What evidence the EU requires for medical devices

A device placed on the EU market must be supported by clinical data that provide sufficient clinical evidence to confirm conformity with the general safety and performance requirements in Annex I, under the normal conditions of its intended use.¹ The manufacturer specifies and justifies the level of clinical evidence needed, and that level must be appropriate to the characteristics of the device and its intended purpose.¹ Regulation (EU) 2017/745 therefore sets a proportionate standard rather than a fixed study type, with one firm rule: for implantable devices and class III devices, clinical investigations must be performed unless a narrow exemption applies.¹

What the evidence has to establish

The clinical evaluation must confirm conformity with the relevant general safety and performance requirements in Annex I, evaluate undesirable side effects and establish the acceptability of the benefit-risk ratio referred to in Sections 1 and 8 of Annex I.¹ The evaluation must be thorough and objective and take into account both favourable and unfavourable data.¹ Its depth and extent must be proportionate to the nature, classification, intended purpose and risks of the device, and to the claims the manufacturer makes about it.¹

Three inputs form the methodological basis of the evaluation under Article 61(3). The first is a critical evaluation of the relevant scientific literature on safety, performance, design characteristics and intended purpose, usable only where equivalence under Section 3 of Annex XIV is demonstrated and where the data adequately demonstrate compliance.¹ The second is a critical evaluation of the results of all available clinical investigations, taking into account whether they were performed under Articles 62 to 80, acts adopted pursuant to Article 81 and Annex XV.¹ The third is consideration of currently available alternative treatment options for the same purpose, where any exist.¹

The clinical evaluation plan

Annex XIV Part A requires the manufacturer to establish and update a clinical evaluation plan. That plan must contain at least the following.

• An identification of the general safety and performance requirements that require support from relevant clinical data.
• A specification of the intended purpose of the device.
• A clear specification of intended target groups with clear indications and contra-indications.
• A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters.
• A specification of methods for examining qualitative and quantitative aspects of clinical safety, with clear reference to residual risks and side effects.
• An indicative list of parameters used to determine the acceptability of the benefit-risk ratio, based on the state of the art in medicine.
• An indication of how benefit-risk issues relating to specific components are to be addressed, such as the use of pharmaceutical substances or non-viable animal or human tissues.
• A clinical development plan.¹

The clinical development plan indicates progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations such as pivotal clinical investigations.¹ It also covers post-market clinical follow-up as described in Part B, with milestones and a description of potential acceptance criteria.¹ Around that plan the manufacturer identifies available clinical data and gaps through a systematic scientific literature review. The manufacturer then appraises the suitability of all relevant data and generates new data through properly designed clinical investigations where outstanding issues remain. Finally, all relevant data is analysed to reach conclusions on safety, clinical performance and clinical benefit.¹

When a clinical investigation is mandatory

For implantable devices and class III devices, clinical investigations must be performed.¹ Article 61(4) sets out one route away from that rule, available only where all three of its conditions are met. The device must have been designed by modification of a device already marketed by the same manufacturer, the modified device must be demonstrated equivalent to the marketed device under Section 3 of Annex XIV with that demonstration endorsed by the notified body, and the clinical evaluation of the marketed device must be sufficient to demonstrate conformity of the modified device.¹ Where that route is used, the notified body must check that the post-market clinical follow-up plan is appropriate and includes post-market studies to demonstrate the safety and performance of the device.¹

A second route is set out in Article 61(6) for implantable and class III devices whose clinical evaluation is based on sufficient clinical data and complies with the relevant product-specific common specification where one is available. It covers devices lawfully placed on the market or put into service under Directive 90/385/EEC or Directive 93/42/EEC.¹ It also covers a defined list of well-established technologies in point (b), together with a longer catalogue of further items.¹ The catalogue includes guidewires, dental implants and bone substitutes. It also includes feeding tubes, reusable surgical instruments and endovascular embolisation coils. The defined list includes the following.

• sutures
• staples
• dental fillings
• dental braces
• tooth crowns
• screws
• wedges
• plates
• wires
• pins
• clips
• connectors

Any case in which Article 61(4) is set aside by virtue of Article 61(6) must be justified by the manufacturer in the clinical evaluation report and by the notified body in the clinical evaluation assessment report.¹

Equivalence and access to the underlying data

Equivalence under Section 3 of Annex XIV rests on three sets of characteristics, all of which must be considered together. The technical characteristics cover similar design, similar conditions of use, similar specifications and properties including physicochemical properties, similar deployment methods where relevant and similar principles of operation and critical performance requirements.¹ The biological characteristics require the same materials or substances in contact with the same human tissues or body fluids, for a similar kind and duration of contact, with similar release characteristics including degradation products and leachables.¹ The clinical characteristics require the same clinical condition or purpose, including similar severity and stage of disease, the same site in the body, a similar population, the same kind of user and similar relevant critical performance.¹

These characteristics must be similar to the extent that there would be no clinically significant difference in safety and clinical performance, and the judgement must rest on proper scientific justification.¹ The manufacturer must clearly demonstrate a sufficient level of access to the data relating to the device claimed as equivalent.¹ Article 61(5) adds further conditions where the equivalent device belongs to another manufacturer, which goes beyond predicate comparison as other jurisdictions use it. The two manufacturers must have a contract that explicitly allows full access to the technical documentation on an ongoing basis, and the original clinical evaluation must have been performed in compliance with this Regulation, with clear evidence of that given to the notified body.¹

Where non-clinical testing alone is accepted

Article 61(10) permits a demonstration of conformity based on non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, where reliance on clinical data is not deemed appropriate.¹ This operates without prejudice to Article 61(4), so it does not displace the investigation requirement for implantable and class III devices.¹ The justification must be based on the results of the manufacturer’s risk management and on the specifics of the interaction between the device and the human body, the clinical performance intended and the claims made.¹ It must be duly substantiated in the technical documentation referred to in Annex II.¹

Products without an intended medical purpose

For the products listed in Annex XVI, the requirement to demonstrate a clinical benefit is read as a requirement to demonstrate the performance of the device.¹ The clinical evaluation must be based on relevant data concerning safety, including data from post-market surveillance and post-market clinical follow-up, and where applicable from specific clinical investigation.¹ Clinical investigations must be performed for those products unless reliance on existing clinical data from an analogous medical device is duly justified.¹

Post-market clinical follow-up

Post-market clinical follow-up is a continuous process that updates the clinical evaluation, and it must be addressed in the manufacturer’s post-market surveillance plan.¹ The manufacturer proactively collects and evaluates clinical data from use of the CE marked device within its intended purpose, to confirm safety and performance throughout the expected lifetime, to ensure the continued acceptability of identified risks and to detect emerging risks on factual evidence.¹ It is performed under a documented method laid down in a PMCF plan.¹

The PMCF plan must specify methods and procedures aimed at confirming safety and performance, identifying previously unknown side effects and monitoring identified side effects and contraindications. It must also aim at identifying and analysing emergent risks, ensuring the continued acceptability of the benefit-risk ratio and identifying possible systematic misuse or off-label use.¹ The plan must include at least the following.

• The general methods and procedures to be applied, such as gathering of clinical experience, user feedback and screening of scientific literature.
• The specific methods and procedures, such as evaluation of suitable registers or PMCF studies.
• A rationale for the appropriateness of those methods and procedures.
• A reference to the relevant parts of the clinical evaluation report and to the risk management referred to in Section 3 of Annex I.
• The specific objectives to be addressed.
• An evaluation of clinical data relating to equivalent or similar devices.
• Reference to any relevant common specification, harmonised standards used and relevant guidance on PMCF.
• A detailed and justified time schedule for PMCF activities.¹

The findings are analysed and documented in a PMCF evaluation report, which forms part of the clinical evaluation report and the technical documentation.¹ For class III devices and implantable devices, that report must be updated at least annually. The same applies, where indicated, to the summary of safety and clinical performance referred to in Article 32.¹ Where PMCF identifies the need for preventive or corrective measures, the manufacturer must implement them.¹

Expert panel consultation before the evidence is generated

For all class III devices and for the class IIb devices referred to in point (b) of Article 54(1), the manufacturer may consult an expert panel under Article 106 before the clinical evaluation or investigation.¹ The purpose is a review of the intended clinical development strategy and of proposals for clinical investigation.¹ The consultation is optional. Where it takes place, the manufacturer must give due consideration to the views expressed and document that consideration in the clinical evaluation report, and no rights may be invoked in respect of those views in any future conformity assessment.¹

Legacy devices and the evidence they run on

Devices holding a certificate issued under Directive 90/385/EEC or Directive 93/42/EEC that remains valid by virtue of Article 120(2) may be placed on the market or put into service until 31 December 2027 for class III devices and class IIb implantable devices, with an exception for items such as sutures, staples, dental fillings, screws and connectors.¹ The date is 31 December 2028 for other class IIb devices, for class IIa devices and for class I devices placed on the market in sterile condition or having a measuring function.¹ Those devices continue to comply with the applicable directive, and there must be no significant changes in design and intended purpose.¹

The conditions in Article 120(3c) also required a quality management system under Article 10(9) by 26 May 2024, a formal application to a notified body by the same date and a signed written agreement by 26 September 2024.¹ The requirements of the Regulation on post-market surveillance, market surveillance, vigilance and registration apply to these devices in place of the corresponding directive requirements.¹ The derogation in Article 120(3f) for class III custom-made implantable devices ran until 26 May 2026 and has expired.¹

Questions people also ask

Does every class III device need a new clinical investigation in the EU?

Clinical investigations must be performed for implantable and class III devices, subject to the exemptions in Article 61(4) and Article 61(6).¹ Article 61(4) applies where the device is a modification of one already marketed by the same manufacturer, equivalence is demonstrated and endorsed by the notified body and the existing clinical evaluation is sufficient. Article 61(6) covers legacy devices lawfully marketed under the old directives and the listed well-established technologies, in each case where the evaluation rests on sufficient clinical data and complies with any relevant product-specific common specification.¹

Can a manufacturer claim equivalence to a competitor’s device?

Article 61(5) allows it under conditions additional to those in Article 61(4). The two manufacturers must have a contract that explicitly allows the second manufacturer full access to the technical documentation on an ongoing basis.¹ The original clinical evaluation must have been performed in compliance with Regulation (EU) 2017/745, and clear evidence of that must be given to the notified body.¹

What is the difference between the clinical evaluation report and the PMCF evaluation report?

The clinical evaluation report documents the clinical evaluation, its results and the clinical evidence derived from it. It forms part of the technical documentation under Annex II, except for custom-made devices.¹ The PMCF evaluation report documents the analysis of post-market clinical follow-up findings and forms part of the clinical evaluation report and of the technical documentation.¹ Its conclusions feed back into the clinical evaluation and into risk management under Section 3 of Annex I.¹

How often must clinical evidence be updated after CE marking?

The clinical evaluation and its documentation must be updated throughout the life cycle of the device with clinical data from the PMCF plan and the post-market surveillance plan referred to in Article 84.¹ For class III devices and implantable devices, the PMCF evaluation report must be updated at least annually. The same applies to the summary of safety and clinical performance where indicated.¹

What evidence applies to products listed in Annex XVI that have no medical purpose?

The clinical benefit requirement is read as a requirement to demonstrate the performance of the device.¹ The evaluation must draw on relevant safety data, including post-market surveillance and PMCF data. Where applicable, it must also draw on specific clinical investigation. Clinical investigations must be performed unless reliance on existing clinical data from an analogous medical device is duly justified.¹

Footnotes

1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Consolidated version of 2026-07-19. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02017R0745-20260719 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²² ↩²³ ↩²⁴ ↩²⁵ ↩²⁶ ↩²⁷ ↩²⁸ ↩²⁹ ↩³⁰ ↩³¹ ↩³² ↩³³ ↩³⁴ ↩³⁵ ↩³⁶ ↩³⁷ ↩³⁸ ↩³⁹ ↩⁴⁰ ↩⁴¹ ↩⁴² ↩⁴³ ↩⁴⁴ ↩⁴⁵ ↩⁴⁶ ↩⁴⁷ ↩⁴⁸ ↩⁴⁹ ↩⁵⁰ ↩⁵¹ ↩⁵² ↩⁵³ ↩⁵⁴ ↩⁵⁵ ↩⁵⁶ ↩⁵⁷ ↩⁵⁸ ↩⁵⁹ ↩⁶⁰