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What is the Requirement for Transparency of Conflicts of Interest with Healthcare Professionals in France?

Following the “Médiator” case and inspired by the Sunshine Act in the United States, the law of December 29, 2011, concerning the strengthening of health safety, known as the “Bertrand Law,” was passed.

This law establishes systematic transparency of links between health industries on one hand, and other actors in the health field on the other. This primarily includes healthcare professionals, but also students, learned societies, associations, media, etc.

The “transparency of links” system, which provides the general public with information on the relationships between health industries and members of the health system, is in line with the “regulation of benefits” system, which aims at the ethics of healthcare professionals. These two legislations interact with each other, with some subtle specificities that distinguish them.

Who is Affected by the System?

The following actors are concerned:


Types of Declaration and Publication

It is appropriate to publicly disclose retrospectively:

  • Agreements: publication of all contracts made between laboratories and a health actor (for example: agreements with coverage of hospitality expenses (catering, transport, accommodation, registration fees at a congress));
  • Service provision contracts (for example: remuneration for clinical expert work);
  • Benefits exceeding 10 euros including taxes (for example, the granting of health product samples);
  • Remunerations awarded (for example: remuneration of a healthcare professional for speaking at an event).


Commercial contracts are excluded.

The typology of benefits and agreements responds to precise definitions that have been clarified by the authorities.

The system requires that pharmaceutical companies, in particular, are obliged to publish information on the public database https://www.transparence.sante.gouv.fr, according to the following frequency:

  • Publication twice a year:
  • First calendar semester, i.e. from January 1st of year N to June 30th of year N: submission on the “transparency-health” website by September 1st of year N.
  • Second half of the calendar year, i.e. from 1 July of year N to 31 December of year N: submission on the “transparency in health” website no later than 1 March of year N+1.

Thus, the general public can access the work links and professional relationships maintained between health industries and actors in the French healthcare system.

In parallel, the European Federation of Pharmaceutical Industries and Associations (EFPIA) has also adopted the “EFPIA code of practice” to frame collaboration with Healthcare Professionals or their Organizations when conflicts of interest exist. This text is applicable to member companies.

ATESSIA supports its clients on all these questions.


Article written by Zarine RAMJAUNY, Junior Legal Consultant

What are the mechanisms for early and compassionate access in France?  

Atessia supports its clients daily in the practical modalities of implementing the French early and compassionate access system, whose subtleties require some explanations. 

On July 1, 2021, the new early and compassionate access system was introduced through 2 decrees, supplemented by 4 orders, with immediate effect. This new system is based on 2 mechanisms for access and coverage by health insurance: 

  • Early Access (AAP)  

Firstly, early access, which targets medicinal products that meet an unmet therapeutic need and may be innovative. The laboratory submits a request for early access authorization (AAP) to the High Authority for Health (HAS) and, for medicinal products not yet authorized under a Marketing Authorization (AMM), to the National Agency for the Safety of Medicines and Health Products (ANSM).  

These authorizations can apply to: 

  • A medicinal product prior to obtaining the AMM in the considered indication (Pre-AMM AAP = AP1), 
  • A medicinal product that already has an AMM in the considered indication, prior to common law coverage by health insurance (Post-AMM AAP = AP2) Interestingly, the product may or may not have an AMM for another indication. As per HAS doctrine, granting early access authorization is reserved for certain specialties meeting the following 5 cumulative eligibility criteria: 

1. Strongly presumed efficacy and safety in the considered indication. 

2. The disease to be treated is severe, rare, or disabling. 

3. There is no “appropriate treatment.” 

4. The implementation of treatment cannot be delayed. 

5. The medicinal product is presumed to be innovative.  

The authorities examine each of these criteria separately, in a relatively strict manner. 

This system also requires concrete commitments from laboratories, which should not be underestimated and need to be weighed with the parent company. 

  • From a REGULATORY standpoint: the laboratory must commit to filing an AMM request within 2 years for an AAP1 or a request for registration within the month following the AMM’s approval for an AAP2. Thus, the timing of the filing is crucial in the project. 
  • From a LOGISTICAL standpoint: the laboratory makes the product available within 2 months following the granting of the AAP (PUI) and ensures it can supply the product to allow continuity of treatments initiated during the entire AAP, for a minimum period of one year (including 3 months of coverage). 
  • From a FINANCIAL standpoint: the laboratory implements a PUT-RD, for data collection and transmission of periodic summary reports. The laboratory finances this data collection (cf. agreement to be signed with health establishments). 
  • The pharmaceutical laboratory is also required to assist prescribers in entering and monitoring the collection of real-life follow-up data of the medicinal product, providing them with the necessary means. 

Two types of compassionate access: 

This system targets two distinct cases, both involving a medicinal product to treat patients with diseases without appropriate treatment in a given therapeutic indication, without being intended to obtain an AMM in France. The requests are managed only by the National Agency for the Safety of Medicines and Health Products (ANSM). 

  1. Either this compassionate access is requested for an unauthorized and unavailable medicinal product in France by a hospital prescriber for a specifically named patient, provided that the ANSM can presume a favorable benefit/risk ratio for a severe, rare, or disabling disease: this is an individual and nominative compassionate access authorization (AAC). 
  1. Or it involves the regulation of a practice, initiated by the ANSM, to secure an off-label prescription practice of a medicinal product available in France, with an AMM for other indications, when it is subject to a well-established off-label prescription on French territory: this is a compassionate prescription framework (CPC).  

Exemptions to compassionate access have been foreseen in the following cases: 

  • Allowing nominative access to medicinal products in development for the indication: this is a “very early” compassionate access. 

The grant by the ANSM is subject to several eligibility conditions, which brings this system closer to early access and can be the gateway to it: 

  • The implementation of the treatment cannot be delayed; 
  • The patient cannot participate in any ongoing research; 
  • The company marketing the medicinal product must commit to filing an early access request within 12 months following the first “pre-precoce compassionate” authorization (18 months for rare diseases). 

For these mechanisms, the designation of a laboratory operating a medicinal product may be necessary, to ensure, if necessary, the import/distribution, pharmacovigilance, quality complaints, or medical information. 

The laboratories now have several years of experience with these new systems, and the emerging trends show the authorities’ willingness to make innovative medicinal products available to French patients and to respond to the personal situations of patients in therapeutic dead ends. 

Article written by Caroline LECUELLE, Consultant in Regulatory Affairs & Pharmaceuticals 

What are the differences between the Mutual Recognition Procedure and the Decentralized Procedure ? 

From a legislative point of view, the mutual recognition procedure is defined by the Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. 

Directive 2004/27/EC subsequently laid the foundations for the decentralised procedure. 

These two procedures are available for all marketing authorisation applications that do not fall within the mandatory scope of the centralised procedure. They are applicable whenever an applicant wishes to register its medicinal product in more than one Member State.  

1/ The Mutual Recognition Procedure (MRP) 

Article 28.2 of Directive 2001/83/EC, as amended, specifies the scope of this procedure: the principle is to extend a national MA already obtained in one of the EU Member States, to one or more other Member States in which the laboratory wishes to market its product. The referent state (or “RMS”), which granted the existing MA, manages the procedure. 

Once the evaluation procedure has been completed, the MAs are issued by each of the competent authorities of the member states concerned. 

Timetable 

After a possible upgrade of the MA dossier, the RMS sends the MA dossier and its assessment report, including the SPC, package leaflet and labeling, to the CMS 14 days before the start of the procedure.  

The concerned Member States must then recognize the authorization already issued by the RMS within 90 days (without clock-stop).  

The procedure may, however, end on Day 60 if the RMS has no further comments.  

The MA (including the SPC, package leaflet and labeling) is recognized by the CMS. 

This period is followed by a 30-day national closing phase to issue the national MA. 

If a Member State has objections to recognizing the dossier’s assessment report, summary of product characteristics (SPC), package leaflet and labeling, on the grounds of a potentially serious risk to public health (as defined by Article 29(1) of Directive 2001/83/EC), the dossier is referred back to the CMDh for further discussion. This procedure lasts 60 days. If the CMDh is unable to reach a decision within 60 days, the application is sent to the CHMP for arbitration (art. 29(4) of Directive 2001/83/EC). This procedure also lasts 60 days. 


2/ The decentralized procedure (DCP) 

This procedure differs from the MRP in two main points :  

  • No marketing must first have been granted in the EU,  
  • The dossier is submitted simultaneously in all Member States.  

In this case, the laboratory asks a member state to act as reference state (“RMS”) for the evaluation among the states in which it wishes to authorize its medicinal product. 

Timetable 

The RMS draws up a preliminary assessment report on the dossier submitted and the draft summary of product characteristics (SPC), package leaflet and labeling. 

This report is submitted to the CMS and the applicant for comments on Day 70 of the procedure. 

On Day 105 of the procedure, the clock stops to allow the applicant to submit answers to the questions raised by the Member States at the end of phase 1. 

When the answers have been submitted, the clock starts again on Day 106, and on Day 120 of the procedure, the RMS circulates at the same time an update of all documents (assessment report, SPC, package leaflet and labeling) to the applicant and the CMS. 

A second phase of Questions and Answers begins, and the procedure may be closed on Day 150 if all comments have been resolved.  

Otherwise, a new 60-day phase begins to finalize outstanding issues.  

The DCP therefore lasts a maximum of 210 days. This period is followed by a 30-day national closing phase to issue the national MA. 

As with the MRP, if there is no consensus between member states, the dossier is referred back to the CMDh for further discussion. This procedure lasts 60 days. If the CMDh is unable to reach a decision within 60 days, the application is sent to the CHMP for arbitration (art. 29(4) of Directive 2001/83/EC). This procedure also lasts 60 days. 

To sum up: 

MRP DCP 
Existing initial national MA  No MA granted in the EU 
No choice of the RMS (national MA already existing th the EU) The choice of the RMS is up to the applicant 
Request a recognition by the other Member States  Simultaneous application to all member states: the RMS evaluates the dossier for the first time (as for the CMS) 
Only one evaluation phase Two evaluation phases 
Decision within 90 days, or up to 150 days in the event of arbitration by the CMDh if no consensus can be reached between Member States. Decision in 210 days (excluding clock-stop period), or up to 270 days in the event of arbitration by the CMDh if no consensus can be reached between Member States. 
MA Dossiers identical in all member states 
Principle of recognition of the evaluation of the Reference Member State (RMS) by the other Member States concerned (CMS) 
The choice of the States involved in these procedures is up to the applicant 
National closing phase of 30 days planned to issue the national MA 
A European Public Assessment Report (PAR) for each medicinal product approved via the MRP/DCP is published in the directory « Mutual Recognition Index » by the RMS on the HMA website. 

ATESSIA supports laboratories throughout the registration process: from the registration strategy to the draft and submission of the marketing authorization applications. 

Article written by Fabien MEDINA, Pharmaceutical and Regulatory Affairs Senior Advisor. 

*ANSM : Agence Nationale de Sécurité du Médicament et des produits de santé (competent authority for medicines and health products) 

What about the classification of Marketing Authorization variations? 

What about the classification of Marketing Authorization variations? 

When a holder wishes to register a medicine in a country, he submits a marketing authorization application (MAA) file to the health authorities. 

Once marketing authorization (MA) has been obtained, this file is not intended to remain unchanged. For each change impacting the product, whether (for example) a change in manufacturing, control, therapeutic indication, packaging, the holder must submit a variation request to the health authorities. 

A variation is therefore a modification of the marketing authorization. 

Modifications to the terms of an European marketing authorization are provided for by Directive 2001/83/EC and Regulation (EC) No 726/2004, and detailed by Regulation (EC) No 1234/2008 of November 24, 2008 concerning the examination of modifications to the terms of an MA for medicinal products for human use and veterinary medicinal products (hereinafter referred to as the “Modifications” regulation) 

This regulation has been applicable since January 1, 2010 to MAs obtained through centralized, decentralized and mutual recognition procedures, and since August 4, 2013 to MAs obtained through national procedures. 

There are 3 types of variations: 

– Type IA variations, also called minor. These are modifications whose repercussions on the quality, safety and efficacy of the medicinal product are considered minimal or non-existent. These modifications may be implemented by the holder without prior review by the authorities. However, not later than 12 months from the date of implementation, the holder must notify this modification simultaneously to all relevant Member States, the competent national authority or the EMA (as applicable) . 

Of note, there are type IAIN variations (IN = immediate notification). They can also be implemented by the holder without prior examination by the authorities. However, notification to the competent authorities must be made within 14 days of implementation. 

– Type IB variations. Also minor, they are defined as variations which are neither minor of type IA, nor major of type II, nor extensions. Within type IB variations, we also find the so-called “unforeseen” variations, which are not included in the initial regulation and which are mentioned in article 5. 

– Type II variations, called major. These are modifications which are not extensions of Marketing Authorization and which may have significant consequences in terms of quality, safety and efficacy. 

Modifications to the terms of a marketing authorization also include extensions of marketing authorization and urgent restriction measures for safety reasons. 

Variations are categorized according to the type of change by the Guidelines relating to the characteristics of the different categories of modifications, to the conduct of the procedures provided for in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of amendments to the terms of a marketing authorization for medicinal products for human use and veterinary medicinal products and the documentation to be submitted under these procedures. There are changes classified as administrative (A), relating to quality (B), or relating to safety, efficacy or pharmacovigilance (C). Changes D concern the plasma master records and the vaccine antigen master records. 

The aim is twice: correctly position each change according to its type and category. To benefit from the type indicated in the classification, you must be able to provide the required documentation and meet the conditions mentioned, otherwise the variation request is likely to be recategorized or even rejected. 

Once these definitions have been established, note that MA holders have the possibility of submitting several modifications concerning one or more MAs in a single request, under the conditions determined by the regulation. It is called a grouping. It is important to mention that not all variations can be “grouped” together. A regulatory strategy must be put in place. 

Finally, the worksharing or task distribution procedure is strongly recommended. It allows MA holders to submit, in a single application, the same type IB, type II modification or the same group of modifications corresponding to one of the cases referred to in Annex III of the regulation provided that it does not include a request for extension, when these elements relate to several MAs held by the same holder, whatever the type of procedure (all combinations being possible), or to several purely national MAs from the same holder in more than one Member State. It was established to avoid duplication of work to evaluate these modifications: they are examined by a single authority, called the “reference authority” and chosen from among the competent authorities of the Member States and the EMA, to on behalf of other authorities concerned. 

Do not hesitate to call on ATESSIA to support you in the development of the regulatory strategy and writing your variation request files, whatever the registration procedure. 

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

What Are the New Rules for Influencers on Social Networks?

Law No. 2023-451 dated June 9, 2023, which aims to regulate commercial influence and combat abuses by influencers on social media platforms, not only defines the concept of an “influencer”, but also introduces the notion of an “influencer’s agent”.

What is an Influencer?

Influencers are any “(…) natural or legal persons who, for a fee, mobilize their reputation among their audience to disseminate content to the public via electronic means. Their goal is to promote either directly or indirectly, goods, services or any cause. They engage in the activity of commercial influence through electronic means” (Article 1).

Examples include a patient, a healthcare professional or a person with a strong reputation.

What is an Influencer Agent?

” I. – An influencer agent’s role is to represent, for a fee, either natural or legal persons engaged int the activity of commercial influence through electronic means as defined in Article 1. This representation involves liaising with other natural or legal persons, and if relevant, their representatives, to promote goods, services or any cause, also for a fee.

II. – Individuals who undertake the activity defined in Section I of this article must take all necessary measures to safeguard f the interests of those they represent, to avoid situations that might lead to conflicts of interest and to ensure their actions align with the stipulation of the current law  (Article 7).

What are the Law’s Obligations?

Supervision of Sponsored Content:

This law creates an obligation for influencers to report any sponsored content. Specifically, any promotion of goods, services or a cause of any kind carried out by an influencer must systematically include the mention “Advertising” or “Commercial collaboration”. This mention must appear clearly, legibly and identifiably on the influencer’s image or video, whatever its format and for the entire duration of its broadcast.

  • Supervision of Published Visuals:

Images should be labelled as “Retouched Images” if they undergo processing to slim or thicken a silhouette or modify face appearance.;

Images should be labelled as “Virtual images” if any artificial intelligence process has been used to generate or modify a face or silhouette.

  • Supervision of Dropshipping Activities:

Influencers are obliged to provide the buyer with all pre-contractual information related to a distance sales agreement. This includes the identity of the supplier and confirmation of product availability. Failure to provide this information can result in influencers being held accountable.

What is Prohibited?

Direct or indirect promotion of the following products and services is prohibited:

  • Aesthetic procedures, processes, techniques, and methods referred to in Article L. 1151-2 of the French Public Health Code, as well as interventions referred to in Article L. 6322-1 of the same code (including aesthetic medical devices (DMs) listed in Annex XVI of Regulation 2017/745 MDR);
  • Procedures, processes, techniques, and methods presented as comparable to, preferable over or substitutes for therapeutic procedures, protocols, or prescriptions;
  • Products considered as nicotine-based that can be consumed and are made, even partially, of nicotine.

What are the Penalties?

Violators may face a fine of up to 300,000 euros and a prison sentence of up to 2 years. To ensure consumer protection, a dedicated team has been set up within the DGCCRF (a French authority, Direction Générale de la Concurrence, de la Consommation et de la Répression des Fraudes), and reports can be submitted via the Signal conso website.

Existing sanctions are reinforced and graduated. The following acts are punishable:

  • Failure to indicate the advertising nature of a video or photo posted by an influencer is now considered a misleading commercial practice;
  • Promotion of a prohibited or regulated product carries the same penalties as online advertising;

Additionally, the authorities have been granted a new power of injunction with penalties. This allows them to compel an influencer to remove non-compliant content or for platforms to suspend the influencer’s account promptly.

Judges and supervisory authorities will tailor penalties according to the severity of the act.

What About Drugs and Medical Devices?

The promotion of medicines to the general public is regulated by the French Public Health Code. With the exception of class I or IIa medical devices, the promotion of a drug, medical device or IVDD to the general public based on a recommendation from people who, through their reputation, can encourage the consumption of the product in question, such as influencers on social networks, is already prohibited by the Public Health Code.


Need assistance in managing influencer communication under contract with your laboratory? Our expert consultants are available to discuss your concerns.

Article written by Zarine RAMJAUNY, Junior Legal Consultant

What are the possible interactions between health industry players and healthcare professionals (HCPs) in France?

Promotional visit for medicinal products in France refers to promotional interactions with healthcare professionals (HCPs) conducted by authorized collaborators from the pharmaceutical industry.

The structural reform of health insurance established by the law of August 13, 2004, resulted in the first Charter of Medical Visit. The objective was to better regulate the commercial and promotional practices of laboratories that could harm the quality of care (creation of Article L.162-17-8 of the Social Security Code).

Since 2008, the scope of the charter has been broadened to include prescribers practicing in health institutions, and not just those from private practices. The latest version of the Charter, dated October 15, 2014, is now titled the “Charter on information provided for the promotion of medicinal products through prospecting or canvassing “

All pharmaceutical companies with an authorization to open as an “Exploitant” and having signed an agreement with the French Economic Committee for Health Products, CEPS, (reimbursable medicinal products), must commit to respecting the Charter, interpreted by a referential established by the High Authority for Health (HAS). The latest version of this reference system came into effect in March 2017. It is the practical application procedure of the Charter, and it is based on this procedure (certification reference system) that certifying bodies, accredited by the French Accreditation Committee (COFRAC), certify companies for their promotional activity. This procedure has two parts: one dedicated to the certification of the activity performed by the “Exploitant” companies themselves, on their own or in co-promotion, as well as the requirements that these companies must meet in the event of outsourcing all or part of their promotional activity. The second part is dedicated to the certification of the promotional activity performed by subcontracting companies.

Companies subject to this system must implement a quality management system that can sustainably meet the requirements of the Charter and its reference system:

  • Definition, implementation, and monitoring of the quality policy for this activity.
  • Initial/continuous training and knowledge evaluation of promotional collaborator  (7 regulatory themes and 2 scientific themes)
  • Respect for ethical rules towards patients, health professionals, competing companies, their own company, and health insurance.
  • Co-promotion and recourse to subcontracting (contract, responsibility, organization, and monitoring).

Pharmaceutical laboratories must prepare for annual certification audits (N: certification, N+1 surveillance, N+2 surveillance, N+3 renewal audit), regularly review their quality management system, monitor the activity of all cross-functional roles involved (marketing, regulatory affairs, medical, field staff: Medical Science Liaison (MSL) and promotional collaborators, etc.). Among the challenges, one is to ensure the regulatory compliance of promotional activity, which is one of the strategic pillars for companies.

Medicines are not the only ones concerned: the Quality Charter for professional practices for products and services reimbursable, published in the JO on March 8, 2022, will apply concomitantly to multiproduct companies, implying a double management of these Charters despite sometimes contradictory injunctions (see LunchWork Atessia x LexCase 20/04/22 “Quality Charter for professional practices for products and services reimbursable”).

It is interesting to note that the rules differ according to the product portfolio of the company: reimbursable or non-reimbursable medicinal products, Medical Devices, food supplements, cosmetics, biocides, everyday consumer products. Hospital visits are subject to additional rules.

The question of samples follows precise rules concerning both  the possible certification, the Law on the Regulation of Benefits, the requirement for transparency of links, the Good Manufacturing Practices (GMP).

What can promotional collaborator say? What can they give to doctors, and what must they give them? How to adapt the rules of the reference system with the digitalization of promotion and the advent of remote visits since the health crisis? And most importantly, what messages to deliver about the therapeutic indications of the marketing authorization , early or compassionate access, and off-label use, taking into account the therapeutic strategy established by the HAS? What part of the discourse should be devoted to job safety and side effects? How to talk about the results of clinical trials?

ATESSIA assists its clients in carrying out annual internal audits in preparation for the certification audits of Exploitant and their subcontractors, writing internal procedures, and training field teams.

Leslie Gorge, Regulatory & Pharmaceutical Affairs Consultant.

For more information

🌐 https://www.atessia.fr/fr/accueil/

Get in touch!

👤 Géraldine BAUDOT-VISSER

hello@atessia.fr

📞 +33 764 273 693

The Chief Pharmaceutical Officer

The Chief Pharmaceutical Officer also called Responsible Pharmacist (RP) is a key role , essential to the organization of any pharmaceutical laboratory involved in the manufacture, exploitation and distribution of medicinal products for human use in France.

The Chief Pharmaceutical Officer ensures  the quality of the medicine and the safety of the patients. Their position, functions, and assignements are defined by the regulations. Their skills are validated by their peers based on practical experience. Their responsibilities are numerous. They must maintain their freedom of judgment and hold pharmaceutical authority within their structure. They can delegate some activities and must be replaced in case of absence.

Positions, functions and Assignements

The Chief Pharmaceutical Officer has a statutory position within a pharmaceutical establishment (manufacturer, operator, depositary or wholesaler-distributor).

They  organize and supervise all pharmaceutical activities: manufacturing and batch release, advertising, information, pharmacovigilance, follow up and withdrawal of batches, distribution, import and export, storage and transport.

The responsibilities attributed to the RP are broader than those of the qualified person within the European Union (directive 2001/83/EC, article 48). They have a personal responsibility for all pharmaceutical activities, unlike the qualified person who exercises operational responsibility for the activities they are responsible for (batch release, follow up and recall of batches, pharmacovigilance).

Their status as well as their functions and assignements are defined in the Public Health Code (Code de la Santé Publique CSP) in articles R.5124-16 to R.5124-41.

Validation of Skills and Practical Experience

Their skills and practical experience are validated by the National Council of the Order of Pharmacists. Decree No. 2022-324 of March 4, 2022, recently modified the terms of the practical experience required for the RP (CSP Articles R.5124-16 à R.5124-18).

The RP is appointed by the competent corporate body of the company and then declares themselves to the competent authority: the ANSM*.

The Responsibilities of the RP

The responsibilities of the RP are of three types:

  • Legal and criminal liability
  • They are a member of the management of the company.
  • They are the main contact of the Health Authorities.
  • They arepersonally responsible for the compliance of the pharmaceutical establishment with the Public Health Code.
  • Disciplinary responsibility
  • Respect for professional ethics
  • Compliance with their deontologic obligations
  • Civil liability

The RP shares civil and criminal liability with the manager(s) of the company.

Freedom of Judgment and Pharmaceutical Authority

Like any pharmacist, the RP preserves their freedom of professional judgment in the exercise of theirfunctions (CSP Article R.4235-3).

They have authority over all pharmaceutical staff (CSP Article R.5124-36) and appoints the delegate pharmacist(s).

Delegation and Replacement

The RP can delegate some pharmaceutical activities. The delegate pharmacist is bound, within the limits of their delegation, to the same obligations as the RP (CSP Article R.4235-68).

In the event of absence, the RP is replaced by an interim responsible pharmacist (CSP Article R.4235-70). The IRP then has the same functions, assignements, and responsibilities as the RP during the replacement period.

ATESSIA supports Chief Pharmaceutical Officer in the performance of their duties: regulatory intelligence, CMC support, advertising, pharmacovigilance, activities related to regulatory affairs and quality assurance, and offers Interim Responsible Pharmacists registered at the Pharmacists Council.

Article written by Christelle PETIT, Pharmaceutical Affairs Advisor and Director.

*ANSM : Agence Nationale de Sécurité du Médicament et des produits de santé (competent authority for medicines and health products)


The serialisation system

Securing the distribution of medicines represents an unprecedented challenge for public health. Although France has always benefited from a particularly secure drug distribution system and a strict legislative framework from the health authorities, the risk of falsified drugs is increasing on a global and European scale.

Faced with this major challenge, Directive 2011/62/EU of the European Parliament and of the Council of June 8, 2011 introduced the serialization system, which details were subsequently specified by Commission Delegated Regulation (EU) 2016/161 of October 2, 2015, in order to strengthen the safety of the distribution chain of medicinal products and to fight against their falsification. The obligations relating to the serialization of medicinal products and anti-counterfeiting devices are applicable since February 9, 2019.

Now 4 years after the entry into force of the European regulation, let’s look back at the implementation of the serialization system.

As a reminder, the serialization device is composed as follows:

  • A tamper-evident device for all drugs, affixed by the manufacturer and verified by the pharmacist to check the integrity of the product before dispensing (e.g. transparent adhesive tape);
  • A unique identifier (UI) on each box of mandatory prescription medication, affixed by the manufacturer and scanned by the pharmacist before dispensing to the patient (datamatrix).

The serialisation system contributes to the implementation of a European system to fight against the introduction of falsified medicines by providing additional security to guarantee the authenticity, safety and quality of medicines on the territory of the European Union. It completes the existing batch traceability by authenticating each box at the time of dispensing.

The implementation of this system required the collective commitment of all the stakeholders in the drug supply chain (manufacturers (CMOs) and Exploitants/Marketing Authorization Holders, wholesalers and distributors, pharmacies and hospitals, software publishers, etc.), as well as the Ministry of Solidarity and Health, the French National Agency for the Safety of Medicines and Health Products (ANSM) and the regional health agencies (ARS).

Indeed, this new system has required organizational changes at all levels, from drug production to delivery to the patient: adapting production lines to implement the unique identifier and the anti-tampering device, adapting the IT systems of all drug professionals, setting up governance bodies at national (NMVO) and European (EMVO) level, adapting procedures, etc.

The question of ultimate responsibility for implementing serialization has been the subject of numerous debates, which have now been settled, with the central issue of downloading unique identifiers at the time of manufacture and the possible outsourcing of this activity. The introduction of the OBP portal registration requirement and fees to finance the infrastructure of national (NMVS) and European (EMVS) repositories systems has also had an impact on the drug chain stakeholders.

WHAT ABOUT THE IMPLEMENTATION OF SERIALIZATION IN PHARMACIES IN FRANCE?

Serialisation is a regulatory obligation for all pharmacies. Indeed, such a system can only operate with the participation of all pharmacies in the Member States in order to ensure that no falsified box is delivered to a patient in the European Union.

This obligation, which came into force on February 9, 2019, was reminded in the Order of February 26, 2021 on good dispensing practices for medicinal products in order to make the obligations incumbent on all pharmacists under European regulations more visible in a text of national scope.

However, to date, despite the health crisis and the strong mobilization of pharmacists, the connection of pharmacies to the system has been delayed and remains insufficient in France. As of February 6, 2023, only 17,901 pharmacies (86.2%) were complying with their obligations to serialize their medicines, with a target of 100% by December 31, 2022.

Given France’s considerable delay in implementing effective verification of the serialization system in pharmacies, a bill was adopted by the Senate on December 14, 2022, defining the financial penalties that may be imposed on pharmacy holders in the event of non-compliance with the obligation to deactivate the unique identifier.

On the page dedicated to serialisation in pharmacies on its website, the Ministry of Health stresses the importance of reaching this 100% objective as soon as possible to guarantee better safety and traceability of medicines for all French people.

Article written by Amélie NICOLAS-VERLEY, Regulatory and Pharmaceutical Affairs Advisor

The APQR review “à la française”

What is an APQR?

Both US and EU Good Manufacturing Practices (GMP) require manufacturers of all authorized medicinal products to perform Annual Product Quality Reviews (APQR in the US, PQR in EU). These reviews are conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product, to highlight any trends and to identify product and process improvements. Such reviews are conducted and documented annually, (taking into account previous reviews), and include a number of review areas.

The Qualified Person is responsible for ensuring that each single batch is manufactured and controlled in compliance with the applicable regulation, in accordance with MA specifications and GMP, and is responsible for the APQR.

What’s special in France?

As it is the case everywhere, APQR duties involve the manufacturer and the MA Holder. But in France, there is another party involved, the Exploitant (see related article “The mysterious thing that an Exploitant is”). The Exploitant can sometimes be the MAH.

Moreover, French GMP specify that when the manufacturer, the MAH and the Exploitant are distinct, all of them are individually responsible for assessing the results of the APQR and evaluating the need to implement corrective and/or preventive actions or to perform any revalidation.

When the MAH is not the manufacturer and/or the Exploitant, contracts/Quality Agreements must be in place to define each party’s responsibilities in performing APQRs.

So, although mainly the manufacturer and the MAH are involved in performing the APQR, all parties including the Exploitant share responsibilities in reviewing the APQR. This means, for every single product exploited, that the APQR has to be received and checked by the Exploitant. This review has to be a critical review, and has to be documented in order to show that the Exploitant is continuously aware of the quality of the product, and is able to challenge the processes in case of any trend is identified.

APQR review is particularly critical as it is highly challenged by ANSM during routine inspections (both in the content and timelines of the review).It is therefore crucial for an Exploitant to have an effective APQR review process in place.

ATESSIA has a dedicated team performing APQR reviews that meet ANSM’s expectations and can help you in getting it right!

Article written by Raphaël DAUVERGNE, Regulatory and Pharmaceutical Affairs Advisors

The consulting profession at ATESSIA

In concrete terms, what does it mean to be a consultant in regulatory and pharmaceutical affairs at ATESSIA, Life science advisors?

At ATESSIA, we firmly believe that consulting is not a job that you do, but a talent that you keep developing. Our consultants have a strong technical background to meet the needs of our customers and a strong experience that allows them to solve complex problems. But it is also their behavioral and interpersonal skills that are necessary for them to succeed in this challenging profession. While the past has been almost exclusively focused on deliverables in the consulting world, at ATESSIA we believe that the present and future are entirely driven by the experience offered to our clients before, during and after the service is provided.

What qualities do we look for in our consultants?

Listening

“He who knows how to listen will become the one who is listened to” – Vizier Ptahhotep

A consultant must have the quality of active listening. Active listening to the needs of the customers enables us to set up innovative solutions in a culture of continuous improvement.

Listening to what the customer says about his needs and problems is the most useful way to be able to propose adequate solutions. In addition to being a good listener, it is also important to ask relevant and open-ended questions and not to impose a method or a solution without having really heard the client’s needs.

At ATESSIA our approach is thoughtful and detail oriented.

Empathy

“The first rule before taking action is to take the place of the other. No real research for the common good will be out of there. “- Abbé Pierre

ATESSIA has chosen to position itself on the axis of human relations. We place the human being at the heart of our strategy, and we behave with empathy towards all our stakeholders. Empathy is an essential quality in the world of consulting, because if we do not put ourselves in the client’s shoes, we will not be able to understand his problem and thus respond to his request. In a world that has become more and more digitalized, we want to cultivate our human qualities that make all the difference.

Empathy is what reflects our signature: placing the human being at the heart of our customer relations.

Sense of urgency

“It doesn’t make sense to hire smart people and then tell them what to do. We hire smart people so they can tell us what to do.” – Steve Jobs

Agility and proactivity infuse everything we do, as well as the wisdom to consider options thoroughly. A sense of urgency allows the consultant to quickly identify potential problems, which then gives him the time to carefully craft solutions. In this unpredictable and ever-changing environment, our consultants respond with agility while remaining calm to get things done in an effective and efficient manner.

Trust

“Trust is a major element: without it, no project will succeed. – Eric Tabarly

ATESSIA’s consultants are committed to establishing a relationship of trust with their clients by understanding their environment and values and by being available and close to them when necessary. Firm believers in a customized approach, our consultants take into account the specificity of our clients’ businesses and the particularity of their operating methods. Our team overcomes obstacles, finds solutions, and delivers outstanding results. To achieve this, we remain transparent about our role and objectives. We pay particular attention to credibility, which depends on clearly communicating all the details of the mission while respecting the deadlines.

Critical thinking

“There is no fair wind for him who does not know where he is going” – Seneca

ATESSIA’s clients appreciate our ability to apply and communicate cutting-edge approaches in a clear and compelling manner. ATESSIA’s consultants base their thinking on the rational data of the cases. Our consultants are critical and independent thinkers who can effectively analyze data and draw conclusions based on the evidence at hand. This critical thinking involves breaking down information based on the available data and drawing logical conclusions based on the facts.

If you are interested in ATESSIA’s consulting world, contact us at hello@atessia.fr

Article written by Hiba MASSOUDY, Human Resources Manager