Anne-Sophie SOHIER

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 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)

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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

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

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