evaluation will remain subject to special requirements.

Transparency

In the spirit of transparency and safety, economic operators must be able to identify who supplied them and to whom they have supplied medical devices. Devices are also to have a Unique Device Identification (UDI) so that they can be traced if necessary. Manufacturers of high risk devices will be required to produce a summary of safety and performance together with key elements of the supporting clinical data and ensure that it is publicly available.

There will be a European databank on medical devices (Eudamed). This will be a central registration database and will contain integrated electronic systems on a European UDI, registration of devices, relevant economic operators, and certificates issued by notified bodies, clinical investigations, vigilance, and market surveillance. Manufacturers/authorised representatives and importers must register themselves and their EU devices on this databank. Importantly, a large amount of this information will be available to the public.

Notified bodies

The powers of, and over, notified bodies have been strengthened considerably. Notified bodies will have the right to carry out unannounced factory inspections and physical or laboratory tests on devices. National authorities remain responsible for notified bodies. However, “joint assessments” will be conducted by experts from other Member States and the Commission in respect of new designations and for monitoring of existing notified bodies. To safeguard objectivity during assessment, employees of the notified body who are engaged in the assessment of medical devices will be rotated periodically.

Clinical evaluation and clinical investigations

The Commission will set up a publicly accessible electronic system. In this system, every clinical investigation (for medical devices) and every interventional clinical performance study and other clinical performance study involving risks for the study subjects (for IVDs), must be registered. The Regulations do not, however, cover non-commercial clinical investigations that do not pursue a regulatory aim.

The concept of “sponsor” as the person ultimately responsible for the conduct of clinical investigations is introduced from the medicinal products sphere. The sponsor may be the manufacturer, his authorised representative or another organisation, e.g. a contract research organisation. Where there are no health and safety/ethical objections, sponsors will submit an application to confirm this. Sponsors may submit a single application through the electronic system (see above) where the investigation is to be carried out in more than one Member State. Health and safety will be assessed centrally but ethical issues will remain a separate topic for each Member State to consider.

Other developments

Manufacturers must report serious incidents and any corrective actions they have implemented on an EU portal. This information will be automatically forwarded to the relevant national authorities.

Within a manufacturer’s organisation there should be a “qualified person” responsible for regulatory compliance.

The concept of the “common technical specification” (CTS) already used for IVDs will be extended to other medical devices. However, under the Medical Devices Regulation, other solutions may be adopted as long as they guarantee an equivalent level of safety and performance.

All manufacturers should have a quality management system (QMS) in place but the requirements of the system depend on the risk classification of the device.

In addition to the above, clear conditions are set for the re-labelling and/or repackaging of medical devices. The Medical Devices Regulation also provides for implant patients to be given essential information on the implanted device such as any warnings or precautions to be taken and sets out strict rules for the reprocessing of single-use devices.

Comment

The initial reaction to the proposals has generally been positive, especially with regard to increased transparency and harmonisation across the EU. However, some concerns have been raised over the scrutiny procedure in that it could potentially cause delays in new and inventive products coming to market without having a positive impact on patient safety. In addition, the requirement for UDIs will require careful consideration to ensure proper compliance does not become too costly.

Consideration of the specific proposals in more detail will be vital to understanding the true implications of the proposed changes, and to ensuring that the transition for those in the medical devices sector, once the new Regulations come into force, is as smooth as possible.