Explanatory Memorandum to COM(2012)541 - In vitro diagnostic medical devices

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dossier COM(2012)541 - In vitro diagnostic medical devices.
source COM(2012)541 EN
date 26-09-2012
1. CONTEXT OF THE PROPOSAL

The current EU regulatory framework for in vitro diagnostic medical devices ('IVDs') consists of Directive 98/79/EC of the European Parliament and of the Council ('the IVD Directive') i IVDs cover a wide range of products that can be used for population screening and disease prevention, diagnosis, monitoring of prescribed treatments and assessment of medical interventions.

Like Council Directive 90/385/EEC on active implantable medical devices (AIMDD) i and Council Directive 93/42/EEC on medical devices (MDD) i the IVD Directive is based on the New Approach and aims to ensure the smooth functioning of the internal market and a high level of protection of human health and safety. IVDs are not subject to any pre-market authorisation by a regulatory authority but to a conformity assessment which, for the majority of devices, is carried out under the sole responsibility of the manufacturer. For the high-risk devices listed in Annex II and devices for self-testing, the conformity assessment involves an independent third party, known as notified body. Notified bodies are designated and monitored by the Member States and act under the control of the national authorities. Once certified, devices bear the CE marking which allows them to circulate freely in the EU/EFTA countries and Turkey.

The existing regulatory framework for in vitro diagnostic medical devices has demonstrated its merits but has also come under criticism in recent years.

In an internal market with 32 participating countries and subject to constant scientific and technological progress, substantial divergences in the interpretation and application of the rules have emerged, thus undermining the main objectives of the Directive, i.e. the safety and performance of IVDs and their free movement.

This revision aims to overcome these flaws and divergences and to further strengthen patient safety. A robust, transparent and sustainable regulatory framework for in vitro diagnostic medical devices that is fit for purpose should be put in place. This framework should be supportive of innovation and the competitiveness of the in vitro diagnostic medical device industry and should allow rapid and cost-efficient market access for innovative IVDs to the benefit of patients and healthcare professionals.

This proposal is adopted alongside a proposal for a Regulation on medical devices that are currently covered by the AIMDD and the MDD. While the specific features of IVDs and of the IVD sector require the adoption of a specific legislation distinct from the legislation on other medical devices, the horizontal aspects common to both sectors have been aligned.

Contents

1.

RESULTS OF CONSULTATIONS WITH THE INTERESTED PARTIES AND IMPACT ASSESSMENTS



In preparation for the impact assessment on this proposal and the proposal for a Regulation on medical devices, the Commission held two public consultations, the first from 8 May to 2 July 2008, and the second from 29 June to 15 September 2010. In both public consultations, the general principles and minimum standards for consultation of interested parties by the Commission were applied; responses received within a reasonable period after the deadlines were taken into account. After analysing all the responses, the Commission published a summary outcome and the individual responses on its website.

The majority of respondents to the 2008 public consultation (in particular Member States and industry) considered the proposed revision to be premature. They pointed to Directive 2007/47/EC of the European Parliament and of the Council, which amended the AIMDD and the MDD and was to be implemented by 21 March 2010, and also to the New Legislative Framework for the Marketing of Products which was due to enter into force with effect from 1 January 2010, and argued that it would be advisable to wait for these changes to be implemented, in order to assess the need for further adjustments better.

The 2010 public consultation focussed on aspects related to the revision of the IVD Directive and showed wide support for this initiative.

During 2009, 2010 and 2011, the issues to be tackled in the revision of the regulatory framework for medical devices and in vitro diagnostic medical devices were regularly discussed at meetings of the Medical Devices Expert Group (MDEG), the Competent Authorities for Medical Devices (CAMD) and specific working groups in the fields of in vitro diagnostic medical devices (IVDs), notified bodies, borderline and classification, clinical investigation and evaluation, vigilance and market surveillance, and in an ad hoc working group on Unique Device Identification (UDI). A special meeting of the MDEG was held on 31 March and 1 April 2011 to discuss issues related to the impact assessment. Moreover, the Heads of Medicines Agencies (HMA) and the CAMD organised joint workshops on the development of the legal framework for medical devices on 27 April and 28 September 2011.

A further special meeting of the MDEG was held on 6 and 13 February 2012 to discuss issues related to the two legislative proposals, based on working documents containing initial drafting proposals. Written comments made on these working documents were taken into account, where appropriate, for the further development of the proposals.

In addition, Commission's representatives regularly participated in conferences to present ongoing work on the legislative initiative and hold discussions with stakeholders. Targeted meetings took place at senior level with representatives from associations representing industry, notified bodies, healthcare professionals and patients.

Aspects linked to the appropriate regulatory framework were also discussed in the course of the Exploratory Process on the Future of the Medical Device Sector organised by the Commission from November 2009 to January 2010. On 22 March 2011, the Commission and the Hungarian Presidency organised a high-level conference on innovation in medical technology, the role of the medical device sector in addressing the healthcare challenges facing Europe and the appropriate regulatory framework for this sector to meet the needs of tomorrow. This conference was followed by Conclusions of the Council of the European Union on innovation in the medical device sector adopted on 6 June 2011. In its Conclusions, the Council requested the Commission to adapt the EU medical device legislation to the needs of tomorrow so as to achieve a suitable, robust, transparent and sustainable regulatory framework, which is central to fostering the development of safe, effective and innovative medical devices for the benefit of European patients and healthcare professionals.

Triggered by the PIP breast implants scandal, the European Parliament adopted on 14 June 2012 a Resolution on defective silicone gel breast implants made by the French company PIP also calling on the Commission to develop an adequate legal framework to guarantee the safety of medical technology.

3.

3. LEGAL ELEMENTS OF THE PROPOSAL 3.1. Scope and definitions (Chapter I)


To a large extent, the scope of the proposed Regulation matches the scope of Directive 98/79/EC, i.e. it covers in vitro diagnostic medical devices. The proposed changes clarify and extend the scope of the IVD Directive. They concern:

· high-risk devices manufactured and used within a single health institution, which are subject to most of the requirements set out in the proposal;

· tests providing information about the predisposition to a medical condition or a disease (e.g. genetic tests) and tests providing information to predict treatment response or reactions (e.g. companion diagnostics), which are considered as in vitro diagnostic medical devices ;

· medical software, which is explicitly mentioned in the definition of IVDs.

To support Member States and the Commission in determining the regulatory status of products, the Commission may set up, in accordance with its internal rules, a group of experts from various sectors (such as IVDs, medical devices, medicinal products, human tissues and cells, cosmetics and biocides).

The definitions section has been significantly extended, aligning the definitions in the field of in vitro diagnostic medical devices with well-established European and international practice, such as the New Legislative Framework for the Marketing of Products and guidance documents produced for in vitro diagnostic medical devices by the Global Harmonization Task-Force (GHTF) .

4.

3.2. Making available of devices, obligations of economic operators, CE marking, free movement (Chapter II)


This chapter covers mainly horizontal issues similar for both medical devices and IVDs. It contains provisions that are typical for product-related internal market legislation and sets out the obligations of the relevant economic operators (manufacturers, authorised representatives of non-EU manufacturers, importers and distributors). It also provides clarification with regard to the adoption and the scope of common technical specifications (CTS) for in vitro diagnostic medical devices.

The legal obligations on manufacturers are proportionate to the risk class of the devices they produce. For example, this means that even though all manufacturers should have a quality management system (QMS) in place to ensure that their products consistently meet the regulatory requirements, the QMS-related responsibilities are stricter for manufacturers of high-risk devices than for manufacturers of low-risk devices.

Key documents for the manufacturer to demonstrate compliance with the legal requirements are the technical documentation and the EU declaration of conformity to be drawn up in respect of the devices placed on the market. Their minimum contents are laid down in Annexes II and III.

The following concepts are new in the field of IVDs:

· A requirement has been introduced that within the manufacturer's organisation a qualified person should be responsible for regulatory compliance. Similar requirements exist in EU legislation on medicinal products and in the national laws transposing the Directive on medical devices in some Member States.

· Since in the case of parallel trade with in vitro diagnostic medical devices application of the principle of free movement of goods varies considerably from one Member State to another and, in many cases, de facto prohibits this practice, clear conditions are set for enterprises involved in relabelling and/or repackaging IVDs.

5.

3.3. Identification and traceability of devices, registration of devices and of economic operators, summary of safety and performance, Eudamed (Chapter III)


This chapter addresses one of the main shortcomings of the current system: its lack of transparency. It consists of:

· a requirement that economic operators shall be able to identify who supplied them and to whom they have supplied IVDs;

· a requirement that manufacturers fit their devices with a Unique Device Identification (UDI) which allows traceability. The UDI system will be implemented gradually and proportionate to the risk class of the devices;

· a requirement that manufacturers/authorised representatives and importers shall register themselves and the devices they place on the EU market in a central European database;

· an obligation for manufacturers of high-risk devices to make publicly available a summary of safety and performance with key elements of the supporting clinical data;

· and the further development of the European databank on medical devices (Eudamed), set up by Commission Decision 2010/227/EU, which will contain integrated electronic systems on a European UDI, on registration of devices, relevant economic operators and certificates issued by notified bodies, on clinical performance studies, on vigilance and on market surveillance. A large part of the information in Eudamed will become publicly available in accordance with the provisions regarding each electronic system.

The establishment of a central registration database will not only provide a high level of transparency but also do away with diverging national registration requirements which have emerged over recent years and which have significantly increased compliance costs for economic operators. It will therefore also contribute to reducing the administrative burden on manufacturers.

6.

3.4. Notified bodies (Chapter IV)


Proper functioning of notified bodies is crucial for ensuring a high level of health and safety and citizens' confidence in the system, which has come under severe criticism in recent years due to significant differences as regards, on the one hand, the designation and monitoring of notified bodies and, on the other, the quality and depth of the conformity assessment performed by them.

In line with the New Legislative Framework for the Marketing of Products, the proposal sets out requirements for national authorities responsible for notified bodies. It leaves the ultimate responsibility for designating and monitoring notified bodies, based on stricter and detailed criteria laid down in Annex VI, with the individual Member State. The proposal thus builds on existing structures already available in most Member States instead of lifting the responsibility to the Union level which might have caused concerns in terms of subsidiarity. But any new designation and, in regular intervals, the monitoring of notified bodies are made subject to joint assessments with experts from other Member States and the Commission, thus ensuring an effective control at Union level.

At the same time, the position of notified bodies vis-à-vis manufacturers will be significantly strengthened, including their right and duty to carry out unannounced factory inspections and to conduct physical or laboratory tests on devices. The proposal also requires rotation of the notified body's personnel involved in the assessment of IVDs at appropriate intervals to strike a reasonable balance between the knowledge and experience required to carry out thorough assessments and the need to ensure continuous objectivity and neutrality in relation to the manufacturer subject to those assessments.

7.

3.5. Classification and conformity assessment (Chapter V)


Annex II to the IVD Directive addresses the level of risk posed by IVD medical devices by means of a positive list system. While this system was adapted to scientific and technological development at the time the IVD Directive was written, today it can no longer keep up with the fast pace of scientific and technological progress. The proposal introduces a new risk-rule based classification system, built on GHTF principles, which replaces the current list of IVD medical devices in Annex II to Directive 98/79/EC.

In the new classification system, IVDs will be divided into four classes of risk: A (lowest risk), B, C and D (highest risk). The conformity assessment procedures have been adapted to match each of these four device classes, using the existing modules established under the New Approach. The conformity assessment procedure for class A devices will be carried out, as a general rule, under the sole responsibility of the manufacturer in view of the low level of vulnerability associated with these products. However, when class A devices are intended for near-patient testing, have a measuring function or are sold sterile, a notified body shall verify respectively the aspects related to design, the measuring function or to the sterilisation process. For devices of classes B, C and D an appropriate level of involvement of a notified body is compulsory proportionate to the risk class, with devices of class D requiring explicit prior approval of the design or of the type of the device and of the quality management system before they may be placed on the market. In the case of class B and C devices, the notified body checks the quality management system and, for class C, the technical documentation of representative samples. After initial certification, notified bodies shall regularly conduct surveillance assessments in the post-market phase.

The different conformity assessment procedures during which the notified body audits the manufacturer's quality management system, checks the technical documentation, examines the design dossier or approves the type of a device are laid down in Annexes VIII to X. They have been tightened and streamlined. One conformity assessment procedure provided for under the IVD Directive (EC verification) has been deleted as the responses to the public consultation highlighted that it was under-used. The concept of batch testing has been clarified. The proposal reinforces the powers and responsibilities of notified bodies and specifies the rules according to which notified bodies perform their assessments, both in the pre-market and the post-market phase, (e.g. documentation to be submitted, scope of the audit, unannounced factory inspections, sample checks) to ensure a level playing field and avoid notified bodies being overly lenient. Manufacturers of devices for performance evaluation continue to be subject to specific provisions.

In addition, the proposal introduces the obligation for notified bodies to notify an expert committee of new applications for conformity assessment of high-risk devices. On scientifically valid health grounds, the expert committee will have the power to request the notified body to submit a preliminary assessment on which the committee can issue comments within a deadline of 60 days, before the notified body can issue a certificate. This scrutiny mechanism empowers the authorities to have a second look at individual assessments and make their views heard before a device is placed on the market. A similar procedure is currently already applied for medical devices manufactured utilising animal tissues (Commission Directive 2003/32/EC[14]). Its use should be the exception rather than the rule and should follow clear and transparent criteria.

8.

3.6. Clinical evidence (Chapter VI)


The proposal spells out the requirements for clinical evidence for in vitro diagnostic medical devices which are proportionate to the risk class. The key obligations are set out in Chapter VI while more detailed provisions are laid down in Annex XII.

While most clinical performance studies follow an observational design and therefore the results obtained are not used for patient management and do not impact treatment decisions, specific requirements have been introduced in Annex XIII for the conduct of interventional clinical performance studies and other clinical performance studies where the conduct of the study, including specimen collection, involves invasive procedures or other risks for the subjects of the studies.

The concept of sponsor is introduced and aligned with the definition used in the recent Commission's proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use which aims at repealing Directive 2001/20/EC[15].

The sponsor can be the manufacturer, his authorised representative or another organisation, in practice often a ‘contract research organisation’ conducting clinical performance studies for the manufacturers. The scope of the proposal, however, remains restricted to clinical performance studies carried out for regulatory purposes, i.e. for obtaining or confirming regulatory approval for market access. Non-commercial clinical performance studies that do not pursue a regulatory purpose are not covered by this Regulation.

In accordance with recognised international ethical principles, every interventional clinical performance study and other clinical performance study involving risks for the subjects of the study shall be registered in a publicly accessible electronic system which the Commission will set up. To ensure synergies with the area of clinical trials on medicinal products, the electronic system on interventional clinical performance studies and other clinical performance studies involving risks for the subjects of the studies should be interoperable with the future EU database to be set up in accordance with the future Regulation on clinical trials on medicinal products for human use.

Before commencing an interventional clinical performance study or any other clinical performance study involving risks for the subjects of the study, the sponsor shall submit an application to confirm that there are no health and safety aspects or ethical aspects which would oppose it. A new possibility will be opened up for sponsors of an interventional clinical performance study or any other clinical performance study involving risks for the subjects of the study to be conducted in more than one Member State: in future they may, if they wish, submit a single application through the electronic system to be set up by the Commission. As a consequence, the health and safety-related aspects regarding the device for performance evaluation will be assessed by the Member States concerned under the direction of a coordinating Member State. The assessment of intrinsically national, local and ethical aspects (e.g. liability, suitability of the investigators and clinical performance studies sites, informed consent), will however, need to be carried out at the level of each Member State concerned which will retain the ultimate responsibility for deciding whether the clinical performance study may be conducted on its territory. In line with the above-mentioned Commission's Proposal for a Regulation on clinical trials on medicinal products, also this proposal leaves it to the Member States to define the organisational set-up at national level for the approval of interventional clinical performance studies or any other clinical performance study involving risks for the subjects of the study. In other words, it moves away from a legally required dualism of two distinct bodies, i.e. a national competent authority and an ethics committee.

9.

3.7. Vigilance and market surveillance (Chapter VII)


A well-functioning vigilance system is the backbone of a robust regulatory framework because complications with devices may come to light only after a certain period of time. The main progress which the proposal will bring in this field is the introduction of an EU portal where manufacturers shall report serious incidents and corrective actions they have taken to reduce the risk of recurrence. The information will be automatically made available to the national authorities concerned. Where the same or similar incidents have occurred, or where a corrective action has to be taken, in more than one Member State, a coordinating authority will take the direction in coordinating the analysis of the case. The emphasis is placed on work- and expertise- sharing to avoid inefficient duplication of procedures.

As regards market surveillance, the main objectives of the proposal are to reinforce the rights and obligations of the national competent authorities, to ensure effective coordination of their market surveillance activities and to clarify the applicable procedures.

10.

3.8. Governance (Chapters VIII and IX)


The Member States will be responsible for implementation of the future Regulation. A central role in achieving harmonised interpretation and practice will be assigned to an expert committee (the Medical Device Coordination Group or MDCG) made up of members appointed by the Member States due to their role and experience in the fields of medical devices and in vitro diagnostic medical devices and set up by Regulation (EU) [Ref. of future Regulation on medical devices] on medical devices[16]. The MDCG and its subgroups will allow to build a forum for discussions with stakeholders. The proposal creates the legal basis that for specific hazards or technologies or for verifying compliance with common technical specifications by devices posing the highest risk, EU reference laboratories, a concept that has proven successful in the food sector, may in the future be designated by the Commission.

As regards the management at EU level, the impact assessment identified as preferred option either the extension of the responsibility of the European Medicines Agency (EMA) to in vitro diagnostic medical devices or the management of the in vitro diagnostic medical devices regulatory system by the Commission. Taking into account the clear preference expressed by stakeholders, including many Member States, the proposal mandates the Commission to provide technical, scientific and logistic support to the MDCG.

11.

3.9. Final provisions (Chapter X)


The proposal empowers the Commission to adopt, where appropriate, either implementing acts to ensure uniform application of this Regulation, or delegated acts to complement the regulatory framework for in vitro diagnostic medical devices over time.

The new Regulation will become applicable five years after its entry into force in order to take into account the significant changes to the classification system for IVDs and to the conformity assessment procedures. This will, on the one hand, allow time to set up a sufficient number of notified bodies, and, on the other hand, mitigate the economic impact on manufacturers. The Commission needs also time to put in place the IT infrastructure and the organisational arrangements necessary for the functioning of the new regulatory system. The designation of notified bodies pursuant to the new requirements and process needs to start shortly after the entry into force of this Regulation in order to ensure that by the date of its application, sufficient notified bodies are designated in accordance with the new rules to avoid any shortage of in vitro diagnostic medical devices on the market. Special transitional provisions are foreseen for the registration of in vitro diagnostic medical devices, relevant economic operators and certificates issued by notified bodies to allow for a smooth transition from registration requirements at national level to a central registration at EU level.

The future Regulation will replace and repeal Directive 98/79/EC of the European Parliament and of the Council.

12.

3.10. Union competence, subsidiarity and legal form


The proposal has a double legal basis, i.e. Article 114 and Article 168(4)(c) of the Treaty on the Functioning of the European Union. With the entry into force of the Lisbon Treaty, the legal basis for the establishment and functioning of the internal market, on which the current Medical Devices Directives were adopted, has been complemented by a specific legal basis to set high standards for the quality and safety of devices for medical use. In regulating IVDs, the Union is exercising its shared power under Article 4 i of the Treaty on the Functioning of the European Union.

Under the current IVD Directive, IVDs that bear the CE marking can, in principle, move freely within the EU. The proposed revision of the existing directive, which will integrate the changes introduced by the Lisbon Treaty regarding public health, can be achieved only at Union level. This is necessary in order to improve the level of protection of public health for all European patients and users, and also to prevent Member States from adopting diverging product regulations which would result in further fragmentation of the internal market. Harmonised rules and procedures allow manufacturers, especially SMEs which make up more than 90% of the IVD sector, to reduce costs related to national regulatory differences, while ensuring a high and equal level of safety throughout the Union. In accordance with the principles of proportionality and subsidiarity, as set out in Article 5 of the Treaty on European Union, this proposal does not go beyond what is necessary in order to achieve those objectives.

The proposal takes the form of a Regulation. This is the appropriate legal instrument as it imposes clear and detailed rules which will become applicable in a uniform manner and at the same time throughout the Union. Diverging transposition of the IVD Directive by Member States has led to different levels of health and safety protection and created obstacles to the internal market which only a Regulation can avoid. Replacing the national transposition measures also has a strong simplification effect since it allows economic operators to conduct their business on the basis of a single regulatory framework, rather than a patchwork of 27 national laws.

The choice of a Regulation, however, does not mean that decision-making is centralised. Member States retain their competence for implementing the harmonised rules, e.g. as regards approval of clinical performance studies, the designation of notified bodies, the assessment of vigilance cases, the conduct of market surveillance and enforcement action (e.g. penalties).

13.

3.11. Fundamental Rights


In line with the Charter of Fundamental Rights of the EU, this proposal seeks to ensure a high level of human health protection (Article 35 of the Charter) and consumer protection (Article 38) by assuring a high level of safety of in vitro diagnostic medical devices made available on the Union market. The proposal affects the freedom of economic operators to conduct business (Article 16) but the obligations imposed on manufacturers, authorised representatives, importers and distributors of in vitro diagnostic medical devices are necessary to guarantee a high level of safety of those products.

The proposal sets guarantees for the protection of personal data. In respect to medical research, the proposal requires that any clinical performance study with participation of human subjects is conducted respecting the human dignity, the right to physical and mental integrity of the persons concerned and the principle of free and informed consent, as required by Articles 1, 3 i and 3(2)(a) of the Charter.

2.

BUDGETARY IMPLICATION



This proposal does not have any additional direct budgetary implication because the cost-relevant arrangements are already covered by the proposal for a Regulation on medical devices. The financial statement of that proposal lists the details of the costs related to the implementation of both Regulations. A thorough discussion on the costs is contained in the impact assessment report.