What are Good Manufacturing Practices (GMP) ? 

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Definition 

Good Manufacturing Practices are a set of principles and guidelines. The first GMPs were published in France in 1978. These guidelines are regularly updated to incorporate regulatory changes. 

The WHO defines Good Manufacturing Practices as “one of the elements of quality assurance, ensuring that products are manufactured and controlled in a uniform manner and to quality standards appropriate to their use and specified in the marketing authorization”. The aim is to guarantee the quality, safety and efficacy of medicinal products. 

These Good Manufacturing Practices provide an understanding of the requirements of European regulations relating to the manufacture of medicinal products. They are one of the standards applicable to health products with marketing authorisation for the European market, as well as to experimental medicinal products. 

The application of GMP by pharmaceutical establishments is verified by the competent authorities during inspections. 

GMP compliance certificates issued by the ANSM following these inspections are published in the European EudraGMDP database. 

Organisation of Good Manufacturing Practices 

The standard is made up of 4 different parts plus appendices and guidelines. The 4 parts are as follows:  

  • Part I: GMP for medicinal products for human use 
  • Part II: GMP for active substances used as starting materials in medicinal products 
  • Part III: GMP-related documents  
  • ICH Q9: “quality risk management” guideline 
  • ICH Q10: “pharmaceutical quality system” guideline 
  • Part IV: GMP specific to innovative therapy medicinal products 

The 10 Principles of Good Manufacturing Practice 

There are 10 fundamental principles applicable to pharmaceutical operations which are taken from these chapters and which must be applied in order to guarantee the compliance of medicines:  

  • Creating procedures: writing operating procedures and instructions to provide a “road map”; 
  • Documentation: provide a precise description of the work in progress to ensure compliance with procedures and traceability; 
  • Validation: proving the correct operation of the systems in place by ensuring validation circuits; 
  • System design: integrating processes, product quality and staff safety right from the design phase of buildings, systems and equipment; 
  • Maintenance: regular and efficient maintenance of systems, installations and equipment; 
  • Skills: developing and clearly demonstrating skills at the workplace; 
  • Contamination prevention: adopting regular and systematic hygiene and cleanliness practices; 
  • Quality first and foremost: regular checks on raw materials and processes (manufacturing, packaging, labelling, etc.); 
  • Quality audits: planning and carrying out regular audits to ensure GMP compliance and the effectiveness of the quality system. 

Conclusion  

Compliance with Good Manufacturing Practices is essential. It is a regulatory obligation for pharmaceutical establishments. It is crucial to ensure product compliance and safety. Furthermore, during inspections by the health authorities, failure to comply with these standards may result in decisions of varying severity, depending on the non-compliance observed. The consequences of inspections can range from administrative warnings to sanctions.  

What are CEPs ?

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CEP : what’s that? 

In Europe, three distinct possibilities exist for presenting information relating to the active substance, from a qualified manufacturer, used in a medicinal product in the marketing authorisation file (MA file): 

– present a complete documentation (sections 3.2.S.1 to 3.2.S.7.3 100% completed according to the requirements of NtA-Vol 2B); 

– present an Active Substance Master File (“ASMF“) which contains an open (non-confidential) part and a closed (confidential) part; 

– present a Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP). 

In this article we will focus on defining what the CEP consists in and why this possibility for recording a source of active substance is particularly interesting. 

  • CEP definition 

The CEP is a document issued by the European Directorate for the Quality of Medicines and Healthcare (“EDQM“) following an official European procedure for Certification of suitability to the monographs of the European Pharmacopoeia (Ph. Eur.) (known as the “Certification procedure”). 

This document certifies that the quality of the substance in question can be adequately controlled by the corresponding Ph. Eur. monograph(s), supplemented if necessary by additional tests appearing on the CEP. It is thus based on the evaluation by EDQM experts of a file submitted by the applicant (in the same way as by the experts of the competent authorities for the MA application file). 

However, a CEP does not allow to confirm compliance with Good Manufacturing Practices (GMP) of the substance concerned and cannot replace the GMP certificate. A CEP can therefore be issued by the EDQM with or without inspection of the manufacturing site. Also a CEP does not replace a certificate of analysis and does not guarantee that a batch of the substance is of appropriate quality. Therefore, vigilance must remain required by the future user of the substance, with the implementation of controls upon receipt of the substance. 

The Certification procedure is applicable to substances for which a general or specific monograph has been adopted by the European Pharmacopoeia Commission (e.g. substance of synthetic origin [active substance or excipient], herbal drugs, herbal drugs preparations, etc.). This procedure does not apply to direct products of genetic expression (proteins), nor to products obtained from human tissues, nor to vaccines or products and preparations derived from blood. Furthermore, although this may have been the case in the past, the EDQM does not accept new CEP applications for substances of biological origin. 

A public list of CEPs with their status is available without access restriction in the EDQM certification database. 

Details of the content of the CEP application file are provided on the EDQM website. New requirements are now in force for the constitution of files by applicants with the entry into force of CEP 2.0 since September 1, 2023. 

  • The different categories of CEP 

There are currently several types of CEPs issued by EDQM depending on the evaluation carried out, including the following simple CEPs: 

– Certificate of chemical purity and microbiological quality (“Chemical CEP”) à e.g.: paracetamol 

– Certificate for herbal drugs and herbal drugs preparations (“Herbal CEP”)à e.g.: lavender oil 

– TSE certificate for substances of animal origin potentially subject to transmissible spongiform encephalopathy (“TSE CEP”) à e.g.: gelatin 

Combined CEPs may also be granted, as follows: 

– Certificate of chemical purity/microbiological quality and sterility à e.g.: sterile amoxicillin sodium 

– Double certificate (chemical + TSE) à e.g.: cholecalciferol 

– Double certificate (chemical + TSE) also covering sterility 

It is possible to claim a particular quality for a substance, this must be duly demonstrated in the file (e.g. sterile, micronised, crushed substance, etc.): this quality will be indicated in the subtitle on the CEP. Furthermore, it is possible to request a CEP for a particular polymorph (as a quality), even if the mention “the substance presents a polymorphism” does not appear in the “Characters” section of the corresponding specific Ph. Eur. monograph. 

  • Recognition of the CEP outside Europe 

Although it is not mandatory for the marketing of substances, the Certification procedure constitutes the preferred option for ensuring that a substance entering in the composition of a medicinal product complies with the specifications of the European Pharmacopoeia, as well as for demonstrating the compliance with TSE risk requirements. 

From a regulatory perspective, CEPs are accepted in all EU Member States and in States that have signed the Convention relative to the elaboration of a European Pharmacopoeia (including the United Kingdom), with the exception of Ukraine. 

According to the information received by the EDQM, the following countries accept CEPs, sometimes under conditions (non-exhaustive list): South Africa, Albania, Algeria, Saudi Arabia, Australia, Azerbaijan, Canada, Georgia, Ghana, Israel, Kyrgyzstan, Malaysia, Morocco, Moldova, New Zealand, Uzbekistan, Singapore, and Tunisia. CEPs are also accepted (under conditions) by the Taiwan Food and Drug Administration. 

CEPs may therefore be accepted in other countries (non-EU or Ph. Eur. members), at the discretion of the authorities of these countries. In such cases, the Competent Authorities will decide on the scope and conditions of acceptance of the CEP (e.g. submission of a partial or complete ASMF in addition to the CEP). The EDQM indicates that it is therefore important to check, in advance, the acceptability and conditions associated with the use of a CEP in these countries. 

Additional requirements may be applied by some non-EU states (e.g. signed, dated and version-controlled documents for specifications and analytical procedures). 

In terms of the MA file, section 3.2.S of the MA holder/applicant for the active substance should also be adapted by making the necessary references to the CEP and/or by providing the data specific to the manufacturer(s) of the finished product using the substance covered by a CEP in the relevant sections of the CTD. 

As a conclusion, the CEP is an essential document for marketing authorisation files in Europe and its evaluation by the EDQM encourages preferred use, the updating of which is less constraining in regulatory terms than other options (e.g. ASMF). Although recognised by a large majority of countries worldwide, it may not be sufficient in itself and may have to be subject to specific requirements of the country in which the MA is registered. 

Source: EDQM -FAQs (February 2024) 

Article written by Isabelle MOUVAULT, Pharmaceutical Affairs Senior Consultant 

What is the European Pharmacopeia ?

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This article deals with the essential information you need to know about the European Pharmacopoeia (whose official acronym is “Ph. Eur.”), a unique reference work relative to the quality control of medicines in the 46 member countries of the Council of Europe. 

  • Presentation of the European Pharmacopoeia 

Ph. Eur. is a collection of official standards which, once published, provide a legal and scientific basis for the quality control of substances for pharmaceutical use and medicines during the development, production and marketing processes. It is available to users, in French and English, in paper format or online (paid service of the European Directorate for the Quality of Medicines and Healthcare (EDQM)). 

The legal basis of the European Pharmacopoeia is the “Convention relative to the elaboration of a European Pharmacopoeia” (European Treaty Series – No. 50) adopted by the Council of Europe in 1964. 

These official standards, presented in chapters and monographs, concern the qualitative and quantitative composition and the tests to be carried out on: medicines, the raw materials used in their production and synthesis intermediates. Therefore, all producers of medicines and/or substances for pharmaceutical use must apply these quality standards in a mandatory way in order to be allowed to market their products within the signatory States of the Convention. 

The role of the Ph. Eur. is to contribute to the protection of public health through the development of recognised common specifications relating to the quality of medicines and their components. These specifications must be appropriate because they constitute, for the patient, one of the fundamental guarantees in terms of the safety of use of medicines. Furthermore, their existence facilitates the free circulation of medicines within Europe and beyond. 

The monographs and other texts of the Ph. Eur. are developed to meet the needs of regulatory authorities (e.g. ANSM, EMA, etc.), services responsible for the quality control of medicines and their constituents as well as manufacturers of medicines and their various components (e.g. active substances, excipients, packaging materials). 

Ph. Eur. brings together member countries and observer countries. 

The member countries of the Ph. Eur. can participate in sessions of the European Pharmacopoeia Commission (EPC). Each Member State, represented by a national delegation, has one vote on all technical questions. A member country may also propose national experts in each of the Ph. Eur expert groups or working groups. 

Ph. Eur. observer countries can participate in the scientific work of the EPC, benefit from European experience in this area and access work relative to the quality control of medicines as well as the analytical methods used. 

The EPC is the decision-making body of the Ph. Eur. and is responsible, as such, for developing and keeping the content of the Pharmacopoeia up to date. This Commission meets behind closed doors three times a year in Strasbourg, in the premises of the EDQM. It is also the EPC which appoints the members of all Expert Groups and Working Groups in charge of developing and revising methods and texts. 

The Expert Groups cover the main scientific topics associated with the quality control of medicines and their constituents. Working Groups are appointed for a specific duration, in order to deal with a specific aspect of the work or a specific subject. 

  • Recognition of Ph. Eur. works worldwide 

The Ph. Eur. is widely used internationally. In fact, the EPC works in close collaboration with all users of the Ph. Eur. across the world considering that globalisation and expansion of international trade in the field of medicines have reinforced the need to develop quality standards of international scope. 

  • Interactions with Ph. Eur. 

The EPC defines a work program based on proposals from, for example, National Pharmacopoeia Authorities, expert groups, manufacturers and EDQM. Manufacturers wishing to participate in the development of a monograph, for example by providing data and samples for approved products and verifying the draft monograph, are encouraged to submit monograph proposals. 

It is possible for users to make proposals for revising monographs. However, these must follow the process defined on the EDQM website and be supported by sufficient data. 

The EDQM Knowledge database provides users with information on the status of general monographs/chapters. If the substance does not appear in this public database, this means that it is not covered by any monograph/general chapter of the Ph. Eur. 

  • The future of European Pharmacopoeia 

The Ph. Eur. has been actively engaged for almost 30 years in the Pharmacopoeia Discussion Group (PDG) alongside the Japanese Pharmacopoeia (JP), the United States Pharmacopoeia (USP) and, since October 5, 2023, the Indian Commission of Pharmacopoeia (IPC). The PDG aims to facilitate the international harmonisation of a selection of pharmacopoeial standards (in particular excipient monographs and certain general chapters) in order to alleviate for manufacturers the difficulties of carrying out analytical procedures according to different modalities, with different acceptance criteria, in order to comply with pharmacopoeial requirements which may vary depending on the regions of the world. 

Priorities for the future of the PDG, and therefore of the Ph. Eur., include the harmonisation of standards for elemental impurities and excipients as well as the modernisation of a large number of general methods and excipient monographs already harmonised. 

Sources: 

– EDQM website (February 2024) 

– EDQM-FAQs (February 2024) 

Article written by Isabelle MOUVAULT, Pharmaceutical Affairs Senior Consultant 

What are the next steps for therapeutic cannabis in France? 

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A bit of history 

In September 2018, a multidisciplinary scientific committee made up of ANSM, healthcare professionals and patients was set up to review scientific knowledge and foreign experience on medical cannabis.   

In December 2018, this committee concludes that the use of cannabis is appropriate for patients in certain clinical situations, and wishes to set up an experiment.  

As of January 2019, a temporary specialised scientific committee (CSST) is being set up with the aim of assessing the relevance and feasibility of making therapeutic cannabis available in France. This CSST is tasked with issuing an opinion on:  

  • the therapeutic value of cannabis in the treatment of certain pathologies;  
  • the modalities for making cannabis available for medical use.  

At the same time, the committee had to define specifications for: 

  • The drugs used during the experiment;  
  • The content of training for doctors and pharmacists and information for patients;  
  • The content of the patient follow-up register.  

Launch of the experimental framework  

On October 25, 2019, the French National Assembly gives the go-ahead for an experiment in the use of medical cannabis.  

Decree no. 2020-1230 of October 7, 2020 on the experimentation of the medical use of cannabis defined in particular:   

  • the duration of the pilot (2 years),   
  • the status of medical cannabis as a narcotic drug,  
  • the number of patients who may be included,  
  • the conditions of treatment,  
  • the setting up of a register to monitor adverse events.  

The Order of October 16, 2020 set out the specifications for cannabis-based medicines used during the experiment provided for in Article 43 of Law no. 2019-1446 of December 24, 2019 on the financing of social security (LFSS) for 2020, together with the conditions for making them available and the therapeutic indications or clinical situations in which they will be used.  

This order defined:  

  • The indications for which medical cannabis products entered the trial,  
  • The authorized pharmaceutical forms:   
  • form for inhalation by vaporization, such as dried flowering tops or granules; 
  • oral form in capsule or equivalent form  
  • oral or sublingual oil form  
  • as well as specifications for the free supply and distribution of cannabis-based medicines for patients taking part in the experiment in the medical use of cannabis.  

The call for applications for therapeutic cannabis suppliers launched on October 19, 2020 by ANSM closed on November 24, 2020. Applications were examined on the basis of strict and demanding specifications in terms of compliance with good cultivation and manufacturing practices, drug quality and securing the distribution circuit as defined in the decree. This examination was carried out by the ANSM, and in particular by its control laboratories, and by experts from the Temporary Specialised Scientific Committee (CSST).  

In all, six supplier/operator pairs were selected for the trial.   

First patient – Start of the trial  

On March 26, 2021, the medical cannabis trial officially began with the inclusion of the first patient at Clermont-Ferrand University Hospital. The experiment will run for 2 years.   

In June 2021, a CSST was set up to monitor the medical cannabis experiment. It is made up of 16 members, including 4 patients and healthcare professionals, general practitioners, specialists in the therapeutic indications selected for medical cannabis, pharmacists and representatives of the Centre Régional de Pharmacovigilance (CRPV) and the Centres d’Evaluation et d’Information sur la Pharmacodépendance-addictovigilance (CEIP-A).  

This committee is involved in monitoring the progress of the experiment and must issue an opinion on the evaluation data collected and on the framework for the marketing and use of medical cannabis.  

2023: the first turning point  

Decree 2023-202 of March 25, 2023, amending Decree 2020-1230 of October 7, 2020:   

  • extends the trial period for the medical use of cannabis by one year;   
  • indicates that medicines with a THC content of over 0.30% are subject to the narcotics regime; conversely, those with a THC content of less than or equal to 0.30% are now subject to the regime for medicines covered by lists I and II of poisonous substances.  

At the same time, various decrees dated March 25, 2023 specify that:  

  • Pharmacovigilance and addictovigilance will now be handled in the same way as for other drugs;   
  • Inhalation granules have been discontinued;  
  • The ANSM is no longer responsible for selecting suppliers and operators of cannabis for medical use. The Direction Générale de la Santé (DGS) is now the competent authority in this area, via a public procurement contract. The medicines used will therefore no longer be supplied free of charge by participating companies.  

End of the experiment  

Article 78 of the Social Security Finance Act of December 26, 2023 puts an end to the experiment.  

As of March 26, 2024, no new patients can be included. Patients included before this date will still be able to benefit from their treatment, with the exception of inhaled forms.  

Other patients will have to wait until a medicine is authorized and available “no later than December 31, 2024” before they can benefit from a cannabis-based treatment for therapeutic use.  

Pending the completion of the work enabling the widespread use of therapeutic cannabis in France, the Ministry has decided to extend coverage for patients still undergoing treatment since the end of the trial on December 31, 2024. 

Therefore, until March 31, 2026, coverage for patients included in the experimentand still undergoing treatment will be provided under the same conditions and, exceptionally, for medications authorised as part of the experiment. 

Key figures of the experiment: 

Since the start of the experiment in March 2021, 3,209 patients have been enrolled, of whom 1,655 were still receiving treatment as of June 13, 2025. 

A growing number of healthcare professionals are involved in this experiment (figures as of June 2025): 

  • 341 registered volunteer referral centers, 
  • More than 700 physicians in referral centers, both in private practice and hospitals, 
  • More than 1,400 pharmacists. 

What’s next?   

Article 78 of the Social Security Finance Act for 2024 creates an ad hoc status for cannabis-based medicines and introduces, for those medicines, the authorisation of use for a 5-year temporary period granted by the French HAs.  

  • Therapeutic indications: 

A decree is expected to define the precise indications for these medications. 

Article 78 of the Social Security Finance Act for 2024 precises that such prescription may only be done if the use of these products meets the special needs of a given patient, and there is no suitable pharmaceutical packsize available, including due to the absence of effective marketing, with, for example, a marketing authorization (article L5121-1 4° of the CSP).  

  • Content of the application for temporary authorisation 

A decree is also pending to define the content of the application for temporary authorisation. A draft notice to applicants was published for consultation by the French HAs in July 2024 and guides future applicants on the expected content of these applications. 

It should be noted that the final texts are still awaiting official publication and that no applications for temporary authorization can be submitted at this time. 

Article written by Isabelle BARBIEUX, Senior Quality Assurance Consultant and Agathe DAUBISSE, Senior Regulatory Affairs Consultant 


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Poisonous Substances: What Use within the Pharmaceutical Industry? 

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Poisonous substances refer to all narcotic drugs, psychotropic substances, or any substances likely to pose a danger to health (classified under “List I” or “List II” depending on the degree of health risk). They are defined in Article R5132-1 of the French Public Health Code. 
When an active substance or a medicinal product is classified as a “poisonous substance,” its dispensing in pharmacies is subject to a mandatory medical prescription. For narcotic drugs, a so-called “secure prescription” must be presented. 

The regulation of poisonous substances therefore covers substances, preparations, plants, and medicinal products. 

Definitions 

Medicines containing poisonous substances are classified either as: 

  • Narcotics; 
  • List I for substances presenting the highest risks to health; 
  • List II for others. 
  •  

Lists I and II of poisonous substances, as mentioned in Article L5132-1 of the Public Health Code, include: 

  • Certain substances classified as hazardous to health under Article L1342-2; 
  • Medicines likely to pose a direct or indirect risk to health; 
  • Human medicines containing substances whose activity or adverse effects require medical monitoring; 
  • Any other product or substance presenting direct or indirect health risks. 
  •  

List I means that a medicine may only be dispensed for the duration stated on the prescription, and renewal is possible only if indicated by the prescriber, up to a maximum of one year. 

List II medicines may be dispensed multiple times from the same prescription for up to 12 months, unless otherwise specified by the prescriber. 

Narcotics and Equivalent Substances 

Narcotic drugs include, in particular, morphine and its derivatives. Their dispensing is subject to very strict rules: they require a secure prescription and may not be dispensed for more than 28 days. 
Some non-narcotic medicines are required to comply, in whole or in part, with the rules applicable to narcotics: these are referred to as “narcotic-like medicines.” 

When a medicine contains multiple substances or preparations subject to different classifications, it is subject to the strictest regime in the following descending order: narcotic, List I, List II. 

In certain cases and under specific conditions, some substances or medicines used in common pathologies, at low doses and/or for short treatment durations, may be exempted from the poisonous substances lists and thus dispensed without prescription. The route of administration, composition, maximum doses or concentrations, and maximum treatment duration are specified in the exemption decision. 

Classification 

Since the decree of February 1, 2022, the ANSM (French National Agency for Medicines and Health Products Safety) is now responsible for: 

  • Classifying substances and medicines intended for human medicine under Lists I and II of poisonous substances; 
  • Classifying any substance, whether intended for human medicine or not, as a narcotic or psychotropic; 
  • Granting exemptions from these lists for certain substances or medicines. 

Previously under the Ministry of Health, this competence now enables ANSM to restrict or limit access to certain medicines if necessary—particularly to ensure appropriate use, patient safety, and to prevent misuse. In coordination with other administrations, this also helps fight against the illicit trafficking of narcotics and psychotropics. 

ANSM decisions will amend the decrees of February 22, 1990 concerning: 

  • Inclusion on poisonous substance lists, 
  • Exemptions from poisonous substance regulations, and 
  • Classification as narcotics or psychotropics. 

Impact on Pharmaceutical Companies 

Industrial pharmaceutical establishments must adapt to the regulatory requirements of this classification, covering activities such as manufacturing, importation, wholesale distribution, and research. Any failure to comply with these regulatory obligations may result in severe sanctions, requiring strict compliance. 

These measures also apply to stakeholders in the veterinary medicines sector. 

The regulation of poisonous substances also imposes additional requirements on the primary and secondary packaging of medicines containing these substances. Labels must include a green or red box in which the pharmacist must indicate the dosage to be followed. 

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Dispensing Rules 

Special rules must also be followed regarding dispensing. Poisonous substances are not eligible for direct access requests (self-medication). 
As a reminder, the ANSM defines the list of medicines that may be displayed in front of the counter in pharmacies as over-the-counter (OTC) products, based on criteria designed to ensure health and patient safety. 

Support from Atessia 

Atessia assists its clients in obtaining authorizations to open pharmaceutical establishments authorized to distribute narcotic medicines, as well as in validating packaging components. 

Article written by Estelle ICARD, Junior Regulatory Affairs and External Communication Advisor  

Therapeutic patient education versus learning programs: what is role for the pharmaceutical industry?

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> Definition and content

Therapeutic patient education (TPE) can be defined in several ways.

The World Health Organization (WHO) gave the following definition in 1996: “Therapeutic patient education aims to help patients acquire or maintain the skills they need to manage their lives with a chronic disease”.

In 2007, the French National Authority for Health (HAS) clarified the specific aims of therapeutic education:

– The acquisition and maintenance by the patient of self-care skills;

– The mobilization or acquisition of coping skills”.

Under the French law no. 2009-879 of July 21, 2009 on hospital reform and patients, health and territories (known as the HPST law), TPE is defined as being “[…] part of the patient’s care pathway. Its aim is to make patients more autonomous by facilitating their compliance with prescribed treatments and improving their quality of life. It is not enforceable against the patient and cannot condition the rate of reimbursement for his or her treatment or for drugs related to his or her illness”.

ETP, as provided for in the French Public Health Code, is divided into three distinct actions:

– Therapeutic patient education programs, which comply with national specifications, are implemented at local level after registration with regional health agencies (ARS). They are proposed to the patient by a healthcare professional and lead to the development of a personalized program;

– Accompaniment programs, which comply with national specifications, are designed to provide assistance and support to patients and their families in managing their disease;

– Learning programs are designed to help patients acquire the technical skills they need to use a medicine/Auto-administration. These programs are implemented by healthcare professionals working on behalf of an operator who may be financed by the company exploiting the medicine. The learning program is proposed by the prescribing physician to the patient. In this case, the ANSM authorizes their implementation, after consulting an approved patient association To this end, the manufacturer submits a training application, justifying the expected benefits for the patient.

> ETP objectives

ETP is based on an individualized approach, considering the specific characteristics of each patient. It involves close collaboration between the patient, healthcare professionals and often the patient’s family and friends. The aim is to foster an in-depth understanding of the disease, its implications and associated treatments. This approach encompasses not only the medical aspects, but also the psychological, social and environmental aspects of health.

– Understanding the disease: ETP enables patients to understand the mechanisms of their disease, their symptoms, treatments and effects. Better knowledge helps patients adhere to treatment and prevent complications.

– Skills acquisition: Patients learn to manage their treatment, recognize the early signs of complications and adopt healthy lifestyle habits.

– Autonomy and decision-making: ETP aims to reinforce patients’ autonomy by giving them the tools they need to actively participate in decisions concerning their health.

> Who can set up this type of program?

Healthcare professionalsOthersLegal entities
> Doctors and specialists: They play an essential role in defining therapeutic objectives and validating educational content;
> Nurses: They are often on the front line in delivering education and educational follow-up to patients;
> Pharmacists: They can help explain treatments and their dosage;
> Psychologists or psychiatrists: They help patients manage the stress and psychological impact of their illness.		> Specialized educators: They are specifically trained to deliver TVE;
> Expert patients: people living with the same pathology can share their experience and provide invaluable support.		> A healthcare establishment (public or private);
> A collective practice structure (health center/health home/health cluster);
> A health network;
> An association;
> The Assurance Maladie (health insurance) for health examination centers and the Sécurité Sociale Agricole (agricultural social security);
> A mutual or other complementary insurance company;
> A foundation;
> A municipality.


> Manufacturers and their medicines, at the heart of TVE… but with less room for manoeuvre:

– Ever more innovative medicines

– Pathologies requiring increasingly advanced patient knowledge/technical gestures

– Image and communication issues, as well as the promotion of public health, may lead the laboratory to wish to support an ETP program especially when self-administering drugs.

In order to remain compliant, it is essential for manufacturers wishing to leverage the benefits of ETP to be aware of the roles and levels of involvement they are allowed to play.

Finally, implementing a TVE program without being authorized to do so is punishable by a fine of up to 30,000 euros.

> Conclusion

Therapeutic patient education represents a major evolution in the way we approach health and illness. In a world where it is becoming commonplace for patients to become experts in their own disease, they are a tool for them to understand, actively participate in their treatment and adopt health-promoting behaviors, while contributing to comprehensive, personalized care.

However, the role of the operator of a medicine is regulated and requires a case-by-case analysis of each project.

In such a context, manufacturers have a role to play, while considering the regulatory complexity imposed by the system and the need to steer clear of the multiple risks associated with their highly regulated field of activity (promotional requalification, contact with patients, granting benefits to patients or healthcare professionals).

Article written by Zarine RAMJAUNY, Legal Advisor

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

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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. 

After more than fifteen years of implementation, France’s transparency of interests framework stands as a benchmark for ethics and regulation in the healthcare sector. Inspired by the U.S. Sunshine Act, the Bertrand Law has strengthened public trust and clarified relationships between industry and healthcare stakeholders. 

With this experience, companies have made transparency a cornerstone of their compliance culture. This pioneering framework paved the way for broader harmonization through the European Pharmaceutical Package and EFPIA initiatives, which require the annual disclosure of Transfers of Value (ToV). 

The recent inclusion of social media influencers highlights the French model’s ability to adapt to new communication trends while maintaining high ethical standards in an ever-evolving environment. 

ATESSIA supports its clients on all these questions. 

Article written by Johanna DROUVILLE, Legal Consultant at ATESSIA

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

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Atessia assists its clients on a daily basis with the practicalities of implementing the French early access programs and compassionate use scheme, the subtleties of which require some explanation. 

This new system has been in place since 1st July 2021 and is based on 2 access and reimbursement mechanisms:  

  • Early access (AAP) 

The first is the early access scheme, dedicated to medicinal products that meet an unmet therapeutic need and are likely to be innovative. The pharmaceutical company submits an application for early access authorisation (AAP) to the French National Authority for Health (HAS) and, for medicinal products not yet authorised under marketing authorisation, to the French National Agency for the Safety of Medicines and Health Products (ANSM).  

These authorisations may apply to : 

– a medicinal product prior to obtaining marketing authorisation for the indication in question (Pre-marketing authorisation AAP = AP1),  

– a medicinal product which already has a marketing authorisation for the indication in question, prior to it being covered by the general health insurance system (Post-marketing authorisation AAP = AP2). 

Interestingly, the product may or may not have marketing authorisation for another indication. 

As indicated in the HAS doctrine, the granting of an AAP is reserved for specific medicinal products that meet the following 5 cumulative eligibility criteria: 

  1. Efficacy and safety are strongly presumed in the indication in question  
  1. The disease to be treated is serious, rare or disabling 
  1. There is no such thing as “appropriate treatment” 
  1. The treatment cannot be deferred 
  1. The drug is presumed to be innovative. 

The authorities examine all these criteria separately, and quite strictly. 

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

  • REGULATORY: The pharmaceutical company must undertake to submit a marketing authorisation application within 2 years for an AP1 or a registration application within one month of obtaining the marketing authorisation for an AP2. The timing of the application is therefore crucial to the project. 
  • LOGISTICS: The pharmaceutical company makes the product available within 2 months of the granting of the AAP and ensures that it can supply the product to allow continuity of treatment for patients initiated throughout the AAP. At the end of the AP, the exploitant pharmaceutical company ensures the continuity of the treatments initiated for a minimum period of one year, of which 3 months are covered by health insurance.  
  • FINANCIAL: The pharmaceutical company sets up a PUT-RD for data collection and the transmission of periodic summary reports. It funds the data collection withing the framework of an agreement signed with health establishments. 
  • The pharmaceutical company is also required to support prescribers in entering and monitoring the collection of real-life monitoring data for the drug, by providing them with the necessary resources. 

Since the implementation of the AP scheme in July 2021, the HAS has published a positive report covering three years of application : 

  • Two types of compassionate access  

This system covers two distinct cases, which have in common the fact that they concern a medicinal product used to treat patients suffering from illnesses for which there is no appropriate treatment, in a given therapeutic indication, without it being intended to obtain marketing authorisation in France. Applications are managed solely by the ANSM. 

  1. 1st mechanism: this compassionate access is requested for an unauthorised drug not available in France by a hospital prescriber for a named patient, provided that the ANSM is able to presume a favourable benefit/risk ratio for a serious, rare or disabling disease: this is an individual and nominative compassionate access authorisation (AAC). 
  1. 2nd mechanism: it is a framework for a practice, at the initiative of the ANSM, with a view to securing the practice of off-label prescribing of a medicinal product available in France, which has marketing authorisation for other indications, when it is the subject of well-established off-label prescribing on French territory : this is a compassionate prescribing framework (CPC). 

Exceptions to compassionate access have been made in the following cases: 

  • Allowing nominative access to medicines in development for the indication: this is a “very early” compassionate access. 
  • The LFSS for 2024 also provides for the possibility of granting compassionate access authorisations in the event of a refusal for early access on the grounds that the drug is not considered innovative enough. 

There are a number of eligibility conditions attached to the ANSM grant, which bring this scheme closer to early access and can be the gateway to it: 

  • treatment cannot be postponed; 
  • the patient cannot take part in any ongoing research; 
  • the company responsible for exploiting the medicinal product must undertake to submit an application for early access program within 12 months of the first ‘compassionate pre-approval’ (18 months for rare diseases).  

Compassionate access schemes differ from early access programs in that their initiation does not rest with the manufacturer, who may be required to implement and fund a PUT-SP. 

Thus, the reform has brought greater predictability for manufacturers and continuity of access up to standard reimbursement. In return, pharmaceutical companies are bound by a number of commitments. 

According to the ANSM report, published in 2024, the use of compassionate access has been stabilising since the 2021 reform. In 2023, a relative decrease of 10% in compassionate access requests was observed. This decrease is partly linked to the granting of marketing authorizations for several Covid-19-related products, which had previously been the subject of numerous compassionate access requests. 

Moreover, the number of medicinal products available under this scheme has remained stable, with 373 made available in 2023. 

For these products, it may be necessary to appoint a pharmaceutical company to operate the medicinal product, in order to ensure import/distribution, pharmacovigilance, quality claims or medical information, as appropriate. 

Pharmaceutical companies now have several years’ experience of these new mecanisms, and the trends that are emerging show a willingness on the part of the authorities to make innovative medicines available to French patients and to respond to the personal situations of patients who have reached a therapeutic impasse. 

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

What about the classification of Marketing Authorization variations? 

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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 

ATESSIA Life Science Advisors, a Catalyst for Regulatory Innovation: Collaborating with UBAQ, ATESSIA Sets a New Standard to Facilitate the Management of Regulatory Challenges in the Health Sector

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An alliance capable of moving mountains.

ATESSIA and UBAQ jointly pave the way for health sector players.

The health sector, constantly evolving and in the spotlight, requires wisely chosen partnerships.

ATESSIA, a consulting and expertise firm in regulatory and pharmaceutical affairs, and UBAQ, a recognized expert in SaaS solutions for Health Tech, naturally meet at the crossroads of their paths.

Their collaboration aims to simplify and strengthen the regulatory management of health industries, each contributing their expertise: ATESSIA with its deep knowledge of the regulatory field, distinctive know-how, and disruptive approach to consulting, and UBAQ with its sharp technological skills and fresh perspective on sector challenges.

Together, they offer a value proposition that combines innovation, expertise, and accessibility.

With this partnership, ATESSIA offers tailored support, deeply focused on quality customer experience, aiming to meet diverse needs and expectations at every interaction level.

“We were looking for a technical solution with an innovative approach to offer our clients. Having been in contact with UBAQ for several years, we now fully trust them and share the same values and ambitions: to support the Health Industries in their regulatory issues, always placing patients at the heart of our solutions.”

Géraldine BAUDOT-VISSER, Doctor of Pharmacy, founder of ATESSIA, and AMARYLYS.


A Tailored Partnership for the Health Industries

Always seeking to add value for health industry players, ATESSIA has teamed up with UBAQ to offer tailored support. This collaboration revolves around implementing an innovative technical tool designed to ease the daily life of health industry professionals. Indeed,

UBAQ aims to provide its clients with regulatory support that goes beyond its SaaS solution, choosing to partner with one of the most renowned firms in this field.

Both companies share a key priority: placing the customer, their experience, and satisfaction at the heart of each solution.

In addition to tool implementation, ATESSIA offers 360° support, covering all business and regulatory issues health industries may face.

This partnership provides an integrated solution, combining ATESSIA’s sharp expertise with an intuitive digital tool to ensure optimal regulatory compliance.

“Partnering with a regulatory affairs firm was obvious for us and is in line with the continuous support we offer our clients. ATESSIA breaks the mold and stands out with a very flexible and innovative approach: this is exactly what we were looking for.”

François CANCELLONI, General Manager and co-founder of UBAQ.


ATESSIA Life Science Advisors: The Strategic Partner in Pharmaceutical Regulatory Navigation

Founded in 2017 by Géraldine BAUDOT-VISSER, Doctor of Pharmacy, ATESSIA Life Science Advisors is an essential player in guiding health industries through regulatory landscape challenges.

With a team of experts and a client-centered approach, ATESSIA ensures compliance and relevance through personalized technical and strategic development support and health product commercialization.

ATESSIA positions itself as a market leader, with its insightful regulatory monitoring service, ATESSIA INTELLIGENCE, handling French and European regulatory subtleties.

ATESSIA’s renown highlights its expertise and commitment to assisting clients in successfully navigating the rigorous and complex world of regulatory and pharmaceutical affairs.


Key Points:

  • Expertise in 6 main areas: Pharmaceutical Affairs, Regulatory Affairs, Quality System Management, Health Product Promotion, Pharmacovigilance, Medical Devices, Regulatory Monitoring.
  • 126 companies subscribed to the regulatory monitoring tool, ATESSIA INTELLIGENCE.
  • Extended presence in Paris, Lyon, Luxembourg, Nice, Bordeaux, Lille, Auxerre, Orléans, and other locations.
  • 98% retention and satisfaction rate, according to the ISO indicator.

UBAQ, European Leader in Health Tech

Founded in 2023 from the merger of Qairn and Clardian (formerly BMI System), UBAQ supports the digital transformation of health industries with a suite of SaaS software.

These software solutions help dematerialize and simplify the application of the particularly strict and constantly evolving regulatory framework. UBAQ offers two solutions:

  • UBAQ DocPromo, which aims to comply with promotional documents.
  • NAYACT Transparency by UBAQ, focusing on the Law of Benefits Framework and transparency of interest links.