MDR Chapter VI — Articles 62 to 82 and Annex XV of Regulation (EU) 2017/745 — is the full regulatory framework that governs clinical investigations of medical devices in the European Union. It sets the general requirements of the investigation (Article 62), informed consent (Article 63), protections for incapacitated subjects, minors, pregnant and breastfeeding women, and subjects in emergency situations (Articles 64 to 68), the application and authorisation pathway with the member states (Articles 70 and 71), the conduct of the investigation and the sponsor's obligations during the study (Articles 72 and 73), post-market clinical follow-up studies (Article 74), amendments and end-of-investigation reporting (Articles 75 to 77), coordinated assessments and corrective measures (Articles 78 and 79), the recording and reporting of serious adverse events and device deficiencies (Articles 80 and 81), and the role of ethics committees (Article 82). Annex XV specifies the documentation content in detail, and EN ISO 14155:2020+A11:2024 is the harmonised Good Clinical Practice standard that operationalises compliance with the chapter. None of it is optional. A startup sponsor reads the whole chapter before the first subject is enrolled.

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

TL;DR

  • MDR Chapter VI covers Articles 62 to 82 and Annex XV of Regulation (EU) 2017/745 — the full legal framework for clinical investigations of medical devices.
  • The chapter sets general requirements, informed consent, protection of vulnerable populations, application and authorisation, conduct, post-market follow-up studies, amendments, end-of-investigation reporting, adverse event reporting, and ethics committee involvement.
  • Annex XV specifies the required content of the clinical investigation plan, the investigator's brochure, the documentation of the device under investigation, and the reporting obligations.
  • EN ISO 14155:2020+A11:2024 is the harmonised Good Clinical Practice standard and the operational floor for compliance with Chapter VI.
  • The chapter applies in full to startup sponsors. There is no proportionality clause that relaxes Chapter VI for small teams.
  • A founder who treats Chapter VI as a chapter to skim rather than to read will miss obligations that have no workaround at the application stage.

Why the whole chapter matters, not just Article 62

Most founders first encounter Chapter VI through Article 62 — the general requirements — and then stop reading. Article 62 is the spine, but it is not the whole skeleton. The chapter contains twenty-one articles and one annex, and each one carries obligations that land on the sponsor before, during, or after the investigation. Skipping any of them is the most common way a startup investigation becomes unauthorisable at the last minute.

The pattern we see is predictable. A small team commits to a study because the device needs clinical evidence under MDR Article 61. They read Article 62, hire a clinical research associate, draft a protocol, and assume the operational detail will fall into place. Two months before the planned first-subject-in date, the ethics committee submission exposes every provision of Articles 63 to 82 that the team never read — insurance, vulnerable-population protections, amendment procedures, adverse event timelines, end-of-investigation reporting. The planned enrolment slips by months. The runway does not stretch to absorb the slip.

This post walks the chapter in order. Each section names the article, summarises what it governs, and states what it means for a startup sponsor. It is not a substitute for reading the Regulation itself — no post can be that — but it is the map a founder can use to know which articles to read carefully before committing to an investigation.

Article 62 — General requirements for clinical investigations conducted to demonstrate conformity

Article 62 is the core provision. It states the general requirements that every clinical investigation conducted to demonstrate conformity of a device must satisfy. The investigation must be designed, authorised, conducted, recorded, and reported in accordance with the provisions of Chapter VI and Annex XV. The rights, safety, dignity, and well-being of subjects must be protected and prevail over all other interests. The clinical data generated must be scientifically valid, reliable, and robust. The foreseeable risks must be weighed against the anticipated benefits, and the benefits must justify the risks.

Article 62(4) lists the conditions every conformity investigation must satisfy — scientific soundness, subject protection, justified risk-benefit balance, a written clinical investigation plan that is followed, informed consent, ethics committee approval, qualified investigators, reliable data, subject data protection, and insurance or indemnification arrangements. Our companion post The Sponsor's Obligations in Clinical Investigations Under MDR Article 62(4) walks through that list in detail.

For the startup sponsor, Article 62 is the article to memorise. Every other article in the chapter either specifies one of its requirements in more detail or adds an obligation on top.

Article 63 — Informed consent

Article 63 governs the informed consent process. Subjects must give freely given, informed, written consent before any procedure related to the clinical investigation. The information provided must be comprehensible, must honestly describe the nature, objectives, benefits, implications, risks, and inconveniences of the investigation, and must make clear the right to withdraw at any time without any resulting detriment.

The sponsor is responsible for the design of the consent documents, the process by which consent is obtained at each site, and the documentation that consent was obtained before any study-specific procedure. Informed consent is not a form to sign. It is a conversation, recorded in writing, that the subject can honestly say they understood.

Our dedicated post Informed Consent Under MDR Article 63 covers the design of the consent process and the common failure modes.

Articles 64 to 68 — Vulnerable populations and specific situations

Articles 64 to 68 add specific protections for subjects who cannot give fully autonomous informed consent, or who are in situations where additional safeguards are required.

Article 64 — Clinical investigations on incapacitated subjects. Additional conditions apply: informed consent of the legally designated representative, direct benefit to the subject expected or minimal risk and minimal burden, and the investigation cannot be performed with equal effectiveness on subjects capable of giving consent.

Article 65 — Clinical investigations on minors. Additional conditions apply: informed consent of the parents or legal representative, assent of the minor where they are capable of forming an opinion, direct benefit expected or minimal risk and minimal burden, and the investigation relates to a condition the minor has or can only be carried out on minors.

Article 66 — Clinical investigations on pregnant or breastfeeding women. Additional conditions apply: direct benefit to the woman, the embryo, foetus, child after birth, or breastfed infant, or minimal risk and minimal burden, and specific measures to minimise risk.

Article 67 — Additional national measures. Member states may maintain additional measures regarding persons performing mandatory military service, persons deprived of liberty, persons who, as a result of a judicial decision, cannot take part in clinical investigations, or persons in residential care institutions.

Article 68 — Clinical investigations in emergency situations. By way of derogation from Article 62(4)(f), from Article 63, and from Articles 64 and 65, informed consent may be obtained and information on the investigation may be given after the decision to include the subject, under specific conditions, where the emergency situation makes prior consent impossible and the investigation relates directly to the medical condition that makes prior consent impossible.

For most startup investigations, Articles 64 to 68 do not apply — the study enrols consenting adults. When they do apply, the sponsor must read them personally and build the additional protections into the clinical investigation plan and the ethics committee submission. These articles are not optional add-ons for the populations they cover.

Articles 70 and 71 — Application and authorisation

Article 70 governs the application for a clinical investigation. The sponsor submits an application to the member state or states in which the investigation is to be conducted. The application is accompanied by the documentation referred to in Annex XV Chapter II — the clinical investigation plan, the investigator's brochure, the documentation of the device under investigation, and the other content Annex XV specifies.

Article 70 also sets the validation and assessment timelines, the conditions under which the member state may request additional information, and the circumstances in which a clinical investigation may commence. Article 71 covers the assessment by the member states, including the scientific and ethical review that must precede authorisation.

For the startup sponsor, Articles 70 and 71 are the gate the investigation passes through before the first subject is enrolled. The content of the application is specified in Annex XV; the timelines are specified in the articles themselves. Planning the investigation with realistic allowance for the assessment period, possible requests for additional information, and the national-level procedures of each member state is the difference between an authorisation that arrives on time and one that does not.

Articles 72 and 73 — Conduct of the investigation

Article 72 governs the conduct of a clinical investigation. The sponsor and the investigator ensure that the investigation is conducted in accordance with the approved clinical investigation plan. The sponsor is responsible for the integrity of the investigation, the quality of the data, the safety of the subjects, and the traceability of the investigational device. The article sets out the responsibilities for monitoring, for maintaining the investigator's site file and the sponsor's trial master file, and for making the documentation available to the competent authority on request.

Article 73 governs the Electronic system on clinical investigations — the EU-level information system through which sponsors submit information and by which the member states and the Commission coordinate. In practice, the functioning of this system has evolved alongside Eudamed; sponsors planning an investigation check the current state of the electronic system at the time of application, because the operational details have changed since the Regulation was drafted and may change again.

The Chapter VI conduct provisions do not scale down for small sponsors. The two-person startup sponsor runs the same monitoring discipline, the same documentation chain, and the same data integrity controls as a large sponsor — at a scope appropriate to the study size, but at the same standard of rigour.

Article 74 — Post-market clinical follow-up studies

Article 74 covers post-market clinical follow-up (PMCF) investigations. When a PMCF investigation is conducted on a CE-marked device within its intended purpose, a simpler notification pathway applies — but specific protections for subjects still apply, and any PMCF investigation that involves additional procedures beyond those used within the intended purpose, or that subjects the participants to additional invasive or burdensome procedures, is treated as a full clinical investigation under Article 62 onwards.

For the startup sponsor, Article 74 is the article to read before calling any post-market study a "light" study. The distinction between a PMCF within intended purpose and a PMCF that crosses into full investigation territory is the line that determines which obligations apply. Getting the line wrong is a common source of compliance problems after CE marking.

Articles 75 to 77 — Amendments and end-of-investigation reporting

Article 75 — Substantial modifications. Changes to the clinical investigation that are substantial — affecting the safety, health, or rights of subjects, or the robustness or reliability of the clinical data — must be notified to the member states concerned, and the modifications may only be implemented after the applicable timelines and conditions are met. The sponsor operates this procedure.

Article 76 — Corrective measures to be taken by member states and information exchange. Member states may take corrective measures — including withdrawing the authorisation, suspending or terminating the investigation, or requiring the sponsor to modify any aspect — where they have objective grounds. The sponsor must comply and inform the other member states and the Commission where applicable.

Article 77 — Information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination. The sponsor notifies the member states concerned of the end of the investigation within 15 days, or within 24 hours for a temporary halt or early termination on safety grounds. A clinical investigation report is submitted within one year of the end of the investigation, or within three months of early termination or temporary halt, with specific exceptions for particular investigation types.

For the startup sponsor, Articles 75 to 77 are where the back half of the investigation lives. Amendments happen in almost every study. End-of-investigation reporting is a real deliverable with a real deadline. Founders who plan only to the last patient visit are underestimating the chapter.

Articles 78 and 79 — Coordinated assessment and further procedural provisions

Article 78 covers the coordinated assessment procedure for clinical investigations to be conducted in more than one member state. A sponsor may propose one of the member states concerned as coordinating member state, and a coordinated assessment is conducted. Article 79 covers the review of the coordinated assessment procedure and related Commission reports.

For most first investigations by startup sponsors, the study runs in one or two member states and the coordinated assessment pathway may or may not apply. Either way, Article 78 is the article to read before committing to a multi-country investigation — the coordination adds complexity that affects timeline and cost.

Articles 80 and 81 — Adverse events and implementing acts

Article 80 — Recording and reporting of adverse events that occur during clinical investigations. The sponsor records and reports to the member states in which the investigation is being conducted all serious adverse events that have a causal relationship with the investigational device, the comparator, or the investigation procedure, or where such a causal relationship is reasonably possible; and all device deficiencies that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate; and any new findings in relation to any of the above. The reporting timelines are short, measured in days for most events and in 24 hours for events that indicate an imminent risk of death, serious injury, or serious illness and that require prompt remedial action for other subjects.

Article 81 — Implementing acts. The Commission may adopt implementing acts laying down the detailed arrangements and procedural aspects necessary for the application of Chapter VI, including harmonised electronic forms, common procedures, and coordination between member states.

Article 80 is the article most often underestimated by small sponsors. The reporting chain must be operational from before the first subject is enrolled, with primary and backup owners named, tested, and documented. A missed Article 80 report is not a clerical slip — it is a compliance failure the competent authority can act on.

Our dedicated post Adverse Event Reporting Under MDR Article 80 walks through the reporting timelines, the assessment of seriousness and causality, and the escalation chain.

Article 82 — Ethics committees and investigations other than those conducted to demonstrate conformity

Article 82 covers clinical investigations that are not conducted for the purposes of demonstrating conformity of a device — investigations with other purposes, including research investigations, post-market studies that fall outside Article 74, and combined studies. For these, the member states may apply national provisions in addition to or in place of the specific procedural requirements of Chapter VI, but the protections for subjects in Articles 62(2), 62(3), 62(4)(b) to (k), 62(6), and Articles 63 to 68 continue to apply.

Ethics committees are referenced throughout Chapter VI and the detailed composition, procedures, and national roles of ethics committees are governed by national law in each member state. The sponsor's obligation is to obtain the positive opinion of the ethics committee of the member state or states where the investigation will run, before the first subject is enrolled. National procedures differ; the absolute requirement for ethics approval does not.

Our dedicated post Ethical Approval for Clinical Investigations Under MDR covers the ethics committee pathway and the typical national variations.

Annex XV — The documentation backbone

Annex XV of Regulation (EU) 2017/745 is the documentation backbone of Chapter VI. It specifies, in detail, the general requirements of a clinical investigation and the content of the documentation the sponsor must produce and submit:

  • Chapter I — General requirements, including the obligation to comply with ethical principles, Good Clinical Practice, and the applicable harmonised standards.
  • Chapter II — The application dossier, including the clinical investigation plan, the investigator's brochure, the documentation of the device under investigation, the CV of the investigators, proof of insurance, and the other content the application must contain.
  • Chapter III — Other obligations of the sponsor, including the obligation to make the full dossier available to the competent authority on request and the obligations related to the investigator and the investigational site.

When a sponsor reads Articles 62 to 82 and asks "but what exactly has to be in the document?" — the answer is in Annex XV. The clinical investigation plan, in particular, has its content specified in Annex XV in a level of detail that leaves no room for improvisation. A CIP that does not cover every item in Annex XV is not ready for submission.

EN ISO 14155:2020+A11:2024 — The operational floor

EN ISO 14155:2020+A11:2024 — Clinical investigation of medical devices for human subjects — Good clinical practice — is the harmonised standard that operationalises Chapter VI. Where the Regulation states an obligation, the standard states how to meet it in practice. Sponsor responsibilities, investigator responsibilities, ethics committee interactions, clinical investigation plan content, informed consent procedures, data management, monitoring, adverse event handling, reporting, archiving — each has a corresponding section in the standard.

A sponsor who reads the Regulation but not the standard has read the obligations but not the procedure for meeting them. A sponsor who reads the standard but not the Regulation has read the procedure but not the legal basis. Both are required reading, and they are read in parallel, not sequentially.

The Subtract to Ship angle

Chapter VI is the part of MDR where Subtract to Ship has the least room to cut. Every article in Articles 62 to 82 and every chapter of Annex XV applies to the investigation that runs. None of them come out in the name of lean execution. The discipline of Subtract to Ship, applied to Chapter VI, is three specific moves.

First, the Evidence Pass is run before the chapter is entered at all. The question "do we need to run a clinical investigation?" is answered honestly before the sponsor commits to Chapter VI. Our methodology pillar The Subtract to Ship Framework for MDR Compliance and the companion post What Is a Clinical Investigation Under MDR? both cover the Evidence Pass in detail. The investigation you do not need to run is the cheapest investigation of all.

Second, when the investigation must run, the scope is cut to the minimum viable study that answers the specific scientific question the clinical evaluation needs. No parallel endpoints for marketing. No over-enrolment for statistical comfort. No multi-country expansion that the regulatory question does not require.

Third, the ceremony around the obligations is cut, not the obligations themselves. A one-page obligations traceability matrix beats a forty-page sponsor manual. A two-person adverse event chain with a documented drill beats a committee structure that exists only on the org chart. The obligation to meet Article 80 stays; the bureaucracy around meeting it comes out.

Reality Check — Where do you stand?

  1. Have you read Articles 62 to 82 of Regulation (EU) 2017/745 personally, in the consolidated text, from start to finish?
  2. Have you read Annex XV — Chapter I, Chapter II, and Chapter III — with the clinical investigation plan content list open next to your draft CIP?
  3. Have you identified which of Articles 64 to 68 apply to your study, and built the additional protections into the plan where they do?
  4. Do you have a realistic timeline for the application under Article 70 and the assessment under Article 71, including allowance for requests for additional information?
  5. Is your monitoring plan under Article 72 executable by your actual team or your contracted CRO — and is the chain of responsibility documented?
  6. If your study is a PMCF investigation, have you checked Article 74 against the design to confirm which pathway applies?
  7. Is the substantial modification procedure under Article 75 written into your sponsor SOPs, so amendments are not handled ad hoc?
  8. Is the end-of-investigation reporting obligation under Article 77 on the project plan with a named owner and a target date?
  9. Is your Article 80 adverse event reporting chain staffed with a primary and a backup, tested before enrolment, and documented in the CIP?
  10. Is your ethics committee pathway under Article 82 and national law clear for every member state where the investigation will run?

Frequently Asked Questions

What is MDR Chapter VI? MDR Chapter VI is the part of Regulation (EU) 2017/745 that governs clinical investigations of medical devices. It runs from Article 62 to Article 82 and is supported by Annex XV, which specifies the documentation content in detail. The chapter covers general requirements, informed consent, protection of vulnerable populations, the application and authorisation pathway, the conduct of the investigation, post-market follow-up studies, amendments, end-of-investigation reporting, adverse event reporting, and the role of ethics committees. EN ISO 14155:2020+A11:2024 is the harmonised Good Clinical Practice standard that operationalises compliance with the chapter.

Which articles in MDR Chapter VI matter most for a startup sponsor? All of them, but the ones that most often surprise startup sponsors are Article 62(4) on the core sponsor conditions, Article 70 on the application pathway, Article 72 on the conduct and monitoring obligations, Article 75 on substantial modifications, Article 77 on end-of-investigation reporting, and Article 80 on adverse event reporting. A sponsor who has operationalised those six articles before the first subject is enrolled is in a substantially better position than a sponsor who has only read Article 62.

Does Annex XV specify what the clinical investigation plan must contain? Yes. Annex XV Chapter II specifies the content of the application dossier, including the clinical investigation plan, the investigator's brochure, the documentation of the device under investigation, the investigator CVs, and the insurance documentation. The CIP content list is detailed enough that any plan missing items from Annex XV is not ready for submission to the competent authority or the ethics committee.

What is the role of EN ISO 14155:2020+A11:2024 in Chapter VI compliance? EN ISO 14155:2020+A11:2024 is the harmonised Good Clinical Practice standard for clinical investigations of medical devices. It operationalises the requirements of MDR Chapter VI — how to meet them in practice, with sections on sponsor, investigator, and ethics committee responsibilities, clinical investigation plan content, informed consent, data management, monitoring, adverse event handling, reporting, and archiving. It is the operational floor for compliance and it is read in parallel with Articles 62 to 82 and Annex XV.

Do the obligations in Chapter VI apply equally to small and large sponsors? Yes. Chapter VI does not contain a proportionality clause that relaxes the obligations for small sponsors. A two-person startup running a twenty-subject investigation carries the same legal obligations as a multinational running a multi-centre Class III trial. The scope of the study is different; the standard to which it must be conducted is the same.

How does MDR Chapter VI relate to ethics committee approval? MDR Chapter VI requires ethics committee approval for every clinical investigation before the first subject is enrolled. The composition, procedures, and national roles of ethics committees are governed by national law in each member state where the investigation runs. Article 62(4) makes the positive opinion of the ethics committee a precondition for the investigation, and Article 82 preserves the application of protective provisions to investigations that are not conducted to demonstrate conformity. The sponsor obtains ethics approval in every participating member state before enrolment — no exceptions, no informal pilots.

What happens if a sponsor fails an obligation in Chapter VI? Consequences depend on which obligation and how serious the failure is. Missing a substantial modification procedure under Article 75, a reporting deadline under Article 77, or an adverse event report under Article 80 can trigger competent authority action ranging from a warning and corrective action plan to suspension or termination of the investigation. Beyond the direct consequences, failures in Chapter VI compliance damage the sponsor's credibility with the authority, the ethics committee, and — eventually — the Notified Body that will review the clinical evaluation.

Sources

  1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, Chapter VI — Clinical evaluation and clinical investigations, Article 62 (general requirements regarding clinical investigations conducted to demonstrate conformity of devices), Article 63 (informed consent), Article 64 (clinical investigations on incapacitated subjects), Article 65 (clinical investigations on minors), Article 66 (clinical investigations on pregnant or breastfeeding women), Article 67 (additional national measures), Article 68 (clinical investigations in emergency situations), Article 70 (application for clinical investigations), Article 71 (assessment by member states), Article 72 (conduct of a clinical investigation), Article 73 (Electronic system on clinical investigations), Article 74 (clinical investigations regarding devices bearing the CE marking), Article 75 (substantial modifications to clinical investigations), Article 76 (corrective measures to be taken by member states and information exchange), Article 77 (information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination), Article 78 (coordinated assessment procedure for clinical investigations), Article 79 (review of coordinated assessment procedure), Article 80 (recording and reporting of adverse events), Article 81 (implementing acts), Article 82 (requirements regarding other clinical investigations), Annex XV (clinical investigations). 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 about to enter MDR Chapter VI for the first time and want the obligations mapped to your specific device, study design, and team before the application goes to the competent authority, Zechmeister Strategic Solutions walks that map with founders — article by article, annex section by annex section, obligation by obligation.