Centralised Procedure

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The centralised procedure is defined by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing the European Medicines Agency (EMA).

This procedure allows obtaining a single marketing authorisation (MA), issued by the European Commission, valid in all Member States of the European Union as well as in the Member States of the European Economic Area (EEA): Iceland, Liechtenstein and Norway.

1/ Scope of application

The centralized procedure is mandatory for certain categories of medicines :

  • advanced therapy medicinal products
  • biotechnology medicinal products
  • medicinal products containing a new, unauthorized active substance used in the treatment of acquired immunodeficiency syndrome (AIDS), cancer, neurodegenerative diseases, diabetes autoimmune diseases and other immune dysfunctions, and viral diseases
    • orphan drugs.

It is optional for other categories of medicines which, although not mandatory, may be of interest at the European level. These include:

  • medicines containing a new active substance that, as of 20 May 2004, was not authorized in the European Union
  • medicines representing a significant therapeutic, scientific, or technical innovation
    • medicinal products presenting an interest for patients at European Union level.

Generic medicines of a reference medicine authorised in the European Union may also be eligible for the centralised procedure.

2/ The actors involved

The Committee for Medicinal Products for Human Use (CHMP), the EMA’s scientific body, is at the core of the centralized procedure. To carry out its pharmacovigilance tasks, the CHMP relies on the scientific assessment and recommendations of the Pharmacovigilance Risk Assessment Committee (PRAC).

The main actors are :

  • The applicant : the holder of the marketing authorisation application.
  • The rapporteurs and co-rapporteurs : two Member States appointed by the CHMP to assess the application and draft the assessment reports.
  • The CHMP : responsible for the scientific review and for providing  an opinion on the benefit/risk balance of the medicinal product.
  • The European Commission : the competent authority for the final marketing authorisation decision, based on the CHMP’s opinion.

3/ Timetable

The total duration of the scientific evaluation is 210 days, excluding clock stops to allow the applicant to answer questions from the CHMP.

Pre-submission

The applicant may arrange a pre-submission meeting with the EMA. These meetings are an essential opportunity to obtain procedural and regulatory advice from the Agency and to ensure that the application complies with the requirements of the centralised procedure.

Submission and validation

The complete dossier is submitted via the EMA portal. A technical validation is carried out, covering the dossier structure (eCTD), as well as a validation of the administrative and regulatory content. Once these validations are completed, the scientific evaluation officially begins on Day 1.

First evaluation (Day 1 to Day 120)

The rapporteurs and co-rapporteurs appointed by the CHMP carry out their initial scientific evaluation and draft a preliminary assessment report, consolidated with comments of the other members of the CHMP.

A peer review is then conducted by the rapporteur and co-rapporteur to harmonize opinions and finalize the list of questions to be addressed to the applicant. Day 120 marks the start of the clock-stop period, during which the applicant typically has up to three months to prepare its response document. Response time is not included in the 210 regulatory days.

Second evaluation (Day 121 to Day 210)

After the clock-stop period, the CHMP resumes the scientific evaluation based on the responses provided by the applicant (Day 121). This phase aims to verify that all questions have been adequately addressed and to finalize the Final Assessment Report (joint assessment) (Day 150).

If some questions remain unresolved or if a point requires clarification, the CHMP may hold a second clock-stop, during which the applicant provides additional information (Day 180).

After this second clock-stop, an oral explanation may be requested by either the applicant or the CHMP (Day 181). This hearing is generally held when the CHMP maintains major objections and allows the applicant to respond directly to the critical points raised by the committee.

Once all the answers to the questions have been received, the Final Assessment Report can be finalized and the CHMP adopts its final opinion on the benefit-risk balance of the medicinal product (Day 210). This opinion may be positive, adopted either by consensus or by an absolute majority of members, or negative. In the event of a negative opinion, the applicant has the right to appeal the decision in accordance with EMA’s procedures.

European Commission Decision

When the CHMP opinion is positive, the European Commission has 67 days to make the final decision on granting the marketing authorisation.

4/ In summary

The centralized procedure is the preferred authorisation route for innovative medicines seeking a European presence. It ensures a harmonized scientific evaluationassessment. However, its complexity requires solid strategic preparation and proven regulatory expertise.

ATESSIA supports pharmaceutical companies in defining their registration strategy, preparing and submitting applications under the centralised procedure, and managing interactions with both the EMA and the European Commission.

Article written by Lamya SAOUSSEN, Junior Regulatory Affairs and External Communication Advisor  

Do “over the counter” medicines exist in France?

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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.

What are direct-access medicines ?

Over-the-counter (OTC) drugs do not constitute a legal category of drugs under French or European law. This concept, imported from Anglo-Saxon countries, refers to drugs that are directly available to patients at authorized dispensing locations. They promote responsible self-medication and patient autonomy.

In France, since July 1, 2008, certain medicines known as officinal medicines (MMO) can be made directly available to the public in pharmacies, under strict conditions. They are referred to in several ways: “self-medication medicines“, “over-the-counter medicines” or “direct access medicines“

A dedicated space in pharmacies

Article R. 4235-55 of the Public Health Code (CSP), authorizes pharmacists to display MMO in a dedicated, clearly identified space located in the immediate vicinity of the dispensing and pharmaceutical record stations.

Their dispensing remains subject to the effective control of the pharmacist, in accordance with the obligation to provide advice imposed on them by the Code of Ethics and Good dispensing practices.

Eligibility Criteria for Inclusion on the MMO List

To be presented for direct public access, medicines must be listed by the Director General of the National Agency for the Safety of Medicines and Health Products (ANSM). Under Article R.5121-202 of the PHC, inclusion is subject to the following conditions:

  • Medicine must not require a mandatory medical prescription (excluding those classified in Lists I and II of poisonous substances, such as narcotics, as well as other medicines subject to restricted prescription);
  • Therapeutic indications, treatment duration, and information provided in the package leaflet must allow safe use by the patient, on pharmacist advice and without a medical prescription: : symptoms must be easily recognisable and must not risk concealing a serious condition;
  • Packaging (weight, volume, number of dosage units) must correspond to the posology and recommended treatment duration indicated in the leaflet;
  • The medicine must not be subject to advertising restrictions for public health reasons;
  • It must not appear on the lists provided for under Article L.162-17 of the Social Security Code, which qualifies for reimbursement by health insurance.

The required documentation for the application is detailed in the ANSM document, “Modalities for Submitting Requests to Add, Modify, or Remove a Medicine from the List of Officinal Medications for Direct Public Access”, available on the ANSM website.

Following review, under Article R.5121-203, the ANSM’s Director General may, by reasoned decision, refuse the listing of medicine on public health grounds, including after reassessment of the benefit-risk balance. The Director General may also suspend or remove a medicine from the list if it no longer meets the criteria of Article R.5121-202 or for any public health reason.

Advertising authorized for the public

Given the criteria imposed by Article R.5121-202, these drugs meet the conditions imposed by Article L.5122-6 of the CSP and may therefore be advertised to the public, subject to obtaining a GP (“Grand Public”) visa. 

The ANSM recommendations specify that reference to the fact that it is an officinal medicine remains possible provided that “it is sober and informative in nature […]”. This reference cannot constitute the main focus of the communication and must not be interpreted in its form as “[…] an official accreditation or label for the advertising message.”

Messages or slogans must not suggest that the medicine is effective or safe.

Conclusion: Balancing Accessibility and Safety

The French regulatory framework allows community pharmacists to provide direct public access to certain non-prescription medicines, provided that their MA permits safe use under pharmacist guidance. This voluntary procedure for MA holders balances healthcare accessibility and patient safety while complying with strict regulatory requirements.




Article written by Arthur DI RUGGIERO, Regulatory Affairs Advisor

Clinical Trials versus Research Involving Human Subjects (RIPH): How Are Pharmaceutical Companies Affected?

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Medical research constitutes an essential lever for the development of new treatments and for the continuous improvement of patient care.

In France, this research is governed by strict regulations designed to protect participants and ensure the integrity of human subjects. The Jardé Law, adopted in March 2012 and fully applied since November 2016, constitutes the legal framework for research involving human subjects (RIPH).

Relationship between the Jardé Law and the European Clinical Trials Framework

It should be noted that clinical trials involving medicinal products are primarily regulated by the EU Clinical Trials Regulation (EU) 536/2014 (CTR), which came into effect on January 31, 2022. This regulation repealed and replaced Directive 2001/20/EC. Since that date, clinical trials on drugs must be submitted via the Clinical Trials Information System (CTIS). As a reminder, any clinical trial with at least one active investigator site in France as of January 31, 2025 had to undergo a transition request to CTIS by its sponsor. The ANSM notice to sponsors provides practical guidance on the submission of applications.

The Jardé Law does not replace the CTR but complements the European framework with specific national requirements, notably regarding the protection of participants, consent and information, research classification, and procedures involving the Committees for the Protection of Persons (CPP).
Other regulatory provisions must also be integrated by sponsors, such as procedures on personal data protection (GDPR, CNIL rfefernce methodologies), procedures related to the use of medicinal products composed wholly or partially of genetically modified organisms (GMOs), and specific rules applicable to certain health products.

Indeed, depending on the nature of the research object, the applicable provisions differ. The Jardé Law thus covers: drugs, medical devices (clinical investigation) in vitro diagnostic medical devices (performance study), cell therapy products, tissues, organs, labile blood products (LBPs), or even research on dietary supplements or cosmetics.

What is the Jardé Law?

The Jardé Law, named after Deputy Olivier Jardé, is a regulation that governs the conditions under which research involving human participants can be conducted in France. It replaces the Huriet-Sérusclat Law of 1988 and aims to strengthen the protection of participants while simplifying and harmonizing procedures, taking into account the level of risk incurred.

The main reference texts include: 

– The Jardé Law, Law No. 2012-300 of March 5, 2012, relating to research involving human subjects. 

– The ordinance, known as the “modified Jardé Law,” relating to research involving human subjects. 

– Decree No. 2016-1537 of November 16, 2016, relating to research involving human subjects. 

Classification of RIPH

Research organized and conducted on human beings with the aim of developing biological or medical knowledge is referred to as “research involving human subjects” (RIPH). There are three types of RIPH:

Category Legal Provisions Framework 
Category 1 Interventional research involving a risk to participants (intervention not justified by usual care)Articles L1121-1 to L1121-17 of the Public Health CodeThese studies require prior authorization from the ANSM (French National Agency for Medicines and Health Products Safety) and a favorable opinion from a Committee for the Protection of Persons (CPP).
Category 2: Interventional research with minimal risks and constraints *Articles L1121-1 to L1121-17 of the Public Health CodeThese studies require a favorable opinion from a CPP, but not authorization from the ANSM.
Category 3: Non-interventional research (observational studies – negligible risks)Article L1121-1 of Public Health CodeThese studies require a favorable opinion from a CPP, but not authorization from the ANSM.

* Research involving drugs cannot in principle fall under Category 2, except for very specific cases defined by regulation. An order sets the criteria to be met to remain within the scope of RIPH 2.

What Are the Implications for the Industry? 

Participant Information and consent

The objective of the Jardé Law is to ensure the safety of participants. Special attention is given to the notions of informed consent and clear, understandable, and fair information.

Industrials, as sponsors, must ensure that participants fully understand the stakes, procedures, risks and constraints, and potential benefits of the study. These requirements are detailed in Articles L1122-1-1 to L1122-2 of the Public Health Code (CSP).

Determination of Competent Authorities and Applicable Procedures

Sponsors must determine the category of their research during the design phase, ensure they obtain the necessary authorizations (CPP and/or ANSM), and define the applicable procedure (CTR/CTIS for drugs).

Interactions with CPPs and the ANSM 

CPPs are French ethics committees (Committees for the Protection of Persons) responsible for evaluating participant protection, the quality of information and consent, and the benefit/risk balance. Interactions with CPPs and the ANSM are essential for the validation of research projects. Good communication and submission of complete dossiers are necessary, in accordance with Articles L1123-6 and L1123-7 of the Public Health Code. For each RIPH, a CPP responsible for assessing the application is selected by random draw. The information system for research involving the human person (SI RIPH 2G) enables the submission of an application for an opinion and the random designation of a CPP. The platform also allows for the declaration of healthy volunteers participating in a study.

Procedures

Before submitting the authorization request dossier (initial authorization and substantial modification) and/or human research opinion request, or routine care research, sponsors must obtain an IDRCB registration number for the research. This number identifies each research conducted in France. For a interventional research authorization and opinion request concerning a medicinal product for human use, sponsors must instead obtain a research registration number in the European CTIS database (formerly: EudraCT).

Subsequently, sponsors will electronically submit the biomedical research authorization and/or opinion request dossier to the ANSM and/or CPP, in accordance with the current orders setting the dossier formats for each type of research. Various “Notices to Sponsors” guide these procedures according to the situation.

Conclusion

The Jardé Law thus ensures the safety of participants in clinical research in France.

For health manufacturers, understanding and complying with these regulations is not only a legal obligation but also a guarantee of the quality of the data generated, particularly for use in a Marketing Authorization Application (MAA) dossier.

By integrating the requirements of the Jardé Law into their processes, manufacturers contribute to the development of innovative treatments while ensuring high ethical standards, in accordance with French and European regulations on this subject.

Atessia supports you in implementing these processes with its expertise in clinical trials.

Article written by Mathilde ISRAEL 

Comprendre EUDAMED

Understanding EUDAMED: The European Database on Medical Devices

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The new regulation (EU) 2017/745 introduces new requirements to enhance the safety of patients and users. One of the novelties of this new regulation is the creation of a European database dedicated to information on medical devices called EUDAMED.

This database will allow:

  • Increased transparency of information on medical devices with public access.
  • Better coordination between Member States in the post-market surveillance of medical devices.

EUDAMED is a secure platform used to collect and share data related to medical devices placed on the European Union market, as well as those undergoing clinical investigation.

The regulation introduces new requirements for the various actors involved in EUDAMED.

This database will consist of six interconnected modules:

Module :  Who needs to record information?Accessible to the public
1-ActorsEconomic operators must register as actors in EUDAMED and provide the required information.– EU and third-country manufacturers,
– Authorized representatives,
– System/procedure pack producers,
– Importers.		Available on a voluntary basis since December 2020 and will be mandatory from Q1 2026.
2-Devices Manufacturers must submit the basic-UDI and information of all devices they place on the EU market into EUDAMED.Only manufacturers.
Registration of medical devices under MDR.
No obligation for legacy devices (if registered in EUDAMED, a new registration will be required for products under MDR, considered as new products).		Available on a voluntary basis since October 2021 and will be mandatory from Q1 2026.
3- Notified Bodies (NB) and CertificatesNotified bodies must register in EUDAMED all information regarding issued, suspended, reinstated, withdrawn, or refused certificates and other restrictions imposed on these certificates. This information is accessible to the public.  Notified Bodies.Available on a voluntary basis since October 2021 and will be mandatory from Q1 2026.
4-Vigilance  Module dedicated to all vigilance and post-market surveillance reports.
– Safety information (Field Safety Notice, FSN),
– Field Safety Corrective Action (FSCA),
– Investigation report of incident causes and corrective measures (MIR),
– Trend report,
– Periodic Safety Update Report (PSUR).  		Manufacturer.Will be mandatory from Q3 2026.
5- Market SurveillanceCoordination of market surveillance actions between the various competent authorities.  Competent authority only.Will be mandatory from Q1 2026.
6- Clinical Investigation/Performance Studies (CI/PS):  This module concerns the registration of clinical investigations (MD) and performance studies (IVD). – Clinical investigation report and summary, – Serious adverse event during clinical investigations.Sponsor.Not yet available.


Source : European commission



And the Distributors?

The MDR imposes no requirements on distributors regarding EUDAMED. They have no secure access to EUDAMED and only have public access. However, some countries may set additional requirements, such as France, which requires distributors to register via the ANSM form.

EUDAMED Deployment Schedule

In October 2019, the European Commission announced a two-year postponement of EUDAMED’s launch to May 2022.

Some modules are already available and can be used voluntarily. A roadmap project was released on July 10, 2024, indicating a full deployment of EUDAMED scheduled for the second quarter of 2027.

On 27 November 2025, the European Commission published Decision (EU) 2025/2371 on the functionality and compliance with specifications for EUDAMED modules:

  • Registration of economic operators” module (ACT module)
  • Medical device registration and UDI database module (UDI/DEV module)
  • Certificates and notified bodies module (NB/CRF module)
    • Market surveillance module (MSU module)

These 4 modules are therefore operational and will be compulsory from 28 May 2026 (i.e. 6 months after publication in the OJEU) in accordance with Regulation (EU) 2024/1860. 


The remaining 2 modules are not currently available:

  • Clinical investigations/performance studies module (CI/PS module)
  • Post-trade surveillance and vigilance module (VGL module)

A roadmap has been updated:



Useful Documents and Guides:

Q&A “on practical aspects related to the implementation of the gradual roll-out of Eudamed pursuant to the MDR and IVDR, as amended by Regulation (EU) 2024/1860 amending Regulations (EU) 2017/745 and (EU) 2017/746 as regards a gradual roll-out of Eudamed, the obligation to inform in case of interruption or discontinuation of supply, and transitional provisions for certain in vitro diagnostic medical devices” (22/11/2024)

USER GUIDES to record the information in EUDAMED

MDCG “EUDAMED”

European Commission – The EUDAMED four first modules will be mandatory to use as from 28 May 2026

OJEU – Commission Decision (EU) 2025/2371 of 26 November 2025 concerning the opinion on the functionality and compliance with functional specifications of certain electronic systems included in the European database on medical devices referred to in Article 34(1) of Regulation (EU) 2017/745 of the European Parliament and of the Council



Article written by Camille Neermul

New ICH M4Q(R2) guidelines: towards a paradigm shift for Module 2.3 and 3 formats

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Background

In Europe, information relating to the quality, safety, and efficacy of the Marketing Authorization Application (MAA) for medicinal products is compiled in a common format known as the Common Technical Document (CTD) format. The CTD format applies in all regions that recognize ICH guidelines. It is currently organized into five Modules: Module 1 is specific to the region, while Modules 2, 3, 4, and 5 are common to all regions (see Figure 1).

Figure 1 : The CTD triangle

The CTD format, described in ICH M4, became the mandatory format for marketing authorization applications for new drugs in Europe in July 2003. Prior to its implementation, marketing authorization dossiers met the requirements of the NtA Volume 2B format (1998 edition).

For industries, the introduction of the CTD format eliminated the need to reformat information submitted to the various ICH regulatory authorities.

Subsequently, the introduction of the ‘eCTD’ (electronic Common Technical Document) format, which first became mandatory in Europe in 2007 for centralized marketing authorizations, revolutionized regulatory practices by harmonizing electronic submissions to ICH regulatory authorities, notably replacing submissions in NeeS (Non-eCTD electronic Submission) format. Information on the eCTD format is available in ICH M8.


Reasons for the revision of ICH M4Q(R1)

In Europe, the content of Module 2.3 (QOS – Quality Overall Summary) and Module 3 of the marketing authorisation dossier meets the requirements detailed in the ICH M4Q(R1) guidelines implemented in July 2003. No revision of this text has been carried out for more than 20 years, which has led legislators to several observations:

Observation #1) The traditional CTD structure is not suited to addressing modern quality concepts.

Since the publication of ICH M4Q(R1), new guidelines ICH Q8 to ICH Q14 have been developed, introducing innovative concepts such as Quality by Design (QbD), Quality Risk Management (QRM) and Life Cycle Management (LCM) approaches, as well as Continuous Manufacturing (CM).

The ICH M4Q(R1) document was not designed to take into account the new quality principles, and integrating them into the current CTD format is not straightforward.

Observation #2) The traditional CTD structure is not suited to handling changes in technologies and product types.

ICH M4Q(R1) was designed primarily for conventional small molecules and is structured around the active substance (Part 32S) and the finished product (Part 32P), with adaptations for biological products. Experience has shown that complex products and new therapeutic modalities (nanomedicines, oligonucleotides and biological products such as vaccines, cell and gene therapies, and tissue-engineered products) as well as combination products often do not fit perfectly into this framework.

Observation #3) The traditional CTD structure creates ambiguity in the organisation and placement of information.

The required modular format (i.e. summary of quality data included in Module 2.3 and detailed information included in Module 3) leaves room for differing interpretations as to which details should be included in Module 2.3 versus Module 3 and often leads to repetition of information. Ambiguity remains regarding the location of information and cross-references between modules.

The management of updates and variations to marketing authorizations throughout the lifecycle, while maintaining consistency in the CTD structure with ICH M4Q(R1), is not optimal.

Observation #4) The traditional CTD structure allows regional differences to remain.

Despite the harmonization of the dossier format within the ICH, additional requirements specific to certain countries/regions often persist, thereby reducing the advantage of having a single format.

Observation #5) The current eCTD format does not allow for the integration of new requirements for electronic and structured data.

The current trend is towards structured, machine-readable submissions and the use of data standards (e.g. ISO IDMP 11615), in line with the future implementation of SPQS (Structured Product Quality Submission) by the EMA, which will lead to future ICH M16 guidelines (see Figure 2).

Figure 2: Interactions between ICH M4Q(R2) and SPQS (future ICH M16)

ICH M4Q(R1) was not designed for such structured content, which complicates automation and prevents data reuse between submissions.

For all these reasons, ICH MQ4(R1) must be redesigned to enable data management and standardisation, thereby promoting the efficiency of the dossier review and approval process.


Overview of the ICH M4Q(R1) revision: current framework versus future framework

Although changes are being made to the location of information in the future Modules 2.3 and 3, these do not alter regulatory expectations. The data used as the basis for regulatory assessment, previously presented in Module 3, will now be included in Module 2.3. Module 3 will now serve as a repository for technical data (protocols, reports, data, etc.) (see Figure 3).

Figure 3: Changes in data location between ICH M4Q(R1) and ICH M4Q(R2)

The future granularity of Module 2.3 and Module 3, as anticipated in the 14 May 2025 draft version of ICH M4Q(R2), is presented in Figure 4 and Figure 5.

Figure 4: Granularity of Module 2.3 according to ICH M4Q(R2) (1)

Figure 4: Granularity of Module 2.3 according to ICH M4Q(R2) (2)

Figure 4: Granularity of Module 2.3 according to ICH M4Q(R2) (3)

Figure 5: Granularity of Module 3 according to ICH M4Q(R2)



Essential information on quality (2.3.3 Core Quality Information (CQI)):

– shall include all information subject to lifecycle management in accordance with regional requirements for post-authorisation changes to ensure product quality.

– shall be maintained throughout the product lifecycle to ensure that product quality information remains current.

The information contained in sections 2.3.1 (General Information), 2.3.2 (Overall Development and Overall Control Strategy), 2.3.4 (Development Summary and Justification), 2.3.5 (Product Lifecycle Management), 2.3.6 (Product Quality Benefit Risk) and Module 3 will be supportive information, which may be modified or supplemented for post-marketing submissions.

In the future ICH M4Q(R2), information will be grouped into specific subsections of materials/components used in manufacturing:

  • drug substances (DS),
  • substances intermediates (SI),
  • raw materials (RM),
  • starting/source materials (SM),
  • excipients (EX),
  • reference materials (RS),
  • impurities (IM),
  • drug products (DP),
  • products intermediates (PI),
  • packaged medicinal products (PM),
  • pharmaceutical products (PH) and
  • medical devices (MD).

Information relating to analytical procedures and facilities that apply to all materials will be presented in dedicated sections.

Each subsection will then be organized according to the following DMCS structure:

  • Description: identifies the material and its key characteristics;
  • Manufacture: outlines the production process and process controls;
  • Control: Control: describes quality control measures such as specifications;
  • Storage: provides stability, container closure information, and retest period/shelf-life

The relationships between Module 2.3 and Module 3 in the context of the DMCS model used for materials/components are illustrated as follows:

 2.3.3 Core Quality Information2.3.4 Development Summary and Justification3.2 Body of Data
 Information related to what the material is and its key characteristics, which is considered necessary to enable marketing authorization and facilitate lifecycle managementScientific and risk-based development summary and justifications related to what the material is and its key characteristicsSupportive information including reports and data related to what the material is and its key characteristics
DescriptionNomenclature, structure, composition, key characteristicsCharacterization summary, formulation development and justificationCharacterization data, formulation development and justification data
ManufactureManufacturing process description, IPCs, critical process parametersProcess development and validation/evaluation summaryProcess development and validation/evaluation data
ControlSpecificationsOverview of batch analysis, justification of specificationsBatch analysis and justification data
StorageContainer closure system description, storage conditions, and retest period/shelf lifeOverview of stability studies, justification of proposed container closure systemContainer closure selection and stability data  



Conclusion

In conclusion, ICH M4Q(R2) aims to promote harmonization of the quality content of dossiers, ideally enabling a single dossier to be submitted in all ICH member countries.

Where required by law, the applicant shall provide any additional region-specific information directly in the relevant section of a separate document, in the form of an addendum to the harmonized base document used in all ICH regions.

Atessia supports pharmaceutical companies in preparing Modules 2.3 and 3.


Sources:

– The CTD Triangle

– ICH M4 Organisation Including the Granularity document that provides guidance on document location and pagination

– Notice to Applicants, Volume 2B incorporating the Common Technical Document (CTD) (May 2008)

– ICH M4Q(R1) CTD on Quality

– ICH M4Q Q&As (R1) Questions & Answers: CTD on Quality

– ICH M4Q(R2) EWG Revision of M4Q(R1) (draft guideline 14 May 2025)

– M4Q(R2) Step 2 presentation (18 June 2025)

– Présentation Finding your way with the new eCTD (ICH-M4Q), Ivica Malnar, Agency for Medicinal Products and Medical Devices (HALMED) (23-24 September 2025)

– ICH M8 electronic Common Technical Document (eCTD) v3.2.2

– ICH M8 electronic Common Technical Document (eCTD) v4.0


Article written by Isabelle MOUVAULT, Senior Advisor in Pharmaceutical Affairs

The Post-Approval Change Management Protocol or “PACMP” 

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In Europe, changes to a marketing authorisation (MA) for a human medicine are covered by Regulation (EC) No. 1234/2008 of November 24, 2008. This regulation has been applicable since January 1, 2010 to MAs obtained in centralized, decentralized and mutual recognition procedures, and since August 4, 2013 to MAs obtained in national procedures. It presents multiple possibilities for classifying the modifications that can be made to a MA, including the Post-Approval Change Management Protocol (known by the acronym “PACMP”) which we will focus on in this article.

Origin and definition 

A PACMP is a regulatory tool providing predictability and transparency in terms of requirements and studies necessary for the implementation of a strictly CMC (for “Chemistry, Manufacturing & Controls”) change, because the approved protocol of the planned changes constitutes an agreement between the MA holder and the regulatory authority. This is a stepwise approach to evaluate modifications, initially allowing for an early evaluation of the modification strategy and, in a 2nd step, a subsequent separate evaluation of the data produced after implementation of the planned changes on the basis of the agreed strategy.

The objective of this tool is to allow faster and more predictable implementation of modifications after approval, given that the MA holder will have previously obtained the agreement of the authorities on the proposed strategy and the tests allowing to check the effect of the modification on the quality of the product. Typically, the variation category designated for reporting changes under a PACMP is at least one category lower than it would normally be (e.g., Type IB instead of Type II). The implementation of the changes planned in an approved PACMP is therefore faster and less risky for the laboratories that request it, which ultimately benefits to the marketing of the drug and therefore to the patient.

In 2012, the EMA compiled a set of questions and answers regarding the PACMP in the document “Questions and answers on post approval change management protocols (EMA/CHMP/CVMP/QWP/586330/2010)”. This document was revised in December 2025 to reflect experience gained since its initial publication, the revision of the regulations on variations (2024), and the associated guidelines on variations (2025) applicable on January 15, 2026. The following topics are covered:

  • Suggestions for PACMP content; 
  • PACMP submission and evaluation mechanisms; 
  • Implementation of the change(s) after finalisation of the studies described in the PACMP; 
  • Types of changes that may be subject to a PACMP; 
  • Multiple changes within the framework of a single PACMP; 
  • Place of the PACMP in the Module 3 of the MA; 
  • PACMP and development according to the traditional approach versus the improved approach (so called “QbD” for “Quality by Design”). 

In 2019, the ICH Q12 guideline “Technical and regulatory considerations for pharmaceutical product lifecycle management“, proposed in order to provide a framework to facilitate the management of changes to chemical properties, manufacturing and control measures after the authorisation, in a more predictable and efficient manner throughout the lifecycle of the product, has reinforced the place of the PACMP as an essential regulatory tool in the management of the lifecycle of medicines in Europe.

Scope of the PACMP use 

The PACMP concerns both CMC modifications relative to the drug substance (DS) and modifications relative to the drug product (DP). It applies to all medicinal products for human use, including biotechnological or biological products, whether a traditional or improved (“QbD”) approach was followed for the development of the product. However, its use is optional.

A PACMP can be applied to a single product, multiple products, or multiple products and multiple sites.

The presence of a PACMP in its MA file involves careful risk analysis and a full understanding of the different risk assessments to ensure that the quality, safety and efficacy of the medicine are never compromised.

It has to be noted that no modification described in a PACMP should result in additional risks to patient safety, product quality or efficacy. Also, a CMC modification that would require human efficacy, safety, or pharmacokinetic/pharmacodynamic data to evaluate the effect of the modification (e.g., certain formulation changes, clinical or nonclinical studies to evaluate new impurities, evaluation of immunogenicity or antigenicity) cannot be included in a PACMP.

Formalisation of the PACMP in the MA file 

The PACMP takes the form of one or more document(s) presented in section 3.2.R “Regional Information” of the MA file. It can be planned as soon as the MA application is made or during a MA variation application (Type II).

MA modifications linked to the PACMP 

The different variations linked to the introduction, deletion or modification of a PACMP in a MA file are presented in the table below. 

Active substance Finished product 
Variation Type II/Q.I.e.2: Introduction of a post-approval change management protocol (PACMP) related to the active substance
> Absence of conditions to be fulfilled.
> Three supportive documentations to be provided:
1. Detailed description for the proposed change.
2. Post-approval change management protocol related to the active substance.
3. Amendment of the relevant section(s) of the dossier		Variation Type II/Q.II.g.2: Introduction of a post-approval change management protocol related to the finished product (PACMP)
> Absence of conditions to be fulfilled.
> Three supportive documentations to be provided:
1. Detailed description for the proposed change.
2. Post-approval change management protocol related to the finished product.
3. Amendment of the relevant section(s) of the dossier. 
Variation Type IA/Q.I.e.3: Deletion of a post-approval change management protocol (PACMP) related to the active substance
> One condition to be fulfilled:
1. The deletion of the post-approval change management protocol related to the active substance is not a result of unexpected events or out of specification results during the implementation of the change(s) described in the protocol and does not have any effect on the already approved information in the dossier.
>Two supportive documentations to be provided:
1. Justification for the proposed deletion.
2. Amendment of the relevant section(s) of the dossier.		Variation Type IA/Q.II.g.3: Deletion of a post-approval change management protocol (PACMP) related to the finished product
> One condition to be fulfilled:
1. The deletion of the post-approval change management protocol related to the finished product is not a result of unexpected events or out of specification results during the implementation of the change(s) described in the protocol and does not have any effect on the already approved information in the dossier.
> Two supportive documentations to be provided:
1. Justification for the proposed deletion.
2. Amendment of the relevant section(s) of the dossier.
Variation Type II/Q.I.e.4(a): Changes to a post-approval change management protocol (PACMP) – Major changes to a post-approval change management protocolVariation Type II/Q.II.g.4(a): Changes to a post-approval change management protocol – Major changes to a post-approval change management protocol
Variation Type IB/Q.I.e.4(b): Changes to a post-approval change management protocol (PACMP) – Minor changes to a post-approval change management protocol that do not change the strategy defined in the protocol
> Absence of conditions to be fulfilled.
> One supportive documentation to be provided:
1. Declaration that the changes do not change the overall strategy defined in the protocol and are not broader than the currently approved protocol.		Variation Type IB/Q.II.g.4(b): Changes to a post-approval change management protocol – Minor changes to a post-approval change management protocol that do not change the strategy defined in the protocol
> Absence of conditions to be fulfilled.
> One supportive documentation to be provided:
1. Declaration that the changes do not change the overall strategy defined in the protocol and are not broader than the currently approved protocol. 
Variation Type IA/Q.I.e.5(a): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IA notification
> One condition to be fulfilled:
1. The proposed change has been performed fully in line with the post-approval change management protocol which requires its notification within 12 months following implementation.
>Three supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Amendment of the relevant section(s) of the dossier.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP.		Variation Type IA/Q.II.g.5(a): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IA notification
> One condition to be fulfilled:
1. The proposed change has been performed fully in line with the post-approval change management protocol which requires its notification within 12 months following implementation.
> Four supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Results of the studies performed and any other supporting documentation in accordance with the post-approval change management protocol.
4. Amendment of the relevant section(s) of the dossier.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP. 
Variation Type IAIN/Q.I.e.5(b): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IAIN notification
>One condition to be fulfilled:
1. The proposed change has been performed fully in line with the post-approval change management protocol, which requires its immediate notification following implementation.
>Four supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Amendment of the relevant section(s) of the dossier.
4. Results of the studies performed in accordance with the post-approval change management protocol.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP.		Variation Type IAIN/Q.II.g.5(b): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IAIN notification
>One condition to be fulfilled:
1. The proposed change has been performed fully in line with the post-approval change management protocol, which requires its immediate notification following implementation.
>Four supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Amendment of the relevant section(s) of the dossier.
4. Results of the studies performed in accordance with the post-approval change management protocol.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP. 
Variation Type IB/Q.I.e.5(c): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IB notification
> Absence of conditions to be fulfilled.
>Four supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Amendment of the relevant section(s) of the dossier.
4. Results of the studies performed in accordance with the post-approval change management protocol.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP.		Variation Type IB/Q.II.g.5(c): Implementation of changes foreseen in a post-approval change management protocol (PACMP) – Implementation of changes foreseen in a PACMP via Type IB notification
> Absence of conditions to be fulfilled.
> Four supportive documentations to be provided:
1. Reference to the post-approval change management protocol.
2. Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol (*).
3. Amendment of the relevant section(s) of the dossier.
4. Results of the studies performed in accordance with the post-approval change management protocol.

(*) In case the acceptance criteria and/or other conditions in the protocol are not met, the change cannot be implemented as a variation of this category and should instead be submitted as variation of the applicable category without PACMP.


The use of PACMP is strongly recommended by regulatory authorities and in line with the latest ICH guidelines (Q8, Q9, Q10, Q12 and Q14). As a result, an increase in this type of variation seems predictable for the years to come.

 
Article written by Isabelle MOUVAULT, Pharmaceutical Affairs Senior Consultant 

MPUP Non GMP

How to manage a non-GMP raw material in your MA files? 

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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

Prescription et délivrance

Conditions for the Prescription and Dispensing of Medicines in France

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The conditions for prescription and dispensing (CPD) define how patients may access a medicine. The prescription and/or dispensing of a medicine may be restricted—meaning reserved for hospital use or to certain physicians (such as specialists), or subject to specific requirements (regarding treatment duration or additional examinations)—in the interest of patient safety.

The prescribing of healthcare products falls within the scope of physicians and certain healthcare professionals, within the limits of their professional practice: dentists, midwives, physiotherapists, podiatrists, nurses, and occupational therapists.

Medicines that present difficulties in use or risks in case of inappropriate use may only be obtained, depending on the case, with a prescription from a physician, dentist, or midwife. These are known as prescription-only medicines (PMO, Rx). They are classified into different categories based on their prescribing and dispensing rules:

  • List I medicines (single dispensing with the same prescription unless otherwise specified by the prescriber) and List II medicines (renewals allowed for up to one month of treatment for a maximum of 12 months).
  • Narcotics: around twenty medicines, including morphine and its derivatives, whose dispensing is subject to very strict rules (secured prescription, batch number and a micro-lettering box to prevent falsification, with quantities limited to 7, 14, or 28 days of treatment).

If a medicine is not included in these lists, it is considered “non-mandatory prescription” (PMF), or even OTC (available over the counter in pharmacies).

As an exception, community pharmacists are authorised to prescribe and administer, to certain populations, the vaccines included in the national immunisation schedule, as well as seasonal influenza and COVID-19 vaccines. They may also dispense, without a prescription, certain prescription-only medicines for the management of sore throats and cystitis in pharmacies, after performing a rapid diagnostic test (TROD).

Some prescription-restricted medicines may be dispensed to the public by a hospital pharmacy (PUI). These medicines are included on the “retrocession” list.

Medicines with Restricted Prescription

This term covers five categories of medicines belonging to List I:

  • Medicines reserved for hospital use (RH): they may only be prescribed, dispensed, and used in hospitals.
  • Hospital-prescription-only medicines: they may only be prescribed in hospitals. They are dispensed in any pharmacy or, in some cases, only in hospital pharmacies.
  • Hospital-only initial prescription medicines: the initial prescription must be issued in a hospital, but renewal prescriptions may be issued by a community physician. Depending on the case, dispensing may occur in hospital or community pharmacies. In some situations, the number of renewals is limited, and a new hospital prescription is required after a set period (usually one year).
  • Medicines restricted to certain specialists: these medicines are complex to use or treat complex diseases. They may be dispensed in hospital or community pharmacies.
  • Medicines requiring special monitoring: patients treated with these medicines must undergo regular monitoring (blood tests, additional examinations, more frequent consultations). The prescription may only be renewed if these monitoring requirements are met.

Regulatory Framework – Directive 2001/83/EC

Directive 2001/83/EC includes articles dedicated to prescription and dispensing requirements.
According to Article 70:

“1. When granting a marketing authorisation for a medicinal product, competent authorities shall specify its classification as either:
— medicinal product subject to medical prescription,
— medicinal product not subject to medical prescription.
They shall apply the criteria set out in Article 71(1).

  1. Competent authorities may establish subcategories for medicinal products that may only be supplied on medical prescription, referring to the following classification:
    a) medicinal products on prescription that may or may not be renewed;
    b) medicinal products subject to special medical prescription;
    c) medicinal products under ‘restricted’ medical prescription, reserved for certain specialised settings.”

These provisions are also reflected in French regulation (Article R5121-36 for prescription conditions and Articles R5121-77 et seq. for restricted-prescription medicines). According to Articles R5121-77 et seq. of the French Public Health Code, the marketing authorisation (MA) defines the prescription and dispensing conditions of a medicine.

The MA of a restricted-prescription medicine may require the prescriber to indicate on the prescription that the patient has been informed of the associated risks.
When the reference medicinal product of a generic is classified in a restricted-prescription category, the generic’s MA follows the same classification.

Evolving Toward Greater Access in Community Pharmacies

Law n° 2020-1525 of 7 December 2020 on accelerating and simplifying public action, integrated into Article L5123-2 of the Public Health Code, illustrates a desire to shift medicines towards community pharmacy distribution.
According to Article L5123-2, any request for inclusion on the hospital formulary of a medicinal product that is not classified as reserved for hospital use must be accompanied by a request for inclusion on the “community list”

Atessia’s Support

Atessia assists pharmaceutical companies in defining or modifying the prescription and dispensing conditions of their medicinal products.

This article was written by Estelle ICARD, Regulatory & Pharmaceutical Affairs Consultant.

Rétrocession

The Hospital-to-Community Dispensing (“Retrocession”) of Hospital Medicines to Outpatients in France

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In France, community pharmacies are the standard point of dispensing for outpatients when medicines are not restricted to hospital use. 

“Retrocession” refers to the dispensing of medicines to outpatients by hospital pharmacies (PUI – pharmacies à usage intérieur), as an exception to or in addition to the community pharmacy supply chain. It is justified by public health or safety reasons listed in the French Public Health Code. 

According to Articles L5126-6 and R5126-58 of the French Public Health Code, and the dedicated page on the ANSM website, medicines must meet the following criteria to be eligible for rétrocession: 

  • not be restricted to hospital use (RH status), 
  • present specific dispensing or administration constraints, 
  • have particular requirements related to supply security, 
  • require monitoring of the prescription or dispensing. 
  •  

Medicines are included on this list for public health reasons, in the interest of patients. 

The retrocession list, initially established in 2004 and managed by the Ministry of Health until 2021, was originally built on the basis of practice and needs. 
Its management was then transferred to the ANSM at the end of 2021 (Decree No. 2021-1531 of 26 November 2021). It is now supplemented by generic medicines corresponding to reference products already listed, or by certain new medicines considered by the ANSM to have added value when dispensed through hospital pharmacies due to safety-of-use or supply considerations. These medicines hold a Marketing Authorisation (MA) or an Import Authorisation (AI). The ANSM has expressed its intention to streamline this list, keeping only medicines that legitimately require access through this distribution channel. 

Decisions to include medicines on the retrocession list are published on the ANSM website approximately every 15 days, depending on the flow of newly granted MAs. A consolidated and updated retrocession list is also available (including antibiotics/antifungals, anticancer agents/immunosuppressants, antivirals, plasma-derived medicinal products, etc.). 

Other medicines may be dispensed through retrocession without being explicitly listed. These include the following categories: magistral or hospital preparations, medicines granted early access or compassionate use. 

The purpose of the retrocession system is to ensure that patients can access certain treatments despite specific distribution, dispensing, or administration constraints, or when particular monitoring of the prescription or dispensing is required, without the need for hospitalisation. 

When medicines have been marketed for several years and sufficient experience has been gathered, their switch to community pharmacy dispensing logically leads to their removal from the retrocession list. 

Atessia supports pharmaceutical companies in defining or modifying the prescribing and dispensing conditions of their medicinal products. 

This article was written by Estelle ICARD, Regulatory & Pharmaceutical Affairs Consultant. 

PCVRR

The PRRC: Person Responsible for Regulatory Compliance 

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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 

  • 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