RIPH classification, RNIPH and European regulation

A dual regulatory reading is indispensable

Any study conducted in France in the field of human health falls within a dual regulatory framework. The national framework derived from the Jardé Law determines whether the study is research involving the human person (RIPH) and, if so, which of the three categories applies — or whether it is research not involving the human person (RNIPH). For certain types of study, a complementary European framework applies in parallel: the CTR (Clinical Trials Regulation) for medicinal products (drugs), the MDR (Medical Device Regulation) for medical devices, and the IVDR (In Vitro Diagnostic Regulation) for in vitro diagnostic medical devices (DMDIV).

These two levels are independent but interlinked. A classification error — or the omission of a European obligation — can lead to incomplete submissions, requests for additional information from the ethics committee (CPP) or the French medicines agency (ANSM), or even a challenge to the study design.

The entry question: participation outside routine care?

The first branching point in the regulatory decision tree is binary and determines everything that follows: does the study require the participation of patients outside routine care?

Answer	Meaning	Direction
YES	The study imposes acts, procedures, or data collection that are not part of routine care	→ RIPH (category 1, 2, or 3) or European regulation (CTR, MDR, IVDR)
NO	All acts are performed in the usual manner; the data collected are those already gathered in routine practice	→ RNIPH (research not involving the human person)

Point of attention — A study based on prospective data collected "on a rolling basis" within the framework of routine care remains directed toward RNIPH if no additional procedure is imposed on the person. Conversely, as soon as a questionnaire, a sample, or an additional consultation is required for the purposes of the research, it shifts to a RIPH classification.

RNIPH: research not involving the human person

RNIPH groups together studies that do not meet the legal definition of "research involving the human person" within the meaning of articles L.1121-1 and R.1121-1 of the Public Health Code. They therefore do not fall under the Jardé Law. Two main cases are covered:

• Studies on data already collected during care or previous research (reuse of retrospective data or prospective data on a rolling basis)
• Studies in which the person participates and data specific to the research are collected, without this participation meeting the legal definition of RIPH

CNIL formalities applicable to RNIPH

Type of data	Reference methodology	Procedure
Medical data and/or biological samples — informable person	MR-004	Declaration of conformity with MR-004 + collective and individual information of the patient + declaration on the Health Data Hub site
Medical data and/or biological samples — non-informable person	Outside MR (case-by-case)	CESREES + CNIL authorization via the Health Data Hub
SNDS data — healthcare establishment	MR-005	Declaration of conformity or CESREES + CNIL authorization depending on the case
SNDS data — healthcare industry players	MR-006	Declaration of conformity or CESREES + CNIL authorization depending on the case
Medico-administrative databases other than PMSI/RPU	Outside MR	CESREES + CNIL authorization via the Health Data Hub

CPP for RNIPH — RNIPH studies do not fall under the ethics committee (CPP) under the Jardé Law. However, an opinion from a local ethics committee may be requested by certain scientific journals or institutions for publication purposes. This is a CER (research ethics committee) and not a CPP.

The three RIPH categories: decision logic

When the study involves participants outside routine care, it falls within the scope of the Jardé Law. The applicable RIPH category then depends on the type of product being evaluated and the level of risk and burden imposed on the participants.

RIPH 1 — Interventional research with non-minimal risk

RIPH 1 applies whenever the study involves an intervention not justified by routine care and presenting a non-minimal risk or burden. It also covers studies concerning:

• A medicinal product (drug) without marketing authorization (AMM), or with an AMM but used outside its indications
• A medical device without CE marking, or used outside the conditions of its instructions for use
• A health product other than a medicinal product (biological products, labile blood products, etc.)
• An invasive act not performed in routine practice (breaching of the skin or mucous membranes outside of care)

Regulatory obligations:

• CPP: favorable opinion mandatory
• Consent: free, informed, and written, obtained before any inclusion
• ANSM authorization: mandatory (depending on the product, via CTR or national procedure)
• Registration on a public registry (CTIS for medicinal products, EUDAMED for medical devices)
• Specific sponsor insurance mandatory
• CNIL: declaration of conformity with MR-001 or CNIL authorization if MR-001 does not apply

RIPH 2 — Interventional research with minimal risks and burdens

RIPH 2 applies to studies involving additional procedures compared to routine care, the risk and burden of which are qualified as minimal according to the list set by ministerial order (order of December 2, 2016, amended by order of February 17, 2021).

The types of intervention falling under RIPH 2 (non-exhaustive list):

• Use of a CE-marked medical device in accordance with the conditions of its instructions (without non-minimal risk)
• Non-invasive extra-corporeal sensors: ECG, EEG, EMG, polysomnography, oximetry, doppler, NIRS, etc.
• Imaging or functional exploration without an invasive act
• Collection of electrophysiological data on material implanted or being implanted for care
• Additional blood sample or additional tube during an already planned sampling (according to regulatory maximum volumes)
• Non-blood biological sample according to the list in the order (saliva, urine, stool, superficial swabbing, etc.)
• Simple randomization between two routine care practices
• Administration of auxiliary medicinal products (authorized, non-experimental medicinal products used for the purposes of the trial)
• Interview or questionnaire not resulting in a modification of care and whose burdens are negligible
• Psychotherapy or cognitive behavioral therapy techniques
• Anthropometric measurements without invasive intervention
• Audio, video, or photo recording outside of medical imaging

Regulatory obligations:

• CPP: favorable opinion mandatory
• Consent: free, informed, and express — the written format is not systematically required by law for RIPH 2, unlike RIPH 1; in practice, it is strongly recommended and often required by the CPPs
• ANSM: information mandatory (submission of the study summary) — this is not an authorization, unlike RIPH 1
• Sponsor insurance required
• CNIL: declaration of conformity with MR-001 or CNIL authorization

Key point — RIPH 2 does not concern experimental medicinal products (without AMM or off-indication). A study evaluating such a medicinal product systematically falls under the CTR and RIPH 1, regardless of the burden imposed.

RIPH 3 — Non-interventional research

RIPH 3 applies to studies in which all acts are performed and all products used in the usual manner, without any additional procedure presenting a risk or burden for the participants. The boundary with RIPH 2 can be tenuous — the order setting the list of RIPH 3 acts (Légifrance, JORFTEXT000036805796) is authoritative.

Examples: cohort on care data without additional acts, retrospective case-control study, practice questionnaire resulting in no modification of care and whose burden is negligible.

Regulatory obligations:

• CPP: favorable opinion mandatory
• Consent: non-objection of the participant after information — no collection of written consent is required
• ANSM authorization: not required
• Sponsor insurance: not mandatory
• CNIL: declaration of conformity with MR-003 or CNIL authorization

Distinction RIPH 1 vs RIPH 2 for consent — RIPH 1: free, informed, and WRITTEN consent mandatory. RIPH 2: free, informed, and EXPRESS consent (the wording of the Jardé Law). Express consent implies an active and unequivocal expression of consent, without the written form being imposed by law; however, most CPPs and sponsors require written formalization in practice.

Comparative table: RNIPH, RIPH 3, RIPH 2, RIPH 1

Criterion	RNIPH	RIPH 3	RIPH 2	RIPH 1
Participation outside routine care	No	No (routine acts only)	Yes (minimal risk/burden)	Yes (non-minimal risk)
Jardé Law applicable	No	Yes	Yes	Yes
CPP	No (CER possible)	Mandatory	Mandatory	Mandatory
Consent	Information per MR	Non-objection	Express (written in practice)	Written mandatory
ANSM	No	No	Information (summary submission)	Authorization
Sponsor insurance	No	No	Required	Mandatory
CNIL reference framework	MR-004 / MR-005 / MR-006	MR-003	MR-001	MR-001
Experimental medicinal products	Not applicable	Not applicable	Excluded (off-AMM or off-indication)	RIPH 1 + CTR 536/2014

European regulations: CTR, MDR, IVDR

CTR No. 536/2014 — Clinical trials on medicinal products

Regulation (EU) No. 536/2014 (CTR) has applied since January 31, 2022 to any clinical trial concerning an investigational medicinal product (IMP) in the EU. It interlinks with the Jardé Law: a study falling under the CTR is in principle a RIPH 1 under French law.

All submissions go through CTIS (Clinical Trials Information System), the EMA platform, following a two-part parallel review:

Part	Object	Competent authority	Note
Part I	Scientific evaluation and safety of the investigational medicinal product	ANSM (reporting Member State for France)	Regulatory deadline: 30 days + possible 12-day extension
Part II	Ethical evaluation and national conditions (recruitment, consent)	Competent CPP in France	Schedule specific to each CPP

The CTR introduces the notion of a low-intervention clinical trial (ECFI), whose pharmacovigilance and monitoring requirements are reduced. An ECFI requires that the medicinal product be authorized (AMM in force in the EU) and used in accordance with its indications. Under French law, an ECFI may correspond to a RIPH 2 — but the two classifications remain independent.

MDR 2017/745 — Medical devices

Regulation (EU) 2017/745 (MDR) governs clinical investigations on medical devices (DM), applicable since May 26, 2021. It applies in particular to medical devices without CE marking, to CE-marked medical devices used outside their intended purpose, and to certain investigator-initiated studies. In France, it overlaps with the Jardé Law (RIPH 1 in the vast majority of cases) with the following obligations:

• Prior ANSM notification before the start (minimum 30 days for most medical devices)
• Mandatory CPP opinion for implantable devices, class III, or first use in humans
• Written consent mandatory
• Registration in EUDAMED (progressive rollout)
• Simplified procedure possible for low-risk investigations (Article 62§4 MDR)

IVDR 2017/746 — In vitro diagnostic medical devices

Regulation (EU) 2017/746 (IVDR) governs performance studies on in vitro diagnostic medical devices (DMDIV), applicable since May 26, 2022. Two regimes:

• Interventional performance studies (EPI): procedures not justified by routine care → ANSM notification and CPP opinion required (RIPH 1 or 2 depending on the burden)
• Non-interventional performance studies: leftover samples or existing data → reduced regime, without systematic ANSM notification, but with applicable CNIL formalities

Articulation table: Jardé Law and European regulations

Type of study	Jardé classif.	EU regulation	Competent authority	Platform
Trial on a medicinal product without AMM or off-indication	RIPH 1	CTR 536/2014	ANSM (Part I) + CPP (Part II)	CTIS
Low-intervention trial on an authorized medicinal product (ECFI)	RIPH 1 or 2 depending on burden	CTR 536/2014 (reduced regime)	ANSM + CPP	CTIS
Investigation on a non-CE medical device or off intended purpose	RIPH 1	MDR 2017/745	ANSM (30-day notif.) + CPP	EUDAMED
Interventional performance study on a DMDIV	RIPH 1 or 2	IVDR 2017/746	ANSM (notif.) + CPP	EUDAMED
Interventional trial outside a health product (e.g., new surgical technique, invasive act)	RIPH 1	Not applicable	ANSM authorization + CPP	ClinicalTrials.gov
Interventional study with minimal risk outside a regulated health product (e.g., questionnaire modifying care, additional blood sample)	RIPH 2	Not applicable	ANSM information + CPP	ClinicalTrials.gov
Observational study without additional acts	RIPH 3	Not applicable	CPP only	ClinicalTrials.gov (recommended)
Study on care data without active participation	RNIPH	Not applicable	CESREES + CNIL via Health Data Hub	Health Data Hub

Frequent gray areas

• Questionnaire during consultation: RIPH 2 or RIPH 3? A questionnaire that does not modify care and whose burdens are negligible → RIPH 3. If it is likely to modify care or results in a specific summons → RIPH 2. The distinction is a case-by-case assessment.
• Additional tube during a routine sampling: An additional tube during a sampling already planned as part of care falls under RIPH 2 according to the order, subject to compliance with the regulatory maximum volumes (order of February 17, 2021).
• Randomization between routine practices: The simple randomization of two routine care practices falls under RIPH 2 according to the ministerial order — and not under RIPH 3 as one might anticipate.
• Medicinal product authorized within its indications: A trial on a medicinal product with an AMM used within its indications may fall under the CTR (ECFI) with a reduced regime. It remains a RIPH 1 under French law if non-routine procedures are imposed, or may be classified as RIPH 2 if the burden is minimal.
• IIS studies without academic exemption: An academic sponsor (university hospital, DRCI) remains fully subject to the CTR or MDR obligations. There is no academic exemption — the classification and obligations depend on the product being evaluated, not on the status of the sponsor.

Conduct this analysis from the very design of the project

The regulatory classification of a research project must take place as soon as the research question is formulated, well before the protocol is written. It simultaneously determines the type of submission, the consent requirements, the CNIL formalities, the insurance budget, and the effective timelines before the first inclusion.

In practice, this analysis is conducted in close collaboration with the sponsoring DRCI (the clinical research office) and the establishment's regulatory referent. An erroneous or late classification can jeopardize the entire submission timeline.