Pharmaceutical companies bringing a product to market in Europe are sometimes not entirely comfortable with the local affiliate requirements they must address in key markets. One of the more complex and poorly understood is the legal framework of the “Exploitant” in France[1].
The Exploitant is defined under the French Public Health Code as the organism responsible for drugs “exploitation”1, under the responsibility of a Responsible Pharmacist[2] “Exploitation” refers to any activity that applies to the commercial operation of medicinal products in France, including advertising, information, pharmacovigilance, storage and distribution (including batch follow up and recalls)1. Indeed, the French Health Authorities require that a specific organization is in place to guarantee a high level of compliance and ensure that all local specific requirements are covered. In other EU markets and, in accordance with the legal framework of the European Directive 2001/83/CE[3], the role is reduced to “distributor” or “wholesaler” with a focus on the storage and distribution activities, though the Exploitant has many other specific obligations[4]
Requiring a Wholesaler Distribution Authorization (WDA)
With regards to the legal frameworks previously mentioned, any pharmaceutical company that wants to market a product in France must obtain the status of Exploitant, meaning that a specific organization under a Responsible Pharmacist’s responsibility has to be implemented.
The level of conformity of this planned organization will then be evaluated through a well-defined dossier that will be evaluated by the French National Agency for Medicines and Health Products Safety (ANSM). The approval from ANSM should permit the applicant to obtain its Wholesaler Distribution Authorization (WDA), which will be recognized across Europe and globally.
Preparing the Exploitant dossier
The ANSM expects companies wishing to market their product in France to submit an electronic dossier in French that details how they will conduct and organize all their in-country pharmaceutical activities under the responsibility or the “Exploitant” –– and who the responsible pharmacist for these activities will be[5].
The dossier comprises two parts: an administrative and a technical section. In the administrative section, companies must include the proof of company identity, the name of the responsible pharmacist, some commitments by the organization and back up implementation, a full description of the premises and documented security measures as well as respective plans, contracts and pictures of the premises and access points.
What most clients find to be the mostpart of the dossier is linked to the technical section, which describes, in detail, each requirement and activity involving the Exploitant. In particular, the technical note must include detailed information about the following:
- Advertising: description of the promotional and non-promotional materials review process, as well as the compliance to the Charte de l’Information Promotionnelle and the associated Référentiel de certification 4 (the legal framework for promotional activities in the field)
- Medical information and Pharmacovigilance organization processes, and particularly the 24/7 availability of the EU-QPPV and local RPV contacts
- The quality system, including staff, management of documentation, deviations and CAPA, audits, trainings, and risk management
- Supply and distribution, including the measures to manage storage and transport (and relevant subcontractors if involved), in particular where there are product complaints and batch recalls
- Follow up of all the subcontracted operations
- The information system, including the infrastructure and all backup and security procedures
- A description of the portfolio
- Assurance that all resources – premises, infrastructure, staff, etc. – will meet compliance requirements regarding the Exploitant status.
Companies should be prepared to reply to specific questions from the ANSM, as the role of the evaluator is to ensure that the dossier covers all requirements.
Navigating the dossier evaluation
Once the electronic dossier has been submitted via the ANSM portal, there is a 30-day post-receipt evaluation period. If the health authorities determine that the dossier is incomplete, companies have to provide the necessary information as quickly as possible to avoid any delay in the evaluation[6].
The evaluator at the health authority may have follow-up questions, which will result in a clock-stop and some delays. With this in mind, it’s important to consider when to file a dossier to avoid times when the company or the agency may have limited availability, for example, over Christmas or in the summer holidays when it is difficult to put together a response, to avoid any rejection of the dossier. After 90 days, if there is no reply from the ANSM, the dossier is considered to be approved, leading to obtaining the nominated WDA from the ANSM. This approval is valid for one year. If activities are finally not implemented, for example, the company has not gone ahead with the opening at the end of this period, the WDA becomes void.
The responsible pharmacist
Exploitant activities must be designed and organized by the responsible pharmacist, usually referred to as the Chief Pharmaceutical Officer (CPO)[7], as he/she is personally involved as the gatekeeper of compliance with the public health code and with professional practices and ethical rules. The CPO is the preferred contact from the ANSM in case of questions for the products marketed by the company on the French market. This person must be a corporate officer with the requisite powers over the company’s pharmaceutical activities, must be a practicing French pharmacist and have appropriate experience.
This person must be involved in every marketing authorization activity, including importation, exportation, violations, promotional information, pharmacovigilance complaints, distribution and storage, and batch monitoring. For example, the responsible pharmacist is the only person able to decide to carry out a product recall in France, in accordance with the ANSM requirements .
The responsible pharmacist also oversees the local quality management system that describes all the processes. And he/she must ensure the marketing authorization is kept up to date with any new data about the drug and to safeguard patients.
There are a number of very specific activities that are required of the responsible pharmacist to ensure the company is in compliance with the French Public Health Code. For example, the Charte de l’information Promotionnelle is an agreement by the pharmaceutical company to adhere to certain ethical rules when a sales representative is visiting a healthcare professional. These include being respectful of validated product information, and ensuring, for example, that no off-label use will be promoted or discussed.
Another requirement relates to medical information. For example, it is mandatory to be available 24/7 and to respond quickly to any questions or concerns from consumers or healthcare providers. Companies are inspected regularly to ensure they meet these requirements.
It’s important to note that the definition of the Exploitant is not included in the European regulations, and the French health authority, the (ANSM), cannot stipulate that the Exploitant be in France since the EU regulation takes precedence. However, it is highly advisable that a company seeking to market a medicinal product in France should hold an Exploitant status locally or partner with a consultancy in France to manage the Exploitant requirements, since many exploitation activities require native French speakers with deep knowledge of the French regulation and specific local requirements.
Do you understand the Exploitant status and how it applies to your products? Have you struggled with managing commercial operations in France? We would be interested in hearing about issues you have faced and the approach you have taken to managing your products in France.
About the author:
Alexia Argouarch, PharmD, is Associate Director, Regulatory Affairs and Quality Assurance, at PharmaLex France.
[1] Public health code, Section 1: Scope and definitions (Articles R5124-1 to R5124-15), Legifrance. https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000043761806
[2] About the Chief Pharmaceutical Officer – Responsible Pharmacist, https://blue-reg.com/service/responsible-pharmacist/
[3] Directive 2001/83/EC, Eur-Lex, European Union. https://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A32001L0083
[4] Dossier de demande d’ouverture d’un établissement pharmaceutique exploitant, ANSM. https://ansm.sante.fr/uploads/2021/04/15/ouverture-exploitant.pdf
[5] Dossier de demande d’ouverture d’un établissement pharmaceutique exploitant, ANSM. https://ansm.sante.fr/uploads/2021/04/15/ouverture-exploitant.pdf
[6] Public health code, Subsection 1: Scope and definitions (Articles R5124- to R5124-15), Legifrance. https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000043544691
[7] Public health code, Subsection 2: Functions and responsibilities of responsible pharmacists. (Items R5124-34 to R5124-37), Legifrance. https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000026446678/2012-10-01
