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The “Convention unique” is now an essential component of conducting commercial clinical research in France. Introduced by the Law on the Modernization of the French Healthcare System of January 26, 2016, to simplify contractual relationships between sponsors and healthcare facilities, it aims to accelerate the launch of studies while ensuring greater transparency regarding research-related costs.

What is a “Convention unique”?

The “Convention unique” is a contract entered into between the industrial sponsor of a research study and the healthcare facility where the study is conducted. The “Convention unique” serves as the reference document for all contractual and financial provisions related to a commercially oriented research study conducted in a healthcare facility, institution, or center.

In particular, its purpose is to define:

•    the terms and conditions for conducting the research;

•    the responsibilities of the various parties;

•    the costs borne by the facility;

•    the financial compensation paid by the sponsor;

•    the terms for covering additional costs associated with the research.

When commercially oriented research involving human subjects takes place in a healthcare facility, institution, or center, it draws upon the expertise and resources of that facility or coordinated practice setting for its implementation. This generates costs and additional expenses for the facility, which bills them—as a service—to the industry sponsor of the research.

This agreement is unique because it brings together, for a single research site, the industry sponsor, the healthcare facility, home, or center, and, where applicable, a third-party entity receiving compensation. It is intended to be used identically by all French healthcare facilities, homes, and centers participating in the same research involving human subjects.

The principle is to establish a harmonized contractual framework that limits the need for specific negotiations at each research center, thereby enhancing France’s appeal for clinical research by reducing the time required to launch studies. The “Convention unique” thus replaces the multiple contracts that could previously be entered into among the various parties involved in conducting the study.

What types of research are covered?

The “Convention unique” must be used for commercial research falling under:

•    Article L.1121-1(1) of the Public Health Code (RIPH 1);

•    Article L.1121-1(2) of the Public Health Code (RIPH 2).

Clinical trials involving drugs, medical devices, or other health products may therefore be subject to this requirement provided they fall within these categories and are conducted in a healthcare facility.

Conversely, non-interventional research (RIPH 3) generally does not fall within the scope of the “Convention unique”. This distinction must be identified as early as the project design phase in order to establish the appropriate contractual framework.

What regulatory changes are expected in 2024?

The framework governing “Convention uniques” was updated in 2024; on August 1, 2024, the Ministry of Health published an information note regarding the use of the “Convention unique” for commercial research involving human subjects. In July 2025, a list of frequently asked questions (FAQ) regarding the use of the “Convention unique” was also published.

The information note details the use of the new agreement template provided for in the decree of July 29, 2024, and provides clarifications regarding:

•    the scope of application of the “Convention unique”;

•    the methods for calculating and billing costs;

•    the management of research-related cost overruns;

•    relationships between sponsors, investigators, and healthcare facilities.

These developments reflect the authorities’ commitment to further harmonize practices while addressing the challenges faced on the ground by healthcare facilities and sponsors.

What are the main challenges for pharmaceutical companies?

Anticipating implementation timelines

Even within a harmonized framework, contract negotiation remains a critical step in launching a study.

Early identification of research sites, cost assessment, and preparation of contractual documents are key factors in minimizing delays.

Managing financial aspects

Determining research costs is often one of the most sensitive points in negotiations. Sponsors must ensure that:

•    the requested services are properly identified;

•    additional costs are justified;

•    the budget remains consistent with the overall clinical development strategy.

Ensuring regulatory compliance

Classifying the research and identifying the applicable contractual framework requires a rigorous regulatory analysis. A misinterpretation can have a significant impact on the project timeline and the sponsor’s obligations.

Ensuring effective coordination among stakeholders

Clinical research departments, healthcare institutions, investigators, CROs, and sponsors are all involved simultaneously throughout the process. Smooth communication and a clear understanding of each party’s responsibilities are often key to success.

Conclusion

The “Convention unique” is a central component of conducting commercial research in French healthcare facilities. While its purpose is to simplify relationships between sponsors and facilities, its implementation requires a thorough understanding of the applicable regulatory framework and associated operational constraints. For pharmaceutical companies, anticipating these challenges as early as the study preparation phase can help reduce start-up delays and ensure the project proceeds smoothly.

Atessia assists you in understanding the regulatory requirements associated with “Convention unique” and clinical trials.

Article written by Emilie BADET, Legal Consultant specializing in Health Law

Definition

The legal basis of “well-established use/ WEU” (well-established use) in Article 10(a) of Directive 2001/83/EC constitutes a specific regulatory pathway for obtaining a marketing authorization (MA) for a medicinal product within the European Union (EU) without having to submit a complete dossier of original preclinical and clinical trials. This is referred to as a literature-based application. This approach relies on the use of existing scientific data demonstrating the efficacy and safety of an active substance with a long-standing and recognized use.

• Recognized medical use for at least 10 years in the EU,

• Efficacy and safety profile demonstrated to be acceptable based on usage,

•Scientific consensus widely documented in the literature.

These criteria imply that the assessment is based on a robust body of scientific evidence, including in particular:

• Publications in peer-reviewed journals,

• Meta-analyses,

•Clinical guidelines,

•Post-marketing experience data.

However, the existence of extensive literature alone is not sufficient to claim well-established medical use. The quality of the data, its relevance, and its suitability for the product under development remain key factors in the evaluation.

A scientific demonstration that goes beyond a simple literature review

One of the most common pitfalls is to view a WEU dossier primarily as a bibliographic exercise. In fact, the authorities generally expect more than just a compilation of publications. MA holders must be able to explain how the data described in the literature can be applied to their product. It is therefore not merely a matter of knowing whether data exist, but of determining to what extent this data supports the product in question and how this demonstration can be robustly documented.

Recent European clarifications have brought the topic of “bridging” back into the spotlight.

“Bridging” refers to a comparative analysis between the drug being submitted for approval and the product(s) cited in the scientific literature, in order to demonstrate that the data from the literature cited to support efficacy and safety are relevant to the specific drug being submitted for approval.

In 2025, the EMA published a Q&A document (“Clinical Pharmacology and Pharmacokinetics: Questions and Answers”) aimed at harmonizing the assessment of “bridging” requirements in applications based on Well-Established Use.

The guiding principle of this document is to demonstrate that the published data pertain to a product sufficiently comparable to the one for which the marketing authorization application is being filed. Depending on the situation, this demonstration may involve pharmaceutical, pharmacokinetic, or clinical analyses to establish the link between the data in the literature and the drug candidate for WEU.

The guidelines do not always provide a direct answer applicable to all scenarios. Rather, they emphasize the importance of a scientific justification tailored to each product and each registration strategy.

Areas in which Atessia can assist applicants:

•Analysis of the relevance of the legal basis under Article 10(a) in light of available bibliographic data;

•Identification of any bridging requirements;

•Structuring the regulatory strategy for the application: assisting you in a thorough review of the application’s overall consistency and the evidence supporting the choices made.

The goal is not to apply a one-size-fits-all approach, but to help applicants clarify the available options and ensure the overall logic of the development.

Sources :

Directive 2001/83/CE

Clinical pharmacology and pharmacokinetics: questions and answers

Article written by Véronique LEWIN, Senior Pharmaceutical Affairs Consultant – CMC

Introduction 

Labelling of medicinal products in France is an important tool to ensure safe use by patients by providing easy to understand key user information. It is also a tool to fight against counterfeiting of medicines.  

Development of labelling for medicines in France is precise task that must take into account multiple regulatory requirements. 

1. Regulatory Framework 

In addition to the information foreseen by annex IIIA of the Marketing authorisation, many other requirements arise from the French regulation.  

-Identification 

Packaging of all medicines must include the national administrative number called code CIP (code identifiant de presentation =  
presentation identifier code) on both outer carton and inner packaging after the terms “Médicament autorisé n° …. » (13° of article R5121-138). 

In addition, in line with the Directive 2001/83/CE and Delegated Regulation (EU) 2016/161, medicines must include  an unique identifier (Articles R5121-138-1 and R5121-138-2) with exception to OTC products or POM products included in Annexe I of Delegated Regulation (EU) 2016/161 which are not requested to include the Unique identifier. In addition, packaging should bear an anti-tampering device on their packaging except for POM products included in Annexe I of Delegated Regulation (EU) 2016/161 . 

In France, the Product Code (PC) (14-digit code) includes the national number (NN). The NN in France is the CIP and the PC corresponds to “0+code CIP” which should appear near the datamatrix and separately from the above mentioned “Médicament autorisé n° …. ». 

-Legal Status 

The legal status must be made available on both outer and inner packaging (17° of article R5121-138).  

All medicines available on prescription are listed on List I or List II which determine how they can be delivered. 

This classification must appear on the packaging with details as follow (Article R5132-15): 

• an empty frame with a red or a green border depending on the List; 

• In the coloured border, the text “respecter les doses prescrites*” in black font must be included; 

• the below information must then be mentioned : 

• “Liste I” or “Liste II”, 

• “Uniquement sur ordonnance”**, 

• “Ne pas avaler” (in case the product is not for oral, sublingual, perlingual or injectable administration) 

In addition, if applicable, other information must appear in case:  

• the medicine is classified as narcotic or psychotic, 

• the medicine is subject to restricted or special prescription. 

When medicines are contained in outer packaging that complies with the aforementioned provisions: 

*The statement “Follow the prescribed doses” is not mandatory for ampoules or other small primary packaging where affixing this statement would not ensure optimal legibility of the information. 

**The statement “Prescription only” is not mandatory for primary packaging containing only a single dose. 

This information is made available in the prescription and delivery information approved by ANSM: 

• within the MA for product authorised via NP, MRP or DCP,  

• or within the blue box for product authorised via the CP. 

-Pregnancy Pictogram 

Requirement to include the Pregnancy pictogram has been introduced in 2017 and is included in Article R5121-139 of the French Public Health code. This pictogram placed on the outer packaging aims at providing patients with information on the risk of using the medicines during pregnancy or in case of childbearing potential. It concerns medicines with teratogenic or foetotoxic effects mentioned in the SmPC (sections 4.6 and 5.3). 

Three situations are possible and the population in scope of the warning must be precisely mentioned below or on the right side of the pictogram: 

DANGER	PROHIBITED	VALPROATE
The triangle must be equilateral and with a side of at least 1 cm. The circle must have a diameter of at least 1 cm. The colour of the form is red with white inner. The pregnant woman must be black.
Population in scope to be determined :  « – l’adolescente ou la femme en âge de procréer, et sans contraception efficace ;  – la femme enceinte ;  – la femme enceinte à compter du [X]e mois de grossesse (lorsque la contre-indication porte sur une période précise de la grossesse). »		Population determined by law.

It is the responsibility of the MAH to determine the level of the pregnancy pictogram and the concerned population. It is highly recommended to ensure traceability of this pictogram determination and to ensure adequate stakeholders are involved. 

These information will be then submitted to the French Agency upon declaration of marketing of the medicine. 

-Pictogram regarding the effect on the ability to drive or use machines 

Medicines which may reduce the ability to drive or operate machines must have a pictogram (warning triangle) (Article R5121-139). Its size is adapted to fit the label.  

Since the ministerial order in 2008, 3 categories of pictograms have been identified for specific active substances (listed in ministerial decrees dated August 2008 and March 2017) in relation with the effect on the ability to drive. In addition, in case the active substance is not listed in the ministerial decree but is known to have such effect (based on section 4.7 of the SmPC), the MAH must include the neutral pictogram.  

Active substance listed in Ministerial Decree			Active substance not listed in Ministerial Decree but known to have effects on the ability to drive and use machines
Level 1	Level 2	Level 3

-Pictogram for medicinal products containing ketoprofen as topical gel to avoid sun exposure of treated skin areas  

-Other pictograms  

Article R5121-139 also states that the outer packaging may include, in addition to the company’s distinctive mark, signs or pictograms explaining some of the labelling information as well as other information consistent with the SmPC if they are useful to patients and not promotional in nature. 

-Logos foreseen in the environmental code 

In addition to the pictograms foreseen in the French pharmaceutical legislation, it is necessary to consider the inclusion of the pictogram “INFOTRI” aiming at explain how to eliminate different elements of the medicinal product. 

This INFOTRI logo is mandatory on all products intended for household use.  

This logo is to be included on one of the packaging elements of medicinal products used by patients (outer packaging or PIL (except of centralised procedure)). This is not requested for medicinal products used by Healthcare Professionals. 

2. Other texts to consider: 

In addition to the regulatory texts, various recommendations from the French HAs and from the EU regulators must be taken into account to develop, review and approve artworks : 

• French texts: 

• Recommendation regarding the labelling of oral solid forms (outside homeopathic medicines), 

• Recommendation for labelling of small volume injectable medicines, 

• Core labelling for paracetamol containing medicines, 

• EU texts: 

• Notice To Applicants : Guideline on the packaging information of medicinal products for human use authorised by the union, 

• CMDh “Blue – Box” requirements 

3. Responsibilities

Validation of artwork for France is under the responsibility of the Chief Pharmaceutical Officer (CPO) of the Exploitant. The validation can be supported by the below proposed table. 

Registration procedure	What references to use
National	Annex IIIB; French labelling  recommandations List provided in Prescription and delivery part of the MA	Article R5121-139 for effect on the ability to drive or use machines + ministerial decree + content of section 4.7 of the SmPC Internal assessment for the determination of the pregnancy pictogram level + sections 4.6 and 5.3 of the SmPC; CIP code provided by ANSM Article of article R5121-138 (point 17°) Article R5132-15 INFOTRI
MR and DC procedures	Annex IIIB; French labelling  recommandations Mock-up approved during the MR or DC procedure List provided in Prescription and delivery part of the MA
Centralised	Annex IIIB; Blue box approved by the ANSM; Mock-up approved by the EMA QRD group

Atessia can support you for the development and review of artworks of medicinal products for the French Market.

Link : https://www.atessia.fr/en/our-services/registration-drafting-and-submitting/

Article written by  Agathe DAUBISSE, Senior Regulatory Affairs Consultant