Wael HAYEK

Ouvrir votre établissement pharmaceutique

How to open a pharmaceutical establishment in France?

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  1. What status for my establishment? 

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

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

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

  1. Who issues the opening authorisation? 

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

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

  1. How to compile your file?  

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

  • Manufacturer/Importer file 
  • Exploitant’s file 
  • Distributor file 

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

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

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

  1. What is the processing time? 

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

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

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

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

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

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

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

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

  • refusal of authorisation for manufacturer and importer applications.  
  • tacit authorisation for other establishments. 

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

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

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

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

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

It should be noted that clinical trials involving medicinal products are primarily regulated by the EU Clinical Trials Regulation (EU) 536/2014 (CTR), which came into effect on January 31, 2022. This regulation replaces Directive 2001/20/EC. As a reminder, any clinical trial with at least one active investigative site in France as of January 31, 2025, must be transitioned to the Clinical Trials Information System (CTIS) by its sponsor before this date. For clinical trials involving medicinal products, the Jardé Law introduces additional requirements to be considered. Other provisions include compliance with CNIL (GDPR), and procedures related to the use of medicinal products composed wholly or partially of genetically modified organisms (GMOs). 

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

What is the Jardé Law? 

The Jardé Law, named after Deputy Olivier Jardé, is a regulation that governs the conditions under which research involving human participants can be conducted. It replaces the Huriet-Sérusclat Law of 1988 and aims to enhance the protection of participants while facilitating the conduct of clinical research. 

The main reference texts include: 

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

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

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

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

Classification of RIPH 

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

Category Legal Provisions Framework 
Category 1 Interventional research involving a risk to participants Articles L1121-1 and L1121-3 of the Public Health Code (CSP) These studies require prior authorization from the ANSM (French National Agency for Medicines and Health Products Safety) and a favorable opinion from a Committee for the Protection of Persons (CPP). 
Category 2: Interventional research with minimal risks and constraints Article L1121-2 of the CSP These studies require a favorable opinion from a CPP, but not authorization from the ANSM. 
Category 3: Non-interventional research Article L1121-1-1 of the CSP These involve observational studies where the risks are absent or negligible. A favorable opinion from a CPP is necessary, but these studies do not require authorization from the ANSM. 

What Are the Implications for the Industry? 

Participant Information 

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

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

Information for the ANSM 

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

Interactions with CPPs and the ANSM 

CPPs are French ethics committees. Interactions with CPPs and the ANSM are essential for the validation of research projects. Good communication and submission of complete dossiers are necessary, in accordance with Articles L1123-6 and L1123-7 of the Public Health Code. 

Procedures 

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

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

Conclusion 

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

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

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

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

Article written by Zarine RAMJAUNY, Legal Consultant 

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

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

Why Outsource CMC Activities? 

  1. Increasing Regulatory Requirements Health authorities are continuously raising the quality standards from development to drug registration and throughout the lifecycle of marketing authorizations (MA**). This trend imposes a significant workload from a CMC perspective, necessitating rigorous and expert management of regulatory dossiers. 
  1. Impact of Mergers and Acquisitions Corporate mergers and acquisitions increase the number of regulatory submissions to reflect changes in supply sources, production site transfers, etc. This dynamic requires increased flexibility and responsiveness to maintain compliance and the continuity of pharmaceutical operations. 
  1. Resource Management Optimization Increasingly complex regulatory requirements necessitate deep knowledge, leading to increased personnel needs and creating a talent shortage. The traditional operational model of pharmaceutical laboratories is often no longer optimized to handle the surplus work related to these CMC activities. Outsourcing complex technical and regulatory aspects reduces workload and improves overall efficiency. 

ATESSIA’s Unique Expertise 

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

Why Choose ATESSIA for Your CMC Needs? 

  1. Cutting-Edge Expertise and Knowledge ATESSIA has multidisciplinary expert teams with in-depth CMC knowledge. Our consultants possess practical experience and a fine understanding of regulatory authorities’ expectations, ensuring the quality of dossiers and compliance with current requirements. 
  1. Cost Reduction and Time Savings ATESSIA has the expertise to efficiently manage CMC activities and offers economical and fast solutions, best adapting to the market entry deadlines desired by its clients. 
  1. Guaranteed Quality Structured around the ISO 9001 standard, ATESSIA ensures impeccable quality at every stage of the product lifecycle. 
  1. Partner for Your R&D Activities ATESSIA has Research Tax Credit approval, enabling you to be supported in your research and development activities. 

Our Commitment to Excellence and Innovation 

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

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

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

hello@atessia.fr

www.atessia.fr 

*CMC: Chemistry Manufacturing and Control

**MA: Marketing Authorization 

The Post-Approval Change Management Protocol or “PACMP” 

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

  • Origin and definition 

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

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

In 2012, the EMA compiled a set of questions and answers regarding the PACMP in the document “Questions and answers on post approval change management protocols (EMA/CHMP/CVMP/QWP/586330/2010)”. The following topics are covered: 

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

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

  • Scope of the PACMP 

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

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

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

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

  • Formalisation of the PACMP in the MA file 

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

  • MA modifications linked to the PACMP 

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

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

> Three supportive documentation to be provided: 
1. Reference to the approved change management protocol. 
2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 
4. Amendment of the relevant section(s) of the dossier. 
Variation Type IB/B.I.e.5b): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires further supportive data 
> Absence of conditions to be fulfilled. 
> Four supportive documentation to be provided: 

1. Reference to the approved change management protocol. 
2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 
3. Results of the studies performed in accordance with the approved change management protocol 
4. Amendment of the relevant section(s) of the dossier 		Variation Type IB/B.II.g.5b): Implementation of changes foreseen in an approved change management protocol – The implementation of the change requires further supportive data 
> Absence of conditions to be fulfilled. 
> Four supportive documentation to be provided: 
1. Reference to the approved change management protocol. 
2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 
3. Results of the studies performed in accordance with the approved change management protocol 
4. Amendment of the relevant section(s) of the dossier. 
Variation Type IB/B.I.e.5c): Implementation of changes foreseen in an approved change management protocol – Implementation of a change for a biological/immunological medicinal product 
> Absence of conditions to be fulfilled. 
> Five supportive documentation to be provided: 

1. Reference to the approved change management protocol. 
2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 
3. Results of the studies performed in accordance with the approved change management protocol 
4. Amendment of the relevant section(s) of the dossier. 
5. Copy of approved specifications of the active substance 		Variation Type IB/B.II.g.5c): Implementation of changes foreseen in an approved change management protocol – Implementation of a change for a biological/immunological medicinal product 
> Absence of conditions to be fulfilled. 
> Five supportive documentation to be provided: 
1. Reference to the approved change management protocol. 
2. Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 
3. Results of the studies performed in accordance with the approved change management protocol 
4. Amendment of the relevant section(s) of the dossier. 
5. Copy of approved specifications of the finished product. 
The use of PACMP is strongly recommended by regulatory authorities and in line with the latest ICH guidelines (Q8, Q9, Q10, Q12 and Q14). As a result, an increase in this type of variation seems predictable for the years to come. 
 
Article written by Isabelle MOUVAULT, Pharmaceutical Affairs Senior Consultant 

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 

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. 
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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. 
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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  

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