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Cell-based regenerative medicine: new challenges for EU legislation and governance

Final Report Summary - EUCELLEX (Cell-based regenerative medicine: new challenges for EU legislation and governance)

Executive Summary:
The EUcelLEX project was aiming at collecting and analysing facts and figures in order to assess the current legislation on the therapeutic use of somatic cells, and to bridge it with the research infrastructure capacity building. Although E.U has adopted 3 Directives on Tissues and cells between 2004 and 2006 to harmonise the procurement, storage and use of cells for therapeutic use in Europe, they are many differences in the way that each EU country has implemented these directives which has led to uneven national rules to be applied. Furthermore, research have not been covered by the initial regulation, thus there is room for questions regarding the legal rules that will have to be posed comparing the existing regulation and practices that will develop in the near future, in particular within the European research infrastructures. Finally many changes have occurred in the scientific, legal and institutional environment of the use of cell leading to the need for an update of this regulation with regards to their implementation in national legislation and their impact on research practice and innovation. The two main domains at stake, one mainly research (Infrastructures), the other mainly medical practice or public health measures (cells) show a gap in their regulation at EU level. The therapeutic use of cells are regulated by EU law whereas their research counterpart are not and are mainly depending on national laws and regulations, except mainly for what is related to clinical trials and data protection. This gap was calling for a coordination action in order to better realise the translational process that cannot be optimised when the full pipeline is not coherently taken into account in legislations. To achieve these objectives, our project relied on a coherent consortium of experts in the fields of cells therapies, cells banks and translational biomedicine, having strong expertise in law and/ or in governance issues. We will end up this project by the publication of a book presenting the main results and findings from the facts and figures collected through the analysis of the literature, through interviews and tools in the different WPs of our project and after the inputs from experts we have invited in the two conferences of consensus.
After 36 months the project has delivered evidence about the contemporary practices around cells and has designed a picture of the “market” and its distribution between the public and private sector. After assessing the pathways of implementation of the “Tissues and Cells” directives, the EUCelLEX consortium has delivered recommendations towards the legislator and the policy makers for improving their communications with researchers and the public. EUCelLEX will also contribute to the discussions for turning the Tissues and Cells Directives into a future Regulation.

Project Context and Objectives:
Biological samples and resources derived from the human body are now regarded as the essential raw material needed for the continued advancement of life science and health-related biotechnology (OECD, 2001). Analysis of human biological material (HBM) will increase understanding of the physio-pathological factors underlying disease and lead to better clinical outcomes. By collecting, transforming and distributing HBM, biobanks are thus key actors in the translation of scientific knowledge into medical practice, in particular for the identification of new clinical biomarkers and the development of new therapeutic approaches such as pharmacogenomics and regenerative medicine. In these latter fields, stem cells research holds promise to generate valuable clinical innovations for a range of common conditions. In view of this progress, EU tends to strongly encourage scientific collaborations within the academic field and between universities and industrial partners in particular in its strategy for innovation. However, the absence of clear European legal instruments on the use of stem cells for research purposes by public and private partners undermines sharing these resources within the EU, thus impairing developments towards a knowledge economy in this important area.
To encourage and maximise the use of HBM in Europe, the European Commission instigated three new Directives in 2004 and 20061, (hereafter Tissue and Cells Directives), to encourage the donation of tissues and cells for transplant purposes in the safeguard of public health (Directive 2004/23/EC, recital 2). Some of the latter apply specifically to banks of tissues and cells, including stem cells and cord blood cells, to be used for regenerative medicine. However, the Tissues and cells Directives are restricted to therapeutic purposes. Thus, 1) basic research is explicitly out of the scope of these Directives [Hervey and Black, 2005] unless applied to the human body (e.g. in clinical trials) and 2) stem cells are covered but are not regulated specifically (Directive 2004/23/EC, recital 7). Additionally, the implementation of these directives by Member States (MS) has led to a heterogeneous regulatory landscape, whereby some MS develop specific classes for cell-derived products, whilst other assimilate them to medicinal products [cf. the results of the Tiss.EU project (FP7, n°202204) and of the REMEDIE project (FP7, n°217180); [Lenk, Hoppe, Beier et al.2011].
In this context a more sustained legal reflection on this complex subject would provide a much needed clarification and timely guidance for policy making.


The EUCelLEX project aims at providing a comprehensive overview of the current knowledge on the regulation of stem cell-based research and therapy in the EU. More specifically, it will rigorously analyse policies and practices for the governance of cell-based activities (applying to stem cells) used by the key institutions involved along the translational pipeline (bench to bedside) of regenerative medicine. It is clear that there is currently a general lack of awareness of the detrimental effects that a heterogeneous regulatory landscape has on European healthcare systems and the EU's knowledge-based society. Our work programme will raise awareness about this problem and highlight the important legal and ethical implications, as well as for governance of cell-based research and therapy and its effects on the health care system in general, and health care delivery to individual patients in particular. The impact will therefore be incurred not only across diverse health care settings within the EU but also at the clinical level. Acting on a European level to engage these issues is absolutely essential due to an increase in multinational research collaborations. Moreover, by doing this work across a range of European countries, the project and the recommendations resulting from it will be more widely applicable. It is envisaged that, drawing on the results of this project, relevant European institutions will act and implement effective measures to support cell-based research in an ethically and legally appropriate manner in the future.

The main objective of EUCelLEX project is to assess the adequacy of the present European legal instruments in order to provide a regulatory framework for the use of stem cells, in light of the recent scientific, legal and institutional developments that have occurred within Europe. The aim is to provide recommendations that will facilitate the use of stem cells in all aspects of the pipeline from research to healthcare.
• Objective 1: to analyse the present European and national legal instruments and policies on the use of stem-cells.
• Objective 2: to compare the existing regulation and the practices that will develop for stem cells in the near future, in particular within research infrastructures, in order to highlight the gaps and to propose sustainable solutions.
• Objective 3: to clarify the legal rules to enforce the drug development chain using stem cells and to govern public/private partnerships (PPP) in the context of translational research and EU level.

To reach these objectives we will:
1/ Gather information on the legal implementation of the Tissue and cells directive, focusing on what is regulated at the European level and what is still regulated at the national level
2/ Integrate this knowledge into a much broader analysis framework covering the whole pipeline from research to care, with a distinct concentration on stem cells and cord blood banks.
3/ Make a background analysis of the field including legislation and literature analysis, jurisprudence analysis and ethical opinions collection using adequate databases at national and European level
4/ Create tools for the involvement of professionals and key stakeholders.
To help in accessing the relevant information in the countries surveyed (mainly the countries involved in the present consortium) we will benefit from the networks in which the leaders of the WPs are already involved and we will create bridges between them.
Some key actors have been already identified such as Key stakeholders:
• Competent authorities i.e. national drug regulation agencies and data protection authorities;
• Eurobarometer;
• Europabio;
• DG SANCO C3 “Health Threats” Unit • Network of professionals (lawyers and policy makers);
• Network ETHIMED (led by Association de Recherche et de Formation en Droit Médical) ;
• European Association for health law;
• BBMRI Nodes;
• European projects (Tiss E.U. Poseidon, RemediE, Academic GMP, EuroStemCell);

The consortium is constituted by 9 partners organised along 7 workpackages (WP):
- WP1 Management and Coordination, Inserm UMR 1027 (E. Rial-Sebbag ; A. Cambon-Thomsen)
- WP2 Stem cells sources and procurement, University of Hungary (J. Sandor) and Legal Pathways (J. Bovenberg)
- WP3 – Stem Cell Use, Oxford University (J. Kaye) and Hannover University (N. Hoppe)
- WP4 – Cord blood banks, McGill University (BM Knoppers, R. Isasi) and Leuven University (H. Nys, P. Borry)
- WP5 – Translational Research, University of Medicine Graz (K. Zatloukal) and INSERM US13 (G. Dagher)
- WP6 – Cells, ethics and societal innovation, CEVIPOF (V. Tournay) and INSERM UMR 1027 (A. Blasimme)
- WP7 – Integration, synthesis and recommendations, Inserm UMR 1027 (E. Rial-Sebbag and A. Cambon-Thomsen)

The strength of EUCelLEX proposal is to analyse the impact of the Tissue and Cells Directive in the context of emergence of infrastructures at EU level and at national level. It was a unique chance to assess the impact of EU legislation on the whole pipeline from basic research to clinical applications.

Project Results:
WP2: Stem cell sources and procurement

D2.1. Report on the comparative legal analysis (M14)

Deliverable D2.1 (Milestone 4) has been successfully completed: A report on the comparative overview of the national regulatory regimes for procurement activities related to stem cell technologies has been produced.

T2.1 – Facts & figures (M1-M7)
Description of work (Annex I):
• We will establish the facts and figures regarding stem cell research, innovations and therapies which are pertinent to our questions, by reviewing both the current state of the science and looking prospectively to future needs for stem cells. This review is to define the scope of our legal analysis, and to confirm or reject our preliminary selection of the types of stem cells – human embryonic stem cells, fetal stem cells and adult stem cells. It will be carried out by way of PubMed review and interviews with leading EU stem cell scientists.

The first task was conducted surveying the literature and gathering facts and figures from legal documents and relevant websites.
According to the Commission’s evaluation of the Regulation on Advanced Therapy Medicinal Products (the Regulation), prior to the entry into force of the Regulation, EU Member States had reported 31 Advanced Therapy Medicinal Products (ATMPs) as being legally on the EU market. After the entry into force of the Regulation, 5 ATMPs have been granted a marketing authorisation, out of 10 applications. Meanwhile, a significant number of existing ATMPs continued to be used, without a marketing authorisation, under derogations granted by Member States (the hospital exemption or otherwise). The marketing authorisation of one autologous product was recently suspended. Faced with these figures, the European Commission now considers, among other measures, the possibility of revising the requirements of the Regulation, with specific consideration of the characteristics of autologous products.
Our review aims to inform the Commission’s revision, by establishing some facts and figures with respect to the cell sources of ATMPs. To that end we seek answers to the following questions. First, what are the numbers of autologous ATMPs, as compared to allogeneic ATMPs? Second, why does the Regulation treat autologous and allogeneic products the same? Third, what are the specific characteristics of autologous products? The answers to these questions suggest a few recommendations for the regulation of autologous ATMPs which are presented in the Summary.

Question (1): Cell sources of ATMPs: Autologous vs. Allogeneic
Questions, queries & sources
Our first question was: what are the numbers of autologous ATMPs, as compared to allogeneic ATMPs?
To answer that question, we formulated the following sub-questions:
(i) what are the cell sources of the ATMPs which have been granted marketing authorisation under the Regulation?
(ii) what are the cell sources of the products which have been classified as ATMPs by the European Medicine Agency (EMA)-Committee for Advanced Therapies (CAT)?
(iii) what are the cell sources of cell therapies registered in the EU Clinical Trial Registry?
(iv) What are the cell sources of cell therapies registered in clinical trial registries worldwide?

To get answers to these questions, we queried the following sources:
1. the EU Pharmaceuticals - Community register;
2. the EMA-CAT summaries of ATMP Classifications;
3. the EU Clinical Trial Registry;
4. The Cell therapy clinical trials – 2014 Report.

Question 2: why does the Regulation treat autologous and allogeneic products the same?
To answer that question we analysed the legal history of the Regulation, including underlying impact assessments and the outcomes of stakeholders’consultations.
Question 3: what are the specific characteristics of autologous ATMPs?
To answer that question, we performed a review of the scientific literature
Main findings:
The majority of ATMPs with a marketing authorisation, a CAT-classification or in clinical trial in the EU, are autologous rather than allogeneic products. This is in line with figures for cell therapies in clinical trials worldwide.
In the legislative history of the Regulation, it was asserted that a regulatory approach based on the distinction between autologous and allogeneic products was artificial. Consideration was given neither to the characteristics of autologous therapies, nor to any, fundamental, distinctions between autologous and allogeneic products. The Commission considered that the issue of limiting administrative burdens for small operators tending to produce autologous products, was best addressed by the hospital exemption. As a result, the Regulation treats autologous and allogeneic products the same; the cell source of an ATMPs (autologous, allogeneic or xenogeneic) is only one of multiple factors in the risk assessment.
The characteristics of autologous products include the fact that the cell is the active therapeutic agent, short shelf-lives, complex supply logistics due to clinically limited time for testing, persistent issues related to variability of the donor derived starting material (both intra- and inter-individual) and constant changes of the product in response to its environment. One of the regulatory implications of these characteristics is that the requirement to demonstrate comparability is an almost “unsurmountable barrier.”

The findings offer a number of suggestions:
• the characteristics of autologous cell therapies trigger the question of whether they should be qualified and regulated as a product, subject to (centralised) marketing authorisation, in the first place;
• revising the marketing authorisation requirements may not suffice, as long as autologous products must meet the comparability requirement;
• rather than revising the requirements, the hospital exemption could be broadened, so as to include routine preparations.
• the goal of the Regulation was to promote public health by creating free (cross border) movement of the (autologous) cell therapy product in the EU. If free movement of the product to (cross-border) patients cannot be achieved, because (i) the cell therapy product is, in essence, a bed- or hospital-side, non scaleable and non-moveable product and/or (ii) the cell therapy product is such that it cannot meet marketing authorisation standards (comparability), then it should be considered to promote free (cross border) movement of patients to the product (prepared at point of care, on hospital exemption quality and safety standards).

T2.2 – Stakes and stakeholder analysis (M7-M10)
Description of work (Annex I):
• The above review will be used to inform our stakeholder analysis. In addition to the obvious stakeholders at the receiving end of stem cell innovation and therapies, we expect specific concerns to be at stake at the sourcing of stem cells – women, parents, newborns, and society at large. The stakeholder analysis should yield an overview of the concerns associated in the procurement of stem cell research, innovation and therapy, on a cell type by cell type basis. This will provide the framework for the assessment of the interactions between EU legislation and the procurement of human stem cells for research and innovation.

The stakeholder report was based on systematic desk research using multiple search and studying official website (90%): mainly based on governmental, ngo and biotech sites and partly (10%) on asking information and interviews. After conducting an in depth legal analysis of the different legal frameworks applying to the procurement activities related to stem cell technologies we concluded to a diverse and fragmented regulatory environment at the national level. The survey was conducted through a comparative analysis in 7 European countries + Canada. We concluded that the regulation is usually done according to the sources (procurement) and to the national ethical values. We complete the picture through analysis of cases and the impact for intellectual property. We conclude that national arrangements beyond the standard normative benchmarks of informed consent, purpose bound use, and justified and necessary intervention could be of interest to other national regulatory regimes. Legal and non-legal regulation of safety, information, or good research and medical practices,44 as published by the responsible bodies and agencies, could be of use in national regimes which lack these regulatory developments. The development of cross-border shared institutional and resource frameworks could offer another area of regulatory innovation, which should also consider the particular ethical issues and the potential cross-border ethical and technical implications.
Deliverable D2.1 (Milestone 4) has been successfully completed

D2.2. Workshop on Mapping the legal differences and Translational Aspects of Stem cell procurement and related report (M20)

T2.3 – Mapping the EU legislation (M10-M18)
Description of work (Annex I):
• We have identified the EU legislation pertinent to the sourcing and procurement of human embryonic, fetal and adult stem cells, as part of the Deliverable D2.1. The same is likely to apply for the EC Regulation on advanced therapy medicinal products, even though the Regulation prima facie only deals with marketing authorization of industrially manufactured products. The impact of the Regulation was reviewed as part of Task 2.1 discussed above.
• By way of reality check, we will interrogate representatives from our identified stakeholders for their experiences with the EU legislation, or lack of such legislation; this will partly be done as part of the Workshop discussed below.

Task 2.4 - Linking EU legislation to stem cell procurement ( Month 18-24)
Description of work (Annex I):
• Next, we will assess the interactions between EU legislation and the procurement of human (embryonic, fetal & adult) stem cells for research and innovation. For the legal part of this analysis we shall also analyze in more details the legal framework of some selected countries and how they have implemented the various pieces of EU legislation we identified earlier. In the analysis of the European legal debates we shall also look at the opinions of the EGE. We shall further assess the relevant case law and the decisions of ethics committees as well. The selected countries will in any event include the Netherlands and Hungary and provided assistance of the other participants represented in this project, Belgium, Canada, France, Germany and the UK.
Facts and figures collected during this task will form a basis to be discussed during a workshop organised at Month 20

Deliverable D2.2 has been completed.
The EUCelLEX Budapest Workshop, titled “Stem Cells from Bench to Bed, from Procurement to Application: Ethical and Legal Challenges” has been held on the 18-19 of May, 2015. We invited key experts from Europe to present their experiences, thoughts and concerns, which will be fed into the panel discussions on the related ethical and legal questions.
The aim of this WS was to discover and examine ethical and legal aspects of different types of human stem cells, their classification, procurement and uses. The workshop brought together scientists, lawyers and philosophers from a number of countries, including stakeholders in the EUCelLEX project. The central focus of discussion between these groups was to identify the regulatory and legal issues that have arisen in light of recent breakthroughs in stem cell research. Participants were be invited to discuss on the basis of current experiences whether there is a need for a more coherent and targeted approach in regulation and whether the functional focus of regulation could be further refined and, potentially, supplemented by other, more specific approaches in regulation.
A report of this Workshop has been provided as Deliverable 2.2

D2.3. Final publication (M36)
Description of work (Annex I):
• Finally, we will assess the effects of the application and implementation of EU legislation on the procurement of human (embryonic, fetal & adult) stem cell research and/or innovation, in a section of Member States. Here too, we will interrogate representatives of stakeholders for their views on said effects and to make sure future EU legislation is informed by their input. Separately, we will also assess the effects of the absence of EU legislation on a particular aspect of the procurement of (a particular type of) stem cells.
Specifically, we will investigate whether a specific Member State law banning the procurement of certain types of stem cells, could capture the ethics of European patent law and thus could have an adverse effect on states with permissive biomedical research regimes, as has been asserted in the aftermath of the ECJ ruling in the Brüstle case that he use of human embryos for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it is patentable, but their use for purposes of scientific research is not patentable.

Deliverable D2.3 (Milestone 30) has been successfully completed.
An article has been published in the European Law Review, with the name “Creating European markets through regulation: the case of the Regulation on advanced therapy medicinal products”
Marton Varju* Judit Sándor
*E.L. Rev. 25
This article analyses the EU regulatory efforts to create a European market for advanced therapy medicinal products. It focuses on the pitfalls of European regulatory intervention in a difficult market which is characterised by multiple, often contradictory stakeholder expectations, rapid scientific and technological change, and ethical diversity. It contends that while the Regulation on Advanced Therapy Medicinal Products was, in principle, equipped to address these challenges, its fundamental paradigms and choices, and its treatment of some of the dilemmas of the emerging technology market, undermined its ability to establish the balanced and sustainable market desired by the EU legislator.

WP3: Stem cell use

D3.2. Publication analysing the governance frameworks identified in Task 3.1 and Task 3.2 (M30)

T3.1 – User Assessment (M3 to M6)
Description of work (Annex I):
• This will involve the identification of the ways that different types of stem cells are used throughout the translational pipeline. This will also establish the types of institutions that conduct research on human cells within the selected jurisdictions, e.g. pharmaceutical companies, universities, hospitals. This will include cataloguing of what stem cells these organisations use to help in the assessment of whether regulation is appropriately targeted.
• Results of T3.1 will be disseminated through the project website

• Assessment completed across various networks e.g. EBiSC and StemBancc including stakeholder analysis of induced pluripotent stem cell users.
• Cooperation with WP5 resulted in the creation of Signavio tool in cooperation with Natalie Bordag (WP5) and Courtney Metz (WP3), which coagulated user data from WP3 into the WP5 online platform.

T3.2 – Regulatory Analysis (M6 to M30)
Description of work (Annex I):
• Identify and document the regulatory regimes deployed to govern the uses of stem cells in the range of institutions identified in T3.1. Documentation of the regulatory landscape within our selected jurisdictions and through comparative analysis identify whether there is significant differences in the ethical basis for each regulatory regime as well as the strengths and weaknesses of different regulatory mechanisms (hard law, soft law, etc) in each jurisdiction. We will compare this with the survey results of users to establish how the regulation of the use of stem cells affects users and to analyse whether it is appropriately targeted.
• Results of T3.2 will be disseminated through the project website and will inform the consortium recommendations document (WP7).

Tasks 3.1 and 3.2 were merge and resulted in:
• Existing WP 3 literature review or regulatory framework and key issues adapted to produce an 18 item questionnaire (D3.2) addressing the major elements of current EU regulation of regenerative medicine and cell banking. The questionnaire is intended to be deployed as an online survey using SurveyMonkey tool to which UOXF has access.
• Local (UOXF) research ethics committee approval application completed and submitted to secure ethical approval to conduct the survey and store and analyse the resulting data. It is anticipated that REC approval will be obtained by early September 2016.
• Liaison underway with representatives of WP5 to expand and adapt the existing EU CelLEX directory of contacts to include more entries suitable to receive the online survey.
• Contacted Maria del Rosario Sànchez-Albor at INSERM to arrange piloting of the draft survey instrument with other consortium members to check comprehensibility and relevance of all items.

The interview grid has been prepared (D3.2) and is addressing the following questions:
Part I: Understanding your institution
Part II: European and National Regulatory Pathways
Part III: The Wider Context and Recommendations
Due to the delay for performing this survey among stakeholder the analysis of the responses is ongoing and will be delivered through a paper to be published in 2017 which will constitute D3.3.

D3.1. Workshop and related report (M33)

T 3.3 – Stakeholder Engagement (M3 to 23)
Description of work (Annex I):
• We will document our findings on stem cell use on the project website in a form that is appropriate for a range of audiences (scientists, policy-makers, patient representatives, etc).
• We will organise and run a stakeholder workshop in Oxford (partner 5) in M23 to gather further inputs, validate our findings and to help generate a more complete picture of the regulation of stem cell use in Europe.

Deliverable D3.1 has been successfully completed
Stakeholder workshop has been held in June, 13 2016 in Edimburgh as a satellite meeting of the International Association of Bioethics congress (M33) in conjunction with WP5 (see D3.1 report).
ELSI 2.0 + EuCelLEX Project Satellite Symposium
Venue: Edinburgh
Date: 14 June 2016
Organised by Oxford University – HelLEx
ELSI 2.0 ( and EUCelLEX ( Project Joint Symposium ‘Exploring International Policy Development in Regenerative Medicine‘ alongside the 13th World Congress of Bioethics in Edinburgh on Tuesday 14th June 2016.
The event has included a Panel session considering ‘Socio-Ethical and Legal (ELSI) Implications of Genome Editing Technologies‘. The session will be Chaired by Dr Sarah Chan, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh.

D3.3. Research findings, details of scholarly publications and paper presentations at conferences and other dissemination activities on project website (M 24 – 36: continuous)
The main publications will be deliver in 2017.

WP4. Cord blood banks

D4.1 Report on the socio-ethical and legal aspects related to the implementation of the Tissues and Cell Directives in the specific case of Cord Blood (CB) banking (M12)

T4.1. Implementation of the Tissues and Cell Directives in the specific case of CB banking (M1 to M12).

Description of work (Annex I):
• To collect, analyse and assess data (socio-ethical and legal) related to the implementation of the Tissues and Cells Directives in the specific case of cord blood (CB) banking in the EU Member States (e.g. Austria, Belgium, France, Germany, Italy, Netherland and UK - MS involved in EUCELLEX) and third countries (e.g. Canada). This will include an analysis of: informed consent processes for the collection of the CB, the legal status and property rights of CB, as well as privacy measures regarding the use of CB.

Deliverable D4.1 (Milestone 9) has been successfully completed.
A report, in the form of a compendium of policy and ethical frameworks surrounding CB for banking, research and clinical applications, has been finalized. The compendium covers 8 countries involved in EUCelLEX (e.g. Austria, Belgium, Canada, France, Germany, Italy, the Netherlands, and the United Kingdom). One EUcelLEX member (Hungary) was no longer included in the comparative study given language barriers and the lack of policies on UCB in the country. The compendium was submitted to a validation process after which multidisciplinary, comparative socio-ethical and legal analysis is currently being conducted.
Preliminary findings of this study have been presented at the EUcelLEX’s 1st International Consensus Conference (Toulouse, March 30th – 31st, 2015). Umbilical Cord Blood Banking: Dualism, Policies and Ethics Abstract Authors: Isasi R., Knoppers B.M. Borry P., Shabani M., Nys H.
Long treated as waste, umbilical cord blood (CB), is today considered a valuable source of multiple stem cells for both research and clinical applications. However, heterogeneous scientific practices and differences in socio-ethical and policy frameworks, together with the co-existence of public and private/commercial networks and institutions, have been identified as obstacles to equitable access to CB. While a public CB bank is established to collect indirect/direct donations in high risk families for allogenic purposes, parents also have options in some EU Member States to store their child’s CB in private biobanks mainly for autologous or familial use.
The EU Tissues and Cells Directives, and the Recommendations and Resolutions (“Directives”) do not specifically address private CB banks; however, they still apply to them. In implementing the “Directives”, member states have aimed to strike a balance between relevant conflicting ethical principles, societal values and legal rights by either prohibiting commercial CB banks, or by strictly regulating the collection of CB for both autologous and allogeneic purposes.
This presentation will focus on the results of the EUCelLeX Project (WP4) international study of the policy and ethical frameworks surrounding CB banking in 8 countries (Austria, Belgium, Canada, France, Germany, Italy, Netherland and UK). We will address convergence and divergence in issues regarding the national implementation of the “Directives”, the legal status and property rights of CB, informed consent processes and privacy measures, etc. Our main goal is to develop policy recommendations to facilitate the interpretation and interoperability of the “Directives”.

D4.2. Publication on the socio-ethical and legal challenges associated with the co-existence of non-for-profit (public) with commercial CB banks (M24)
T4.2 – The duality of public/private not for profit CB banks and commercial CB banks (M13 to 24)
Description of work (Annex I):
• To study the co-existence of public networks, commercial companies (for profit) and hybrids UCB Banks.
• To analyse the relevant socio-ethical & legal issues arising in the use of UCB for allogenic and autologous purposes.

Deliverable D4.2 has been successfully completed.
Two publications have discussed policy issues associated with the commercialization and public-private partnerships arising in the context of biological material, including umbilical cord blood (Nature Review Genetics; Journal of Law and the Biosciences). In these reviews we have identified amongst the dilemmas of obtaining funding from commercial entities, in the biobanking area: the adverse effect on public trust and the effect on consent.
We conclude that Policy development should be informed by further analyses that include an exploration of what the public finds most troubling about industry involvement, research on the role and possible impact of a return of benefits to the relevant community, and a consideration of governance and consent strategies that allow valuable research to proceed while still preserving the interests of both biobank participants and the public.

D4.3. Publication on the ethical and legal issues and challenges related to the international sharing of CB for research purposes (M24)
T4.3. To compare the current European Directives to the regulatory framework in place in Canada (M1 to M24)

Description of work (Annex I):
• To conduct a critical international comparative analysis of the policy (ethical, legal, regulatory) approaches adopted in the countries under study and compare them with the approaches taken in Canada.

Deliverable D4.3 (Milestone 10) has been completed.
Preliminary results of this study were presented at the EUCelLEX Workshop of the WP2, organized by P3-CEU and P4-LP, entitled “Stem Cells from Bed to Bench, from Procurement to Application: Ethical and Legal Challenges” (Budapest, May 18th – 19th, 2015). This presentation has compared a number of national regulatory frameworks on regenerative medicine. There is considerable variety as to the instruments used, the institutional framework established, and in relation to the linkage found between law and science and its ethics. Most of the regulatory frameworks pursue concurrent agendas, focus following the precautionary principle on risk and safety, and aim to establish an appropriate and proportionate balance between risks and benefits. Current regulatory challenges arise from the attempts of some jurisdictions to integrate emerging technologies into existing frameworks, originally designed for the regulation of pharmaceuticals and medical devices. Other jurisdictions have limited guidance, relying on case-by-case approaches. This is often seen as an advantage to researchers, allowing for accelerated licensing, although the actual public costs of operating such regulatory frameworks could be excessive. She also mentioned some technical issues in the application of the regulatory frameworks which could considerable hinder research and development, such as the product classification rules of the different regulatory frameworks making it very difficult to select the right regulatory pathway for complex cell based products. Further technical difficulties may come from more distant regulatory areas, such as GMP or GCP regulation, from the regulatory framework trying to reconcile the demand for flexibility and its obligation to avoid uncertainty, from the regulatory framework introducing sufficiently complex and effective rules and ensuring through different means that stakeholders can actually comply with those rules and follow the regulatory avenue offered, or from the regulatory compliance representing excessive costs for developers with generally insufficient resources and expertise. In sum, the regulatory framework must create a careful balance between securing that safe, effective and quality products reach patients and ensuring that stakeholder confidence in the effectiveness of the system is maintained. In view of this international variance, Rosario Isasi ended her talk by emphasizing the importance of international harmony in regulation.

D4.4. Publication on the international comparative landscape of national, regional and international policies regarding stem-cell based research (integration with all work packages) (M36)

T4.4. Implementation of current Directives and guidelines with respect to research use of cord blood in public biobanks (M24 to M36).
Description of work (Annex I):
• To collect, analyse and assess data (socio-ethical and legal) related to the implementation of the Tissues and Cells Directives and other relevant international and European guidelines in the specific case of UCB banking in the EU Member States (MS involved in EUCelLEX, e.g. Austria, Belgium, France, Germany, Hungary, Italy, Netherland and UK) and Canada. This will include the study of the following elements: consent, right to withdraw consent and the future autonomy of the child.

Deliverable D4.4 (Milestone 11) has been completed.
We achieved part of this deliverable through the publication in the Journal of Law, Medicine & Ethics on the future autonomy of the child in relation to the right not to know. In this paper we have acknowledged that in the last few decades, great progress has been made in both genetic and genomic research. The development of the Human Genome Project has increased our knowledge of the genetic basis of diseases and has given a tremendous momentum to the development of new technologies that make widespread genetic testing possible and has increased the availability of previously inaccessible genetic information. Two examples of this exponential evolution are the increasing implementation of next-generation sequencing technologies in the clinical context and the expanding commercial offer of genetic tests directly-to-consumers.
A second publication has been published in which principle of datasharing are being discussed in relation with informed consent, the right to withdraw, respect for privacy and data access committees (EMBO Mol Med.).
A third publication has been performed in which societal perspectives and representations on biobanks have been collected (Peer J).

D4.5. Workshop and related report (M26)

T4.5. Organization of a workshop and related report (M20 to 26)
Description of work (Annex I):
• To organize a workshop to bring together international experts on ethical and legal issues surrounding UCB research. A special focus will be on the duality between public and private UCB banks.

Deliverable D4.5 has been completed.
In December 3rd 2015, WP4 organized a half-day workshop on the scientific, ethical and legal aspects of the Umbilical cord blood Banking. The main purpose of the workshop was to bring experts in the field of cord blood banking together and discuss challenges associated with the cord blood banking, research activities of these banks and also their potential private-public partnerships.
The workshop was started with a talk on the scientific aspects of cord blood donation, banking and clinical applications. In the course of this talk, an Austrian experience of cord blood banking was discussed. In the following session, a Canadian experience of building a national cord blood bank was presented and the associated ethical and legal concerns with constructing such banks were outlined. A comparative study of the existing laws and regulations on the cord blood banking was the focus of the following talk. This presentation provided a summary of a work that was resulted from a previous task of the Work Package 4. The workshop was continued by a presentation on the challenges associated with public-private partnerships in population biobanks and the implications for public trust on biobanking. The final presentation provided a summary of the points discussed during the workshop, and also an outline of the existing models of cord blood banks and the associated ethical and legal concerns. The workshop was concluded by a final group discussion on the policy implications of the recent developments in umbilical cord blood banking.
The workshop benefited from the contribution of the international legal, ethical and scientific experts in the field of cord blood banking and put forward further points for consideration.
A report of this Workshop has been provided as Deliverable 4.5.

WP5: Translational research

D5.1. Catalogue on the intersections between therapy and research (M10)

T5.1 – Overcome roadblocks. Sub-task :1 Identification of roadblocks (M3-M7)
Description of work (Annex I):
• This task aims at identifying the differences and similarities in the processes of translational research by contrasting the processes for therapy and those for research in a science-based table.
• Methodologically, categorising types of stem cells and indicating their potential usage in the context of therapy and research will be contrasted with the current legal requirement in coordination with WP2 and 3 in order to identify the roadblocks for both therapy and research.

Deliverable D5.1 has been successfully completed.
To identify and analyse roadblock as well as to enable active stakeholder engagement the idea arose to apply a process oriented approach instead of classical collections of lists. Therefore the depiction of the process "the how is it done in reality?" of stem cell therapy and research should be easily understandable irrespective of the readers background. The process concentrates on an aggregation level to show best for which activity which regulations, legislations and directives apply.

For us the process will serves as an orientation structure, showing the succession in therapy and research, including all possible types of stem cells and applications even currently non-existing but in literature discussed ones.

The technical platform chosen to describe the process was Signavio, a professional, collaborative process design platform which is free for academic use and publication as in our case for the EUCelLEX project. This allows two different usages:
ϖ At foremost and first within the project: the idea is to ease everyone's work and collaboration:
➢ Structuring the collection of links, documents, regulations, legislations, directions or even comments according to the activities
➢ Integration of results (e.g. comparisons of legislations concerning a specific activity between different member states) structured according to the activities.
➢ The main advantage is that all collections and results become clearly represented and easily available to all partners.
b. At later stages dissemination:
o Publication or presentation to the public. The ideal would be that
• stem cell scientists can orient and identify much faster the needed information on the regulations applicable to their research/therapy
• politicians could quickly gain deeper understanding
• Legislators can more easily streamline European legislation also by structuring legislation more process oriented
• Ongoing stakeholder engagement e.g. general feedback, wiki system, comment posting, providing templates for single steps/activities
o Type and time of dissemination is in the future and open to joint discussion: open access journal publication with the process figure and link collection as supplementary material, publication of the process figure and dictionary on our homepage, integrating a wiki on our homepage for the dictionary part ...
We prepared a draft for the catalogue and collected feedback from some of partners on a one on one basis. After that, the process description was discussed with WP5 partners (P1a & b-Inserm, P2-LUH, P4-LP) in a telco, organized on July 15th 2014, accepted and distributed within EUCelLEX partners via the Signavio platform.
We invited all the partners to login into the Signavio platform to access the process and sharing information and comments about this. We provided a short description of the Signavio platform, as oriented to our needs as possible, together with the Signavio User Manual, for a description of all possible technical features.
Briefly, after getting in, a process portal with three frames opens. In the left frame you can select the view of process (Signavio calls a process a document). The process itself is visualized in the middle frame. For us the process will serves as an orientation structure, showing the succession in therapy and research, including all possible types of stem cells and applications even currently non-existing but in literature discussed ones. Should need be this process can be changed, adapted, expanded or copied. On the right frame you can see the preview of the dictionary. Clicking on legends shows the generic description of box types, and comments displays all comments in the diagram. A major advantage of this platform is the possibility to work and communicate among each other at the same time.
The result of this collaboration was presented at the EUCelLEX’s 1st International Consensus Conference (Toulouse, March 30th – 31st, 2015), in the workshop 1: Legal classifications of cell products.
We are discussing with all the partners about other dissemination possibilities.

D5.2. Legal assessment (M15)

T5.1. Overcome roadblocks. Sub-task 2: Practical assessment of roadblocks (M7-M15)
Description of work (Annex I):
• In coordination with WP2, we will collect from the identified stakeholders (Infrastructures) the concrete processes and procedures developed by the implementation of the different directives for research on the one hand and for therapy on the other.
• We will identify differences and similarities of the two approaches and will underline gaps left over by the directives especially focusing on transnational access restrictions and the issue of specific informed consent. The aim is to lay the ground for a coherent and harmonized directive that covers the spectrum from research to therapeutic applications.

Deliverable D5.2 has been completed.
The process of stem cell research, stem cell therapy and translation from research to therapy was submitted to experts in the field including Prof. Christian Chabannon and Prof. James Adjaye. They modified the scheme depicted in figure 1 to (i) identify existing concrete processes and procedures implementing the different directives for research and therapy, (ii) identify process differences/similarities and (iii) highlighting gaps left by directives especially transnational and specific informed consent.

From the data delivered via the Signavio platform we present our findings during the WS in Edinburgh and we gathered some comments from the participants (D5.3).

D5.3. Meeting for Stakeholder Engagement (M33)

T5.2. Stakeholder engagement (M15-M20)
Description of work (Annex I):
• Set up a stakeholder engagement process to link private and public partners’needs (e.g. IMI, BBMRI, ECRIN) and to discuss knowledge transfer, in particular the patent issue and the role of pre-competitive research and its implications on data protection and intellectual property rights.
• After the identification of strategies, the latter will be discussed during a dedicated meeting.

Deliverable D5.3 has been successfully completed.
Parallel sessions of WP3 and WP5 within the ELSI 2.0 and EUCelLEX Project Satellite Symposium at the 13th World Congress of Bioethics organized by the International Association of Bioethics (IAB) in Edinburgh on Tuesday 14 June 2016.
The topic of the WS within the session was: Stem cell Research Scientists meet Ethicists
Chair: Prof. Kurt Zatloukal and Prof. Georges Dagher
Invited speakers:
1) Prof. Christian Chabannon, Paoli Calmettes Institute, Marseille, France: ‘Human Stem Cell Banking & Therapeutics’.
2) Prof. Dr Peter Schlenke, Department of Blood Group, Serology and Transfusion Medicine, Graz, Austria: Title TBC.
3) Prof. Dr James A. Adjaye, Institute for Stem Cell Research and Regenerative Medicine, University Hospital of Duesseldorf – UKD, Germany: ‘Patient-derived induced pluripotent stem cell lines: applications and ethical concerns'.
Appropriate speakers for the subtopics: 3 speakers were invited from scientific as well as private partner (e.g. IMI, BBMRI, ECRIN) to link private and public partners’ needs
A report has been provided as Deliverable 5.3.

D5.4. Legal recommendations for the use of stem cells in toxicology (M25)

T5.2 – Stakeholder engagement (M15-M20)
Description of work (Annex I):
• Set up a stakeholder engagement process to link private and public partners’needs (e.g. IMI, BBMRI, ECRIN) and to discuss knowledge transfer, in particular the patent issue and the role of pre-competitive research and its implications on data protection and intellectual property rights.
• After the identification of strategies, the latter will be discussed during a dedicated meeting organised at M20.

Deliverable D5.4. has been successfully completed.
Report includes the following topics :
-Stem cells and toxicity testing (In vivo and in vitro systems, Current and potential uses of stem cells of toxicity testing, Stem Cell Pre-clinical Models and Clinical Trial in a Dish)
-Legal and patent issues
-European Patent Convention (National courts and European Court of Justice)
-Data protection
Conclusion and Aspects: After isolation of the first human embryonic stem cells (Thomson et al., 1998), there was a strong focus on the application of hESC in regenerative medicine. This would require a well controlled, animal-free system, which is able to generate exactly the types and amount of cells needed on a reproducible basis. Human stem cell-derived in vitro models hold great potential for the development of biologically relevant models for evaluating the toxicity of substances to humans. Due to the concurrent and more lucrative demand for stem cell technologies in the fields of regenerative medicine and drug development, scientific discoveries are occurring at a rapid pace and technological obstacles are being resolved (Ward, 2013). Now is an appropriate time to more fully apply this emerging technology to the development of human cell and tissue-based models for assessing human health endpoints in toxicological studies.

WP6: Cells, ethics and societal innovation

D6.1 Involved stakeholders who accepted to participate, with contacts and description of their regulatory and/or professional activity (M18)

T6.1 – Identify and contact stakeholders
Description of work (Annex I):
• In order to gather data about innovations and potential changes related to the use of human cells under the current regulatory framework, we will collaborate with WP1 to contact relevant stakeholders. These will include selected members of the EMA (especially those involved in the Committee for Advanced Therapies), members of national health councils, representatives of companies active in the field of tissue and cell medicine and, where relevant, representatives of patients associations. Interviews may be conducted with selected stakeholders in order to collect more specific data for the project.

Deliverable D6.1 has been successfully completed.
Based on relevant literature and previous activities, we have worked out a list of stakeholders that includes scientists, patients’ associations and policy makers.
Stakeholders have been mapped based on the controversies isolated in T6.2. We are in the process of contacting the following list of people:
▪ Paolo Bianco, Pathologist, La Sapienza in Rome
▪ Chris Mason, RegenMed Bioprocessing Programme, member of the UK S.Cell Foundation
▪ Reinhold G. ErbenPathophysiologist, President of the REMEDIC program of the European Science Foundation (program held from 2008 to 2013)
▪ Ramadan Jashari, MD, Board Member of European Association of Tissue Banks, Member of the EC Project on « Good Tissue Practices », 2008-2011.

▪ Regulators:
• Charles Kessler, European Commission, DG Research
• Nicolas Ferry
French representative at the EMA’s Committee for Advanced Therapies, Director of ANSM (Agence nationale de sécurité du médicament et des produits de santé)
• Nicolas Rossignol
Involved in the preparation of the ATMP directive, worked at the DG Enterprise and Industry, Unit Pharmaceuticals, from 2003 to 2008.
• Cathie Vielle
Head of the European Pharmacopoeia Department, EDQM (CoE). Works on the EMA - EDQM collaboration for standardization of biological medical products.
• Joana Namorado
MD, DG Research, Scientific Officer, Ethics, Stem Cells and Gender Sector.
▪ Patients organizations: François Houÿez, Health Policy Advisor at the European Organisation for Rare Diseases (NGO), representative of patients at the EMA’s Patients’ and Consumers’ Working Party.
▪ Industries:
• Cécile Orsini, Sanofi, Senior Scientist, R&D Médecine Régénérative
• Frédéric Revah, Director Genethon.

These stakeholders have been interviewed following a methodology that has already been established. Furthermore, we noticed the emergence of new sociotechnical synergies regarding adaptive pathways for drug development that we deem important to include in our work. We have established contact with key figures in this respect, including one EMA official (Hans-Georg Eichler) and the director of the New Drug Development Paradigms (NEWDIGS) program at MIT’s Centre for Biomedical Innovation (Cambridge, MA – USA). The work of these people is relevant for the scope of our project since, their new approach is being negotiated at NEWDIGS with the strong involvement of EMA, which has recently launched a pilot to test the new pathways. This new modality of drug development embodies a regulatory imaginary that has very much been prominent in regenerative medicine and may offer new regulatory routes for the development of ATMP too.

Meanwhile, we have solidified our contacts with key figures in the field of genetically modified Hematopoietic SCs (TIGET, Milan – recently on Science for groundbreaking clinical success in this field): they are currently expanding their technique to other diseases, each of which presents peculiar ethical and societal aspects due to the target population and the design of the clinical studies.
We have also integrated data from selected IPS fieldworks to determine whether these techniques and infrastructure involve derived or competitive societal imaginary, compared to expectations surrounding stem cells obtained through other methods

D6.2. Dossier containing the data collected and interpreted by WP6 (M24).

T6.2 – Data collection and interpretation (M6 to M24).
Description of work (Annex I):
• WP6 leaders will interact with stakeholders and WPs 2, 3 and 4 to collect data about controversial cases regarding storage, basic research and clinical use of human cells. Those cases will be selected on the basis of their ethical and societal relevance with respect to the present regulatory framework: they will thus represent a repertoire of concrete issues that impinge on the future governance of cells use. Data will be collected in a dossier and will be interpreted according to the analytic approaches developed and already practiced by WP6 coordinators.

Deliverable D6.2is successfully completed.
• Corpus web of stem cell community
We specify an ad hoc analytic notion of social representation in biomedecine. We find that this notion is not independent of what makes the stem cell community, the feeling of belonging to it. For that, we use Benedict Anderson’s work regarding components of collective imaginaries.
We chose to explore social representations of stem cell communities by constructing 2 corpus of databases :
- the first one is related to publications on stem cells (key words, citations, journal) with Scopus (scientometric analysis);
- the second one is related to Stem Cell controversies (mapping and analysis of the active website) with Hyphe* software. This task begins with the inventory of controversies on unproven stem cell therapies and relevant stakeholders (scientific societies, Tissue banking, lobbies, companies, Science Centers, Translational infrastructures) in stem cell debates prepared for this purpose (T6.1. – involved stakeholders).
* Hyphe is an Open Source software developed by the Médialab of Sciences Po Paris. It is composed of a server application that has to be installed on a server, and a web interface accessible from any HTML5 browser (Google Chrome, Firefox...).
Hyphe is a web corpus curation tool designed to allow a researcher setting-up a web corpus, consisting in an organized selection of web pages and hyperlinks. A corpus obtained with Hyphe has the same methodological properties as in social sciences; it is a set of contents curated by the user for specific research questions. Hyphe embeds a web crawler charged of harvesting web contents. However this crawler is driven from a specific curation interface. The corpus curation process involves selection, optimized prospection and visualization. Optimized prospection proposes the most cited resources for selection, because they have a high probability to be relevant. The more resources you curate and the more precise is your selection, the more efficient is the prospection. In addition you can monitor the corpus as a network to visualize some of its properties like clusters or structural holes. The list of resources can be exported as a list in different formats and the network can be exported as a GEXF. Then it can be analysed and explored in a network visualization software like Gephi.
Hyphe is a mean to study spontaneous articulations of stem cells on the World Wide Web (blogs, forums, institutional websites, public pages of social networks and exhibitions...). It aims at detecting communities effects (where) and argument specialization (what) using a web corpus built on the topic.
A sample of temporary results:

• Specific focuses on controversies related to translational medicine
From our work on social representations of stem cells, we are isolating controversies to collect data. In particular we selected the Stamina case, the Regenexx case and the Celltex case. Our preliminary data confirm that the public debate around unproven cell therapies, far from being restricted to pure regulatory conflicts, decidedly extends to embrace a host of socio-political issues, as specific socio-technical imaginaries are forming around the clinical translation of stem cells.
One of the first activities we implemented in order to start a groundwork on these themes has been the organization of an interdisciplinary panel at the IPSA (International Political Science Association) conference in Montreal (22 July 2014) about representations related to bio-products and (in)-stability of their institutions. 3 communications related to stem cells:
This panel explores relationships between biology and politics, with a focus on the governance of life-related technologies and their public exhibition.
Moreover we have integrated in our work the emerging issue of adaptive licensing as a new way of imagining the translational pipeline of stem cell research in Europe (and in the US). Ethical considerations concerning the risks that patients can be allowed to take play a central role in this issue. Furthermore, the trade-off between evidence and access to new product is a common theme, both in the controversies we analyse and in the regulatory proposals that we are documenting.

• Qualitative Analysis and semi-structured interviews. A social representation of what?
Our aim was to make isolate disjunctive imaginings of technological future(s) linked to stem cells and their uses. To this aim we developed the following reading grid.
1. Stem Cell public(s). We call publics those stakeholders whose practices rely on specific representations of stem cells. These publics can be existing, virtual or imagined by stem cell producers and operators (both academic, industrial), patients, regulators and decision makers: a social representation of something implies a target public.
2. The material organization of stem cell practices. The social representation of stem cell practices inscribes an imagined future into cellular materiality, thereby constituting socio-technical imaginaries: a social representation of something implies having an idea of its future.
3. Stem cells and the State. Usefulness of stem cell products for the society, the state, the population(s). The relation of public and private agency to be efficient in stem cell practices: a social representation of something implies having a specific relation to the territorial dimension – sovereignty – of the State.

The hypothesis we made is that stakeholders do not necessarily have the same views on these three aspects (publics, materiality and the State) related to their representations of stem cells.

D6.3. Workshop and related report (M32).

T6.3. Organize a workshop.
Description of work (Annex I):
• In coordination with WP1, we will organize a workshop that will include stakeholders as well as all other project members. The aims of the workshop will be to: present the collected data, discuss selected cases that represent a challenge for current regulatory arrangements, and lay down the bases for a strategic document.

Organized by Virginie Tournay (CNRS, CEVIPOF 7048), Alessandro Blasimme (INSERM U 1027 Toulouse III, University of Zurich, Switzerland, Adeline Néron (EHESS-IFRIS France), a Workshop has been held in 11-12 May 2016 in Paris, with the subject : “Stem Cells in Translation: The Governance of Clinical Promise in Regenerative Medicine”
This Workshop aimed to bring together academic experts on regenerative medicine and stem cells. An overall focus was narratives on stem cells research and clinical translation, regarding their promises and governance models. First we worked on the general formulation of the issue and its incentives. A call for proposals was released in different networks.
(see:«stem-cells-translation-governance-clinical-promise-regenerative-medicine» ).
A report has been provided as Deliverable 6.3.

WP7: Integration, synthesis and recommendations

D7.1. Draft recommendations (M34)
T7.1 – Synthesis
T7.2 – Recommendations strategy.
Sub-task 1. Elaboration of the recommendations.
Description of work (Annex I):
• In order to integrate work realised by the different partners, we will use the results of the deliverables, of the workshops and of the first conference of consensus provide a synthesis and some analysis of the first tracks in order to develop some recommendations. The objective of this synthesis is to compile the results of the various coordination activities carried out in the project, but also to provide specific added value that is more than the sum of single contributions.
In the meantime, we will use this work to build the frame of a book constituted by the synthesis and oriented towards academics. This main subtask will be to discuss the topics and to identify potential contributors to this book (to be finalised in task 7.2)

See D7.3

D7.2. EUCELLEX final international conference of consensus and report (M36)

T7.2 – Recommendations strategy.
Sub-task 1. Elaboration of the recommendations.
Description of work (Annex I):
• The first generation recommendations will be drafted by P1a and will be submitted for discussion to all consortium’s members. Subsequent exchanges, associating also stakeholders, will be performed by mails, telephone discussions and will be finalized at a consensus Conference towards the end of the project.
During the development of the recommendations, external reviewers will be appointed upon proposal of WP participants, with the aim to provide comments on these recommendations. The goal is to reach a consensus on ethical and legal high quality standards to be applied in the field of stem cells but also to provide guidance to the European Commission on future actions.
During this Conference will also be discussed the dissemination plan of the recommendations, their publications in high impact factor journals but also their dissemination modality to stem cells key stakeholders.

Under the topic “Engaging stakeholders for responsible stem cells research” the EUCelLEX Final International Conference was held in Paris in September 2016, the 22nd and 23rd (M36, as initially planned).
The aim of the conference was to set up a Task Force for improving the collaboration of key stakeholders involved in the questions raised by the use of stem cells.
This event was structured in two parties:
• On the 22nd of September, the EUCelLEX consortium presented the results of the analysis of the current European and national legislations in regards to the practices that are due to develop in the near future and of the recommendations to the European Commission. We insisted on the setting up of national and international research infrastructures and we presented our draft about recommendations to the European Commission (task 7.1).
The program consisted of plenary sessions and round tables.
• On the 23rd of September, we proposed a joint workshop with the the European Association of Health Law, about “Stem cells banking, legal conditions and governance issues“. This has resulted in the setting-up of an Interest group on Biobanks (leaders AM Duguet and E. Rial-Sebbag) with the involvement of some of the EUCelLEX partners.

Relevant information about this event was provided and periodic updated in the project Website (Homepage and dedicated page).

A report has been provided as Deliverable 7.2

D7.3. Final book Table of content (M18)

T7.2 – Recommendations strategy.
Sub-task 2. Preparation of EUCelLEX book.
Description of work (Annex I):
• The final outcome for this project is to disseminate through the publication of a book, the results gathered by all the WPs. This publication will come in addition to the partners individual publications. For the need of the elaboration of the blueprint we will propose and choose the key results we want to highlight and those which can be considered as key issues for the future of Stem cells research in the future. The spirit of the book will be to deliver the picture of the ELSI issues on Stem cells by the end of the project, and to open rooms for discussions in the future. For this second part we will confirm and invite guests to contribute.

We have started the production of the book to be published in early 2017. The synopsis of this ebook (to be published in an electronic version, contract already realized with the Editor on behal of the EUcelLEX consortium) entitled “Governing Stem cells Regenerative medicine in Europe: the vision and recommendations from the EUcelLEX project” has been produced (D7.3). In this book we will present the main results and findings from the facts and figures collected through the analysis of the literature, through interviews and tools in the different workpackages of our project and after the inputs from experts we have invited in the two conferences of consensus.
After this introduction the book will be composed by the following chapters:
• Chapter 2. WP2 Stem cells sources and procurement, University of Hungary (Judit Sandor, HU) and Legal Pathways (Jasper Bovenberg, NL)
• Chapter 3. WP3 Stem cell uses, Oxford University (Jane Kaye, UK) and Hannover University (Nils Hoppe, GE)
• Chapter 4. WP4 Cord blood banks, McGill University (Bartha Knoppers, Rosario Isasi, CAN) and Leuven University (Herman Nys, Pascal Borry, BEL)
• Chapter 5. WP5 Translational research, University of Medicine Graz (Kurt Zatloukal, AUST) and INSERM US13 (Georges Dagher, FR)
• Chapter 6. WP6 Cells, Ethics and societal innovation, CEVIPOF (Virginie Tournay, FR) and INSERM UMR 1027 (Alessandro Blasimme, CH)
We will end this book by pooling together the different recommendations we have discussed in WP7:
• Chapter 7. WP7 Final recommendations of the EUCelLEX project.

Potential Impact:
1. Scientific dissemination.
All the WPs’ members were involved in strong communication and dissemination activities either through publications or communications activities.

The members of EUCelLEX have published in high level journals either in Biomedical Sciences or in Social and humanities journals (n. 13 in peer review journals).In addition they have contributed through book chapters (n.6) and proceedings of workshops (n.3). The variety of the modes of publication should be noticed as a will to be inclusive in order to be and stay connected to the Biomedical Sciences world and close to the ongoing progresses in Stem cells activities.

Some publications activities are pending to be achieved in 2017:
- Three articles are submitted:
o Marton Varju and Judit Sándor, “Generic or Specific? The Frames of Stem Cell Procurement Regulation in Europe”, Center for Ethics and Law in Biomedicine, Central European University, Budapest, submitted to SCRIPT-ed.
o Alessandro Blasimme, “Play at your own risk: regenerative medicine and the logic of moral segregation”; in ordinary extraordinary. Ethnographies of risk, limits and exposure. Edited by Beata Świtek, Hannah Swee and Allen Abramson; Palgrave Macmillan (NY).
o Cells’safety in Europe: towards an Ethical Safety, E. Rial-Sebbag, A. Mahalatchimy, A-M Duguet, International Journal of Bioethics, accepted.
- We are preparing the ebook to be published by January 2017 (see D7.3) presenting the whole architecture of the project, its objectives, the main results by WP and the recommendations we want to address to the Commission and the policy makers.

All WPs have presented their findings towards various communities in Social and humanities congresses and in the biomedical arena (Oral presentations n.44 poster n.6). Most of them have been presented in International meetings in English but, in order to engage the national communities and in particular patients ’organisations, some have been done in local languages.

2- Public dissemination.
In order to raise awareness about the EUCelLEX project and to ensure communication with all relevant stakeholders including the public, WP1 has proposed some tools at an early stage of the project. We have developed a website composed in two parts: a public part and a private part. The public part is delivering global information on the governance of Stem Cells in Europe and worldwide through a systematic survey of relevant scientific articles presented on the website and an access to the directory composed by the main stakeholders in Stem Cells. The articles are presented in order to rapidly identify those produced on behalf of the EUCelLEX partners. The public part of the website is also providing information about the EUCelLEX project, its objectives, the description of the partners and of the WPs. The website has also served to inform about the 4 workshops and the 2 conferences organised on behalf of the project. It delivers links to various resources serving as basic information on stem cells. The private part was dedicated to the communication within the consortium. This area was used to exchange documents and discuss internal issues.
In addition we have realised flyers about the project in collaboration with the Science communication department of Inserm. These flyers were sent to all the partners in order to be distributed in their local institutions but also in the conferences they were attended.

3- Engagement with stakeholders.
EUCelLEX, in the second part of its « life », has decided to engage into networking activities towards new partners in order to raise awareness on the project and its outcomes and to identify future collaborations to be enforced even after the end of the project. As one of our goals was to set up a European task-force on Stem cells, we first engage with individuals representing various stakeholders (researchers in biology, biomedical sciences, social and humanities; representative of Agencies such as the Committee of Advanced Therapies or EMA). We then decided to enlarge this first circle to involve more institutional actors such as patients’ organisations, infrastructures, institutes and the public. These networking activities were organized first with already identified organisations (such as the Association de Recherche et de Formation en Droit medical) and were extended in the life course of the project notably towards foreign institutions (e.i. Japan). These stakeholders were invited to present at the final EUCelLEX conference entitled “Engaging stakeholders for responsible Stem Cells research” held in Paris in September 2016. All the WPs have contributed to identify the relevant stakeholders; it has resulted in the completion of a Directory on the website of EUCelLEX. In addition, some specific research has been performed involving these stakeholders either through the completion of interviews (WP2 and WP6) or through their involvement in the 4 workshops (Budapest, Toulouse, Paris and Edinburgh) and the 2 conferences (Toulouse and Paris) organized by the partners.

In addition we have conducted specific actions towards the recognition of the work done in EUCelLEX and beyond:
1/ Collaboration action with the Revive Labex (
Rationale and Objectives of Revive Consortium.
Major advancements in stem cell biology have paved the way for concerted research activities on the fundamental biology of stem cells and their applications in the clinic. The medical potential of stem cells will require the development of, and reinforcement of, studies ranging from those in vivo using a variety of model organisms, to cell-based therapies in the clinic. The principal objective of Revive is to unite academic and industrial Partners to consolidate and facilitate research on stem cells in the context of fundamental biology, disease, regenerative medicine and ageing. This consortium is made of of 6 academic Partners (Institut Pasteur, INSERM, CNRS, INRA, UPMC-Paris VI, ENVA) representing 22 scientific and medical (Institut Cochin, Européen G. Pompidou and Pitié-Salpétrière Hospitals) research teams developing close interactions with selected biotech companies. It is funded the ANR "Laboratoire d'Excellence" programme (2011 - 2019) with research activity on stem cells in regenerative biology and medicine.
We have organized with Revive a seminar in June 2016 towards the funders of Institut Pasteur in order to present the issues and challenges raised by Stem cells tourism, with the contribution of E. Rial-Sebbag and Alessandro Blasimme. Since this meeting we have intensified our relationships notably through the setting up of the French Society of Stem cells.

2/ Creation of the French Society of Stem cells.
EUCelLEX has been identified at playing a major role in the governance of Stem Cells at the European level. To this end E. Rial-Sebbag has been invited to the creation of the French Society of Stem cells ( in November 2016 and encouraged to coordinate a working group on the ELSI issues. This Society intends to play a major role in France for discussing with the funders for increasing the research resources and to link with the relevant societies in Europe. The coordination team puts strong emphasis on the needs to include in their activities reflections on ELSI.

3/ Cooperation with Associations in law.
- Association française de recherche et de formation en droit médical (ARFDM).
The French partner (Inserm) has a long standing cooperation with the ARFDM. In particular, they have developed collaborations with Chinese Universities in the past. This experience was brought for enforcing the activities of EUCelLEX. This led to various communications presented by students in China and also to the realization of a dedicated workshop in September 2016. This has taken the form of a joint workshop (ARFDM – EUcelLEX, see annex 1).

- European Association of Health law (EAHL).
E. Rial-Sebbag is an elected member of the General Assembly of the EAHL. Due to this position she has reinforced the interest of this association for the legal and ethical questions posed by the uses of Stem cells in Europe. This has led to the organization of a joint meeting during the final conference of EUCelLEX organized in Paris entitled “Stem cells banking, legal conditions and governance issues“where speakers from both partners were invited to present. This collaboration has been opened up thanks to the creation at the same time of an Interest Group of Biobanks where members of EUCelLEX have expressed their interest to be part of.

4/ Common representation of Substances of Human Origin’s (SoHO) EU
Finally our group has been contacted to contribute to a call launched by DG SANTE aiming at identifying relevant stakeholders interested in participating in ad-hoc meetings with representatives of Members of the Competent Authorities on Substance of Human Origin. This group has been selected ( and will contribute to the future discussions of the needs to turn the Tissues and cells directive into a regulation.
Our group is probably the most invested in the ethical and legal questions and the work done in EUCelLEX for assessing the current legal European frameworks will be highly valuable.
This group is led by John Armitage, President of European Eye Bank Association with the contribution of:
- European Association of Tissue Banks (EATB);
- European Society for Blood and Marrow Transplantation (EBMT);
- European Eye Bank Association (EEBA);
- European Blood Alliance (EBA).
- European projects such as AGORA and EUcelLEX.

The main goal of this consortium is to provide representative technical expertise to the European decision making organizations in the field of SoHO.
In particular, the aforementioned Associations would wish to be formally represented in official consultation forums so as to provide technical information to be used in drafting of new legislation and revising existing legislation. The information will be gathered by surveying technical experts working in the field among our members, including but not limited to tissue establishments, academic GMP-facilities and technical experts.

This common representation identified the main activities and goals:
- Promote ethical principles (non-financial gain, voluntary and altruistic donation) by demonstrating their impact for the quality and safety of T&C;
- Sponsor the high value of SoHO’s therapies;
- Promote the safety and quality and the development of new therapies;
- Provide technical inputs to the drafting of directives and regulations by the EC;
- Influence the establishing of rules and limits applied to ATMP classification and borderline products (where classification of a product based on genes, cells or tissues is not clear) based on technical knowledge;
- Encourage procedures’ harmonization regarding Hospital exemption performed by different member states;
- Promote T&C/ATMP sufficiency at EU level;
- Ensure affordability and support patient’s accessibility to new treatments (lower cost/public sector);
- Respond on behalf of the AGORA network on ATMP regulatory framework

List of Websites:
The address of the project public website is:

Relevant contacts:

Partner 1, INSERM
Project coordinator : Dr Emmanuelle Rial-Sebbag
Directrice de recherches Inserm
UMR 1027, Inserm, Université de Toulouse - Université Paul Sabatier -Toulouse III,
Responsable Equipe 4: "Trajectoires d'innovations en santé : enjeux bioéthiques et impact en santé publique"
37, allées Jules Guesde, 31073 Toulouse Cedex (France)
Tel : +33 (0)5 61 14.56.16 - Fax : +33 (0)5 61 14.56.23
E-mail :

Co-leader WP1 and WP7: Dr Anne Cambon-Thomsen
Directrice de recherche émérite au CNRS
UMR 1027, Inserm, Univ Toulouse III - Paul Sabatier
37 allées Jules Guesde F-31000 Toulouse (France)
Tel : +33 (0)5 61 14 59 59 - Fax : +33 (0)5 61 14 56 23
Mobile: +33 (0)6 79 41 13 48 Skype: act_pro
E-mail :

Co-leader WP5 : Dr Georges Dagher
Infrastructure BIOBANQUES -Inserm US13
Hopital de la Salpétrière
47, Bvd de l’Hôpital - 75013 Paris
+331 42 16 25 61
+336 75 36 79 47

Co-leader WP6: Dr Alessandro Blasimme
University of Zurich
Epidemiology, Biostatistics and Prevention Institute - Health Ethics and Policy Lab
Phone: +44 634 49 53

Partner 2, Leibniz Universitaet Hannover
Co-leader WP3 : Prof Nils Hoppe
CELLS - Centre for Ethics and Law in the Life Sciences
Institut für Philosophie
Leibniz Universität Hannover
Am Klagesmarkt 14-17
D - 30159 Hannover | Germany

Partner 3, Central European University, Budapest
Co-leader WP2: Prof Judit Sandor
Centre for Ethics and Law in Biomedicine (CELAB)

Partner 4, Legal Pathways
Co-leader WP2 : Dr Jasper Bovenberg
Legal Pathways Institute for Health and Bio-law
Aerdenhout, the Netherlands

Partner 5, Oxford University
Co-leader WP3: Prof Jane Kaye
Centre for Health, Law and Emerging Technologies (HeLEX)
Wellcome Trust University Award Holder
Nuffield Department of Population Health, University of Oxford
Ewert House, Ewert Place, Banbury Road, Summertown, Oxford, OX2 7DD, United Kingdom
Skype: jane_kaye Direct: +44(0)1865 287898

Partner 6, Medical University of Graz
Co-leader WP5: Prof Kurt Zatloukal
Medical University of Graz/Institut of Pathology
Auenbruggerplatz 25/1, 8036 Graz, Austria

Partner 7, Fondation Nationale des Sciences Politiques
Co-leader WP6: Virginie Tournay
Chargée de recherche CNRS/ Permanent CNRS Researcher
CEVIPOF. Centre de recherches politiques de Sciences Po
98, rue de l'Université. 75 007 Paris
tél. +33 (0)1 45 49 77 27

Partner 8, KU Leuven
Co-leader WP4: Prof Herman Nys
Center for Biomedical Ethics and Law

Partner 9, McGill University
Co-leader WP4 : Prof. Bartha Maria Knoppers, Ph.D O.C. O.Q.
Canada Research Chair in Law and Medicine
Director, Centre of Genomics and Policy
Faculty of Medicine, Dept. of Human Genetics,
McGill University,
740 Dr. Penfield Avenue, Room 5214,
Montreal, QC., Canada H3A 0G1
Tel: 514 398 8866 - Fax: 514 398 8954