Framing and legitimating EU legal regulation of human gene-editing technologies: key facets and functions of an imaginary.

Gene-editing technologies, ie those able to make changes in the DNA of an organism, are the object of global competition and a regulatory race between countries and regions. There is an attempt to craft legal frameworks protective enough for users, but flexible enough for developers of gene-editing technologies. This article examines the imaginary built into the framing of EU-level legal regulation of human gene-editing technologies and identifies its three key related facets: the tension around naturalness; safeguarding morality and ethics; and the pursuit of medical objectives for the protection of human health. Concerns around the use of gene-editing technologies in relation to eugenics and human enhancement have produced a multifaceted imaginary. We argue that this imaginary not only places a limit on EU-level regulation, despite a strong EU competence in respect of the internal market, but also seeks to ensure its legitimation.

[Chapter 2. Clinical trials of advanced therapy medicinal products: which future for the European regulation]. / Chapitre 2. Les essais cliniques de médicaments de thérapie innovante : quel avenir pour la réglementation européenne.

In relation to the ?hot? topic of regenerative medicine, European Union law established a specific legal framework for advanced therapy medicinal products, manufactured from human or animal genes, cells or tissues. However, these medicinal products do not have always to be submitted to clinical trials as legal requirements vary according to the intended use: market of the whole of Member States, compassionate use, and hospital exemption. Moreover, specificities of these medicinal products make clinical trials difficult to be conducted. This paper highlights the consecutive competition between regulations and products that takes roots in the tension between the challenges of patients' safety and quick access to innovative treatments. It also shows the regulatory flexibility currently favored to ensure the necessary balance between safety and availability, is not without limits.

The emerging landscape of reimbursement of regenerative medicine products in the UK: publications, policies and politics.

AIM: This paper aims to map the trends and analyze key institutional dynamics that constitute the policies for reimbursement of regenerative medicine (RM), especially in the UK. MATERIALS & METHODS: Two quantitative publications studies using Google Scholar and a qualitative study based on a larger study of 43 semi-structured interviews. RESULTS: Reimbursement has been a growing topic of publications specific to RM and independent from orphan drugs. Risk-sharing schemes receive attention among others for dealing with RM reimbursement. Trade organizations have been especially involved on RM reimbursement issues and have proposed solutions. CONCLUSION: The policy and institutional landscape of reimbursement studies in RM is a highly variegated and conflictual one and in its infancy.

Chapitre 6. Cells? safety in Europe: Towards an ethical safety.

To encourage and maximise the use of human biological material in Europe, the European Commission instigated a main Directive in 2004 (Directive 2004/23/EC), four technical ones in 2006 (Commission Directives 2006/17/EC and 2006/86/EC) and in 2015 (Commission Directives (EU) 2015/565 and (EU) 2015/566). They encourage the donation of tissues and cells for transplant purposes in the safeguard of public health. Another major aim of Directive 2004/23/EC is to guarantee recipients' safety in transplantation. Hence, measures for accreditation of establishments storing, preparing and distributing tissues and cells are required to be implemented in Members States' jurisdictions. In addition, adequate training is required for the personnel directly involved in such activities. Despite the adoption of a ?full legislation,? the EU legal framework for cells cannot be seen as totally harmonized. In this article we first address the issues posed at the European level by the uses of human cells as therapeutic agent with regards to their qualification: body elements? Medicinal product? We study the ways to address these bioethical dilemmas at an EU level. Then we discuss the impact of this qualification in terms of safety through the definition of safety's measures and their limits regarding the directive's scope. We conclude with the emergence of an ?ethical safety?.

REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

Cell-based regenerative therapies are presented as being able to cure the diseases of the twenty-first century, especially those coming from the degeneration of the aging human body. But their specific nature based on biological materials raises particular challenging issues on how regulation should frame biomedical innovation for society's benefit regarding public health. The European Union (EU) supports the development of cell-based regenerative therapies that are medicinal products with a specific regulation providing their wide access to the European market for European patients. However, once these medicinal products have obtained a European marketing authorisation, they are still far away from being fully accessible to European patients in all EU Member States. Whereas there is much written on the EU regulatory system for new biotechnologies, there is no systematic legal study comparing the insurance provisions in two EU countries. Focussing on the situation in the UK and France that are based on two different healthcare systems, this paper is based on a comparative methodological approach. It raises the question of regulatory reimbursement mechanisms that determine access to innovative treatments and their consequences for social protection systems in the general context of public health. After having compared the French and English regulations of cell-based regenerative therapy regarding pricing and reimbursement, this papers analyses how England and France are addressing two main challenges of cell-based regenerative therapy, to take into account their long-term benefit through their potential curative nature and their high upfront cost, towards their adoption within the English and French healthcare systems. It concludes that England and France have different general legal frameworks that are not specific to the reimbursement of cell-based regenerative therapy, although their two current and respective trends would bring more convergence between the two systems while addressing the main challenges for the reimbursement of these therapies. Nevertheless, despite their current differences, neither the English nor the French national healthcare system has yet approved the reimbursement of cell-based regenerative therapies. The paper highlights where both systems could be learning from each others' experiences to favour the adoption of cell-based regenerative therapies through the adaptation of their reimbursement methodologies. It also emphasises the gap between market access and patients' access, and it calls for research and discussions through reflexive agencies such as the Regenerative Medicine Expert Group in the UK.

Are there specific translational challenges in regenerative medicine? Lessons from other fields.

There is concern that translation 'from bench to bedside' within regenerative medicine (RM) will fail to materialize, or will be dismally slow, due to various challenges arising from the highly novel and disruptive nature of RM. In this article, we provide a summary of these challenges, and we critically engage with the notion that such challenges are specific to RM. It is important, we argue, not to overstate the exceptional nature of RM, as valuable lessons can be learned from elsewhere in medicine. Using several examples of technology adoption, we suggest that emerging RM products and procedures will have to work hard to find or create an adoption space if translation into the clinic is to be successful.

[Academic cell therapy facilities are challenged by European regulation on advanced therapy medicinal products]. / Les unités de thérapie cellulaire à l'épreuve de la réglementation sur les médicaments de thérapie innovante.

Regulation (EC) n° 1394/2007 from the European Parliament and the Council describes a new category of health products termed « Advanced Therapy Medicinal Products ¼ (ATMPs). ATMPs derive from cell engineering, tissue engineering or genetic manipulations, and can in some instances be combined with medical devices. ATMPs are distributed and administered to patients, after biotechnology or pharmaceutical companies have obtained a marketing authorization that is granted by the European Commission on the basis of the European Medicines Agency (EMA) assessment. Seven years after the publication of the regulation, few of these therapies have received a marketing authorization, and even fewer have met commercial success, suggesting that a number of medical and economic issues still need to be sorted out in order to achieve sustainability in this field. The coexistence of three sets of rules for three categories of health products that are biologically and medically related - ATMPs, ATMPs produced under the hospital exemption rule, and cell therapy products (CTPs) (a specific legal category in France) that have long been used in hematopoietic cell transplantation - constitutes a complex regulatory framework. This situation raises significant issues for historical as well as emerging operators in this moving field that are discussed thereafter.

Communication of results and disclosure of incidental findings in longitudinal paediatric research.

BACKGROUND: Communicating results to research participants is an issue frequently discussed in terms of ethics. It has specific features when involving large-scale paediatric cohorts. High-throughput biological explorations reveal also incidental findings of medical relevance. This work analyses existing frameworks for managing such issues and proposes a policy grounded in the experience acquired in the FP7 EU project MeDALL-Mechanisms of the Development of ALLergy. METHODS: A bibliographical analysis was performed using law, ethics and academic documentation. Empirical data were acquired through informed consent forms from 9 of the 13 cohorts used in MeDALL and from replies to a general questionnaire (n = 10) on ethical issues sent to consortium members. Group discussions and expert consultations were conducted during project meetings. RESULTS: The notions of research results and incidental findings remain ambiguous as no agreed definition exists. The most appropriate terms are communication of results and disclosure of incidental findings. No legal norm and no specific guidance govern these issues in paediatric research at European level. Relevant policies depend on decisions in each cohort or project. The policy proposed states that these issues should be discussed during the informed consent process, with due attention to involvement of children, and a balance of interests between children, parents and society. A moral duty for researchers to communicate such information only applies if certain medical and social criteria are met. CONCLUSIONS: As there is no consensus within European Birth cohorts how to deal with results and incidental findings, we propose a general policy.

The European Medicines Agency: a public health European agency?

The European Medicines Agency (EMA) is a European Agency as it is a decentralized body governed by European public law; it has its own legal personality and is also distinct from the European Union institutions (Council, Parliament, Commission, etc.). The EMA presents itself, and is commonly recognised, as a public health agency. This is notably supported by its recent transition from the Regional Direction of Research to the Regional Direction of Public Health. Four recognized principles of public health can be identified as such: assessment, transparency, precaution and independence. These principles appear to be closely linked to those forming the basis of good European governance regarding agencies: efficacy, coherence, openness, participation and responsibility. Thus, it is interesting to study how these principles are applied by the EMA in order to assess the reality of its qualification as a Public Health European Agency. The principles of assessment and transparency seem to be largely applied whereas the principles of precaution and independence are more problematic.

The legal landscape for advanced therapies: material and institutional implementation of European Union rules in France and the United Kingdom.

In 2007, the European Union adopted a lex specialis, Regulation (EC) No. 1394/2007 on advanced therapy medicinal products (ATMPs), a new legal category of medical product in regenerative medicine. The regulation applies to ATMPs prepared industrially or manufactured by a method involving an industrial process. It also provides a hospital exemption, which means that medicinal products not regulated by EU law do not benefit from a harmonized regime across the European Union but have to respect national laws. This article describes the recent EU laws, and contrasts two national regimes, asking how France and the United Kingdom regulate ATMPs which do and do not fall under the scope of Regulation (EC) No. 1394/2007. What are the different legal categories and their enforceable regimes, and how does the evolution of these highly complex regimes interact with the material world of regenerative medicine and the regulatory bodies and socioeconomic actors participating in it?