MDR Clinical Investigations: The Pathway Decision Guide (Plus Every Deadline You Need to Track)
Article 62, 74, or 82? A practical walk-through of MDCG 2021-6 Rev. 1, the decision tree, the documentation, and the timelines that decide whether your clinical investigation lands in regulatory good standing or stalls before first patient in.
Every clinical investigation under the EU Medical Device Regulation (MDR, Regulation (EU) 2017/745) starts with the same question: which article applies to my study? The answer determines the documentation set, the submission procedure, the notification timelines, and the reporting obligations that follow. An incorrect classification can lead to delays at submission, Member State rejection, or non-conformities identified during conformity assessment.
The Medical Device Coordination Group has been refining its guidance on this since 2021. The current reference, MDCG 2021-6 Rev. 1 (December 2023), adds 19 new questions and clarifications to the original Q&A and includes a decision tree (Annex I) plus a quick-reference summary of the three regulatory pathways: Article 62, Article 74, and Article 82. This guide turns that document into something teams can actually use when product management asks "do we need to notify anyone before we start enrolling?"
This guide walks through the decision tree step by step, covers the three special cases addressed by MDCG 2021-6 Rev. 1, and closes with the full set of deadlines from kick-off to documentation retention.
Three pathways, one regulation
Every MDR clinical investigation is governed by one of three articles. They are not interchangeable, and the choice is driven by the regulatory status of the device and the purpose of the study, not by who is sponsoring it or how the data will be used downstream.
| Pathway | When it applies | What it triggers |
|---|---|---|
| Article 62 | Clinical investigations conducted to demonstrate conformity (i.e. as part of the route to CE marking, or for non-CE-marked devices intended to be CE marked) | Full Annex XV Ch. II documentation; authorisation under Art. 70(7)(b) for Class III and implantable devices, notification under Art. 70(7)(a) for others |
| Article 74(1) | Post-Market Clinical Follow-up (PMCF) on a CE-marked device, within its intended purpose, with additional procedures that are burdensome or invasive | Same documentation as Art. 62, but a lighter procedural regime — notification to the Member State at least 30 days before commencement |
| Article 82 | Any other clinical investigation not conducted for conformity assessment (e.g. PMCF without burdensome/invasive procedures, investigator-initiated studies, in-house and custom-made device studies) | National provisions apply; minimum MDR requirements only — check the relevant National Competent Authority (NCA) for submission specifics |
Note that Article 74(2) covers a different scenario: a CE-marked device being investigated outside its intended purpose. In that case, the full pre-market clinical investigation regime under Art. 62 to 81 applies, effectively treating it as a new device.
With those three pathways in mind, here is how to navigate to the right one.
Step 1: Is the device CE-marked?
This is the first fork in the decision tree. Three answers are possible.
Not yet CE marked, and the investigation supports CE marking. You are in Article 62 territory. This is the classic pre-market clinical investigation, with Annex XV Chapter II documentation and the full authorisation/notification regime depending on device class. Pilot studies and first-in-human studies fall here too, MDCG 2021-6 Rev. 1 (Q9) is explicit that early feasibility work, with limited enrolment and preliminary safety/performance objectives, should default to Article 62. When in doubt, apply Article 62 is the safe default.
Not yet CE marked, and the investigation is not for conformity assessment. You are in Article 82. Minimum MDR requirements apply, plus whatever the relevant NCA expects. Check the Member State's website before submitting.
Already CE marked. Move to Step 2.
There is also a fourth path: devices not intended to be CE marked, typically custom-made devices (Article 2(3)) and in-house manufactured devices governed by Article 5(5). Investigations involving these devices, when not conducted for conformity assessment, fall under Article 82. When they are conducted for conformity assessment (rare but possible), Article 62 applies and Annex I GSPR remain relevant.
Step 2: Is the CE-marked device used within its intended purpose?
If the device is CE marked, the next question is whether your study uses it inside the bounds of its intended purpose as defined in the IFU, EU Declaration of Conformity, labelling, CER, and SSCP (the Q12 reference in the MDCG document).
Outside intended purpose. When a CE-marked device is investigated outside its intended purpose, Article 74(2) routes the study back to the full Article 62 to 81 regime: same documentation, same authorisation/notification procedure, same reporting obligations. This applies whenever a team seeks to extend a CE-marked device to a new indication.
Within intended purpose. Move to Step 3.
Step 3: Are there additional burdensome or invasive procedures?
This is the question that decides Article 74(1) versus Article 82 for a PMCF study on a CE-marked device used as intended.
Yes, there are additional burdensome or invasive procedures. Article 74(1) applies. Documentation is the same as Article 62 (Annex XV Ch. II), but the procedural pathway is lighter: a notification to the Member State at least 30 days before commencement is required. If you are unsure whether your additional procedures qualify as burdensome or invasive, MDCG 2021-6 Rev. 1 (Q13) advises consulting the NCA before assuming.
No additional burdensome or invasive procedures. Article 82 applies. National provisions govern, and registration in a public database is encouraged but not always mandatory.
Other PMCF activities (e.g. investigator-initiated, registry-style studies). Also Article 82, with the same caveat — check national rules.
Three special cases that warrant careful attention
Three scenarios sit at the edges of the decision tree and require a closer reading of MDCG 2021-6 Rev. 1.
Combination products (device + medicinal). When the product combines a medical device and a medicinal product, the Annex III flowchart in MDCG 2021-6 Rev. 1 is the relevant reference. A dual submission may be required: one under MDR and one under the Clinical Trials Regulation (Regulation (EU) 536/2014).
Custom-made and in-house devices. Annex I General Safety and Performance Requirements still apply to custom-made devices (Article 2(3)). In-house manufactured devices fall under Article 5(5). When investigations on these devices are conducted for conformity assessment purposes, Article 62 applies. When they are not, Article 82 governs.
Pilot and first-in-human studies. Q9 of MDCG 2021-6 Rev. 1 is unambiguous: these are generally Article 62. Limited enrolment does not let you opt out of pre-market documentation. The intent is preliminary safety/performance evidence, but the regulatory framing is still Article 62.
Quick-reference decision keys
The five questions below mirror the logic of MDCG 2021-6 Rev. 1 Annex I and can be used as a checklist before submission.
- Is the device CE marked? If no, jump to Section 2 above. If yes, continue.
- Is the device used within its intended purpose? Check IFU, EU DoC, labelling, CER, SSCP. If no, the full Article 62 to 81 regime applies via Article 74(2).
- Are additional procedures burdensome or invasive? If yes, Article 74(1) notification (30 days). If unsure, consult the NCA.
- Is data being collected for conformity assessment? If yes, Article 62 documentation requirements apply.
- Is this a combination product (device + medicinal)? If yes, see Annex III flowchart and prepare for a possible dual MDR + CTR submission.
The deadlines that decide whether your file stays clean
Once you know which article applies, the operational question becomes timing. MDCG 2021-6 Rev. 1 sets out a specific calendar that runs from notification through to document retention. Miss any of these and you are creating either a regulatory finding or a non-conformity at conformity assessment.
| Event | Trigger | Deadline |
|---|---|---|
| PMCF notification (Art. 74(1)) | Before commencement of the clinical investigation | At least 30 days prior |
| Substantial modification notification (Art. 75) | After document issuance | Within 1 week |
| Substantial modification implementation | After Member State notification | Allowed after 38 days if no objection (extendable by 7 days for expert consultation) |
| End of clinical investigation notification | When the CI ends in a Member State | Notify each MS within 15 days |
| Early termination on safety grounds | Termination due to safety concerns | Notify within 24 hours |
| Clinical investigation report submission | Global end of CI | Within 1 year (or 3 months if early termination or temporary halt) |
| Study documentation retention | After CI end | At least 10 years for general medical devices, 15 years for implantable devices |
A few notes on how the regulation defines these timelines.
The 30-day PMCF notification under Article 74(1) is a regulatory minimum. Individual Member States may impose additional national review periods on top of it, so the effective lead time depends on jurisdiction.
For the substantial modification window (1 week to notify, 38 days to implement, plus a possible 7-day expert extension), the trigger under Article 75 is the issuance of the document describing the modification — not the date the change takes effect operationally.
The 24-hour safety termination notification applies regardless of weekends, holidays, or time zones.
The document retention requirements (10 / 15 years) apply to the entire study documentation set, not just the final report, and the retention period starts at CI end rather than last patient out.
What to do this week
If you are mid-project and unsure which pathway applies, three artefacts will usually settle it: the device's IFU and EU DoC (to confirm intended purpose), the protocol synopsis (to identify additional procedures), and the relevant National Competent Authority guidance (to confirm submission specifics under Article 82 if that is where you land). The conclusion can then be documented in the Clinical Investigation Plan with a direct reference to the MDCG 2021-6 Rev. 1 question that supported the decision, building the audit-ready paper trail that the Notified Body will expect during conformity assessment.
If you are starting a new clinical investigation, anchoring the pathway decision before protocol finalisation keeps the documentation set, submission timelines, and safety reporting requirements consistent from the start. A change of pathway (for example from Article 82 to Article 62) later in the project requires re-aligning all three.
The bottom line
The decision tree in Annex I of MDCG 2021-6 Rev. 1, combined with the quick-reference summary and the deadline calendar above, are the core operational references for any MDR clinical investigation. Together they cover both the upfront pathway decision and the ongoing notification and reporting obligations.
For organisations managing multiple device lines under MDR, the same logic applies in parallel: each clinical investigation needs its own pathway determination, its own documentation set, and its own deadline tracker. The decision tree does not get more complex with scale, but the operational coordination across parallel investigations does.
Source: MDCG 2021-6 Rev. 1, "Regulation (EU) 2017/745 — Questions & Answers regarding clinical investigations" (December 2023). Available from the European Commission's health portal. This guide is informational and does not constitute regulatory advice; consult your Notified Body or National Competent Authority for project-specific decisions.