Wael HAYEK

French always do it different 

In many domains, French people like to stand out, either in a positive or negative way. 

In the Healthcare field, France has set a system that is highly effective, and very protective for the patient, but at the price of a heavy state involvement and of one of the most complex regulations. 

As a result, understanding the regulatory specificities of France is key for entering the French market. 

ATESSIA can help you in this process and provide you assistance and expertise. 

Here are a few areas where France follows its own, often complicated and restrictive, rules. 

The substances used in a medicinal product intended for the European market, including for export, are defined as raw materials for pharmaceutical use (RMP). They can be active (active substance) or inert (excipients). 

Whether the medicinal products are intended for human or veterinary use, only active substances manufactured and distributed in accordance with European Good Manufacturing Practices (GMP – Part II) and Good Distribution Practices (GDP), introduced by article L.5138-3 of the French Heath Code, can be used. 

Thus, when applying for a marketing authorization or for certain applications to modify the marketing authorization, the notice to applicants requires the submission of a signed QP declaration by the qualified person of the manufacturing site and/or of the certification of the batches of the finished product attesting that the active substance used is manufactured in accordance with good manufacturing practices. 

Concerning the excipients used in medicinal products for human or veterinary use, there is no enforceable standard in the national or European regulations and they are not subject to the QP declaration in the marketing authorization file. It is up to the manufacturer or distributor of the finished product to define its quality system the applicable standard(s) for the manufacture or distribution of the excipient, according to its/their intended use(s). This exercise will be carried out in consultation with pharmaceutical users on the basis of the results obtained during a formal quality risk assessment (GMP point 5.29). It should be noted that ANSM recommends, at a minimum, the IPEC/PQG GMP & GDP reference systems.  

However, it is recognized that for some raw materials, their pharmaceutical use may represent only a minor fraction of their other industrial uses (agri-food, cosmetics or others). Thus, their producers may not have the objective of meeting the specific requirements of pharmaceutical customers. 

The EMA’s Q&A Part 1 reaffirms that compliance with the above-mentioned standards is a legal obligation and that, in the event of difficulties in guaranteeing a supply of satisfactory quality, alternative GMP sources must be sought out, qualified and, if necessary, registered. In the case of a source identified on European territory, the establishment must apply for authorization or registration from the competent authority of the Member State in which it is established. In case of import from a third country to the European territory, the source of the identified active substance will be conditioned by the provision of a written confirmation from the competent authority of the exporting third country. This document attests that the applicable standards are at least equivalent to the GMP defined by the European Union.  

In exceptional circumstances these same EMA Q&A Part 1 introduces the possibility for manufacturing authorization holders (of the finished product) to assess and document the extent to which GMP is met, and to provide a risk-based justification for the acceptance of any deviation. At the MA level, the QP declaration should detail the rationale for stating that the standards applied provide the same level of assurance as GMP. The EMA will collect the experience gained with this approach, which can be used as a basis for discussion of possible future related changes to the guidelines. 

However, at the national level, the ANSM does not, for example, explicitly provide for derogations or for exceptional circumstances, unlike the EMA for centralized MA. When informed in advance of a particular context (such as medicinal products of major therapeutic interest or the absence of a therapeutic alternative), the competent authorities could then request additional information or carry out an inspection to ensure that the establishment complies with the standards in force in the Union. Thus, this situation can only be transitory, since these alternative sources (in the EU or in third countries) and/or their principals can request an express request for an inspection of the raw materials from a competent authority of one of the member states in order to obtain a certificate of conformity. 

The control of the supply chain is the key word. Deficiencies in the qualification and monitoring process of suppliers and/or manufacturers of raw materials are regularly the subject of injunctions issued by the ANSM against pharmaceutical establishments (2 for the year 2024 and 2 for the year 2025). For the alternative identified source, this may be a hindrance (compulsion to comply with the opposable standards) or an opportunity (to comply with them in order to enter the EU market for UPMPs). A mutualization of supplies (and on-site audits) can also be an interesting approach to encourage the source to seize this opportunity.  

This article was written by Véronique LEWIN, Senior Consultant in CMC Regulatory Affairs

Article 15 of Regulation (EU) 2017/745 on medical devices and Article 15 of Regulation (EU) 2017/746 on in vitro diagnostic medical devices formally introduce the requirement for each manufacturer (and each authorised representative) to designate a Person Responsible for Regulatory Compliance (PRRC). This requirement aims to ensure the continuous compliance of devices placed on the market, regardless of their class or medical purpose. 

This obligation applies to all types of devices: 

• Implantable or non-implantable 

• Active or non-active 

• Standard or custom-made 

• With or without a medical purpose 

Who Needs a PRRC? 

• Manufacturers  

All manufacturers placing CE-marked medical devices on the EU market are required to appoint a PRRC. 

• Authorised Representatives (ARs) 

EU-based authorised representatives acting on behalf of non-EU manufacturers are also required to designate a PRRC. 

Other economic operators such as distributors, importers, and assemblers are not required to have a PRRC. 

Roles and Responsibilities of the PRRC 

The PRRC plays a critical role throughout the regulatory lifecycle of a medical device. The main responsibilities include : 

• Verifying the conformity of devices prior to their release, relying on the manufacturer’s quality management system. 

• Preparing and updating technical documentation, including the EU declaration of conformity. 

• Post-market surveillance obligations: monitoring device performance and safety after it has been placed on the market. 

• Reporting obligations to competent authorities in the event of incidents or significant changes. 

• Submitting declarations in case of clinical investigations and performance studies, as required by the regulation. 

🔒 Independence Guarantee : The regulation ensures that the PRRC cannot be disadvantaged in carrying out their duties, whether they are an employee of the company or an external party. 

Required Qualifications to Act as a PRRC 

There are two possible routes to qualify as a PRRC, as set out in the regulation: 

1. Academic Path + Experience 

• A diploma (or certificate) in law, medicine, pharmacy, or another relevant scientific discipline. 

• ≥ 1 year of professional experience in regulatory affairs or quality management systems related to medical devices/or in vitro diagnostic medical devices. 

• For custom-made devices: ≥ 2 years of experience in a relevant manufacturing field. 

2. Professional Experience Path 

• ≥ 4 years of professional experience in regulatory affairs or quality systems applicable to medical devices /or in vitro diagnostic medical devices. 

. 

PRRC Role Based on Company Size 

The regulation acknowledges structural differences between large companies and SMEs: 

• Large enterprises: The PRRC must be a permanent part of the organization. 

• Micro and small enterprises*: The PRRC role can be outsourced, provided the person is permanently and continuously available. 

Multiple PRRCs: If more than one person is appointed, they share joint responsibility for regulatory compliance. Their respective responsibilities must be clearly defined in writing, and each individual must meet the qualification requirements. 

Registration and Compliance 

Since the Regulation came into effect on 26 May 2021, the contact details of the PRRC must be registered in EUDAMED, the European database for medical devices. 
(See our blog post on EUDAMED for more details.) 

Useful References 

• Article 15 of Regulation (EU) 2017/745 on medical devices 

• Article 15 of Regulation (EU) 2017/746 on in vitro diagnostic medical devices 

• SNITEM Guide – The Person Responsible for Regulatory Compliance 

*Commission Recommendation 2003/361/ΕC of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises: 

-Within the SME category, a small enterprise is defined as an enterprise which employs fewer than 50 persons and whose annual turnover and/or annual balance sheet total does not exceed EUR 10 million. 

-Within the SME category, a microenterprise is defined as an enterprise which employs fewer than 10 persons and whose annual turnover and/or annual balance sheet total does not exceed EUR 2 million. 

Article written by Camille NEERMUL, Senior Consultant in Quality and Regulatory Affairs for medical devices 

Legal basis: 

When marketing authorization holders wish to register a medicine in Europe, they submit a marketing authorisation (MA) application to the health authorities.  

Once marketing authorisation has been obtained, it is the responsibility of the marketing authorisation holder to keep the dossier up to date and to report any changes that affect the marketing authorisation. These changes may be of various types (administrative, quality, safety).  To do this, the marketing authorisation holder must submit a notification or a variation application to the competent health authorities.  

A variation is a modification to the marketing authorisation.  

There are also other types of MA modifications, known as MA extensions. 

Changes to the terms of a European marketing authorisation are provided for in Directive 2001/83/EC and Regulation (EC) No 726/2004, and detailed in Regulation (EC) No 1234/2008 on the examination of variations to the terms of marketing authorisations for medicinal products for human use (hereinafter referred to as the ‘Variations’ Regulation). New guidelines to facilitate the interpretation and application of the Variations Regulation were published in the Official Journal on 22 September 2025 and are applicable on 15 January 2026. The Annex to these guidelines provides details of the classification of variations. These guidelines cover the following categories of variations, defined in Article 2 of the Variations Regulation: 

— Minor variations of Type IA, 

— Minor variations of Type IB, 

— Major variations of Type II, 

— Extensions, 

— Urgent safety restrictions. 

Any modification must be classified in one of the above categories. However, in some cases, the distinction between a Type II (major) variation or an extension is complex. 

Definitions: 

1. Type II variations 

Type II variations are considered as major variations. These are variations which are not extensions of marketing authorisations and may have a significant impact on the quality, safety or efficacy of the medicinal product concerned. This type of variation is generally assessed within 60 days, but shorter assessment periods (30 days for safety-related variations) or longer periods (90 days for indication extensions) may be necessary. 

2. Extensions 

Certain changes to a marketing authorisation must be considered as fundamentally altering the terms of that authorisation and therefore cannot be granted through a variation procedure. Annex I of the Variations Regulation sets out a list of changes to be considered as extensions; the two main changes requiring an extension are:  

– Changes to the active substance(s): 

– Changes to strength, pharmaceutical form and route of administration 

According to Article 19 of the « modification » Regulation, an application for an extension shall be evaluated and granted in accordance with the same procedure as for the initial marketing authorisation to which it relates.  

The extension may either be granted as a new marketing authorisation (national procedures, MRP and DCP) or included in the initial marketing authorisation to which it refers (centralised procedure). 

In all cases, the new MA obtained is part of the global marketing authorisation and is not eligible to additional data protection (except in cases of ‘significant’ indication extensions based on comparative data). 

The assessment timetable for an extension is the same as that for an initial marketing authorisation application. 

In practice 

Experience has shown problems in the classification of extension applications versus variations particularly regarding the items pharmaceutical form and strength. The « GUIDELINE ON THE CATEGORISATION OF EXTENSION APPLICATIONS (EA) versus VARIATIONS APPLICATIONS (V) » (Revision 4 – July 2019), proposes a harmonised and agreed interpretation of the Standard terms, with the aim of facilitating the application of the Regulation on variations throughout the EU and helping in the classification of requests.   

The main principles of classification of extensions versus type II variations are as follows: 

^*: unless the modification results in a change to the strength, pharmaceutical form or route of administration. 

The guideline also provides examples presented as table for more complex cases. 

It is important to note that variation requests may be grouped together with a marketing authorisation extension request. The assessment period applied to variations will be that of the marketing authorisation extension. 

In summary 

Apart from the question of the regulatory classification of the application (variation or extension), numerous practical questions may arise when compiling the application: 

– Will my brand name be affected? 

– How should I submit my extension request? 

– What data should I generate? 

– Can I group extension submissions with other types of variations? 

– Do I need to meet pediatric requirements in my extension application? 

– How should I integrate this extension into the eCTD? 

ATESSIA can assist you in developing your regulatory strategy and drafting your variation or extension application dossiers, regardless of the registration procedure. 

This article was written by Anne-Valérie Angérard, senior regulatory affairs consultant.