Wael HAYEK, auteur sur Atessia

ATESSIA, Your Guide to Efficient Regulatory Affairs in the Pharma Industry

In the intricate and highly regulated world of pharmaceuticals and healthcare, ATESSIA stands out as a consulting firm dedicated to guiding companies through the complexities of regulatory affairs. Recognizing the critical role of compliance and patient safety, ATESSIA offers comprehensive expertise that spans scientific documentation, clinical trials, regulatory submissions, and pharmacovigilance. By ensuring seamless collaboration with regulatory authorities across multiple jurisdictions, ATESSIA helps companies achieve compliance while driving growth and maintaining a strong focus on patient welfare and product efficacy.

Regulatory Affairs: a Growth Engine

Regulatory affairs are far more than a checklist of tasks—they represent a strategic driver of growth and innovation within the pharmaceutical and medical device sectors. At their core, they ensure that products meet the highest safety and quality standards, from development to commercialization. This involves aligning manufacturing processes with legal requirements, maintaining ongoing communication with regulatory authorities, and managing the vast documentation required for regulatory submissions.

Regulatory affairs also operate as a vital connector, fostering collaboration across clinical, medical, and marketing teams to ensure that every stage of product development adheres to regulatory standards. Beyond compliance, they enable strategic growth by guiding research and development efforts, supporting faster market access through regulatory frameworks, and facilitating partnerships and licensing agreements. Moreover, regulatory expertise ensures that companies can enter new markets efficiently, navigating diverse local requirements while maintaining compliance for existing products as regulations evolve.

Balancing Regulatory Workload

An overburdened regulatory workload can strain a company’s resources, stifling growth and innovation. ATESSIA’s solutions address this challenge by alleviating internal pressures, allowing teams to focus on core activities such as clinical trials and market strategy.

By partnering with ATESSIA, companies gain access to a balanced approach to regulatory affairs. ATESSIA’s expertise accelerates market access by efficiently managing regulatory submissions and ensures operations remain cost-effective and controlled. As an independent consultancy, ATESSIA provides objective and unbiased advice, enabling clients to navigate the complexities of the regulatory landscape with confidence.

What makes french Regulatory Affairs unique and how can ATESSIA Help?

The French pharmaceutical market presents unique challenges and opportunities due to its distinct regulatory environment. Stringent requirements from the ANSM (Agence Nationale de Sécurité du Médicament et des Produits de Santé), coupled with specific laws such as the Public Health Code, create a complex framework for compliance. ATESSIA acts as a strategic partner for international companies, offering expert guidance to navigate these complexities and thrive in the French market.

Key challenges include obtaining Exploitant status, adhering to packaging and labeling requirements, maintaining robust pharmacovigilance systems, and complying with strict advertising and anti-gift regulations. ATESSIA also supports companies in negotiating pricing and reimbursement with the HAS (Haute Autorité de Santé) and the CEPS (Comité Économique des Produits de Santé), ensuring optimal market entry strategies and compliance.

ATESSIA’s Commitment to Customer Experience

Led by Géraldine Baudot-Visser, ATESSIA is built on a foundation of precision, flexibility, and a deep understanding of client needs. The company prioritizes tailored solutions, crafting regulatory strategies that align with each client’s specific context, sector, and objectives. With a commitment to transparency, ATESSIA ensures clear and open communication throughout every project, empowering clients to make informed decisions confidently.

This long-term partnership approach positions ATESSIA as more than just a regulatory consultant. By adapting to changing regulatory environments and supporting clients as they grow, ATESSIA becomes an essential ally in achieving compliance and fostering sustainable growth.

ATESSIA transforms regulatory affairs from an operational challenge into a strategic tool for success. By providing unparalleled support and expertise, the company helps pharmaceutical businesses navigate complex landscapes, achieve compliance, and capitalize on growth opportunities.

For more information, visit www.atessia.fr or reach out via email at hello@atessia.fr. ATESSIA’s team is ready to help optimize your regulatory affairs and support your strategic objectives.

To read the full article on Silicon Review, click here!

ATESSIA Named Among the “5 Best Pharma Consulting Companies to Watch in 2024”

Company, Non classé

We are proud to be featured in The Silicon Review, a recognition that highlights our unwavering commitment to excellence in regulatory affairs.

In the pharmaceutical industry, regulatory compliance is more than a requirement—it is the foundation for driving innovation and safeguarding patient health. At ATESSIA, we tackle these challenges with precision and a strategic approach, helping our clients achieve their long-term goals.

Why partner with ATESSIA?

Streamlined Processes: We simplify regulatory workflows, enabling your teams to focus on innovation and clinical success.

Accelerated Market Entry: With deep expertise in French regulatory requirements (Exploitant status, pricing, market authorizations), we ensure a smooth entry into the French market.

Sustainable Compliance: Our tailored strategies align regulatory adherence with your budget and timeline constraints.

Independent Expertise: As an autonomous consultancy, we offer objective guidance backed by in-depth knowledge of the pharmaceutical landscape.

This achievement represents a key milestone in our mission to transform regulatory affairs into a strategic advantage for our clients.

Let’s stay connected ! Our services

Learn more: Read the article

Forbes – ATESSIA, Life Science Advisors : The Regulatory and Pharmaceutical Affairs Consulting Firm Dedicated to the Healthcare Industry

Company / Consulting, Géraldine Baudot-Visser, Healthcare industry, Life Science Advisors, Pharmaceutical affairs, Regulatory affairs

Leveraging its expertise, ATESSIA supports a wide range of health products, with a particular focus on pharmaceuticals and medical devices. Through a tailored and rigorous approach, the firm helps its clients navigate complex regulatory landscapes, ensuring compliance and innovation in their projects.

More Human, More Agile

“I founded ATESSIA, Life Science Advisors, with the conviction that regulatory and pharmaceutical affairs consulting could be reimagined through a more human and agile lens,” explains Géraldine Baudot-Visser. Drawing on several years of experience in the pharmaceutical industry and renowned consulting firms, I recognized the opportunity to create a company that prioritizes client satisfaction and the empowerment of its experts while ensuring unwavering excellence in the pharmaceutical field.” The initial challenges naturally revolved around gaining the trust of the first clients and dismantling stereotypes about consulting. The firm needed to prove that rigor and creativity can coexist and demonstrate that a consulting firm can combine cutting-edge expertise with a bespoke approach. Striking the balance between managing a young company and delivering excellence has been a top priority since day one. For the founder, the goal was clear: to become a reference in regulatory consulting in the French and European markets within a few years, despite competition from established firms.

Tailor-Made Solutions, Continuously Enhanced

Every phase of ATESSIA’s growth has been driven by the ambition to establish itself as a leader while rallying employees around its clients’ challenges. Each step has also been an opportunity to reinvent, innovate, and grow while staying true to its values to ensure a client-centered approach. “For example,” says the founder, “our regulatory intelligence service is essential for our pharmaceutical clients, achieving a satisfaction and retention rate exceeding 90%. This success reflects our ability to provide tailored support and anticipate market changes, meeting the most demanding expectations of our partners.” This commitment to exceeding expectations relies on a team capable of anticipating, adapting, and ensuring compliance with the strictest standards. This collective dynamic keeps ATESSIA at the forefront, offering clients ever more efficient, custom-tailored solutions.

An Excellence-Driven Approach

“Our clients choose us because they seek far more than standardized solutions. At ATESSIA, we work with the precision of master artisans, designing bespoke solutions perfectly adapted to the specificities of each project in a highly regulated environment. Like the finest craftsmen of traditional expertise, we pay particular attention to ensuring impeccable quality in our services to provide reliable technical support to our clients,” shares Géraldine Baudot-Visser. This excellence-driven approach makes ATESSIA a trusted partner for its clients. The consulting firm builds strong relationships founded on attentive listening, in-depth expertise, and the ability to anticipate market changes. This proactive, personalized vision allows ATESSIA to deliver solutions that are always perfectly adapted and tailored.

“Every contribution we make to the healthcare industry, no matter how modest, has the potential to impact someone’s life somewhere. This gives profound meaning to what we do and makes every project-whether centered on pharmaceutical facilities, system quality, or innovation-much more than just a mission for us: it’s an opportunity to actively contribute to improving patients’ lives. This responsibility is a source of immense and invaluable pride,” she concludes.

https://www.forbes.fr/mediasfrance/atessia/

Understanding EUDAMED: The European Database on Medical Devices

_Blog

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-Actors	Economic 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 Certificates	. Notified 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 Surveillance	Coordination 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. The dates present in the EUDAMED roadmap are provisional and in “Draft” mode. No dates are official at this stage.

Recently, on January 21, 2024, the European Commission published a proposal to amend regulation (EU) 2017/745 on medical devices (MDR) and regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) concerning the gradual deployment of EUDAMED. This proposal suggests a gradual implementation of EUDAMED modules once validated, potentially starting in Q4 2025. This proposal will need to be adopted and published in the Official Journal by May 2024.

Useful Documents and Guides:

– EUDAMED Release Note

– EUDAMED Roadmap

MDR Transition: New Responsibilities and Major Changes in the Medical Device Industry

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Since 1994, medical devices have had to comply with the requirements of European Directives 93/42/EEC and 90/385/EEC. Conformity with this regulation allows the affixing of the CE marking, enabling the free circulation of medical devices within the European Union (EU).

The European Union has recently revised this regulation through the European Regulation 2017/745/EU for medical devices (MDR), which finally came into effect on May 26, 2021. The adoption of a regulation instead of a directive ensures uniformity in the regulatory framework through its direct application.

This new regulation imposes new responsibilities on economic operators involved in the supply chain of medical devices: manufacturer, authorized representative, importer, distributor.

What are the main changes introduced by this new regulation (MDR)?

– Redesignation of Notified Bodies (NB) under MDR and EU control of Notified Bodies (NB)

– Improved traceability through the Unique Device Identification (UDI)

– Inclusion of certain aesthetic devices with the same characteristics and risk profile as medical devices covered by the regulation

– Enhanced transparency through EUDAMED, the medical device database

– Strengthened requirements for clinical data and post-market surveillance

What transition periods will apply?

Initially, the MDR was to come into effect on May 26, 2020. Due to the COVID-19 health crisis in 2020, the EU decided to postpone this date through Regulation (EU) 2020/561.

The implementation date was thus postponed to May 26, 2021, with a transition period for manufacturers with medical devices already on the European market (“LEGACY DEVICES”) until May 26, 2024 (end of the issuance of certificates under the directive) and the availability of these medical devices on the market until May 26, 2025. However, for class I medical devices and new medical devices entering the European market, they had to comply with the MDR since May 26, 2021.

On March 20, 2023, the EU assessed a potential shortage risk for many medical devices and adopted Regulation EU 2023/607, amending Regulation (EU) 2017/745 concerning transitional provisions (Article 120).

The extension dates of certificates under Directive 93/43/EEC are extended based on the class of the medical device:

However, manufacturers covered by this extension must meet the following conditions:

1/ The devices continue to comply with Directive 90/385/EEC or Directive 93/42/EEC, as applicable. ;

2/ There are no significant changes to the design and intended use.;

3/ The devices do not present an unacceptable risk to the health or safety of patients, users, or other persons, considering other aspects related to public health protection. ;

4/ no later than 26 May 2024, the manufacturer has put in place a quality management system in accordance with Article 10(9); ;

5/ The manufacturer or authorized representative has lodged a formal conformity assessment request under the MDR for a medical device or a replacement device to a Notified Body by September 26, 2024, and the Notified Body and the manufacturer have signed a written agreement.

Special case for custom-made class III implantable devices – transitional period introduced:

The conformity assessment of custom-made class III implantable devices requires an assessment by a Notified Body.

Custom-made class III implantable medical devices can be placed on the market without the corresponding certificate until May 26, 2026, provided that the manufacturer has submitted an application to a designated Notified Body under the MDR before May 26, 2024, and has signed a contract with that Notified Body before September 26, 2024.

MDR requirements applicable from May 26, 2021:

However, it is important to note that certain MDR requirements shall apply to devices since May 26, 2021, such as requirements related to post-market surveillance, market surveillance, vigilance, and the registration of economic operators.

Removal of the availability date:

Additionally, Regulation EU 2023/607 completely removes the availability deadline, allowing “LEGACY DEVICES” to be available without a deadline (still respecting the device’s usage limit date). This removal also applies to in vitro diagnostic medical devices marketed before May 26, 2022, in Regulation (EU) 2017/746 (IVDR).

Are CE certificates under the directives still valid during this extension period?

Certificates that expired before the entry into force of Regulation 2023/607 (March 20, 2023) should only be considered valid if:

– Either before the certificate’s expiration date, the manufacturer and Notified Body signed a conformity assessment agreement before the certificate’s expiration date.

– Or if a competent authority has granted a derogation.

Notified Bodies can no longer issue or modify CE certificates under the directives since May 26, 2021. Therefore, they are considered extended unless they have been withdrawn.

Manufacturers can issue a self-declaration confirming that they comply with the extension conditions, indicating the end date of the transition period (the medical devices covered by the extension must be clearly specified). At the manufacturer’s request, the Notified Body can also issue a confirmation letter.

It is important to remember that despite these delays, manufacturers must now act toward this new regulation. The submission period to Notified Bodies can take from 6 to 18 months, depending on the Notified Body and the medical device.

Atessia supports its clients through all stages of MDR compliance.

Quelle substitution des médicaments biologiques en France?

Biological medicinal products substitution in France?

_Blog / ATESSIA, Biological medicine, Biosimilar medicine, Interchangeable medicine, Reference medicine

Biological medicinal products are used in the treatment of numerous pathologies, such as diabetes, cancer and autoimmune diseases. Any biological medicinal product whose patent has fallen into the public domain can be copied: this is known as a “biosimilar”. A biosimilar is a medicinal product which, like any biological medicinal product, is produced from or derived from a cell or living organism, and whose efficacy and side effects are equivalent to those of its reference biological medicinal product. By February 2022, 67 biosimilar medicinal products had been authorized in the European Union.

The marketing authorization of a biosimilar medicinal product must meet strict regulatory requirements to demonstrate that its pharmaceutical quality, efficacy and safety are clinically equivalent to those of the reference biologic medicinal product.

The availability of biosimilar medicinal products has a dual benefit:

– Public health, by facilitating access to care: increasing the number of biologics available helps to limit supply tensions and prevent stock-outs and/or production accidents. This guarantees patients continued access to their treatments.

– Economic: stimulating competition and lowering the price of biological medicinal products, while guaranteeing the safety and quality of treatments.

Since biosimilar medicinal products are derived from living organisms, they cannot be strictly identical to reference products. Consequently, the substitution principle, which applies to chemical medicinal products and their generics, cannot be applied automatically.

However, in the light of advances in knowledge, interchangeability and substitution during initial prescription or treatment can now be envisaged under strict conditions and within the framework of the indications, dosage regimens and routes of administration common to the reference product.

In order to guarantee proper use and safety during substitution, this substitution must be introduced gradually, initially for a limited number of medicines. The right of substitution for biosimilars is decided at national level by each member state. In France, the order of April 12, 2022 sets out the first two groups of biosimilars that can be substituted in pharmacies within a specific framework: filgrastim and pegfilgrastim (immunostimulant-cytokine agents). To date, only these two active substances are eligible for substitution in pharmacies.

What’s the latest on biosimilar substitution in France?

Pharmacists may substitute biologics under certain conditions:

– The similar biological medicinal product dispensed belongs to the same similar biological group as the biological medicinal product prescribed, within the reference list of similar biological groups published by ANSM,

– This similar biological group is included in a list established by a joint order of the ministers responsible for health and social security, issued after consultation with the ANSM (the consolidated order of April 12, 2022),

– The prescriber has not excluded the possibility of this substitution by expressly stating so on the prescription,

– The pharmacist must indicate the name of the medicinal product dispensed on the prescription and inform the prescriber and patient of the substitution.

The gradual introduction of substitution will make it possible to :

– evaluate in real-life situations the prescribing and dispensing circuit following substitution of biologics by the pharmacist;

– guarantee the proper use of biosimilar medicinal products and appropriate clinical monitoring of patients (traceability, reporting and assessment of adverse events) in the same way as the reference medicinal product,

– and to improve information and support for patients and healthcare professionals.

The reference list of similar biological groups is automatically completed when a new biosimilar MA is granted. It is regularly updated on the ANSM website. It should be noted that this list is not intended to present substitutable or interchangeable biological medicinal products. In this respect, ANSM will make available the list of substitutable biological medicinal products on its website.

Glossary :

– Biological medicinal product (article L.5121-1, paragraph 14 of the French Public Health Code): “any medicinal product whose active substance is produced from or extracted from a biological source and whose characterization and quality determination require a combination of physical, chemical and biological tests as well as knowledge of its manufacturing process and control”.

– Biosimilar” medicinal product (article L.5121-1, paragraph 15 of the French Public Health Code) “any biological medicinal product with the same qualitative and quantitative composition in active substance and the same pharmaceutical form as a reference biological medicinal product, but which does not meet the conditions laid down in 5° of this article to be considered as a generic, due to differences linked in particular to the variability of the raw material or the manufacturing processes, and requiring the production of additional preclinical and clinical data under conditions determined by regulation”.

– Reference medicinal product: biological medicinal product approved in the EU that a company developing a biosimilar medicinal product chooses as a reference point for direct comparison of quality, safety and efficacy.

– Interchangeability: refers to the possibility of replacing one medicinal product with another that is intended to have the same clinical effect. Interchangeability can be achieved in two ways:

– Permutation: when a prescriber substitutes one medicinal product for another with the same therapeutic intent.

– Substitution: the practice of dispensing a medicinal product in place of another equivalent and interchangeable medicinal product, without reference to the prescriber.

This article was written by Leslie Gorge.

Ouvrir votre établissement pharmaceutique

How to open a pharmaceutical establishment in France?

_Blog / ATESSIA, Authorisation to open a pharmaceutical establishment, Compile file, exploitant, Importer, Manufacturer, PHC, Processing time

What status for my establishment?

In France, the Public Health Code (PHC) defines different status:

Status	Authorised activities
Manufacturer	Manufacture of medicinal products, products or objects referred to in Article L. 4211-1 of the PHC
Importer	Import, storage, quality control and release of batches of medicinal products, products or objects referred to in Article L. 4211-1 from: States not members of the European Community or parties to the Agreement on the European Economic Area Or other Member States of the European Community or parties to the Agreement on the European Economic Area when the medicinal products, products or articles have been manufactured by an establishment not authorised under Article 40 of Directive 2001/83 of 6 November 2001 on the Community code relating to medicinal products for human use.
Exploitant	Exploitation of medicinal products other than investigational medicinal products, generators, kits and precursors mentioned in 3° of article L. 4211-1.
Depositary	Storage of medicinal products, products, objects or articles of which it is not the owner, with a view to their wholesale distribution and as is for the order and on behalf of: – one or more Exploitant of medicinal products, generators, kits or precursors mentioned in 3° of article L. 4211-1; – or of one or more manufacturers or importers of dressing objects or articles presented as complying with the Pharmacopoeia mentioned in 2° of article L. 4211-1 of the PHC.
Wholesaler	Purchase and storage of medicinal products, other than investigational medicinal products, with a view to their wholesale distribution as such
Wholesale distributor of pharmaceutical products other than medicinal products	Purchase and storage of intermediate products intended for further processing by an authorised manufacturer or of products, objects, articles, generators, kits or precursors referred to in 2° and 3° of Article L. 4211-1, with a view to their wholesale distribution and as such
Export Wholesale Distributor	Purchase and storage of medicinal products other than experimental medicinal products, products, objects, articles, generators, kits or precursors referred to in 2° and 3° of Article L. 4211-1, medicinal plants referred to in 5° of Article L. 4211-1, with a view to their export as such
Humanitarian wholesale distributor	Acquisition, free of charge or against payment, and storage of medicinal products other than investigational medicinal products, with a view to their wholesale distribution or export
Distributors of investigational medicinal products	Storage of investigational medicinal products manufactured or imported by companies or organisations defined in 1° or 2° of this Article (R.5124-2), with a view to their distribution as such for the order and on behalf of one or more sponsors defined in Article L. 1121-1
Wholesale distributor of medicinal plants	Storage and controls and operations necessary for the wholesale and bulk distribution, in sachet-doses, fragments or in a fresh or dried state of medicinal plants mentioned in 5° of Article L. 4211-1
Wholesale distributor of gases for medical purposes,	Purchase and storage of packaged gases for medical use, with a view to their wholesale distribution and as such
Wholesale distributor of the Armed Forces Health Service	Wholesale distribution of the medicinal products, products or objects referred to in Article L. 5124-8;
Pharmaceutical establishment for the protection of the population in the face of serious health threats	Purchase, manufacture, import and export of products necessary for the protection of the population against serious health threats, with a view to their distribution.
Pharmaceutical purchasing centre	Purchase and storage of medicinal products other than experimental medicinal products, with the exception of medicinal products reimbursed by compulsory health insurance schemes, with a view to their wholesale distribution as such to pharmacists who are the owners of a dispensing service either in their own name and on their own behalf, or in order and on behalf of pharmacists who are members of a dispensing or the structures mentioned in Article D. 5125-24-16

Some status are cumulative for all or part of an activity related to its status for the same legal institution. Example: a pharmaceutical establishment may be granted Exploitant status and may be granted manufacturer status limited to batch certification.

Who issues the opening authorisation?

The Public Health Code specifies that the authorisation to open a pharmaceutical establishment is issued by the Director General of the National Agency for the Safety of Medicines and Health Products (ANSM). This opening authorisation is made public on EudraGMP. The start of the activity therefore requires prior authorisation from the ANSM to ensure that the project complies with the regulations and to verify that the necessary resources are available and that they will be implemented. This can be a challenge, for example when early access is about to start, or when a drug is being launched. Indeed, the Exploitant must be designated.

The opinion of the competent central council of the National Order of Pharmacists is required within 2 months for any opening of a pharmaceutical establishment, except for a pharmaceutical establishment dependent on the central pharmacy of the armed forces or the health supply establishments of the armed forces health service. At the end of the 2 months, the Director General of the ANSM can make a decision.

How to compile your file?

For the opening of a pharmaceutical establishment, the ANSM website has 3 types of files available depending on the desired status:

Manufacturer/Importer file

Exploitant’s file

Distributor file

In the event of a combination of activities, as in our example above for example, 2 files must be completed.

The application to be submitted must comply with the decision of 1 October 2019 on the submission of applications for authorisation to open and amend the initial authorisations of the pharmaceutical establishments mentioned in Article R. 5124-2 of the Public Health Code, except for establishments under the authority of the Minister for the Armed Forces (cf. Article R. 5124-5 of PHC).

Such a project includes essential areas of vigilance to carry it out. The constitution of the file requires defining the appropriate status according to the desired activity, anticipating the implementation of the desired organization to write a file that is as compliant as possible with what will be carried out in the future establishment as well as with the regulations in force. The ANSM is particularly attentive to the aspects of pharmaceutical liability, compliance with GxP and security of the premises. Identifying the pharmacist in charge upstream is a crucial point.

What is the processing time?

No pharmaceutical operation may be carried out within the establishment until the authorisation to open has been obtained.

Depending on the desired activity, the applicant submits an application for authorisation to open a site to the ANSM via the dedicated secure platform “Démarches Simplifiées”.

Under the Public Health Code, the Director General of the ANSM is required to notify his decision within 90 days.

Once the file has been submitted by the Responsible Pharmacist in charge of the future establishment via « Démarches Simplifiées », the Responsible Pharmacist receives an email acknowledging receipt of the file.

The admissibility period begins. It lasts for 30 days from the date on which the application is received by ANSM, and allows the content of the application to be analysed: missing documents, incorrect naming of documents, etc. If the ANSM does not receive any requests within 30 days, the application is considered “admissible” and the processing can begin.

The ANSM may ask the applicant for any additional information. The 90-day period is then suspended from the date of notification to the Responsible Pharmacist of the request for additional information by the Director General of the ANSM, until receipt of the information requested.

The ANSM may also carry out an inspection during the processing period to ensure the accuracy of the information provided by the applicant.

If ANSM does not respond within 90 days, this is equivalent to:

refusal of authorisation for manufacturer and importer applications.

tacit authorisation for other establishments.

In recent years, Atessia has opened, modified or relocated more than a dozen pharmaceutical establishments.

This article was written by Isabelle BARBIEUX, Senior Quality Assurance Consultant.

The Jardé Law and Research Involving Human Subjects (RIPH): How Are Pharmaceutical Companies Affected?

_Blog / ATESSIA

Medical research is essential for the development of new treatments and the improvement of healthcare.

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 enforced since November 2016, is the legal framework for research involving human subjects (RIPH).

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 replaces Directive 2001/20/EC. As a reminder, any clinical trial with at least one active investigative site in France as of January 31, 2025, must be transitioned to the Clinical Trials Information System (CTIS) by its sponsor before this date. For clinical trials involving medicinal products, the Jardé Law introduces additional requirements to be considered. Other provisions include compliance with CNIL (GDPR), and procedures related to the use of medicinal products composed wholly or partially of genetically modified organisms (GMOs).

Depending on whether the research concerns a medicinal product or another health product, such as medical devices (clinical investigation) and in vitro diagnostic medical devices (performance study), cell therapy preparations, tissues, organs, labile blood products (LBPs), or even research on dietary supplements or cosmetics, the applicable regulations vary.

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. It replaces the Huriet-Sérusclat Law of 1988 and aims to enhance the protection of participants while facilitating the conduct of clinical research.

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.

– The Public Health Code (Articles L1121-1 to L1126-11), which details the specific obligations for different categories of research.

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	Articles L1121-1 and L1121-3 of the Public Health Code (CSP)	These 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	Article L1121-2 of the CSP	These studies require a favorable opinion from a CPP, but not authorization from the ANSM.
Category 3: Non-interventional research	Article L1121-1-1 of the CSP	These involve observational studies where the risks are absent or negligible. A favorable opinion from a CPP is necessary, but these studies do not require authorization from the ANSM.

What Are the Implications for the Industry?

Participant Information

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 information.

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

Information for the ANSM

Manufacturers must determine the category of their research during the design phase and ensure they obtain the necessary authorizations. Notably, for RIPH involving medicinal products, they cannot be classified as RIPH 2. An order specifies the criteria to remain within the scope of RIPH 2. For category 1 RIPH, this involves submitting a complete dossier to the ANSM and obtaining a favorable opinion from a CPP (Article L1121-4 of the CSP). Since 2022, for clinical trials on medicinal products, the CTR requires submission through the CTIS platform. Proper classification of your RIPH is a prerequisite for any procedure.

Interactions with CPPs and the ANSM

CPPs are French ethics committees. 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.

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 biomedical research authorization and opinion request concerning a medicinal product for human use, sponsors must 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 regulations on this matter.

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

Article written by Zarine RAMJAUNY, Legal Consultant

The Excellence of ATESSIA’s CMC: Your Partner in Technical and Regulatory Affairs

_Blog / CMC needs, Management Optimization, Mergers & Acquisitions, Outsourcing CMC Activities, Regulatory Requirements

In a constantly evolving pharmaceutical industrial environment, regulatory requirements for quality data are becoming increasingly complex. Health authorities are continually updating guidelines, increasing CMC demands on regulatory affairs professionals. Faced with this complexity, revising the operational model and utilizing external expertise are essential solutions to overcome these challenges and meet market demands.

Why Outsource CMC Activities?

Increasing Regulatory Requirements Health authorities are continuously raising the quality standards from development to drug registration and throughout the lifecycle of marketing authorizations (MA**). This trend imposes a significant workload from a CMC perspective, necessitating rigorous and expert management of regulatory dossiers.

Impact of Mergers and Acquisitions Corporate mergers and acquisitions increase the number of regulatory submissions to reflect changes in supply sources, production site transfers, etc. This dynamic requires increased flexibility and responsiveness to maintain compliance and the continuity of pharmaceutical operations.

Resource Management Optimization Increasingly complex regulatory requirements necessitate deep knowledge, leading to increased personnel needs and creating a talent shortage. The traditional operational model of pharmaceutical laboratories is often no longer optimized to handle the surplus work related to these CMC activities. Outsourcing complex technical and regulatory aspects reduces workload and improves overall efficiency.

ATESSIA’s Unique Expertise

ATESSIA was founded by Géraldine Baudot-Visser, a recognized expert in the technical-regulatory field. With a doctorate in pharmacy, extensive experience in R&D and regulatory affairs, Géraldine created ATESSIA to offer an innovative and client-centered approach. Her solid CMC expertise, acquired within major pharmaceutical laboratories and consulting firms, is at the heart of the service offering.

Why Choose ATESSIA for Your CMC Needs?

Cutting-Edge Expertise and Knowledge ATESSIA has multidisciplinary expert teams with in-depth CMC knowledge. Our consultants possess practical experience and a fine understanding of regulatory authorities’ expectations, ensuring the quality of dossiers and compliance with current requirements.

Cost Reduction and Time Savings ATESSIA has the expertise to efficiently manage CMC activities and offers economical and fast solutions, best adapting to the market entry deadlines desired by its clients.

Guaranteed Quality Structured around the ISO 9001 standard, ATESSIA ensures impeccable quality at every stage of the product lifecycle.

Partner for Your R&D Activities ATESSIA has Research Tax Credit approval, enabling you to be supported in your research and development activities.

Our Commitment to Excellence and Innovation

At ATESSIA, we stand out with our agile and tailored approach, integrating feedback and specific needs of each client. Our flexibility and ability to integrate new technologies allow us to offer innovative solutions adapted to evolving market demands.

Choosing ATESSIA for your CMC needs ensures expert and personalized support, capable of transforming your regulatory challenges into successes. Our commitment to excellence and innovation guarantees optimal results that ensure your competitiveness in the market.

To learn more about our CMC services and other regulatory and pharmaceutical affairs offerings, and to discover how we can support you, contact us today.

hello@atessia.fr

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*CMC: Chemistry Manufacturing and Control

**MA: Marketing Authorization

The Post-Approval Change Management Protocol or “PACMP”

_Blog

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 step-wise approach to evaluating modifications, initially allowing for an early evaluation of the modification strategy and, in a 2^nd 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)”. 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

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 and veterinary 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/B.I.e.2: Introduction of a post approval change management protocol related to the active substance > Absence of conditions to be fulfilled. > Three supportive documentation to be provided: 1. Detailed description for the proposed change. 2. Change management protocol related to the active substance. 3. Amendment of the relevant section(s) of the dossier	Variation Type II/B.II.g.2: Introduction of a post approval change management protocol related to the finished product > Absence of conditions to be fulfilled. > Three supportive documentation to be provided: 1. Detailed description for the proposed change. 2. Change management protocol related to the finished product. 3. Amendment of the relevant section(s) of the dossier.
Variation Type IAIN/B.I.e.3: Deletion of an approved change management protocol related to the active substance > One condition to be fulfilled: 1. The deletion of the approved 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 documentation to be provided: 1. Justification for the proposed deletion. 2. Amendment of the relevant section(s) of the dossier.	Variation Type IA_IN/B.II.g.3: Deletion of an approved change management protocol related to the finished product > One condition to be fulfilled: 1. The deletion of the approved 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 documentation to be provided: 1. Justification for the proposed deletion. 2. Amendment of the relevant section(s) of the dossier.
Variation Type II/B.I.e.4a): Changes to an approved change management protocol – Major changes to an approved change management protocol	Variation Type II/B.II.g.4a): Changes to an approved change management protocol – Major changes to an approved change management protocol
Variation Type IB/B.I.e.4b): Changes to an approved change management protocol – Minor changes to an approved 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 any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products.	Variation Type IB/B.II.g.4b): Changes to an approved change management protocol – Minor changes to an approved 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 any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products.
Variation Type IA_IN/B.I.e.5a): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires no further supportive data > One condition to be fulfilled: 1. The proposed change has been performed fully in line with the approved change management protocol. > Three supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 4. Amendment of the relevant section(s) of the dossier.	Variation Type IA_IN/B.II.g.5a): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires no further supportive data > One condition to be fulfilled: 1. The proposed change has been performed fully in line with the approved change management protocol, which requires its immediate notification following implementation. > Three supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 4. Amendment of the relevant section(s) of the dossier.
Variation Type IB/B.I.e.5b): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires further supportive data > Absence of conditions to be fulfilled. > Four supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 3. Results of the studies performed in accordance with the approved change management protocol 4. Amendment of the relevant section(s) of the dossier	Variation Type IB/B.II.g.5b): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires further supportive data > Absence of conditions to be fulfilled. > Four supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 3. Results of the studies performed in accordance with the approved change management protocol 4. Amendment of the relevant section(s) of the dossier.
Variation Type IB/B.I.e.5c): Implementation of changes foreseen in an approved change management protocol – Implementation of a change for a biological/immunological medicinal product > Absence of conditions to be fulfilled. > Five supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 3. Results of the studies performed in accordance with the approved change management protocol 4. Amendment of the relevant section(s) of the dossier. 5. Copy of approved specifications of the active substance	Variation Type IB/B.II.g.5c): Implementation of changes foreseen in an approved change management protocol – Implementation of a change for a biological/immunological medicinal product > Absence of conditions to be fulfilled. > Five supportive documentation to be provided: 1. Reference to the approved change management protocol. 2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 3. Results of the studies performed in accordance with the approved change management protocol 4. Amendment of the relevant section(s) of the dossier. 5. Copy of approved specifications of the finished product.

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