Every clinical investigation of a medical device in the European Union requires a positive opinion from the ethics committee of each member state in which the investigation runs, before the first subject is enrolled. The requirement is anchored in MDR Article 62(4)(b), which makes favourable ethics committee opinion a precondition for conducting the investigation, and in MDR Article 82, which preserves ethics committee protections for investigations outside the conformity pathway. The content of the submission is specified by Annex XV of Regulation (EU) 2017/745 — the clinical investigation plan, the investigator's brochure, the informed consent documentation required by Article 63, the investigator CVs, the insurance evidence, and the national forms. The operational procedure is governed by EN ISO 14155:2020+A11:2024, the harmonised Good Clinical Practice standard. National law determines which committee reviews, how it sits, and how long the review takes. The absolute requirement for approval before enrolment does not vary by member state, device class, or sponsor size.

By Tibor Zechmeister and Felix Lenhard. Last updated 10 April 2026.

TL;DR

  • Ethics committee approval is a precondition for every MDR clinical investigation under Article 62(4)(b). No approval, no first subject.
  • MDR Article 82 preserves the ethics protections for clinical investigations that are not conducted to demonstrate conformity.
  • The submission dossier is built from Annex XV Chapter II content — CIP, investigator's brochure, device documentation, consent materials, investigator CVs, insurance — plus national-specific forms.
  • EN ISO 14155:2020+A11:2024 is the operational standard for the ethics review process, the informed consent procedures, and the sponsor's ongoing communication with the committee.
  • National law determines composition, procedure, and timelines. What does not vary is the absolute requirement for a positive opinion before enrolment.
  • Substantial modifications under Article 75 and serious adverse events under Article 80 trigger further ethics committee obligations during the study.

The Vienna submission that came back twice

A founder we worked with, running a small cardiovascular startup, treated the ethics committee submission as a paperwork exercise to be handled by the clinical research associate in the last week before the target first-subject-in date. The clinical investigation plan was ready. The investigator's brochure was drafted. The consent form was copied from a template a colleague had sent over. The insurance certificate was in the founder's inbox, unopened.

The first submission came back within two weeks. The committee had questions about the risk-benefit discussion in the consent form, the translation of the patient information into the local language, and the scope of the insurance — the sum insured fell short of the national minimum for investigational studies. The second submission came back a month later with a follow-up question on the independence of the principal investigator from the sponsor. Each cycle cost four to six weeks. The planned first-subject-in date slipped by three months. The runway did not have three months to give away.

Nothing about the committee's behaviour was unreasonable. Each question pointed at a real deficiency. The founder had assumed ethics review was a rubber stamp for a well-designed study. It is not. It is a scientific, ethical, and procedural review conducted by people whose job is to protect subjects from poorly prepared sponsors. A well-prepared submission passes on the first cycle. A rushed submission enters a loop that no amount of apology fixes.

This post explains what the ethics committee actually checks, how to build a submission that passes on the first cycle, and where the post-approval obligations live during and after the study. It is the companion to our Chapter VI walkthrough in MDR Chapter VI: Clinical Investigations — The Full Regulatory Framework and to the when-is-it-required question we covered in What Is a Clinical Investigation Under MDR?.

The role of the ethics committee under MDR

The ethics committee is the independent body that reviews the ethical, scientific, and procedural acceptability of a clinical investigation before it may proceed. Its role is anchored in two places in the Regulation.

MDR Article 62(4)(b) lists the conditions every clinical investigation conducted to demonstrate conformity must satisfy. Among them is the condition that the investigation has been the subject of a favourable opinion by an ethics committee — constituted in accordance with national law — in the member state or states where the investigation is planned. This is not a procedural nicety. It is a precondition. Without the positive opinion, the investigation cannot legally proceed, and the competent authority cannot authorise it.

MDR Article 82 addresses clinical investigations that are not conducted for the purpose of demonstrating conformity of a device — research investigations, post-market investigations outside the Article 74 pathway, and combined studies. Article 82 preserves the application of the core subject-protection provisions, including the involvement of ethics committees, and allows member states to apply additional national provisions. The practical effect is that ethics committee approval is required across the full range of clinical investigations a sponsor may run on a medical device, not only the narrower set of pre-market conformity studies.

The composition of the ethics committee, its procedures, its review timelines, and the specific documents it requires are governed by national law in each member state. There is no EU-level harmonised ethics committee for medical device investigations. A sponsor running in Germany, Austria, and France is navigating three national systems in parallel, each with its own forms, fees, languages, and procedural expectations.

What is harmonised is the obligation. Every member state in which the investigation runs must give its positive opinion before enrolment opens in that member state. There are no exceptions for small sponsors, for low-risk devices, or for pilot phases. The two-person startup running a single-site twenty-subject investigation is held to the same absolute rule as the multinational running a ten-country Class III trial.

How to prepare the submission — the how-to

The submission is not a single document. It is a dossier assembled from content specified by Annex XV and the national forms of the committee concerned. Prepared properly, it passes on the first cycle. The steps below are the sequence we use with startup sponsors.

Step 1 — Confirm which committee reviews

Identify the ethics committee with jurisdiction for the planned investigational site or sites under the national law of the member state concerned. In some member states, a single national committee reviews all medical device investigations. In others, the committee is tied to the institution hosting the investigator. In others still, a central committee plus a local committee both have to weigh in. This is determined before the CIP is finalised, not after, because the committee's procedural rules may affect the content and format of the submission.

Step 2 — Finalise the clinical investigation plan to Annex XV content

The CIP submitted to the ethics committee must cover the full content list specified in Annex XV Chapter II. A CIP missing items from Annex XV will not pass committee review on the first cycle, because the committee's scientific reviewers will flag each gap. Our companion post Writing a Clinical Investigation Plan (CIP) Under MDR Article 62 walks the content list item by item.

Step 3 — Build the investigator's brochure to Annex XV Chapter II

The investigator's brochure summarises the device, the pre-clinical data, the prior clinical experience where it exists, the known risks, and the rationale for the investigation. Annex XV specifies what it must contain. Committees read it carefully because it is the honest summary of what is known and what is not known at the time the investigation begins. A thin investigator's brochure is a red flag for both scientific and ethical review.

Step 4 — Draft the informed consent documents to Article 63

Informed consent documents are typically the single most scrutinised part of the ethics submission. They must comply with MDR Article 63 — freely given, informed, written consent, with comprehensible information on the nature, objectives, benefits, implications, risks, and inconveniences of the investigation, and on the subject's right to withdraw without detriment. They must be in the language the subject actually speaks. They must match the risk-benefit discussion in the CIP. They must not overstate the benefits or understate the risks. Committees reject consent forms for small infractions — marketing-sounding language, missing contact points for complaints, missing right-to-withdraw statements. Treat the consent documents as the second-most important part of the dossier after the CIP.

Step 5 — Assemble the supporting documentation

Investigator CVs demonstrating qualification and independence from the sponsor. Site suitability evidence. Insurance certificates that meet the national minimum sum insured for investigational studies — this is a recurring stumbling block and must be checked against national law in each member state before the CIP is finalised. Data protection documentation covering the processing of subject data under the GDPR. National-specific forms required by the committee concerned.

Step 6 — Submit, and plan for review cycles

Submit the dossier through the national procedure of the committee concerned. The review clock starts at validation, not at receipt. Plan for one review cycle as the realistic case and a second as the contingency. A committee that comes back with no questions at all is the exception. A committee that comes back with two or three substantive questions is the rule for well-prepared dossiers. A committee that comes back with twenty questions is what a rushed dossier looks like, and the project timeline will not recover.

What the committee actually checks

Ethics committees review on three axes. Understanding the axes in advance is the difference between a submission that looks right and a submission that passes review.

Scientific validity. Is the investigation scientifically sound? Is the hypothesis clear? Are the endpoints appropriate? Is the sample size justified? Is the statistical analysis plan appropriate? Will the study actually answer the question it is designed to answer? A scientifically invalid investigation cannot be ethical, because it exposes subjects to risk without producing usable evidence. The CIP carries this weight.

Subject protection. Are the foreseeable risks justified by the expected benefits? Is the informed consent genuine? Are vulnerable populations protected in accordance with Articles 64 to 68 where applicable? Is the investigator qualified and independent? Is the insurance adequate? Is the risk management plan under EN ISO 14971:2019+A11:2021 reflected in the investigational procedures? Is the stopping rule defined?

Procedural compliance. Does the dossier contain every Annex XV element? Are the national-specific forms complete? Is the data protection documentation in order? Is the sponsor's regulatory responsibility chain clear? Are the reporting obligations under Articles 75, 77, and 80 acknowledged in the CIP, so the committee knows the sponsor is aware of them?

A sponsor who walks into ethics review with a dossier that addresses all three axes, directly and honestly, is in a position to pass on the first cycle. A sponsor who addresses only one or two of them is not.

Timelines — what is realistic

The review timeline is set by national law, and it varies meaningfully between member states. What does not vary is the structural shape. Validation of the dossier — a check that the required documents are present — is typically a matter of days to a few weeks. Substantive scientific and ethical review runs on a longer clock, commonly measured in weeks to a few months, depending on the committee's schedule and the complexity of the investigation. A request for additional information pauses the clock until the sponsor responds. A second round of questions pauses it again.

Planning a first-subject-in date four weeks after submission is magical thinking for almost every national system. Planning it three months after submission is realistic for a well-prepared dossier in many member states. Planning it six months after submission is realistic for a dossier that the committee is likely to bounce at least once. The founder who plans backwards from the first-subject-in date without allowance for review cycles is the founder whose runway burns in review loops.

The application to the competent authority under MDR Article 70 runs on its own clock, often in parallel with ethics review in some member states and sequentially in others. Sponsors check the national procedure for every member state where the investigation will run, before finalising the project plan.

Amendments — Article 75 and the committee

Substantial modifications to a clinical investigation under MDR Article 75 require notification to the competent authority and, under the national procedure, typically a fresh review by the ethics committee. A substantial modification is one that could affect the safety, health, or rights of subjects, or the robustness or reliability of the clinical data — changes to the investigational device, changes to the protocol, changes to the consent form, changes to the investigator team, changes to the monitoring plan. A sponsor who intends to make any of these changes runs them through the substantial modification procedure rather than implementing them quietly.

The practical rule we give founders: if a change matters enough that you are considering whether to notify, notify. The downside of over-notifying is a review cycle the sponsor wanted anyway. The downside of under-notifying is a finding of non-compliance the competent authority and the committee can act on.

Adverse events — Article 80 and the committee

Under MDR Article 80, the sponsor records and reports serious adverse events and device deficiencies that might have led to a serious adverse event to the member states in which the investigation is conducted. The reporting chain includes the competent authority and, under national procedure, typically the ethics committee. Reporting timelines are short — measured in days for most events, and in 24 hours for events indicating an imminent risk requiring prompt remedial action for other subjects.

Operationally, the Article 80 chain must be staffed, tested, and documented before the first subject is enrolled. Primary and backup owners named. Out-of-hours coverage defined. The path from an investigator reporting an event at the site to a submission landing at the authority and the committee within the required timeline rehearsed, not assumed. Our dedicated post Adverse Event Reporting Under MDR Article 80 walks the chain in detail.

Common mistakes sponsors make

The same errors repeat across startup submissions. A short list.

Treating ethics review as paperwork. It is a substantive scientific and ethical review. A dossier prepared in the last week before the target first-subject-in date is a dossier that will not pass cleanly.

Copying consent templates without adapting them. A consent form from another study, or worse from a template bank, almost never matches the specific risks, benefits, and procedures of the current investigation. Committees read carefully and catch this immediately.

Underfunded insurance. The national minimum sum insured for investigational studies varies and must be verified for every member state. A certificate that looks adequate at headquarters may fall short of the national requirement at the site.

Missing or mis-specified independence of the principal investigator. Committees check that the investigator has a documented independence from the sponsor and no conflicts of interest that could bias the conduct of the investigation. A founder-as-investigator arrangement is almost always a problem.

Ignoring the post-approval obligations. The sponsor's relationship with the committee does not end at the positive opinion. Substantial modifications under Article 75, adverse event reporting under Article 80 and national procedure, and end-of-investigation reporting under Article 77 all continue throughout the study and beyond.

The Subtract to Ship angle

Ethics review is one of the parts of MDR where the Subtract to Ship discipline looks from the outside like it applies the least — every obligation stays, every document is required, every review step runs. That is true. What Subtract to Ship cuts here is not obligations but ceremony.

The CIP is written once, to Annex XV content, and used for the competent authority, the ethics committee, the Notified Body review of the CER, and the archive. No parallel versions tailored for each audience. The investigator's brochure is the single source of truth on the device. No marketing brochure dressed up as an investigator's brochure. The consent form is drafted by the people who actually understand the risks — the principal investigator and the sponsor medical lead — not by a template service.

The sponsor obligations chain is operationalised on one page, not in a forty-page sponsor manual. Who reports what, to whom, within which timeline, with which backup. Rehearsed before enrolment. Posted where the people who have to act on it can actually see it. Our methodology pillar The Subtract to Ship Framework for MDR Compliance covers the principle — cut the ceremony, not the compliance.

Reality Check — Where do you stand?

  1. Do you know which ethics committee has jurisdiction for each planned investigational site under the national law of every member state where you will run?
  2. Is your CIP built against the Annex XV Chapter II content list, item by item, with no gaps?
  3. Has your informed consent form been drafted specifically for this investigation by the people who understand the risks, rather than copied from a template?
  4. Is your insurance certificate verified against the national minimum sum insured in every member state where the investigation will run?
  5. Is the principal investigator documented as independent from the sponsor, with no conflicts of interest that could bias the conduct?
  6. Have you planned the project timeline with realistic allowance for at least one ethics review cycle and a contingency for a second?
  7. Is your substantial modification procedure under Article 75 written into your sponsor SOPs, so amendments are not handled ad hoc?
  8. Is your Article 80 adverse event reporting chain staffed, tested, and documented before the first subject is enrolled, with named primary and backup owners?

Frequently Asked Questions

Do all MDR clinical investigations need ethics committee approval? Yes. Every clinical investigation on human subjects under MDR requires a favourable opinion from the ethics committee of each member state in which the investigation runs, before the first subject is enrolled. The requirement is anchored in MDR Article 62(4)(b) for conformity investigations and preserved by MDR Article 82 for investigations that are not conducted to demonstrate conformity. There are no exceptions for small sponsors, low-risk devices, or pilot phases.

Which law governs ethics committees for MDR investigations? The composition, procedures, and review timelines of ethics committees are governed by national law in each member state where the investigation runs. The absolute requirement for a favourable opinion before enrolment is set by MDR Article 62(4)(b) and preserved by Article 82. A sponsor running in multiple member states navigates multiple national systems in parallel.

What documents go into an ethics committee submission under MDR? The core dossier is built from the content specified in Annex XV Chapter II of Regulation (EU) 2017/745 — the clinical investigation plan, the investigator's brochure, the documentation of the device under investigation, the investigator CVs, proof of insurance, and the informed consent documents required by Article 63 — plus the national-specific forms required by the committee concerned. EN ISO 14155:2020+A11:2024 operationalises the content and the procedures.

How long does ethics committee review take under MDR? Timelines are set by national law and vary meaningfully between member states. Validation is typically measured in days to a few weeks. Substantive scientific and ethical review is typically measured in weeks to a few months. Requests for additional information pause the clock until the sponsor responds. A realistic project plan budgets for at least one review cycle and a contingency for a second.

Do substantial modifications need a new ethics committee review? Under MDR Article 75, substantial modifications — changes that could affect the safety, health, or rights of subjects, or the robustness or reliability of the clinical data — require notification to the competent authority and typically a fresh review by the ethics committee under the national procedure. A sponsor who is considering whether a change is substantial should default to notification rather than silent implementation.

Does the ethics committee need to see adverse event reports during the study? Yes. Under MDR Article 80 and the national procedure in the member state concerned, the sponsor reports serious adverse events and device deficiencies that might have led to a serious adverse event to the competent authority and, typically, to the ethics committee. Reporting timelines are short and the chain must be staffed and tested before the first subject is enrolled.

What standard governs the ethics review process in practice? EN ISO 14155:2020+A11:2024 — Clinical investigation of medical devices for human subjects — Good clinical practice — is the harmonised standard that operationalises compliance with MDR Chapter VI, including the ethics committee interactions, the informed consent procedures, and the sponsor's ongoing communication with the committee throughout the investigation.

Sources

  1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, Article 62(4) (conditions for clinical investigations conducted to demonstrate conformity, including favourable ethics committee opinion), Article 63 (informed consent), Article 70 (application for clinical investigations), Article 75 (substantial modifications), Article 80 (recording and reporting of adverse events), Article 82 (requirements regarding other clinical investigations, including preserved ethics committee protections), Annex XV (clinical investigations — documentation content). Official Journal L 117, 5.5.2017.
  2. EN ISO 14155:2020+A11:2024 — Clinical investigation of medical devices for human subjects — Good clinical practice.

This post sits in the Clinical Evaluation & Clinical Investigations cluster of the Subtract to Ship: MDR blog. Authored by Felix Lenhard and Tibor Zechmeister. If you are preparing an ethics committee submission for an MDR clinical investigation and want the dossier pressure-tested against Annex XV, Article 63, and the national procedure of every member state where you will run, Zechmeister Strategic Solutions walks that preparation with founders — document by document, committee by committee, before the submission clock starts.