# WHICH ACTORS TO INFLUENCE THE ADOPTION OF EU GUIDELINES FOR ADVANCED THERAPY MEDICINAL PRODUCTS?

**Aurelie Mahalatchy:** Permanent Researcher in law at the French National Centre for Scientific Research (CNRS, chargée de recherche; Low Faculty, UMR 7318 International, Comparative and European laws (DICE) CERIC, CNRS, Aix Marseille Univ, Toulon University, Pau & Pays de l'Adour University, Aix-en-Provence, France; Coordinator of 1-Biolex project; Deputy coordinator and NPI4 leader of EuroGCT project).

**Valentin Bruneel:** Research Engineer, CNRS, UMR 7318 International, Comparative and European laws (DICE) CERIC, CNRS, Aix Mmeule Univ, Toulon University, Pau & Pays de l'Adour University, Aix-en-Provence, France

## Background and Methodology

Genes, cells, and tissues based medicinal products are specifically regulated as Advanced Therapy Medicinal Products (ATMPs) within the European Union (EU) from the adoption of Regulation (EC) n°1394/2007 on ATMPs. Beyond legislative requirements, the complexity and scientific difficulty of these medicines, as well as the necessary flexibility to take into account the evolutions and the scientific and regulatory experience gained has led to the development of an important amount of guidelines in the field. These guidelines have mainly been adopted by the European Medicines Agency (EMA), the European regulatory agency especially in charge of the scientific assessment of medicines to be commercialised in the EU. Some of them have also been adopted by the European Commission (EC) which notably grants the final marketing authorization for ATMPs on the basis of EMA's assessment to enter the EU market. The adoption of EU guidelines involves a public consultation procedure to gather comments from stakeholders and interested parties.

These comments are then considered to establish the final version of the guidelines to be adopted as reference documents in the field.

Who are these actors influencing the adoption of EU guidelines for Advanced Therapy Medicinal Products?

Our research team searched both the EMA and EC websites in order to identify all guidance documents specific to ATMPs. This led to the establishment of a list of 57 documents, among which 27 guidelines. This poster is dedicated to guidelines only.

Out of all 27 applicable guidelines identified, we considered only those for which a consultation process report was available. For older guidelines, sometimes no consultation was organized, and sometimes the subsequent report was not available on the EC website.

Once all guidelines and associated reports on public consultation were collected, we identified all the actors involved in the consultation process: this led to the establishment of a database with 195 organisations corresponding to thirteen guidelines for which dates of production range from 2006 to 2022.

For every guideline, we collected its title, date of publication, as well as the type of therapy to which it referred (either Advanced Therapy Medicinal Products (ATMPs) generally, medicinal products based on Genetically Modified Organisms (GMO MP), Cell Therapy and Tissue Engineering Products (CT and TEP), or Gene Therapy Medicinal Products (GTMP)).

For each guideline, all organisations participating in the public consultation process were indexed and sorted in a table. Additional information was collected on the organisation's websites, regarding their typology, country of registration and specific activity.

The typology of organisations was constructed using all information available to sort out organisations to clearly identify the main polarizations between them.

## Main figures

<table><caption>Table 1: Numbers of organisations involved in different types of guidelines</caption><thead><tr><th>Guideline</th><th>Author</th><th>Theme</th><th>Date</th><th>Number of orgs</th></tr></thead><tbody><tr><td>Non-clinical testing for inadherent germline transmission of gene transfer vectors</td><td>EMA</td><td>GTMP</td><td>10/11/2006</td><td>4</td></tr><tr><td>Environmental risk assessments for medicinal products containing, or consisting of, genetically modified organisms (GMOs)</td><td>EMA</td><td>GMO MP</td><td>10/12/2006</td><td>4</td></tr><tr><td>Human cell-based medicinal products</td><td>EMA</td><td>CT and TEP</td><td>21/04/2008</td><td>20</td></tr><tr><td>Non-clinical studies required before first clinical use of gene therapy medicinal products</td><td>EMA</td><td>GTMP</td><td>30/05/2008</td><td>4</td></tr><tr><td>Scientific requirements for the environmental risk assessment of gene-therapy medicinal products</td><td>EMA</td><td>GTMP</td><td>30/05/2008</td><td>7</td></tr><tr><td>Follow-up of patients administered with gene therapy medicinal products</td><td>EMA</td><td>GTMP</td><td>22/02/2009</td><td>1</td></tr><tr><td>Guidance on the minimum quality and non-clinical data for certification of advanced therapy medicinal products</td><td>EMA</td><td>ATMPs</td><td>15/10/2010</td><td>6</td></tr><tr><td>Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer</td><td>EMA</td><td>ATMPs</td><td>21/07/2016</td><td>4</td></tr><tr><td>Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products</td><td>EC</td><td>ATMPs</td><td>22/11/2016</td><td>55</td></tr><tr><td>Quality, preclinical and clinical aspects of gene therapy medicinal products</td><td>EMA</td><td>GTMP</td><td>22/05/2018</td><td>29</td></tr><tr><td>Guidance on Good Clinical Practice specific to Advanced Therapy Medicinal products</td><td>EC</td><td>ATMPs</td><td>10/10/2019</td><td>34</td></tr><tr><td>Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells</td><td>EMA</td><td>GMO MP</td><td>12/11/2020</td><td>20</td></tr><tr><td>Guidance on core SMcP, Labelling and Package Leaflet for advanced therapy medicinal products (ATMPs) containing genetically modified cells</td><td>EMA</td><td>ATMPs</td><td>10/05/2022</td><td>9</td></tr></tbody></table>

## Results

* 11/15 guidelines have been adopted from 2000.

* 11/13 guidelines have been established by EMA while 2/15 guidelines have been established by EMA.

* 4/15 guidelines relate to ATMPs in general.

## Discussion

* There is a wide scale of involvement in public consultation processes, ranging from only 1 to 55 organisations having been involved. The number of organisations involved in public consultation processes is linked to the guidelines' topics and not to a potential increase due to better awareness of the process with time.

* Almost half of the guidelines for which a report on public consultation is available, have been adopted in the field of GTMP, which highlights the rise of this type of ATMPs as the particular need for adequate guidance for their development and commercialisation in the EU. On the opposite, only one guideline covers CT & TEP together.
* The guidelines which involved the highest number of organisations during the public consultation processes are the ones adopted by the EC. This can be explained

by both their highest legal value and the wider scope of their topic on particularly challenging aspects of ATMPs development. Good Manufacturing Practice and Good Clinical Practice specific to ATMPs.

by their highest legal value and the wider scope of their topic on particularly challenging aspects of ATMPs development. Good Manufacturing Practice and Good Clinical Practice specific to ATMPs.

by both their highest legal value and the wider scope of their topic on particularly challenging aspects of ATMPs development. Good Manufacturing Practice and Good Clinical Practice specific to ATMPs.

by both their highest legal value and the wider scope of their topic on particularly challenging aspects of ATMPs development. Good Manufacturing Practice and Good Clinical Practice specific to ATMPs.

* The other guidelines involving a high number of organisations during the public consultation processes relates to wide scientific aspects of the main types of ATMPs: Quality, preclinical and clinical aspects of gene therapy medicinal products for GTMP (29), Human cell-based medicinal products for CT & TEP (20), and Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells for GMC MP (20). Here also, the guideline on GTMP has involved more participation than for other types of products. Guidelines on CT & TEP and on GMO MP have involved some number of organisations, even though only the first one covers two sub-categories of ATMPs explicitly defined at the legislative level (Regulation (EC) n°1394/2007 and Directive 2009/120/EC).

* The other guidelines involving less organisations (9 maximum) relate to various types of ATMPs, or ATMPs generally and they cover very particular scientific (e.g., potency testing) or regulatory (e.g., packaging & labelling) aspects of their development, or specific procedure (e.g., certification).

## Organisations' profile

<figure><img src="image_160.png" /><figcaption>Graph 1: Type of organisations involved in the consultation process of ATMPs guidelines.</figcaption></figure>

Discussion: Companies and business associations account for almost half of all contributions (47%). Community organisations (3%) and individuals (2%), on the contrary, seldom contribute. As for public sector organisations, such as national bodies and academic institutions, they hold the middle ground (24%). These results can be explained by the availability of means (human and financial ones in particular regarding necessary time and knowledge) to contribute to the process of public consultation.

<figure><img src="image_161.png" /><figcaption>Graph 2: Organisations involved in the consultation process of ATMPs guidelines by country.</figcaption></figure>

Discussion: The countries most represented are the most active in the development of ATMPs: UK, Belgium, USA, France, Germany, Italy and the Netherlands. Nevertheless, the important involvement of Belgium (20%) should be put in perspective with the European institutions being mainly established in Brussels, which leads to an important amount of organisations having their headquarters almost here.

The important involvement of the UK (24%) can be explained by the UK being one of the leading countries in the field, although almost all public consultations processes considered (12/13) occurred before Brexit. Thus, such main position of the UK may change in the future. The important involvement of the USA (14%) can be astonishing given that the public consultations relate to European regulation. However, it reveals how much the field is international and how much the European Market is targeted by external countries, especially the USA.

## Most contributing organisations

<table><caption>Table 3a: Organisations by number of contributions</caption><thead><tr><th>Number of contributions</th><th>Organisations</th></tr></thead><tbody><tr><td>Three or more</td><td>9</td></tr><tr><td>Two</td><td>25</td></tr><tr><td>One</td><td>115</td></tr></tbody></table>

Out of the 9 organisations which have contributed to 3 or more guidelines:

* 4/9 are located in Belgium.

* 4/9 are Business Associations.

* 5/9 are from the private sector (Company or Business Association).

* 2/9 are Networks/Innovation Organisations.

<table><caption>Table 2b: Name, type and country of organisations contributing to 3 or more guidelines</caption><thead><tr><th>Organisation</th><th>Type</th><th>Country</th><th>Number of contributions</th></tr></thead><tbody><tr><td>European Federation of Pharmaceutical Industries and Associations (EFPIA)</td><td>Business Association</td><td>Belgium</td><td>6</td></tr><tr><td>European Association for Biopharmaceuticals (EuBioph)</td><td>Business Association</td><td>Belgium</td><td>5</td></tr><tr><td>Alliance for Regenerative Medicine (ARM)</td><td>Networks/Innovation Organisation</td><td>USA</td><td>4</td></tr><tr><td>Cell and Gene Therapy Catarupt</td><td>Networks/Innovation Organisation</td><td>UK</td><td>4</td></tr><tr><td>European Association of Hospital Pharmacists (EAPM)</td><td>Professional Organisation</td><td>Belgium</td><td>4</td></tr><tr><td>European Biopharmaceutical Enterprises (EBE)</td><td>Business Association</td><td>Belgium</td><td>4</td></tr><tr><td>International Society for Cell & Gene Therapy (iSGT)</td><td>Learned Society</td><td>Canada</td><td>4</td></tr><tr><td>German Pharmaceutical Industry Association (BPI eV)</td><td>Business Association</td><td>Germany</td><td>5</td></tr><tr><td>Vasin Consulting Life Sciences (VCLS)</td><td>Company/Business Organisation</td><td>France</td><td>5</td></tr></tbody></table>

## Discussion

* As long as only few organisations have contributed to 2 and to 3 or more consultations, and 78,2% of the organisations contribute only once to a consultation process on ATMPs guidelines, it appears the contribution are based on the topics of the guidelines rather than on an habit to be involved in this process.

* Among organisations contributing most often, the private sector is leader given the means it can dedicate to this activity, and Belgium is the most represented country given the strategic position of being in Brussels to know and influence EU policy and regulation. Surprisingly, the public sector, mainly represented by National bodies and academic/ research institution, does not appear among the organisations contributing the most often to public consultation regarding ATMPs guidelines. It implies a participation based on the topics of the guidelines rather than an habit. Although this can be understood based for academic/ research institution which generally focus on specific area of research even in the delimited field of ATMP, it is more questionable for national bodies, and especially national authorities, such as national medicines agencies, which could have been considered as the main contact point for ATMP developers, despite main EMA competence, given national languages and their potential interface's role between the EMA and ATMPs developers located in National EU Member States.

## General conclusion

* Most guidelines have been adopted after the adoption of Regulation (EC) n°1394/2007 on 15 March 2007 and have contributed to its practical implementation.

* Most guidelines applicable to ATMPs have been established by the EMA. It highlights both the main role of the agency in this field and the technical specificity of ATMPs. Guidelines on Good Manufacturing Practice and on Good Clinical Practice specific to ATMPs have been adopted by the EC in accordance with the provisions of Regulation (EC) n°1394/2007.

* More EMA guidelines but more contributions on EC guidelines due to highest legal value and wider scope of their topic on particularly challenging aspects of ATMPs development.

* A wide scale of involvement in the public consultation processes: from 1 to 53 organisations.

* The more general a guideline is, the more contributions it obtains.

* Involvement in the public consultations processes is linked to the guidelines' topics, and neither to a potential increase due to better awareness of the process on time nor to an habit to contribute even for national regulators.

### GTMP is the category of ATMPs raising the most of interest

* The private sector is leader in answering public consultation on ATMPs guidelines, both regarding the overall amount of contributions and the organisations that contributed the most often.

* The countries most represented are the UK, Belgium, USA, France, Germany, Italy and the Netherlands

* The major involvement of the UK may change in the future following Brexit.

* The important involvement of the USA reveals how much the field is international and how much the European Market is targeted by external countries, especially the USA.

* The important involvement of Belgium should be put in perspective with the European institutions being mainly established in Brussels which leads to an important amount of organisations having their headquarters there and to organisations that may be more used to EU policy and regulation (Belgium is the most represented country among the organisations contributing most often).
# Comparing actors participating in the adoption process of SoHO and ATMP regulations at the European level

**V. BRUNEL, A. MAHALATCHIMY,** Comparing actors participating in the adoption process of SoHO and ATMP regulations at the European level, European Society for Gene & Cell Therapy Congress 2023, Brussels, Belgium, 24-27 October 2023 (POSTER available at https://shs.hal.science/halshs-04290588v1)

## Abstract

Genes, cells, and tissues based medicinal products are regulated as Advanced Therapy Medicinal Products (ATMPs) within the European Union (EU). Nevertheless, the very first steps of development of ATMPs, i.e. donation, procurement and testing of human cells and tissues, are governed by the tissues and cells Directive. The latter is being revised and the European Commission has adopted a proposal for a new regulation covering Substances of Human Origin (SoHO) more widely. Both the regulation on ATMPs and the current proposal for a regulation on SoHO, as EU legislative acts, have involved a public consultation procedure to gather comments from stakeholders and interested parties.
How similar or different are the actors that influence the framing of EU legislation applicable to gene and cell therapy?

Our poster aims at mapping these actors for both ATMPs and SoHO, and their potential changes over time, to identify possible differences and/or convergences as to who exactly has been involved in ATMPs and SoHO regulations.

The identification of answers to the relevant public consultation procedures has led to the establishment of a database with 530 contributions corresponding to both ATMPs and SoHO regulations' documents. The participating organisations have been classified by type (Business, Academia, National bodies, etc.) and country according to the documents they commented on.

Findings concern firstly the main differences between SoHO and ATMPs regarding participating organisations. Secondly, some organisations also revealed themselves as particularly active in both areas of ATMPs and SoHO, which highlights their interest for the entire development cycle of ATMPs and its related legislation.

Contrasting the repartition of stakeholders interested in ATMPs and SoHO may indeed explain some of the differences in the way the regulation is being constructed and its level of detail: the more a type of organisations is involved, the more it has a chance to impact the regulation's framing according to its own specific interests.
# Comparing actors participating in the adoption process of SoHo and ATMP regulations at the European level

## Aurélie Mahalatchimy (1), Valentin Brunel (2)

## INTRODUCTION

* Genes, cells, and tissues based medicinal products are regulated as Advanced Therapy Medicinal Products (ATMPs) within the European Union (EU). Nevertheless, the very first steps of development of ATMPs, i.e. donation, procurement and testing of human cells and tissues, are governed by the tissues and cells Directive. The latter is being revised and the European Commission has adopted a proposal for a new regulation covering Substances of Human Origin (SoHO) more widely. Both the regulation on ATMPs and the current proposal for a regulation on SoHO, as EU legislative acts, have involved a public consultation procedure to gather comments from stakeholders and interested parties. These comments are then taken into account to adapt the legislative frameworks.

* Legislation on SoHO apply to the first stage of developments of all ATMPs, and is also wider as it applies to the use of human origin substance for therapeutic purposes which are not ATMPs.

* Who are these actors influencing the adoption and evolution of EU regulation and legislative acts for Advanced Therapy Medicinal Products and are they different from those influencing the legislation on Substances of Human Origin?

## METHODOLOGY AND CORPUS

* Our research team identified all consultations relative to legislative acts pertaining to both Substances of Human Origin (SoHo) and Advanced Therapy Medicinal Products (ATMPs). This led to the establishment of a list of 5 documents. Once all public consultations were collected, we identified all the actors involved in the consultation process: this led to the establishment of a database with 530 contributions from 352 organisations corresponding to the five public consultations.

* For every legislative act public consultation, we collected its title, date of publication, as well as the type of therapy to which it referred (either Advanced Therapy Medicinal Products (ATMPs) or SoHo).

* For each consultation, all organizations participating in the public consultation process were indexed and sorted in a table. Additional information was collected on the organisations' websites, regarding their typology, country of registration and specific activity.

* The typology of organisations was constructed using all information available in order to sort out organisations to clearly identify the main polarizations between them. For organisations participating in SoHO consultations, we had to change the classification already available on the EU website, since it was declarative and many contributors did not fill in the right category, according to our standards.

## FINDINGS: PROFILE OF PARTICIPATING ORGANISATIONS IN SoHO AND ATMPs

<figure><img src="image_162.png" /><figcaption>Figures 1, 2: Types of participating organisations in SoHO and ATMP consultations</figcaption></figure>

<figure><img src="image_163.png" /><figcaption>Figures 3, 4: Countries of participating organisations in SoHO and ATMP consultations</figcaption></figure>

### Main similarities

* Companies/Business organisations = first most participating organisations in both SoHO (22%) and ATMP (27%) consultations

* National Bodies = second most and equally participating organisations in both SoHO and ATMP consultations (21%)

* Patients & Consumer Organisations have almost equally contributed to SoHO consultations (5%) and ATMP consultations (4%) and they are in sixth position in both cases.

### Main differences

* Academic/Research institutions have very much (third position) participated in ATMP consultations (20%), almost equally to National Bodies, and contrary to SoHO consultations (6%).

* Business Associations have participated more in ATMP consultations (fourth position with 13%) than in SoHO consultations (shared fifth position with 6%).

* Individuals have far more participated in SoHO consultations (fourth position with 9%) than in ATMP consultations (shared last position with 2%).

* Professional Organisations, Academic/Research Institutions, Business Associations, Networks/Innovation Organisations & movements have similarly participated in SoHO consultations (shared fifth position with 6%).

* Networks/Innovation Organisations & movements and Professional Organisations have participated twice as much in SoHO consultations (shared fifth position with 6%) as in ATMP consultations (respectively 3% and 2%).

* Organisations classified as "Other Non-Governmental organisations" and "NA" for "Not Available" information have participated in SoHO consultations (respectively 5% and 3%) and not in ATMP consultations.

* Learned Societies have slightly more contributed to SoHO consultations (11%) than to ATMP consultations (8%), but they appear in third position in the former and in fifth position only in the latter.

### Main similarities

* With the exception of the UK and the USA, the countries that contributed the most to both SoHO and ATMP consultations are the same: Belgium, France, Germany, the Netherlands, Spain, and Italy.

### Main differences

* The UK and USA were part of the countries contributing most to ATMP consultations (respectively 16% and 12%), but not to SoHO consultations (3% in both cases).

* More EU countries have contributed to SoHO consultations.

* Canada has clearly appeared as country participating in ATMPs consultations (2%) and not in SoHO consultations.

* France, Germany, and the Netherlands which were among the countries contributing most to SoHO consultations (with Belgium) participated slightly more to ATMP consultations.

## FINDINGS: ORGANISATIONS PARTICIPATING TO BOTH SoHO AND ATMPs CONSULTATIONS

<table><thead><tr><th>Name of the organisations</th><th>France</th><th>Italy</th></tr></thead><tbody><tr><td>Comité National d'Etude</td><td>National Bodies</td><td>Italy</td></tr><tr><td>Ensemble d'Etudes sur l'Adour</td><td>National Bodies</td><td>France</td></tr><tr><td>EUROPE - Europe Contribution of Pharmaceutical Entrepreneurs</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Association for Medicinal Products</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Association of Hospital Pharmacies</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Association of Hospital Pharmacies (EAPHA)</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Association of Trade Unions</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Eye Bank Association (EBA)</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Federation of Pharmaceutical Associations (EFPA)</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Red Cross Agency</td><td>National Bodies</td><td>UK</td></tr></tbody></table>

<table><thead><tr><th>Name of the organisations</th><th>Belgium</th><th>France</th><th>Italy</th><th>Spain</th><th>UK</th></tr></thead><tbody><tr><td>European Red Cross</td><td>National Bodies</td><td>Belgium</td><td>Italy</td><td>Spain</td><td>UK</td></tr><tr><td>European Eye Bank</td><td>National Bodies</td><td>Belgium</td><td>Italy</td><td>Spain</td><td>UK</td></tr><tr><td>European Federation of Trade Unions</td><td>National Bodies</td><td>Belgium</td><td>Italy</td><td>Spain</td><td>UK</td></tr><tr><td>European Medicines Agency</td><td>National Bodies</td><td>Belgium</td><td>Italy</td><td>Spain</td><td>UK</td></tr></tbody></table>

* Only 18 organisations out of a total of 352 [AM1] identified organisations participated in both a SoHO and an ATMP consultations (51/AM2) [1].

* Among them, regarding their typology:

* National bodies (5/18, 27,8%) and Learned Societies (4/18, 22,2%) have been the most represented.

* Academic/Research Institutions and Business associations holds the middle ground (3/18, 16,7% for each category).

* Companies/Business Organisations, Patient & Consumer Organisations, and Professional Organisations have been the less represented (1/18, 5,6% each).

* Among them, regarding their countries:

* Belgium has been the most represented (6/18, 33,3%), followed by Italy and Netherlands (3/18, 16,7% each), then France and Germany (2/18, 11,1% each), and finally Finland and the UK (1, 5,6% each). However, although the EMA counted for the UK for country's attribution purpose (as it was based there before Brexit), it is a European Union agency.

* No Networks/Innovation organisations & movements, Individuals, Other Non-Governmental organisations participated in both a SoHO and an ATMP consultations.

## Conclusions

### Comparing the types of organisations participating in SoHO & ATMPs consultations respectively

* Companies/Business Organisations and National Bodies are the 2 types of organisations most participating in both SoHO and ATMP consultations.

* National Bodies have highly and equally participated in both SoHO and ATMP consultations (21%).

* ATMP consultations highlight a stronger participation of private organisations (27% of Companies/Business Organisations in first position and 13% of business associations in fourth position) and of Academic/research institutions (20%, third position) in addition to National bodies (21%, second position).

* SoHO consultations highlight a stronger participation of Learned Societies (11%, third position) and Individuals (9%, fourth position) in addition to Companies/Business Organisations (22%, first position) and National bodies (21%, second position).

### Comparing the countries of organisations participating in SoHO & ATMPs consultations respectively

* Apart from the UK and the USA which contributed far more to ATMP consultations, the countries that contributed the most to both SoHO and ATMP consultations are the same. In descending order: Belgium, France, Germany, the Netherlands, Spain, and Italy.

* For the UK, Brexit occurred just before SoHO consultations and the UK was part of the EU during ATMP consultations.

* The important involvement of Belgium to both ATMP and SoHO consultations should be put in perspective with the European institutions being mainly established in Brussels, which leads to an important amount of organisations having their headquarters there.

* Leading European countries in the field of ATMP and use of SoHO for therapeutic purposes.

* The important involvement of the USA (12%) and the visible involvement of Canada (2%) in ATMP consultations can be astonishing given that the public consultations relate to European regulation. However, it reveals how much the ATMP field is international and how much the European Market is targeted by external countries, especially the USA.

* Contrary to the noticeable international dimension of ATMP consultations, the SoHO consultations have involved more EU countries.

### Only few organisations participated to both a SoHO & an ATMP consultations

* Only 5% of the 352 identified organisations participated in both a SoHO and an ATMP consultations.

* The strongest participation of National bodies to both a SoHO and an ATMP consultations can be explained by their functions.

* Contrary to the analysis of organisations that answered to ATMP and SoHO separately (See figures 1 & 2), Business associations have been more active than single Companies/Business Organisations when contributing to both a SoHO and an ATMP consultations.

* The countries represented in the 18 organisations that participated in both a SoHO and an ATMP consultations correspond to the most active European countries in both fields, except for Spain and Finland (See figures 3 & 4).

<footnote n="1">1. Permanent Researcher in law at the French National Centre for Scientific Research (CNRS, CR), Law Faculty, UMR 7318 International, Comparative and European laws (DICE) CERIC, CNRS, Aix Marseille Univ., Toulon Univ., Pau & Pays de l'Adour Univ., Aix-en-Provence, France; Coordinator of I-BioLex project; Deputy coordinator and WP4 leader of EuroGCT project.</footnote>

<footnote n="2">2. CNRS Research Engineer, UMR 7318 DICE CERIC, CNRS, Aix Marseille Univ., Toulon Univ., Pau & Pays de l'Adour Univ., Aix-en-Provence, France. Contact: valentin.BRUNEL@univ-amu.fr</footnote>
# An exploratory analysis on the involvement of European organisations in the field of biomedical innovation

A. SCHEER, V. BRUNEL, S. GUION, I. CHIV, M. MORELL, M. DURAND, O. JOANINA, V. ANDRIEU, A. MAHALATCHIMY, An exploratory analysis on the involvement of European organisations in the field of biomedical innovation, European Society for Gene & Cell Therapy Congress 2023, Brussels, Belgium, 24-27 October 2023 (POSTER available at https://shs.hal.science/halshs-04290569v1)

## Abstract

Many actors influence the framing of EU legislation and regulation applicable to gene and cell therapy. Nevertheless, one can wonder how much their activity is focusing on gene and cell therapy or whether it is part of a wider set of activities taking place in the more general theme of biomedical innovation. From an identification of the actors involved in the public consultation process of adoption of Regulations on Advanced Therapy Medicinal Products, on substances of human origin, and of guidance applicable to ATMPs, a few of them have been selected in order to conduct more specific analysis. Our selection process for this pilot analysis included the following criteria: European level organisation, degree of the involvement in the above-mentioned consultation processes, combination between organisations the names of which imply either a very specific or a general remit. Another choice has been to include European organisations particularly relevant for pharmacists, as professionals involved all along the medicinal products' life cycle. It resulted in a set of 13 European organisations: 5 business associations (Medtech Europe, European Federation of Pharmaceutical Industries and Associations, European Biopharmaceutical Enterprises, European Associations for Bioindustries, European Confederation of Pharmaceutical Entrepreneurs), 2 professional organisations (European Industrial Pharmacists Group, European Association of Hospital Pharmacists), 4 learned societies (European Society of Gene and Cell Therapy, European Society for Blood and Bone Marrow Transplantation, European Eye Bank Association, European Association of Tissue Banks, European Association of Hospital Pharmacists), 1 research institution taking the form of European project (European Network for the Advancement of Clinical Gene Transfer & Therapy), 1 European network based on national medicines agencies (EU innovation network). Then, in depth research has been conducted on the website of each organisation in order to identify their activity within and beyond gene and cell therapy regarding biomedical innovation in general. On the one hand, this poster highlights the main results concerning their organization: especially structure, governance, potential change of name or merger over time, as well as specific or general working committees. On the second hand, their fields of activity are described following an analysis based on a set of keywords. Whereas some keywords are heavily used by all organisations (gene therapy, cell therapy for example), others are more specific (orphan medicine) and others very rare (organoid).
# AN EXPLORATORY ANALYSIS ON THE INVOLVEMENT OF EUROPEAN ORGANISATIONS IN THE FIELD OF BIOMEDICAL INNOVATION

A. Scheer¹, V. Bruneq, S. Guion¹, L. Chiv¹, M. Morell¹, M. Durdan¹, O. Jacina², V. Andriez², A. Mahaalchimist²

¹Pharmacy Resident, Manette Public University (AP-IM) and Faculty of Pharmacy, Aix-Marseille, France. ²Research Engineer, CNRS, UMR 7318 International, Comparative and European laws (DICE), CERIC, CNRS, Aix Marseille University, Toulouse University, Fau & Pape de l'Adour University, Aix-en-Provence, France. ³Students in 4th year of Pharmaceutical Sciences, industry and research track, Aix-Marseille University, France. ⁴Senior lecturer in Industrial Pharmacy and Pharmaceutical Regulation, Faculty of Pharmacy, Aix-Marseille University, Research Unit Microbes Evolution Physiology and Infection (MEPI) Aix-Marseille University, IRO, France. ⁵Permanent Researcher in law at the French National Centre for Scientific Research: Research (CNRS, CR), Law Faculty, UMR 7318 DICE CERIC, CNRS, Aix Marseille University, Toulouse University, Aix-en-Provence, France.

Acknowledgements: This work has been supported by the European Union's Horizon 2020 research and innovation programme under grant agreement No 965241 and by ANR-funded iBioLex project (ANR-20-CE26-0007-01).

## INTRODUCTION AND METHODOLOGY

Many actors influence the framing of EU legislation and regulation applicable to gene and cell therapy. Nevertheless, one can wonder how much their activity is focusing on gene and cell therapy or whether it is part of a wider set of activities taking place in the more general theme of biomedical innovation. Biomedical innovation has been considered widely as a set of processes and products based on biological elements of human or animal origin intended to generate both improvement in health and economic competitiveness.

From an identification of the actors involved in the public consultation process of adoption of European Regulation n°1394/2007 on Advanced Therapy Medicinal Products, of guidance applicable to ATMPs and adopted either by the European Medicines Agency or by the European Commission, and on the Proposal for a European Regulation on substances of human origin, and of guidance applicable to ATMPs, a few of them have been selected in order to conduct more specific analysis. Our selection process for this pilot analysis included the following criteria: European level organisation, degree of the involvement in the above-mentioned consultation processes, combination between organisations the names of which imply either a very specific or a general merit. Another choice has been to include European organisations particularly relevant for pharmacists, as professionals involved all along the medicinal products' life cycle.

It resulted in a set of 33 European organisations including 3 business associations, 2 professional organisations, 4 learned societies, 1 research institution taking the form of European project, 1 European network based on national medicines agencies.

Then, in depth research has been conducted by pharmaceutical sciences students between January and April 2023 on the website of each organisation in order to identify their activity within and beyond gene and cell therapy regarding biomedical innovation in general. First, we analysed their structure, governance, typology and possible name changes or mergers over time. Second, we collected the occurrences of general and specific keywords relating to biomedical innovations both through an exploration of the tabi dedicated to their production and by using the "search" function when it exists on the websites of the studied organisations.

Beyond "biomedical innovation" itself, the general keywords used were: therapeutic innovation, innovative medicine, regenerative medicine, biotechnologies, advanced therapies, orphan medicine, advanced therapy medicinal products, gene therapy, cell therapy, tissue engineering, genome editing.

This analysis is considered to be exploratory as a limited number of organisations has been studied from the interests of the pharmaceutical sciences students involved and the feasibility required a limited number of keywords to be searched for. For terms that are similar to our keywords may have been mentioned on the websites of the organisations studied although we have not searched for them. For instance, "genome editing" and "cell therapy" were searched for but not "gene editing" and "cellular therapy". Nevertheless, some of these similar keywords have been identified when they appeared in the names of working groups of the organisations studied.

### Type and date of creation of every organisation

<table><thead><tr><th>ORGANISATION</th><th>TYPE</th><th>CREATION DATE</th></tr></thead><tbody><tr><td>European Federation of Pharmaceutical Industries and Associations (EPFIA)</td><td>Business association</td><td>1978</td></tr><tr><td>The European Association for Bioindustries (EuBio)</td><td>Business association</td><td>1996</td></tr><tr><td>European Biopharmaceutical Enterprises (EBE)</td><td>Business association</td><td>2000</td></tr><tr><td>European Confederation of Pharmaceutical Entrepreneurs (EUCOPE)</td><td>Business association</td><td>2008</td></tr><tr><td>MedTech Europe</td><td>Business association</td><td>2012</td></tr><tr><td>European association of tissue and cell banks (EATCB)</td><td>learned Society</td><td>1499</td></tr><tr><td>European group for Blood and Bone Marrow Transplantation (EBMT)</td><td>learned Society</td><td>1974</td></tr><tr><td>European Eye Bank Association (EEBA)</td><td>learned Society</td><td>1889</td></tr><tr><td>European Society of Gene and Cell Therapy (ESGCT)</td><td>learned Society</td><td>1992</td></tr><tr><td>European Industrial Pharmacists Group (EIPG)</td><td>Professional organisation</td><td>1966</td></tr><tr><td>European association of hospital pharmacist (EAHP)</td><td>Professional organisation</td><td>1969</td></tr><tr><td>European Network for the Advancement of Clinical Gene Transfer &amp; Therapy (CLINIGENE)</td><td>Research Project</td><td>2006-2011</td></tr><tr><td>European Innovation Network (EIN)</td><td>European network</td><td>2015</td></tr></tbody></table>

## RESULTS

### Main elements of structure

#### Mergers among 2 business associations studied

MedTech Europe is a 2021 merger of EDMA and Eucomede. EPFIA & European Biopharmaceutical Entreprises (EBE) collaborated for a long time (common members, papers...) until EBE has become a specialized group of EPFA.

#### Changes of names of 2 learned societies

Working Group on Human Gene Transfer and Therapy (EWGT) > 1998; European Society of Gene Therapy (ESGT) > 2007; European Society of Gene and Cell Therapy (ESCT).

European association of tissue banks (EATB) > 2016; European association of tissue and cell banks (EATCB).

### Reading grid

Not often/rarely (<25%)

Slightly often (≥25%)

Fairly often (50%)

Very often (≥75%)

Always (100%)

### Groups targeting biomedical innovations in the organisations studied in 2023

#### EUCOPE

Orphan Medical Product Working Group; Cell and Gene Therapies Working Group; Genomics Working Group

#### EERA

Advanced Therapy Medicinal Products SIG (extraordinary)

#### ESGCT

Accessibility of gene therapy Committee; Gene editing Committee; Oncolytic & cancer gene therapy Committee; ...

#### EBMT

Cellular Therapy & Immunobiology Working Party; ...

#### EAHP

SIG Hospital Pharmacist's Preparedness for in-vivo gene therapy medicinal products

Each of the organisation studied has its own structure, and is composed of groups whose titles refer to therapeutic areas and/or regulatory issues.

### Occurrences of general terms within the production of the organisations

<table><thead><tr><th></th><th>Biomaterial innovation</th><th>Therapeutic innovation</th><th>Innovative medicine</th><th>Regenerative medicine</th><th>Biotechnology</th><th>Advanced therapies</th><th>Nonmedicine</th><th>Organoid</th></tr></thead><tbody><tr><td>European Federation of Pharmaceutical Industries and Associations (EPFIA)</td><td>7%</td><td>4%</td><td>7%</td><td>7%</td><td>14%</td><td>14%</td><td>0%</td><td>0%</td></tr><tr><td>European Associations for Bioindustries (EuBio)</td><td>5%</td><td>5%</td><td>14%</td><td>32%</td><td>23%</td><td>45%</td><td>0%</td><td>0%</td></tr><tr><td>European Confederation of Pharmaceutical Entrepreneurs (EUCOPE)</td><td>0%</td><td>0%</td><td>23%</td><td>14%</td><td>0%</td><td>23%</td><td>3%</td><td>0%</td></tr><tr><td>Med Tech Europe</td><td>0%</td><td>0%</td><td>50%</td><td>50%</td><td>50%</td><td>50%</td><td>0%</td><td>0%</td></tr><tr><td>European association of tissue and cell banks (EATCB)</td><td>50%</td><td>75%</td><td>50%</td><td>75%</td><td>100%</td><td>75%</td><td>0%</td><td>50%</td></tr><tr><td>European Society for Blood and Bone Marrow Transplantation (EBMT)</td><td>0%</td><td>6%</td><td>3%</td><td>9%</td><td>9%</td><td>20%</td><td>0%</td><td>0%</td></tr><tr><td>European Eye Bank Association (EEBA)</td><td>50%</td><td>50%</td><td>0%</td><td>50%</td><td>50%</td><td>50%</td><td>0%</td><td>0%</td></tr><tr><td>European Society of Gene and Cell Therapy (ESGCT)</td><td>0%</td><td>0%</td><td>9%</td><td>9%</td><td>0%</td><td>18%</td><td>0%</td><td>0%</td></tr><tr><td>European Industrial Pharmacists Group (EIPG)</td><td>0%</td><td>0%</td><td>50%</td><td>50%</td><td>50%</td><td>50%</td><td>0%</td><td>0%</td></tr><tr><td>European association of hospital pharmacists (EAHP)</td><td>50%</td><td>83%</td><td>50%</td><td>50%</td><td>50%</td><td>50%</td><td>0%</td><td>0%</td></tr></tbody></table>

### MAIN RESULTS

* "Advanced therapies" is the most used term. It is the only one that has been used by every organisations in our study, whatever their typology. However, its use has been quantitatively various ranging from not often/rarely (<25%) to very often (≥ 75%) without obvious result linking the quantity of use of this term to the type of organisation using it.

* "Regenerative medicine" and "innovative medicine" have been very used by the studied organisations (9 out of 13) in both cases). Nevertheless, the use of "innovative medicine" appears much more contrasted (being either not often/rarely or very often) than the use of "regenerative medicine" that appears all along our pradition scale of use.

* "Biotechnology" has also been very used (8 out of 10 organisations), its use has been less clearly contrasted than for "innovative medicine" but also slightly less contrasted than for "regenerative medicine".

* "Therapeutic innovation" and "biomedical innovation" have been used respectively by 6/10 and 5/10 organisations. Their use has been quite equally contrasted (Not often or rarely used by half of the organisations and fairly often or more for the other half). However, contrary to "biomedical innovation", "therapeutic innovation" has been used very often by 2/3 of the organisations that used this term.

* "Nanomedicine" and "organoid" have been the less used terms. They are the only terms that have been mentioned only by one organisation (respectively <5% EUCOPE as a business association, and 53% EATCB as a learned society) among the 10 studied.

* The results underline that nanomedicine and organoids are still relatively untapped by the studied organisations, notably business associations.

* The only occurrence of the term "organoid" comes from the EATCB, with a high frequency (50%), which indicates a significant interest on the part of this learned society in this emerging topic.

### Occurrences of specific terms related to gene and cell within the production of the organisations

<table><thead><tr><th></th><th>Biological medicine</th><th>Orphan medicine</th><th>Advanced therapy</th><th>Gene therapy</th><th>Cell therapy</th><th>Tissue engineering</th><th>Genome editing</th></tr></thead><tbody><tr><td>European Federation of Pharmaceutical Industries and Associations (EPFIA)</td><td>11%</td><td>25%</td><td>4%</td><td>14%</td><td>11%</td><td>0%</td><td>0%</td></tr><tr><td>European Associations for Bioindustries (EuBio)</td><td>0%</td><td>9%</td><td>45%</td><td>45%</td><td>32%</td><td>5%</td><td>50%</td></tr><tr><td>European Confederation of Pharmaceutical Entrepreneurs (EUCOPE)</td><td>0%</td><td>0%</td><td>100%</td><td>0%</td><td>0%</td><td>0%</td><td>0%</td></tr><tr><td>MedTech Europe</td><td>0%</td><td>0%</td><td>50%</td><td>75%</td><td>30%</td><td>10%</td><td>50%</td></tr><tr><td>European association of tissue and cell banks (EATCB)</td><td>100%</td><td>25%</td><td>100%</td><td>50%</td><td>100%</td><td>100%</td><td>25%</td></tr><tr><td>European Society for Blood and Bone Marrow Transplantation (EBMT)</td><td>6%</td><td>0%</td><td>14%</td><td>23%</td><td>19%</td><td>9%</td><td>9%</td></tr><tr><td>European Eye Bank Association (EEBA)</td><td>50%</td><td>0%</td><td>50%</td><td>0%</td><td>100%</td><td>100%</td><td>0%</td></tr><tr><td>European Society of Gene and Cell Therapy (ESGCT)</td><td>1%</td><td>0%</td><td>9%</td><td>82%</td><td>45%</td><td>9%</td><td>27%</td></tr><tr><td>European Industrial Pharmacists Group (EIPG)</td><td>0%</td><td>0%</td><td>100%</td><td>0%</td><td>0%</td><td>0%</td><td>0%</td></tr><tr><td>European association of hospital pharmacists (EAHP)</td><td>17%</td><td>33%</td><td>50%</td><td>0%</td><td>0%</td><td>0%</td><td>0%</td></tr></tbody></table>

### MAIN RESULTS

* **Advanced Therapy Medicinal Product:** This specific term is the most frequently found in our analysis, regardless of the type of organisation studied. It has been found on every organisation's websites. It should be noted that the term does not appear frequently on the ESGCT website although we have not searched for the acronym (ATMP), which may be more frequently used.

* **Cell Therapy** is the second most frequently used term among the keywords we researched. There is a strong representation of learned societies. All of them have used it frequently.

* **Tissue engineering, Gene therapy and Biological medicine** have been found in the same number of websites (6/7/10) among the studied organisations. They have been particularly used by learned societies.

* **Genome editing** has been used by half of the organisations we studied. This specific term is over-represented by the 2 business associations that have mentioned it.

* **Orphan Medicine** is the most underused specific term among the selected keywords. It has been mentioned by 4/10 organisations only and quite rarely regardless of the type of organisation studied.

## CONCLUSION

* Half of the organisations we studied have one (or more) specific working Group/Committee/Council (hereafter groups) targeting biomedical innovations regarding our keywords and related terms. When these groups exist, they are more frequently found in learned societies (4/5). Among these groups, all have titles closer to our specific keywords than to our general ones.

* Using groups targeting biomedical innovations enabled us to minimise any bias and limits we might have introduced through our choice of keywords: for EUCOPE, no occurrence of "orphan medicine" have been found in our study, but there is a group which targets this type of medicines. Its involvement in this therapeutic area is therefore confirmed.

* The appearance of the term "genome editing" mainly for business associations suggests that this is a subject of interest for the industrial field.

* Although we have considered the EIPG to be a professional organisation representing industrial pharmacists, our study shows many points of convergence with MedTech Europe. This can be explained by the industrial aspect of this organisation.

* Among the learned societies, the 2 associations of banks (EATCB & EEBA) have been the most active. EATCB appears clearly has the organisation using the most our selected keywords among all the organisations studied. EBMT & ESGCT have used quite similarly our keywords with only one significant difference: the emphasis is on gene therapy for ESGCT while it is on cell therapy for EBMT. In our study, the term "gene therapy" occurred 1.8 times more frequently than "cell therapy" for the ESGCT.

* EBMT, ESGCT and EAHP distinguish themselves from the other organisations studied by their number of groups.

* The EBMT and the ESGCT appear to be the two learned societies with the closest links in their areas of interest.

Despite changing its name to include cell therapy, the ESGCT remains more active in the field of gene therapy, which is confirmed by the titles of its working groups.
# Innovative therapy in European Parliament's positions: a numerical science-based vocabulary analysis

T. ALLOUCHE, V. BRUNEL, F. BECHET, M. GLINEL, A. MAHALATCHIMY, Innovative therapy in European Parliament's positions: a numerical science-based vocabulary analysis, European Society for Gene & Cell Therapy Congress 2023, Brussels, Belgium, 24-27 October 2023 (POSTER available at https://shs.hal.science/halshs-04290599v1)

## Abstract

The European Parliament has regularly been involved in the framing of innovative therapy, including gene and cell therapy.

Through the evolution of European Union (EU) law, the European Parliament has been more and more involved in the adoption of EU binding law. Indeed, the co-decision procedure (i.e. the joint adoption of legislative acts both by the European Parliament and the Council of the European Union) has become the ordinary legislative procedure from the adoption of the Lisbon Treaty in 2007. But the Parliament has also been involved in other types of procedures such as the consultation or cooperation procedures. Such participation takes the form of documents that are called European Parliament' positions. The latter constitute an interesting corpus to be studied where ones want to know more about the fields of activities of the European Parliament as the European institution representing EU citizens.

Focusing on innovative therapy in a wide meaning, this poster aims at conducting an exhaustive study of the mention of terms related to this topic in European Parliament's positions.

From the official website of EU law (EUR-Lex), we constructed a database comprising all positions of the European Parliament, with available metadata. The database was then searched in order to find every occurrence of a selected vocabulary on innovative therapy, including general terms such as “biomedical innovation” or more specific terms such as “gene therapy”, “cell therapy” or “advanced therapy medicinal products”. We thus were able to see what terms were used and when they were first mentioned, and in what kind of texts they were most present. In our corpus of texts including our selected terms, another point of interest was the way this vocabulary was interconnected, allowing us to group words according to their co-occurrence in documents. From a legislative mapping perspective, we were also able to see which legal basis were more often used, as well as which documents were citing each other. This work is presented under the form of a network graph comprising all documents and their interrelations.

We finally developed thanks to Natural Language Processing methods a model of all documents containing our selected terms in order to find by means of textual similarity metrics other relevant documents for which these terms could have eluded. This complementary corpus could later be used for further research on innovative therapy in European Parliament's positions, beyond our initially selected vocabulary.
# Innovative therapy in European Parliament's positions: a numerical science-based vocabulary analysis

T. Allouche (1), V. Brunel (2), F. Béchet (3), M. Glinel (4), A. Mahalatchimy (5)

1. Masters student in Computer Science, Aix Marseille University

2. Research Engineer, CNRS, UMR 7318 International Comparative and European laws (DICE) CERIC, CNRS, Aix Marseille Univ., Toulon Univ., Pau & Pays de l'Adour Univ., Aix-en-Provence, France

3. Computer Science Professor, Director of LIS, UMR 7020 - CNRS / AMU / UT/LN

4. Post-doctoral fellow in the I-Biolex project, UMR 7318 DICE CERIC, CNRS, Aix Marseille Univ., Toulon Univ., Pau & Pays de l'Adour Univ., Aix-en-Provence, France.

5. EuroGCT Deputy coordinator and WP4 leader Permanent. Researcher in law at the French National Centre for Scientific Research (CNRS, charge de recherche), Law Faculty, UMR 7318 DICE CERIC, CNRS, Aix Marseille Univ., Toulon Univ., Pau & Pays de l'Adour Univ., Aix-en-Provence, France. Contact: valentin.BRUNEL@univ-smu.fr / This work has been supported by ANR-funded I-Biolex project (ANR-20-CE26-0007-01) by the European Union's Horizon 2020 EuroGCT project (GA-NO 945364); and the Institut Lavalais (Aix Marseille Université)

## INTRODUCTION
Through the evolution of European Union (EU) law, the European Parliament has been more and more involved in the adoption of EU binding law. Indeed, the co-decision procedure (i.e. the joint adoption of legislative acts both by the European Parliament and the Council of the European Union) has become the ordinary legislative procedure from the adoption of the Lisbon Treaty in 2007. But the Parliament has also been involved in other types of procedures such as the consultation or cooperation procedures. Such participation takes the form of documents that are called European Parliament's positions. The latter constitute an interesting area to know more about the fields of activities of the European Parliament, as the European institution representing EU citizens. Focusing on innovative therapy in a wide meaning, this poster aims at conducting an exhaustive study of the mention of terms related to this topic in European Parliament's positions.

## METHODOLOGY AND CORPUS
From the official website of EU law (EUR-Lex), we constructed a database comprising all positions of the European Parliament, with available metadata. This metadata mainly includes the date and type of documents, as well as the related legal basis and all instruments cited. The database was then searched in order to find every occurrence of a selected vocabulary on innovative therapy, including general terms such as "biomedical innovation" or more specific terms such as "gene therapy", "cell therapy" or "advanced therapy medicinal products". We thus were able to see what terms were used and when they were first mentioned, and in what kind of texts they were most present. In our corpus of texts including our selected terms, another point of interest was the way this vocabulary was interconnected, allowing us to group words according to their co-occurrence in documents. From a legislative mapping perspective, we were also able to see which legal basis were more often used, as well as which documents were citing each other. This work is presented under the form of a network graph comprising all documents and their interrelations.

## Findings 1.1: Frequency over time and by category of keywords

<figure><img src="image_164.png" /></figure>

Using the database from Eur-Lex, our first task was to look for occurrences of our selected vocabulary. The first graph shows through time the frequency of each occurrence.

<caption>Graph 1: Frequency of keyword occurrences in our corpus by date</caption>

* All our keywords relating to organoids have never appeared among the EP resolutions: Organoid, Organ on a chip, Body on a chip, Cerebroid, Cerebral organoid, Brain organoid, neural organoid, Gastruloid, Blastoid, Iblastoid, Tumouroid.

* 4 keywords have never appeared: Biomedical innovation, Tissue engineering, Advanced medicine, Biological medicine.

* 4 keywords have appeared the most: Biotechnology, Cloning, Orphan medicinal product, Stem cell

* Biotechnology has appeared the most and in 20 different documents, by descending order, especially:

* Around 1998: Research funding (4th framework programme), directive on legal protection of biotechnological inventions, directive on genetically modified organisms (GMOs)

* Around 2006: Research funding (7th framework programme)

* Around 2014: Research funding (Horizon 2020) and Regulation related to the Nagoya Protocol on Access to Genetic Resources

* Around 2020: research funding (InvestEU & Horizon Europe)

* In 2011: directive on GMOs

* Cloning has also appeared a lot and in 15 different documents, by descending order, especially:

* In 2015 on a finally withdrawn proposal of a directive on the cloning of animals

* Around 1998: research funding (fifth framework programme) and directive on the legal protection of biotechnological

* Between 2007 & 2010: novel foods and on organic production

* In 2006: research funding (7th framework programme)

* In 2013: research funding (Horizon 2020)

* Stem cell has also appeared a lot and in 11 different documents, by descending order, especially:

* In 2013: research funding (Horizon 2020)

* Around 2020: research funding (Horizon Europe, InvestEU)

* In 2019: research funding (Horizon Europe, InvestEU)

* In 2006: research funding (7th framework programme)

* Orphan medicinal product has also appeared a lot and in 7 different documents, by descending order of occurrence, especially:

* In 1999: Regulation on Orphan medicinal products (most occurrence)

* In 2019: Regulation on Health Technology Assessment (HTA)

* In 1998, 2009 on actions on rare diseases and in 2014 on a proposal related to the use of the regulatory procedure with scrutiny

* Advanced therapy medicinal product (ATMP) has not appeared many times, but in 9 different documents, especially:

* In 2007: Regulation on ATMP

* In 2010: Regulation on pharmacovigilance

* In 2014: Regulation on medical devices and proposal related to the use of the regulatory procedure with scrutiny

* In 2019 & 2020: research funding (Horizon Europe, InvestEU, EU4Health) and a regulation related to the use of the regulatory procedure with scrutiny

* Several keywords that do not appear a lot for a long time have clearly appeared around 2020: therapeutic innovation, genome editing, nanomedicine:

* Genome editing and nanomedicine in same 2019 text > research funding (7th framework programme)

* Therapeutic innovation in Regulation on HTA

## Findings 1.2: Clustering of keywords

We then set out to create a series of groups or clusters, based on terms which were more often present in the same documents. Below is the list of every cluster:

### Cluster A: Biotechnology / Stem cell/Cloning

Common keywords for these 3 keywords: 7th framework programme, Horizon 2020, InvestEU & Horizon Europe, and directive on legal protection of biotechnological inventions (For Biotechnology and cloning only)

⇒ The most common texts relate to research funding.

### Cluster B: Advanced therapy medicinal product / Advanced therapy / Gene therapy / Innovative medicine

There is not 1 common text for these 4 keywords. But: 1 for Advanced therapy, Innovative medicine: Horizon 2020 (2013) and 1 for Advanced therapy, Gene therapy, Advanced therapy medicinal product: Horizon Europe (2019)

⇒ They all relate to research funding.

### Cluster C: Nanomedicine / Genome editing / Regenerative Medicine / Cell therapy

Not 1 common text: for these 4 keywords. But: 1 for Nanomedicine, RM, Cell Therapy: Horizon 2020 (2013) and 1 for Nanomedicine, Genome editing: Horizon Europe (2019)

⇒ They all relate to research funding.

### Cluster D: Orphan medicinal product / Orphan medicine / Therapeutic innovation
2 texts related to Regulation on Health Technology Assessment (2019 & 2018) are common to these 3 keywords, and 1 text related to Action on rare diseases (2009) is common to European medicinal product, Orphan medicine

⇒ The most common texts relate to Regulation on Health Technology Assessment.

## Findings 2: Networks between documents

<figure><img src="image_165.png" /></figure>

In accordance with our objectives, we looked at all instruments cited in every document of our corpus containing at least one of our keywords.

The graph on the left is the result of a network analysis conducted on these instruments. Its principle is straightforward: when a document comprised another as an instrument cited in the Eur-Lex metadata, a link was declared between both. The documents having more relations are thus those either that cited the most documents, or were cited by most, or both.

<caption>Graph 2: Network of instruments cited</caption>

### Main results

* Among the 7 resolutions the most cited, 3 lead to a directive and 4 to a regulation.

* Only one of the most cited texts relates to a final text that has not been adopted yet (52022AP0317 on promotion of use from renewable sources).

* The topics covered by descending order are the following: Animal Health (transmissible animal diseases) > European Maritime, Fisheries and Aquaculture Fund > medical devices > promotion of energy from renewable sources > quality of water intended for human consumption > Internal Security Fund > industrial emissions (integrated pollution prevention and control)

* Regarding the dates of the most cited texts: 3 are from 2019, 2 from 2014, 1 from 2022, and 1 from 2009

### Main conclusions

* The legal nature of the act to which the resolutions relate does not seem to have an impact on its importance regarding its citation quantity.

* The citation quantity is not linked to the outcome of the legal procedure.

* The topics appear various.

* Nevertheless, they are mainly crossing health and environmental fields

* Among the 7 different topics, 2 relate to a fund (Fisheries and Internal security)

* Only one text directly relates to pharmaceutical and it covers medical devices and not medicinal products

* The dates of texts range from 2009 to 2022, and mainly from 2014 to 2019.

The analysis of the most cited legal basis has no interest for our studies as it highlights the legal rules for the involvement of the European Parliament in the adoption of legal acts. Indeed, the most cited legal basis are the ones that empowered and framed the involvement of the European Parliament in the legal procedures: mainly Articles of the Treaty relating to the ordinary legislative procedure (current and previous versions), European Parliament's rules of procedures, and adaptation of legal acts for the use of the regulatory procedure with scrutiny. Thus, it relates to the legal technique only and not to the topic of our study.

## Findings 3: Exploratory analysis

Once all documents containing our selected vocabulary were identified, we wished to conduct an automated research of associated documents. The method consists in producing a vector representation of each document in the collection in order to be able to compute a similarity metric. To produce these vector representations, we can define a common vocabulary for all documents and compute a weight for each term in a given document to obtain its vector. Regardless of the method used to produce these vectors, finding new relevant documents consists in looking for the nearest neighbours of target documents in the document vector space. We performed a preliminary experiment using this methodology using the TF/IDF weighting method. Unfortunately, this analysis did not yield interesting results so far, as documents with similar vectors did not seem to match our theme of innovation in biotechnologies. Future research may comprise the use of more advanced weighting methods based on embedding as well as considering document graphs. However, the very strong homogeneity of Parliament resolutions' texts makes this sort of tool difficult to operate.

### Conclusion

#### On the occurrences of keywords

* As Biomedical innovation, Tissue engineering, Advanced Medicine and Biological Medicine have not been found and are not legal terms, it may be thought that the EP is using preferentially the legal term. Nevertheless, although Orphan medicinal product has been more used than orphan medicine, the latter has been found, even if it is not the legal term.

* Biotechnology has appeared the most both in general texts on research funding and in more specific texts (legal protection of biotechnological inventions, Nagoya Protocol on Access to Genetic Resources, GMOs).

* Cloning has appeared a lot both in general texts on research funding and in more specific texts (proposal of a directive on the cloning of animals, legal protection of biotechnological inventions, novel foods and on organic production)

* Stem cell has also appeared a lot but only in general texts on research funding.

* Orphan medicinal product has also appeared a lot mainly in texts related directly to these products or to rare diseases, but also to Health Technology Assessment.

* ATMP has not appeared many times but in more different documents than Orphan medicinal product (9 vs.7). They relate to ATMP specifically but also to a specific stage of their development phase (pharmacovigilance) and to medical device as a potentially closed legal category and relevant regulation (e.g. Combined ATMP). They also relate to more general topics such as research funding and the use of the regulatory procedure with scrutiny.

#### On the networks between documents

* The appearance of our keywords in the most cited texts is not linked to the importance of the final legal act (legal nature) or to the outcome of the legal procedure (adoption or not of the final legal act). Thus, the quantity of citation of a text containing our keywords is more linked to its topic than to its technico-legal context.

* The topics of the most cited texts are transversal to health and environmental issues.

* Contrary to expectations, our keywords had very little to do with pharmaceuticals, as only one text (on medical devices and not on medicines) in this field stood out.

* There may be an unforeseen parameter on the Eur-Lex website that promotes the most recent texts. This may have biased our results.

While the European Parliament has been known to tackle ethical questions, it has not yet identified organoids as a field to be considered.

In contrast, Biotechnology (e.g., directives on legal protection of biotechnological inventions and on GMOs), Orphan medicinal product (e.g., Regulation on HTA) and Cloning (e.g., withdrawn proposal of a directive on the cloning of animals) have been highly found, and the most found among European Parliament's opinions proposing amendments due to ethical, legal, and societal issues at stake.

Both the analysis by occurrence of keywords and the analysis by clusters of keywords found together show that Biomedical Innovation related keywords appear more in texts related to research funding. Nevertheless, cluster 4 is distinct and specific as none of its keywords (Orphan medicinal product, Orphan medicine, Therapeutic innovation) appear in texts related to research funding.

Both Orphan medicinal product and Advanced Therapy Medicinal Product appear in more various texts (beyond general research funding for the latter) but also texts that have more specific topics as linked to these particularly regulated types of medicinal products.
# Mapping regulators' early interactions procedures to support innovation

A. DELAGE, L.-S. GILBERT, A. MAHALATCHIMY, Mapping regulators' early interactions procedures to support innovation, European Society for Gene & Cell Therapy Congress 2023, Brussels, Belgium, 24-27 October 2023 (POSTER available at https://hal.univ-lyon2.fr/CERIC/halshs-04290584v1)

## Abstract

In an effort to help stakeholders to overcome the legal and scientific challenges raised during the development of a medicinal product, procedures, such as scientific advice, have been established in the European Union to enable early contact with regulators, especially in the field of gene and cell therapy. These procedures help to support innovation. They are various: some are available for all medicines and others target innovative medicines or Advanced Therapy Medicinal Products (ATMPs); some are legislative or regulatory schemes, others put into place services; some benefit to all types of medicines' developer, others target a specific type of developer. These procedures for early interactions between stakeholders and regulators are available to facilitate communication between institutions and medicine developers all along the medicine's life-cycle, but the main focus is on the pre-marketing authorisation phase. The exchanges occurring between regulators and the seeker of interaction can impact the chances an ATMP has to enter on the market. Thus, the aim is to foster their development by helping developers to navigate the regulatory pathways adequately for ATMPs to meet quality, safety, and efficacy requirements according to robust evidence to obtain marketing authorisation and access to patients. Knowing all the procedures, who can ask for them, which procedure to use, and with which regulator can be a challenge. Moreover, the extent of the possible support is often overlooked. This poster describes and discusses the multiple existing options available to ATMPs' developers to overcome challenges during the pre-marketing authorisation phase through early interactions with regulators, here focusing on the European Medicines Agency and National agencies. Communicating on the early procedures available at national and European levels will help to identify potential gaps and raise developers' awareness of the different procedures available to support the marketing authorisation of ATMPs.
<figure><img src="image_166.png" /></figure>

Faculté de Droit et
de Science Politique
Aix Marseille Université

<figure><img src="image_167.png" /></figure>

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<figure><img src="image_169.png" /></figure>

<figure><img src="image_170.png" /></figure>

<figure><img src="image_171.png" /></figure>

I-BIOLEX

anr®

# Mapping regulators' early interactions procedures to support innovation

Auxane Delage¹, Luc-Sylvain Gilbert², Dr. Hsin-Yu Kuo³, Dr. Anna Couturier⁴, Dr. Aurélie Mahalatchimy⁵

¹EuroGCT Information Officer on Ethical, Legal & Societal issues (ELS), Research Engineer and PhD student in law, Law Faculty, UMR 7318 International, Comparative and European laws, DICE CERIC, CNRS, Aix Marseille Univ, Toulouse Univ., Aix-en-Provence, France, ²EuroGCT Information Officer on ELS, Research Engineer in law, UMR 7318 DICE CERIC, CNRS, Aix Marseille Univ, Toulouse Univ., Aix-en-Provence, France, ³EuroGCT Information Officer on ATMP Product Development Pathway, Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, UK, ⁴EuroGCT Project Manager, Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, UK, ⁵EuroGCT Deputy coordinator and WP4 leader, Permanent Researcher in law at the French National Centre for Scientific Research (CNRS CR), Low Faculty, UMR 7318 DICE CERIC, CNRS, Aix Marseille Univ, Toulouse Univ., Aix-en-Provence, France. Acknowledgements This work has been supported by European Union's Horizon 2020 EuroGCT project (GA, No 985241) and by ANR-funded I-biolex project (ANR-20-CE26-0037-BF).

## Introduction & Aim

Early interactions procedures with regulators are implemented to support innovative medicines development, and the specific challenges they face.

The support comes in the form of services and regulatory procedures allowing medicines' developers to interact with regulators through existing mechanisms during the development of a medicinal product.

The procedures are generally dependent on the type of product developed, and on the status of the stakeholder trying to contact the regulator early. This entails a case-by-case approach to support innovation. The regulators have designed relevant tools to support different types of actors with specific challenges (SMEs, academia, industry). In addition to dedicated services and procedures, guidance developed by regulators as well as regulators' participation in various meetings also aim to support medicines' development, even though these aspects will not be considered here.

Despite limited human resources (EU and national level), Regulators have established new ways to facilitate dialogue between the institutions and the stakeholders where gaps and needs have been identified. The poster showcases the principal mechanisms in place in the European Union (EU) and in the Member States of the EEA regarding both innovative medicines and Advanced Therapy Medicinal Products (ATMPs) specifically. Communicating on the existing support at both levels bridges the knowledge gap on the existing opportunities for early interactions with regulators.

## EMA's services and procedures to support innovation medicines' development

<table><thead><tr><th>Academia/Non-profit</th><th>SME status holder</th><th>All types of developers</th></tr></thead><tbody><tr><td colspan="3"><strong>What type of medicine am I developing?</strong></td></tr><tr><td><strong>ATMPs</strong><br>Support to meet regulatory requirements on quality, safety & efficacy, possible until the submission of marketing authorisation applications</td><td><strong>Innovative medicines</strong><br>Special incentives To gather robust data on the medicines' benefits and risks, to optimise development plans, and to enable accelerated assessment</td><td><strong>ATMPs</strong><br>Dedicated advices and procedures (e.g. to comply with legal requirements) & fee reductions</td><td><strong>Innovative medicines</strong><br>Scientific assessment by CAT of quality data and, when available, non-clinical data generated</td><td><strong>ATMPs?</strong><br>To gather robust data on the medicines' benefits and risks, to optimise development plans, and to enable accelerated assessment</td></tr><tr><td>ATMP Pilot Academic</td><td><strong>PRIority Medicines (PRIME)</strong></td><td><strong>SME Office</strong><br>Certification procedure</td><td><strong> PRIority Medicines (PRIME)</strong></td><td>Free of charge meetings with multi-disciplinary group on scientific, regulatory issues</td></tr><tr><td></td><td></td><td></td><td><strong>Scientific advice</strong><br>Innovation Task Force briefing meetings</td><td>Discussions with experts in quality assessment & OMP inspections<br>Quality innovation group</td></tr><tr><td></td><td></td><td></td><td></td><td>Recommendation on classification</td></tr></tbody></table>

## Interactions with multiple regulators to support medicines' development

## Interactions with national competent authorities

Medicine developers can contact national competent authorities to interact with one or multiple regulators(s) at national level. List of national competent authorities in the EEA available on EMA's website.

**Available Procedures →** scientific advice, Simultaneous National Scientific Advice (ex.)

**Available services →** innovation offices (ex.)

Some EEA countries have national competent agencies but no innovation offices and do not offer SNSA.

No innovation office = No interaction for example Iceland no innovation office but offers national advice.

Innovation offices and participation in Simultaneous National Scientific Advice (SNSA) in EEA countries and the UK

☐ Countries with innovation offices

☐ Countries without innovation offices

☐ Innovation office and leading or participating in SNSA

☐ Innovation office and observer role in SNSA

☐ 2 innovation offices: 1 leading or participating role and 1 observer role in SNSA

### EMA + FDA

Clearer understanding of EMA & FDA respective regulatory requirements & scientific recommendations on product's development

What type of medicine am I developing?

Innovative medicine

Hybrid or complex generic product

Parallel scientific advice

Pilot Parallel advice

### EMA + HTA Bodies

Health technology development

Scientific advice from EMA & individual recommendations from HTA bodies on initial evidence generation for MAA/Reimbursement, and Post Licensing Evidence Generation

Parallel EMA/HTA body Scientific Advice for the Interim Period

FDA: Food and Drug administration, HTA: Health Technology Assessment bodies, EMA: European Medicines Agency, NAA: Marketing Authorisation Applications, OMP: Good Manufacturing Practices

### Any contribution is warmly welcome!

Please join the EuroGCT ELSI Network of Expertise: provide draft content of entries, lay summaries of your research papers, to translate existing entries, to review draft entries, to provide useful updated resources.

To get involved in this collaborative work please contact the EuroGCT Information officers on ELSI:

Auxane Delage: auxane.delage@univ-amu.fr

Luc-Sylvain Gilbert: luc.gilbert@univ-amu.fr

All contributions will be credited on the EuroGCT website

<figure><img src="image_172.png" /></figure>

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# A comparative study of national schemes and services for “early interaction” with Regulators

A. DELAGE, L.-S. GILBERT, J. VERAN, V. ROBY, A. MAHALATCHIMY, A comparative study of national schemes and services for “early interaction” with Regulators, ESGCT 2025, 7-10 October 2025, Sevilla, Spain (POSTER available at https://hal.science/AO-DROIT/halshs-05314257v1)

## Abstract

Regulators, here understood as national medicines agencies, are supporting the development of innovative medicines in the field of Gene and Cell therapy by creating dedicated schemes and services. These are designed to help developers in the pursuit of making new medicines available for patients. Although such regulatory support can be provided all along the product's life cycle, regulators generally recommend developers to look for support as early on in the development of a product as possible. Such possibility of obtaining regulatory support can be called “early interaction” with regulators. While “early interactions” existing at the European level are particularly relevant for Advanced Therapy Medicinal Products (ATMPs) for which marketing authorisation is granted under the centralised procedure, the national scale is of the utmost importance. Indeed, the National regulators are most of the time the first contacts for any developer. Beyond the interest in using one's own mother tongue, several decisions (eg. Clinical trials authorization despite the single application via the European Union (EU) portal), rules and procedures (eg. ATMPs under the hospital exemption) fall under the remit of each Member State. Therefore, the first intention should always be to enter into contact with the regulator of the country where the medicine is developed. However, all countries are not equal when it comes to supporting the development of medicines. The purpose of this research is to identify the opportunities, as well as differences and gaps in availability and choices for developers of innovative medicines seeking early support at the national level. The availability of national support schemes can be a piece of information allowing to complete our understanding of the different national approaches towards gene and cell therapy. Most Member States have procedures for developers to enter into early contact. But a closer look into the available procedures shows discrepancies in the availability and access to regulatory advice across Member States. A possible explanation can be the resources and priorities of the Member State regarding innovative medicines. A few number of countries have no dedicated support procedures or services available to advice medicine developers' individually. Others have an array of possible schemes for various questions depending on the level of precision and formalism needed by the developers. While most of them have services such as innovation offices or scientific advice, others don't. Therefore, this study aims to provide a first overview of the available national procedures within the European Economic Area (EEA). Without reaching exhaustivity (due to language barrier and accessibility of resources) but tending towards it, the focus is on establishing a list of different types of available schemes at the national level. By doing so, the study provides starting point comparison and discussion on the choices available across countries and the diversity of the available procedures to support gene and cell therapy development in the EU.
Inserm

Hôpitaux
Universitaires
de Marseille

ap·
hm

amU

Faculté de docteur
Aix-Marseille Université

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Funded by
the European Union

<figure><img src="image_178.png" /></figure>

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I-BIOLEX

anr®

# A comparative study of national schemes and services for "early interaction" with Regulators

Auxane Delage¹, Luc-Sylvain Gilbert², Julie Véran³, Valentin Roby⁴, Aurélie Mahalatchimy⁵

¹EuroGCT Information Officer on Ethical, Legal & Societal Issues (EUSI), Research Engineer and PhD student in law, Law Faculty, Aix Marseille Univ, CNRS, DICE, Aix-en-Provence, France. ²EuroGCT Information Officer on EUSI, Research Engineer in law, Law Faculty, Aix Marseille Univ, CNRS, DICE, Aix-en-Provence, France. ³Cell therapy/Advanced Therapy Medicinal Products Unit, Center for Clinical Investigation in Biotherapy (INSERM CIC 1409), Marseille University Hospital (AP-HU), Inserm CBT-1409-AMJ-AP-HM-IPC, Marseille, France. ⁴Research Engineer in law, EuroGCT and I-Biolex research projects, Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France. ⁵EuroGCT Deputy coordinator and WP4 leader, Permanent researcher in law at the French National Centre for Scientific Research (CNRS, CR), Law Faculty, Aix Marseille Univ, CNRS, DICE, Aix-en-Provence, France.

Acknowledgements: This work has been supported by European Union's Horizon 2020 EuroGCT project (GA No 965241) and by ANR-funded I-Biolex project (ANR-20-CE26-0007-01).

## Introduction & Methodology

National regulators, here understood as National Medicines Agencies, are supporting the development of innovative medicines in the field of Gene and Cell therapy by creating dedicated schemes and services. They are the first contact point for any developer. Beyond the interest in using one's own mother tongue, several decisions (e.g., Clinical trials authorization despite the single application via the European Union (EU) portal), rules and procedures (e.g., ATMPs under the hospital exemption) fall under the remit of each Member State. Therefore, the first intention should always be to enter into contact with the regulator of the country where the medicine is developed. However, all countries are not equal when it comes to supporting the development of medicines. The purpose of this research is to identify the opportunities, as well as differences and gaps in availability and choices for developers of innovative medicines seeking early support at the national level. The availability of national support schemes can be a piece of information allowing to complete our understanding of the different national approaches towards gene and cell therapy. If most Member States have procedures and services for developers' early contact with, their availability and access show discrepancies between States. Between September 2023 and September 2025, research and updates have been undertaken on each European Economic Area (EEA) and EU National regulators websites. National regulators have been punctually contacted where information was not found on national websites and when appropriate contact was available. Beyond Simultaneous National Scientific Advice (SNSA) which allows interactions with multiple national regulators, the studied States have also dedicated services (often called innovation offices) and other procedures which this study aims at showing. In the remit of this study the mention N/A is indistinctly used when no services or procedures is available, if nothing has been found or if the information is not provided.

## Innovation offices and participation in SNSA in EEA countries and the UK

<figure><img src="image_180.png" /><figcaption>EEA countries ranked by number of found types of interaction procedures with one regulator</figcaption></figure>

<figure><img src="image_181.png" /></figure>

## Scientific Advice procedures and linked fees for human medicines in EEA countries

<table><caption>Comparative fees for Human medicine Scientific Advice</caption><thead><tr><th>Country</th><th>Status</th><th>Name of advice procedure</th><th>Fee</th><th>Rate basis criteria</th><th>Fee incentives</th></tr></thead><tbody><tr><td>Austria</td><td>✓</td><td>National Scientific Advice (NASA)</td><td>Yes</td><td>Novelty of active substance</td><td>N/A</td></tr><tr><td>Belgium</td><td>✓</td><td>Scientific-technical advice</td><td>Yes</td><td>Type of product</td><td>Yes</td></tr><tr><td>Bulgaria</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Croatia</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>Complexity of request</td><td>N/A</td></tr><tr><td>Cyprus</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Czech Republic</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Denmark</td><td>✓</td><td>National Scientific Advice</td><td>Yes</td><td>Scope of advice</td><td>No</td></tr><tr><td>Estonia</td><td>✓</td><td>Scientific advice and pre-submission consultation</td><td>Yes</td><td>N/A</td><td>Yes</td></tr><tr><td>Finland</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>France</td><td>✓</td><td>Scientific advice</td><td>No</td><td>N/A</td><td>N/A</td></tr><tr><td>Germany</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>Complexity of request</td><td>N/A</td></tr><tr><td>Greece</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Hungary</td><td>✓</td><td>Scientific advice / Consultancy</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Iceland</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Ireland</td><td>✓</td><td>General Advice on regulatory requirements and general guidance on technical or scientific issue</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Italy</td><td>✓</td><td>Innovation meeting incl. scientific advice</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Latvia</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>Type of advice: regulatory or scientific advice</td><td>No</td></tr><tr><td>Liechtenstein</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Lithuania</td><td>✓</td><td>Scientific-Regulatory Advice (RSA)</td><td>Yes</td><td>Stage of development</td><td>No</td></tr><tr><td>Luxembourg</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Malta</td><td>✓</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Netherlands</td><td>✓</td><td>Scientific advice and Joint scientific advice</td><td>Yes</td><td>Complexity of request</td><td>Yes</td></tr><tr><td>Norway</td><td>X</td><td>Scientific & Regulatory Advice</td><td>Yes</td><td>N/A</td><td>N/A</td></tr><tr><td>Poland</td><td>✓</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Portugal</td><td>✓</td><td>Regulatory & Scientific Advice (RSA)</td><td>Yes</td><td>Regulatory or scientific + fields (Clinical, pre-clinical.)</td><td>N/A</td></tr><tr><td>Romania</td><td>X</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Slovakia</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>Complexity and field</td><td>No</td></tr><tr><td>Slovenia</td><td>✓</td><td>Scientific advice</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>Spain</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>Complexity and field</td><td>Yes</td></tr><tr><td>Sweden</td><td>✓</td><td>Scientific advice</td><td>Yes</td><td>N/A</td><td>Yes</td></tr></tbody></table>

<figure><img src="image_182.png" /></figure>

Any contribution is warmly welcome!

Please join the EuroGCT eUSi network of expertise: provide draft content of entities, lay summaries of your research papers, to translate existing entries, to review draft entries, to provide useful updated resources. To get involved in this collaborative work please contact the EuroGCT information officers on eUSi:

<figure><img src="image_183.png" /><figcaption>Proportion of EEA countries with found Scientific advice procedures</figcaption></figure>

<figure><img src="image_184.png" /></figure>

Auxane Delage: auxane.delage@univ-amu.fr

Luc-Sylvain Gilbert: luc.gilbert@univ-emu.fr

Valentin Roby: valentin.roby@univ-amu.fr

All contributions are credited on the EuroGCT website.

## Discussion and Conclusion

### 1. Information accessibility

* Minor difficulties in finding information

- Website in at least 2 languages except for Poland

- Some information are less easy to find like the fees and their related incentives

- Similar procedures may have different names in different countries

* Most countries provide accessible information on the available procedures with more or less details.

### 2. Availability of services and procedures

* As of April 2025, 1/3 of countries have no innovation office and 1/3 of countries UK have no innovation office

* 23% have no interaction procedure, 50% have one, 26,7% have 2 or more.

* Types of procedures are various: Scientific Advice, Pre-submission meetings, portfolio/innovation meetings, informal regulatory guidance, Classification services, specific type of advice (e.g. ondoropon with DIA/DIP in Germany)

* 2 countries have an innovation office for SNSA and no specific national procedure (Poland & Luxembourg)

* 5 countries have specific national procedures but no innovation office (Iceland, Latvia, Lithuania, Slovenia & Slovakia).

### 3. Combining results

- Most countries have available services or procedures (83.3%).

- Only 5 countries have no services or procedures (Bulgaria, Cyprus, Lithuania, Greece, Romania). These are Eastern European countries where dedicated services or procedure may not be needed to answer the demand of developers for early interaction or are not political priorities for the country. An exploration can be the resources and the national priorities of the country.

* In the EEA, national early interactions are generally available and accessible: they are various.

### 4. The procedure of Scientific Advice

* Scientific advice (SA) is by far the most available procedure in EEA countries: more than 70% of EEA countries have a procedure of SA, or that can be assimilated to SA (not necessarily the exact same scope)

* SA fees vary between countries:

- 3 countries have very large scales of prices (Germany, Netherlands & Belgium).

- The larger the scale the more limiting it could be for developers to know what the final cost will be (e.g. Germany).

- A higher cost or lack of fee incentives can be linked to some extent to the GDP, available resources and support policies of the country.

- In countries where fee incentives are available these are linked to the status of the developer: SMEs, Academia and/or Non-profit org. are targeted similarly to EMA's SA.

* Scientific Advice is the main interaction procedure with or without payable fees and targeted developers incentives
<figure><img src="image_185.png" /></figure>
VII
Guidance
# Mapping the ATMPs Guidance Landscape

**V. ROBY, A. SCHEER, J. VERAN, F. SABATIER, A. MAHALATCHIMY, Mapping the ATMPs Guidance Landscape, European Society for Gene & Cell Therapy Congress 2023, Brussels, Belgium, 24-27 October 2023 (POSTER available at https://shs.hal.science/halshs-04290574v1)**

## Abstract

Relatively new as an autonomous legal category within the European Union (EU) context with the adoption of the Regulation N°1394/2007 of 13 November 2007 on advanced therapy medicinal products, gene therapy, cell therapy, and tissue engineering medicinal products are also subject of a quite significant amount of soft law production. Indeed, the recent and rapid evolution in these areas and the “youth” of their regulation raise many questions regarding these special rules, their interaction with already existing and more general ones, the requirements for the development of such medicines, their marketing authorisation, their classification, etc. To answer those questions and to dispel as many doubts as possible, guidance documents have been issued by several organisations within the EU context, foremost among them the European Medicines Agency, but also the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) as well as the European Council Directorate for the Quality of Medicines & Healthcare (EDQM) through the publication of the European Pharmacopeia. This soft law that contributed to regulating ATMPs even before the adoption of specific regulation consists in a disparate collection of documents in terms of types (guidelines/notes for guidance, reflection papers, concept papers, points to consider, position statements, questions and answers, etc.), in terms of topics (scientific guidelines, procedural advices, guidance on clinical trials, on production, manufacture, etc.) and in terms of authors as already mentioned. The result is a sea of texts in which it may be laborious to navigate, especially with ATMPs being biological medicinal products and hence a priori within the scope of guidance for general and biological medicinal products unless specific guidance exists. This is why our contribution, in the form of a poster, seeks to map a landscape of all relevant guidance available in this field to improve access to it and to facilitate its understanding for developers, marketing authorisation applicants and/or holders, academia, health professionals, etc. First by listing and classifying all institutional authors of these guidance documents identified through internet searches, giving the occasion to assess and to graphically visualise the distribution of each one's contribution in the overall production of such texts, as well as to determine their territorial scope. Second by determining the interactions and overlaps between guidance papers applicable to ATMPs and those applicable to other general or specific medicinal products categories such as biological or biotechnological medicinal products with which ATMPs share the most guidance in common, as well as immunological or blood/plasma medicines and by representing them in the form of easy-to-read diagrams.
<figure><img src="image_186.png" /></figure>

Faculté de Pharmacie
Aix-Marseille Université

<figure><img src="image_187.png" /></figure>

<figure><img src="image_188.png" /></figure>

<figure><img src="image_189.png" /></figure>

Hôpitaux
universitaires
de Marseille

<figure><img src="image_190.png" /></figure>

<figure><img src="image_191.png" /></figure>

C2VN
Centre de Recherche et de Nutrition

<figure><img src="image_192.png" /></figure>

<figure><img src="image_193.png" /></figure>

Faculté de Droit et
de Science Politique
Aix-Marseille Université

Inserm

# MAPPING THE ATMPs GUIDANCE LANDSCAPE

Valentin BORY: Research Engineer in Law, Law Faculty; UMR 7318 International, Comparative and European Law (DICE) CERIC, CNRS, Aix Marseille University, Toulouse University, Pan & Pays de l'Auvergne, Aix-en-Provence, France.

Anatole SCHEER: Intern in pharmacy, Marseille Public Hospital (AP-FM), Biopharmaceutical Clinical Investigation Center, Marseille, France.

Julie YERAN: Responsible of Cell therapy / Advanced Therapy Medicinal Products' production at Marseille Public Hospital (AP-FM), Biopharmaceutical Clinical Investigation Center, Marseille, France.

Acknowledgements: This work has been supported by the European Union's Horizon 2020 EurGCT project (C.A. No 853247) and by ANR funded H1LoV project (ANR 26 C3LS 0007-01).

Flоренсе SARAH: Professor of Hematology and Bloodbank, Pharmaceutical Sciences Faculty; C2VN Inserm IRD 126 AIX Marseille University, Director of the cell therapy research centre at Marseille Public Hospital (AP-FM), Marseille, France.

Annelie MAHALATIHM: Permanent Researcher in law at the French National Centre for Scientific Research (CNES, CR), Law Faculty, UMR 7318 DICE CERIC CNRS, Aix Marseille University, Toulouse University, Pan & Pays de l'Auvergne, Aix-en-Provence, France.

Contact: annelie.mahalati.htm@anr.fr

## Introduction and Methodology

Quite early on and well in advance on the adoption of the Regulation N° 1394/2007 of 13 November 2007 on Advanced Therapy Medicinal Products (ATMP), the European Commission (EC), the European Medicines Agency (EMA), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the European Directorate for the Quality of Medicines & Healthcare (EQDM) (developed guidance documents to address the specific requirements for Gene Therapy (GT), Cell Therapy (CT) and Tissue engineering (TE)).

Guidance are here defined as all technical and scientific documents (mainly but not only guidelines) aiming to help medicines developers and marketing authorization applicants to comply with regulatory, ethical and methodological requirements and to better prepare marketing authorization applications.

This poster aims to identify and map all the guidance applicable to ATMPs, taking into account their diverse natures, topics and authors, as well as their potential overlapping with other categories of biological medicinal products.

First, we classified the biological medicinal products according to the European Union (EU) legal nomenclature (Fig. 1).

Then, we compiled and listed all the current guidance related to those different topics, basing our research on the dedicated sections on the above-mentioned institutions websites, and by completing the respective search engines using pre-determined keywords.

<figure><img src="image_194.png" /></figure>

After deducting the overlapping documents, 213 Current guidance applicable to the 7 different categories of biological medicinal products were listed. To assess the anteriority of these documents, we also sought for their First versions (i.e. first disclosed discussions on a specific guidance), reaching the number of 320 available texts all versions included (First and Current). To these 320 documents, we should add to the counting 19 texts from European Pharmaceupia (EQDM texts) that we were not able to analyse thoroughly (e.g no access to their "First" versions), as not being freely accessible.

Focusing on ATMPs, among these 232 Current texts (213 from EMA, ICH and EC and 19 from EQDM):

105 covered ATMPs (1st analysis) 87 from EMA, ICH and EC and 18 from EQDM, 138 all available versions considered (First, Current and EQDM).

Due to the impossibility to fully access to the 18 EQDM documents applicable to ATMPs, those have been excluded from the more thorough analysis on overlapping, bringing to the number of 120 all-versions-included guidance studied (from EMA, ICH and European Commission) (2nd analysis on overlapping)

<figure><img src="image_195.png" /><figcaption>Table 1a: Guidance documents sorted by sources</figcaption></figure>

<figure><img src="image_196.png" /><figcaption>Table 1b: Guidance documents sorted by categories of ATMPs</figcaption></figure>

## Analysis based on the list of Current ATMPs guidance

* The default type of document for ATMPs keeps being Guidelines or Notes for Guidance (NFG) with 52 on 105 (19,5%).

* Still, heterogeneity of the type of guidance:

* Many new types of documents emerged from the 2000's position statements, questions and answers, on procedural advices, etc.

* Category "Other" = quite diverse (points to consider: flowchart, action plan, etc).

* Mainly noticeable for "all ATMPs" category.

* High needs for guidance of all kinds for this dynamic and innovative sector.

* Relatively balanced distribution of guidelines from EMA and ICH among documents applicable to all ATMPs, GT and CT&E:

* 23 guidelines authored by EMA (21,9% of the total).

* 21 guidelines authored by ICH (20% of the total).

* However, when adding the 6 EMA NFG it brings the EMA Guidelines/NFG number to 29 (27,6% of the total), slightly tempering the latter observation.

* Various distribution of texts according to their authors:

* EMA = author of the majority of documents (60/103, 57,1%) → Agency functions of authorisation, supervision and control of ATMP.

* ICH = second author (24/105, 22,5% of the total).

* EQDM = third main author (10/105, 17,1% of the total).

* EC = author of fewer documents (3/105, 2,9% of the total).

* Centrality of the EMA role in the production of soft law for ATMPs at EU level

* Significantly larger amount of guidance applicable to all ATMPs (62/105, 59% of the total):

* Among them, only 2 strictly specific to ATMPs. A number remaining higher than for those dedicated solely to GT (24) or to CT&E (19).

* The 36 left consist in more general-scoped documents, most of them being guidelines (28) and NFG (4), mainly issued by ICH (19).

* Most of the time, TE products are covered by documents applicable to both CT and TE

* Only 1 guidance document from EMA (a Reflection paper) is strictly and solely applicable to TE

* CT & TE gathered under a single section on EMA Website (as in our study).

* Relatively close distribution between GT (24 texts, 22,9% of the total) and CT&E (19 texts, 18,1% of the total). But higher presence of EQDM texts for CT&E (12) than for GT (6).

* EQDM texts constitute more than half of the guidance applicable to CT&E (12/19), the rest being composed of "only" 7 EMA documents compared to 13 EMA, 6 EQDM and 5 ICH texts for GT.

* The adoption period running from 1994 to 2013 shows a significantly dynamic sector requiring frequent and up-to-date guidance. However, for CT&E guidance, the adoption time range is quite shorter (2000 to 2016), while for GT it started earlier (1994) and finished later (2021).

* Possible explanations:

* A smaller number of accessible documents specific to CT&E (12 being non-free accessible EQDM documents)

* EMA-level requirements for CT&E covered by more general guidance applicable to all ATMPs, or even by broader-scoped documents;

* Strong interest for GT from the beginning of the 1990's as well as recently with the development of CAR-T cells-based medicines.

## Analysis of the individualised overlapping between ATMPs Guidance

This first diagram (Fig. 2) illustrates the overlapping of ATMPs guidance (first: and Current versions included) with the individualised other categories of medicinal products. The existing overlapping between those latter is therefore not visible.

* **70/120 (58,3% of the total) strictly specific to ATMPs → Particular needs & requirements for ATMPs.**

* **Observable strong relation of Biologicals (AS, FP and BS) with ATMPs → Not surprising as ATMPs are biological medicinal products, but:**

* **Stronger link with Active substances (3) common guidance, 27,5% of the total) → Transitivity of this category.**

* **More tenurous link with Finished products (18/120, 15,1% of the total) → Total number of guidance lower in this category; Finished products are the sub-categories of and for ATMPs (i.e. GT and CT&E) → Guidance relating to**

Finished ATMPs to be found in documents dedicated to these sub-categories, and not in broader-scoped documents.

* **Very little intersections with Biosimilars: 1 guidance (1,7% of the total) being the First and Current versions of the same document**

* → Absence for now to our knowledge, of authorised biosimilar ATMP.

* **Biotechnologicals = the third biggest intersection (15/120, 13,3% of the total) → Relative proximity in terms of requirements.**

* → ATMPs equated with Biotechnologicals before adoption of 2007 Regulation on ATMPs.

* **Smallest intersections are with Immunologicals with only 2 documents (first and Current versions of the same document) shared with ATMPs (1,7% of the total) and with Blood/plasma medicines with only 1 document common with these latter (0,8% of the total).**

<figure><img src="image_197.png" /><figcaption>Figure 2: Diagram of individualised overlapping between ATMPs guidance documents</figcaption></figure>

<figure><img src="image_198.png" /><figcaption>Figure 3: Overlapping and non-overlapping between guidance applicable to ATMPs and to other categories of biological medicinal products</figcaption></figure>

## General conclusion

* The singularity of ATMPs is quite well reflected through their guidance landscape with a high number and diversity of specific documents. This shows a strong need of merit requirements inherent to this innovative class of medicines.

* The large quantity and high diversity of guidance may come with complexity and confusion, many documents overlapping.

* Almost no difference is made between CT and TE medicinal products in guidance documents, implying that the legal distinction resulting from the 2007 Regulation on ATMPs is – at least for now – irrelevant for guidance purposes.

## Analysis of the overall intersections between ATMPs Guidance

* **Active substances and Biotechnologicals appear closely related**

* The biggest intersection of 7 Guidance (5,8% of the total) between ATMPs, Active substances and Biotechnologicals only.

* They share 13 guidance documents in total, the maximum of documents shared between two non-ATMPs categories: → Confirmation of the importance of Active substances and Biotechnologicals categories within ATMPs guidance.

* **Finished products is the most isolated category with 14 documents on 18 shared with nothing but ATMPs.**

* The little intersections of ATMPs with Biosimilars and Immunologicals are also shared with Biotechnologicals.

* → Confirms the transitivity of Biotechnologicals and the blurred differentiation with the general category of biological medicinal products.

* In contrast, ATMPs-Blood/plasma intersection shared exclusively with Active substances:

* Blood/plasma category = very isolated not only from ATMPs, but also from other categories of specific biological medicinal products, including the most transversal one (Biotechnologicals).

* → Requirements for Blood/plasma medicines and for ATMPs are very different.

<figure><img src="image_199.png" /><figcaption>Figure 4: Overlapping between guidance applicable to ATMPs and to other categories of biological medicinal products</figcaption></figure>

* The near absence of link between ATMPs and Biosimilars suggests the latter were not thought for ATMPs. Similar to widely used biological medicinal products, the purpose of their regulation is to make them more accessible and affordable for patients. The fact that very few ATMPs have been authorised and widely used can justify this very little overlapping. Moreover, we could not find any data on the existence of an EU authorised biosimilar of ATMPs (see L. Gilbert & A. Mahalatihamy. Biosimilars of ATMP: Specificities of the marketing authorisation dossier for biosimilars, EuroGCT website, February 2023. https://www.eurogct.org/research-pathways/communalisation/market-access-atmps/expediting-marketing-authorisation-3).

<footnote>* Biosimilars (BS) that we chose to include in the Biologicals category with Active substances and Finished products with regards to their nature and definition.</footnote>
<figure><img src="image_200.png" /></figure>
VIII
French policy
# Organoids and organs-on-chip in gene and cell therapy: which innovation strategies in France?

A. BOTTACCI, G. NICOLAS, A. MAHALATCHIMY, Organoids and organs-on-chip in gene and cell therapy: which innovation strategies in France? ESGCT 2025, 7-10 October 2025, Sevilla, Spain (POSTER available at https://shs.hal.science/halshs-05314478v1)

## Abstract

Organoids and organs-on-chip (O&OOCs) technologies are quickly becoming ubiquitous in health research and may also offer new perspectives in healthcare in the future. In the field of gene and cell therapy, they are mainly used in pre-clinical development for disease modelling, drug screening and toxicology. They also share a special connection with Advanced Therapy Medicinal Products – the legal category under which they would fall under if used as medicines in the future. To harness their potential, combined efforts from researchers, start-ups, industrial manufacturers, investors and regulatory bodies are required to structure this new technological sector and provide adequate funding. In France, stakeholders involved in pre-clinical and clinical research are organizing themselves around this novel technological sector by establishing new partnerships. Their aim is to standardize practices at the national level to elaborate and define new norms and standards in collaboration with national regulatory agencies that could subsequently be submitted to European decision-makers. In parallel, the necessary funds are being provided under the national strategy France 2030, a multiannual, 54-billion-euros plan designed to massively invest in innovative technologies. One of the Priority research programmes and equipment (PEPR) under this plan is specifically dedicated to funding research on O&OOCs for 48,4 million euros. France 2030 also contains an 800 million euros Health Innovation Plan with earmarked funds for Biotherapies and Bioproduction of novel therapies. Thus, a variety of financing options are available to researchers, start-ups and industry partners that are either working specifically on O&OOCs or using them in their research, including in the development of health technologies. This poster will provide an overview of the ongoing efforts to structure and finance this fast-growing technological sector in France. It will illustrate and discuss how the highly innovative and cross-cutting nature of O&OOCs enables them to benefit from both targeted and broad innovation strategies, including those related to gene and cell therapy. This work aims to support European stakeholders in identifying French networks and potential partners, as well as inspire similar initiatives abroad.