Medical devices

Medical devices are products or equipment intended for a medical purpose. In the European Union (EU) they must undergo a conformity assessment to demonstrate they meet legal requirements to ensure they are safe and perform as intended. They are regulated at EU Member State level, but the European Medicines Agency (EMA) is involved in the regulatory process.

Manufacturers can place a CE (Conformité Européenne) mark on a medical device once it has passed a conformity assessment.

The conformity assessment usually involves an audit of the manufacturer's quality system and, depending on the type of device, a review of technical documentation from the manufacturer on the safety and performance of the device.

EU Member States designate accredited notified bodies to conduct conformity assessments.

For certain high-risk devices, notified bodies must request an opinion from specific expert panels before issuing a CE certificate. These expert panels benefit from EMA's technical and scientific support.

In some cases, the notified body must seek a scientific opinion from EMA before issuing a CE certificate.

EMA has different regulatory responsibilities for different categories of medical device, including in vitro diagnostics:

Notified body must seek EMA scientific opinion on quality, safety, and usefulness of ancillary medicinal substance if ancillary substance:

• Is derived from human blood or plasma
• Has been previously evaluated by EMA
• Falls in mandatory scope of centralised procedure

Also on this topic

Medical device legislation

The Regulations on Medical Devices (Regulation (EU) 2017/745) and on In Vitro Diagnostic Devices (Regulation (EU) 2017/746) changed the European legal framework for medical devices, introducing new responsibilities for EMA and national competent authorities in the assessment of certain categories of medical device.

• The Medical Devices Regulation applies since 26 May 2021. Manufacturers must comply with the Regulation when placing new medical devices on the market. It repeals Directive 93/42/EEC on medical devices and the Directive 90/385/EEC on active implantable medical devices.
• The In Vitro Diagnostic Devices Regulation applies since 26 May 2022. It repeals Directive 98/79/EC of the European Parliament and of the Council on in vitro diagnostic medical devices.

Question-and-answer guidance on the implementation of these Regulations is available below.

Questions and answers on implementation of the medical devices and in vitro diagnostic medical devices Regulations ((EU) 2017/745 and (EU) 2017/746)

English (EN) (412.32 KB - PDF)

Questions and answers on implementation of the medical devices and in vitro diagnostic medical devices Regulations ((EU) 2017/745 and (EU) 2017/746) - tracked changes

English (EN) (438.76 KB - PDF)

According to the current medical devices legislative framework, the EMA mainly provides scientific opinions to notified bodies through consultation procedures.

EMA's regulatory role is limited to the assessment of certain categories of medical devices and in vitro diagnostics, and in the context of medicinal products used in combination with a medical device.

EMA can only address questions under its remit.

Medicinal products used in combination with a medical device

Some medicines are used in combination with a medical device, usually to enable the delivery of the medicine.

If the principal intended action is achieved by the medicine, it is considered a medicinal product that includes a medical device.

The entire product is regulated under EU pharmaceutical legislation (Directive 2001/83/EC or Regulation (EC) No 726/2004) and must obtain a marketing authorisation for a medicinal product.

The device part of the combination may require a conformity assessment, as follows:

• Medicinal product and device form a single integrated product
• Examples include:
  • pre-filled syringes and pens
  • patches for transdermal drug delivery
  • pre-filled inhalers
  • Marketing authorisation application should include a CE certificate for the device or, if not CE marked but would need to be certified if marketed separately, applicant must include an opinion from a notified body on conformity of device
  • Requirement applies since 26 May 2021 under article 117 of Medical Devices Regulation
  • Requirement does not apply to Class I devices (non-sterile, non-measuring)
  • Medicinal product and device are separate items contained in same pack or obtained separately
  • Examples include:
    • reusable pen for insulin cartridges
    • tablet delivery system with controller for pain management
    • Must be CE marked in accordance with EU medical devices legislation

    Role of EMA

    EMA is responsible for evaluating the quality, safety and efficacy of marketing authorisation applications assessed through the centralised procedure, including the safety and performance of a medical device in relation to its use with a medicinal product.

    The medical device may be co-packaged with, obtained separately from or integral to the medicinal product.

    EMA issued a final guideline on quality documentation for medicinal products that include a medical device in July 2021. This clarifies expectations laid down in Directive 2001/83/EC and addresses obligations in the Medical Devices Regulation, in particular under Article 117.

    EMA recommends reading the guideline in conjunction with the Q&A on the implementation of the Medical Device Regulation and In Vitro Diagnostic Devices Regulation.

    Guideline on quality documentation for medicinal products when used with a medical device - First version

    Adopted Legal effective date: 01/01/2022 Reference Number: EMA/CHMP/QWP/BWP/259165/2019

    English (EN) (311.32 KB - PDF)

    First published: 23/07/2021

    Medical devices with an ancillary medicinal substance

    A medical device may contain an ancillary medicinal substance to support the proper functioning of the device. These products fall under the medical devices legislation and must be CE marked.

    Examples of medical devices with an ancillary medicinal substance include:

    • drug-eluting stents;
    • bone cement containing an antibiotic;
    • catheters coated with heparin or an antibiotic agent;
    • condoms coated with spermicides.

    Role of EMA

    Before it can issue a CE certificate, the notified body must seek a scientific opinion from EMA on the quality and safety of the ancillary substance if it is derived from human blood or human plasma, or if it is within the scope of the centralised procedure for the authorisation of medicines.

    For other substances, the notified body can seek the opinion from a national competent authority or from EMA e.g. in cases where EMA has already evaluated a medicine containing the same medicinal substance.

    For information on the consultation procedure to seek an EMA scientific opinion, see:

    Companion diagnostics ('in vitro diagnostics')

    A companion diagnostic is an in vitro diagnostic test that supports the safe and effective use of a specific medicinal product, by identifying patients that are suitable or unsuitable for treatment.

    The In Vitro Diagnostic Devices Regulation (Regulation (EU) 2017/746) introduces a new classification system for companion diagnostics and the obligation to undergo a conformity assessment by a notified body.

    The Regulation applies from 26 May 2022, following a five-year transition period.

    Role of EMA

    Before it can issue a CE certificate, the notified body must seek a scientific opinion from EMA on the suitability of the companion diagnostic to the medicinal product concerned if:

    • the medicinal product falls exclusively within the scope of the centralised procedure for the authorisation of medicines, or
    • the medicinal product is already authorised through the centralised procedure, or
    • a marketing authorisation application for the medicinal product has been submitted through the centralised procedure.

    For other substances, the notified body can seek the opinion from a national competent authority or EMA.

    A guidance document is available on the consultation procedure whereby notified bodies seek a scientific opinion from EMA. This is joined by a question-and-answer (Q&A) document on practical arrangements.

    This guidance should help notified bodies, device manufacturers and medicinal product applicants understand the procedural aspects of the consultation process.

    The FAQ document below provides an overview of EMA’s line of thinking on issues related to predictive biomarker-guided medicinal product development and assessment involving companion diagnostic (CDx).

    Guidance on the procedural aspects for the consultation to the European Medicines Agency by a notified body on companion diagnostics

    Adopted Legal effective date: 01/07/2022 Reference Number: EMA/198592/2022

    English (EN) (233.01 KB - PDF)

    First published: 01/07/2022

    Questions & answers - Practical arrangements on the companion diagnostics consultation procedure to the European Medicines Agency by notified bodies

    Reference Number: EMA/619893/2022

    English (EN) (152.67 KB - PDF)

    First published: 20/12/2021 Last updated: 31/07/2023

    Frequently asked questions on medicinal products development and assessment involving companion diagnostic (CDx)

    Reference Number: EMA/CHMP/821321/2022

    English (EN) (167.05 KB - PDF)

    First published: 06/12/2023

    Notified bodies should use the application forms below to request an initial or follow-up consultation.

    Letter of intent for the submission of a consultation to the European Medicines Agency by a notified body on a companion diagnostic in accordance with Regulation (EU) 2017/746

    Reference Number: EMA/781233/2021

    English (EN) (117.99 KB - DOCX)

    First published: 08/07/2022 Last updated: 31/07/2023

    Application form for initial consultation by a notified body on a companion diagnostic

    English (EN) (128.43 KB - DOCX)

    First published: 20/12/2021 Last updated: 01/07/2022

    Application form for follow-up consultation procedure by a notified body on a companion diagnostic

    English (EN) (124.25 KB - DOCX)

    First published: 01/07/2022

    Consultation on companion diagnostic - Assessment report template

    English (EN) (140.95 KB - DOCX)

    First published: 20/12/2021 Last updated: 01/07/2022

    Submitted comments on 'Draft guidance on the procedural aspects for the consultation to the European Medicines Agency by a notified body on companion diagnostics'

    English (EN) (561.2 KB - PDF)

    First published: 01/07/2022

    For more information:

    Medical devices made of substances that are systemically absorbed

    Some medical devices are made of substances that are absorbed by the human body to achieve their intended purpose.

    These devices are normally introduced into the human body via an orifice or applied to the skin.

    Role of EMA

    Before it can issue a CE certificate, the notified body must seek a scientific opinion from EMA or a national competent authority on the compliance of the substance with the requirements laid down in Annex I to Directive 2001/83/EC.

    EMA will provide further information on the consultation procedure between the notified body and a competent authority or EMA.

    Borderline products

    Borderline products are complex healthcare products for which there is uncertainty over which regulatory framework applies.

    Common borderlines are between medicinal products, medical devices, cosmetics, biocidal products, herbal medicines and food supplements.

    National competent authorities classify borderline products either as medicinal products or, for example, as medical devices on a case-by-case basis. This determines the applicable regulatory framework.

    Applicants who are unclear on the correct classification of their product should consult a national competent authority and provide information on the product's composition and constituents, a scientific explanation of the mode of action and its intended purpose.

    Role of EMA

    The Medical Devices Regulation foresees that the European Commission may consult EMA on products that borderline with medicines.

    EMA's Innovation Task Force provides advice to medicine developers on eligibility to EMA procedures relating to the research and development of borderline products.

    High-risk medical devices

    For certain high-risk devices, the Regulations on Medical Devices (Regulation (EU) 2017/745) and on In Vitro Diagnostic Devices (Regulation (EU) 2017/746) require notified bodies to consult expert panels before issuing a CE certificate.

    These high-risk medical devices include:

    • Class III implantable devices and class IIb active devices that are intended to administer or remove medicinal products from the body
    • Class D in vitro diagnostic medical devices

    The expert panels' opinions and views are currently available on the European Commission's website:

    • European Commission: List of opinions on class III implantable devices and class IIb devices under the CECP
    • European Commission: List of views on class D devices under the PECP
      

    In line with the Regulation on Medical Devices, the expert panels have started to provide advice to the Medical Device Coordination Group (MDCG). This advice is currently available on the European Commission's website.

    They are also foreseen to advise the European Commission, national competent authorities in EU Member States and notified bodies, if needed.

    The implementation of these activities is gradual. EMA will provide further information for stakeholders when available.

    For more information, see:

    Role of EMA

    EMA provides administrative, technical and scientific support to the expert panels, in accordance with the Regulation on EMA's Reinforced Role (Regulation (EU) 2022/123). For more information, see Crisis preparedness and management.

    Working instructions for Notified Bodies on the application of Article 54 of Regulation (EU) 2017/745 on medical devices and Article 48 of Regulation (EU) 2017/746 on in vitro diagnostic medical devices

    Reference Number: EMA/416077/2023

    English (EN) (2.29 MB - PDF)

    First published: 02/02/2024

    Scientific advice pilot for high-risk medical devices

    EMA is running a pilot that enables the expert panels to provide scientific advice for manufacturers of high-risk medical devices.

    For more information on the pilot, including related presentations and a letter of interest template that can serve as guidance for applicants, see:

    • Information session on the pilot for expert panels’ scientific advice to manufacturers of high-risk medical devices (25/01/2023)
    • EMA pilots scientific advice for certain high-risk medical devices (27/02/2023)

    EMA invites EU-based manufacturers or their authorised representatives to apply for a third phase of the pilot by 30 June 2024. They can use the following application form:

    For the third pilot phase, applicants can indicate if they would be willing to have an HTA body observe their project. In such cases, EMA will inform them whether this will be possible.

    Applicants can address any questions to the expert panel secretariat at eu-operations-expamed@ema.europa.eu.

    In the first round, the expert panels selected six applications focused on fields such as circulatory system, orthopaedics, neurology and dentistry.

    EMA will publish further information on the pilot's progress, including its second round, in due course.

    As the current pilot phase includes a limited number of scientific advice procedures, the expert panels prioritise applications that can cover varied medical areas and device types.

    Experts uphold three prioritisation criteria:

    • devices used by a relatively small group of patients to help diagnose or treat a disease or condition - for instance, so-called orphan devices and those for paediatricuse;
    • devices that help address unmet medical needs - for example, devices for medical conditions that are life threatening or can cause permanent impairment, and for which the treatment currently available is insufficient or carrying significant risks for patients;
    • novel devices that can have a major clinical or health impact.

    Applications from small and medium-sized enterprises (SMEs) receive special attention to ensure their representation in the pilot.

    As per the Medical Devices Regulation (Article 61(2) of Regulation (EU) 2017/745), scientific advice for medical devices refers to intended clinical development strategies and clinical investigation proposals. It covers:

    • class III medical devices;
    • class IIb active medical devices intended to administer or remove medicinal products from the body.

    Expert panels support for orphan medical devices: pilot programme

    EMA is inviting manufacturers of high-risk medical devices and notified bodies to apply for its pilot programme to support orphan medical devices. The pilot programme will provide free advice on a possible orphan device status and on the clinical evaluation of orphan medical devices.

    This will help both new orphan medical devices and legacy medical devices, which are transitioning under rules of the Medical Device Regulation (EU) 2017/745 (MDR). Concretely, it will help bring new orphan medical devices onto the EU market while also keeping legacy medical devices on the EU market.

    The pilot programme will run until the end of 2025, subject to available resources.

    It is designed to establish a long-term process for requesting orphan device support from the expert panels.

    How it works

    For selected proposals from manufacturers, the expert panels will advise:

    • regarding a possible orphan status of a device;
    • and on the clinical development strategy and / or proposals for clinical investigation for the respective device.

    For selected proposals from notified bodies, the expert panels will advise:

    • either on a possible orphan status of a device;
    • or on the data required for the clinical evaluation during an ongoing conformity assessment.

    Notified bodies will submit their advice request in cooperation with the orphan device manufacturer.

    The request for advice depends on the stage of development of the device. It may include an opinion on:

    • orphan device status;
    • data sets required for the clinical evaluation as part of the conformity assessment;
    • review of the justification regarding the limited clinical data;​
    • acceptability of clinical uncertainty and limitations in the data sets;
    • acceptability of the proposed post-market clinical follow-up activities.

    The pilot programme will prioritise certain groups of orphan medical devices:

    • Devices for treating medical conditions that are life threatening or cause permanent impairment of a body function
    • Devices intended for children
    • Novel devices with a potential major clinical benefit

    How to apply

    Submit your application at any time via the dedicated portal linked below:

    In your application, you should clearly elaborate on:

    • specific issues to be addressed concerning the orphan device status and / or the clinical data set needed for the pre-market clinical evaluation;
    • post-market clinical follow-up activities to address the limitations in the pre-market clinical data.

    Guidance

    Guidance is available to help determine when a medical device or an accessory for a medical device should be regarded as ‘orphan’.

    The guidance also provides a benchmark to manufacturers and notified bodies on the clinical evaluation of orphan devices which require clinical data evidence to demonstrate conformity with the MDR.

    The Medical Devices Coordination Group (MDCG) published the guidance in June 2024:

    Related content

    • Ancillary medicinal substances in medical devices
    • Crisis preparedness and management