Updated on 11 Apr 2025:
'Companion diagnostics ('in vitro diagnostics') - Current guidance' section
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:
| Medical device category | EMA responsibility |
|---|---|
| Medicines used in combination with a medical device | EMA assesses safety and effectiveness of medicines used in combination with medical device within centralised procedure application for medicinal product |
| Medical devices with an ancillary medicinal substance | Notified body must seek EMA scientific opinion on quality, safety, and usefulness of ancillary medicinal substance if ancillary substance:
|
| Companion diagnostics | Notified body must seek EMA scientific opinion on suitability of companion diagnostic to medicinal product if the latter falls in scope of centralised procedure |
| Medical devices made of substances that are systemically absorbed | Notified body must seek scientific opinion of a competent authority - EMA provides scientific opinion on compliance of substance with requirements in Annex I of Directive 2001/83/EC |
| High-risk medical devices | EMA supports medical device expert panels that provide opinions and views to notified bodies on scientific assessment of certain high-risk medical devices and in vitro diagnostics |
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.
Question-and-answer guidance on the implementation of these Regulations is available below.
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.
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:
| Type of combination | Illustration | Conformity assessment of device |
|---|---|---|
| Integral |
|
|
| Co-packaged or obtained separately |
|
|
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.
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:
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.
EMA publishes consultation procedure public assessment reports (CPAR) on its scientific opinions.
For information on the consultation procedure to seek an EMA scientific opinion, see:
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.
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:
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).
Notified bodies should use the application forms below to request an initial or follow-up consultation.
For more information:
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.
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 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.
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.
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:
For more information, see:
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.
EMA is offering clinical advice to manufacturers of high-risk medical devices through expert panels.
The expert panels advise on intended clinical development strategies and clinical investigation proposals. This is line with the Medical Devices Regulation (Article 61(2) of Regulation (EU) 2017/745).
The advice applies for the following devices:
Guidance for manufacturers is available below, including step-by-step instructions.
EMA ensures the expert panel secretariat. It coordinates the advice procedure and acts as the main contact point for applicants.
The regular advice procedure is in place as of February 2025.
EMA successfully established this procedure via a pilot launched in February 2023.
An interim report on the pilot in also available below.
For more information, see:
You can request this type of advice if you are an EU-based manufacturer or their authorised representative.
To do so, create an EMA account via the link below:
To request advice, open the 'letter of interest' form available on the dedicated portal linked below (if you already have an EMA account):
Note that the link above also serves to request advice on orphan medical devices.
Find more information on the 'Expert panels support for orphan medical devices: pilot programme' section on this page.
To correctly complete and submit the letter of interest form, select the “Scientific Advice according to Art. 61(2) of the MDR” option from the corresponding drop-down list.
While you can submit a letter of interest at any time, you can only submit the required final briefing document according to the 2025 timetable available below:
A briefing document template (in PDF format) is available for information.
Applicants will receive a Word version of this template that they need to fill in during the application.
For any questions not addressed in the guidance available in this section, you can get in touch at eu-operations-expamed@ema.europa.eu.
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.
Four applications will be selected as test cases for the first phase of the pilot.
The pilot is designed to establish a long-term process for requesting orphan device support from the expert panels.
For selected proposals from manufacturers, the expert panels will advise:
For selected proposals from notified bodies, the expert panels will advise:
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:
The pilot programme will prioritise certain groups of orphan medical devices:
Submit your application at any time via the dedicated portal linked below:
Please note that to access the application you need to log in with your EMA account. If you do not have one, please visit the EMA Account Management website and follow the steps under 'Create an EMA account'.
In your application, you should clearly elaborate on:
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:
Application templates in PDF format are provided for information purposes. Word documents to be filled in will be sent to the applicant during the procedure: