1 Introduction
Stem cell technologies, including the procurement of stem cells for research or for therapeutic purposes, are subject to fairly extensive regulation in Europe both at national and supranational level. Predominantly, the relevant regulatory instruments deal with questions which usually appear in the regulation of emerging biomedical technologies, such as risk, quality and safety, the ethics of biomedicine and biomedical research, or the achievement of public health objectives. Stem cell technology-specific measures, if they are available, address matters which have direct connection with the procurement and use of stem cells in biomedicine. The most frequently regulated is the determining of the permitted sources of stem cells. In most countries, these and other relevant regulatory frames are covered as integral parts of broader measures regulating generic areas, such as assisted reproduction, tissue and cell donation, or biomedical research. Only a few states have adopted instruments which are dedicated per se to stem cell technologies. These address certain issues prioritised in the local and European bio-legal discourse – for example, the availability of supernumerary human embryos for stem cell procurement – rather than regulating the technological domain comprehensively.
In this article, we examine the different regulatory regimes in Europe through the different frames they employ in regulating stem cell procurement. This comparative exercise is carried out to assess – considering the potential held by stem cell technologies in terms of future public health benefits, in particular their application in regenerative medicine – whether their regulation in stem cell technology-specific measures should be preferred over the use of general biomedical regulation. This issue bears relevance from the perspective of the broader dilemma specific to technology regulation, namely the ensuring of an adequate “connection” between rules and the technology regulated. The diversity of provisions governing the relevant regulatory frames as revealed in this article indicates that, in their current state, the regulatory systems examined operate as mixed regimes offering different – both generic and specific – solutions, which in turn suggests the availability of multiple practices in securing the connection between stem cell technologies and the diverse rules applicable to them. On this basis, there may be a case for considering inter-systemic regulatory learning and borrowing provided that, having regard to the significant public health benefits promised, the connection between rules and stem cell technologies is sought to be improved by regulators.
This article is structured as follows. Firstly, it examines the broader basis in regulatory theory for comparing the regulatory frames as covered in the different systems of biomedical technology regulation in Europe, namely the dilemma of connecting rules with the technology regulated and the related issue of choosing between generic or specific provisions to secure regulatory connection. This is then followed by a comparative overview of the frames of stem cell technology regulation in different European states with a focus on the regulation of stem cell procurement. The article closes with an analysis of the regulatory variety and trends revealed by the comparative exercise having regard to the considerable diversity of solutions and practices. The legal material and ideas discussed in this work follow from the legal mapping report prepared in the EUCelLEX research project financed from the EU 7th Framework Programme, which examined and compared the regulation of stem cell procurement in Canada and a select group of states in Europe.
2 Regulatory frames and technology regulation: A regulatory tango
When analysing the regulation of stem cell technologies and the technologies of stem cell procurement,
In this interplay, law and legal regulation participate with limited capabilities. Its desire to distinguish between the different components of the technology and accordingly set up categorisations assigning prohibitive or permissive rules to the components identified
With these uncertainties in mind, revisiting which regulatory frames are used by different regulatory regimes and how they – employing generic or technology-specific provisions regulating those frames – connect with the technology regulated is not only a justifiable, but also necessary exercise. In the stem cell domain, there are significant public health objectives at stake, as promised by the emerging biomedical area of regenerative medicine. Realising these should not be hindered by rules which are inadequately connected with the technology or with particular dimensions of that technology. The concept of connecting regulation to the technology in question was raised in the discourse in regulatory theory.
The regulatory connection discourse, in analysing the problems of securing adequate connection, also touched upon the choice between generic and technology-specific rules in the regulation of the relevant regulatory frames. It did not propose definitive answers in this regard, rather it highlighted the dilemmas and pointed to the ongoing interplay between rules and the technology regulated.
Table 1. The national measures available to regulate stem cell procurement.
Austria | Act on Medically Assisted Reproduction | Act on Tissue Quality and Safety | ||
Belgium | Act on Medically Assisted Reproduction and on the Fate of Supernumerary Embryos and Gametes | Act on the Procurement and Use of Human Bodily Material for Medical Purposes and for Purposes of Scientific Research | Act on Research on In Vitro Human Embryos | |
France | Public Health Code | |||
Germany | Embryo Protection act | Stem Cell Act | Transplantations Act | Transfusions Act |
Hungary | Act on Health Care | |||
The Netherlands | Embryo Act | Foetal Tissue Act | Act on the Quality and Safety of Body Material | Act on Medical Research involving Human Subjects |
United Kingdom | Human Tissue Act 2004 | Human Fertilisation and Embryology Act 1990 |
3 The frames of stem cell procurement regulation in Europe
The instruments (Table 1) which directly or indirectly regulate the procurement of stem cells in different states in Europe reveal a variety of frames connecting the rules with the technology. Although most regulatory frames are shared, partly as a result of EU regulation,
As is evident from Table 1, only a few of the national regulatory systems examined intervene at the level of stem cells, and even fewer at the level of hESC or iPSC.
The introduction of stem cell-specific instruments, when that was considered necessary, and the alternative of introducing stem cell-specific rules into generic measures seem to have followed different objectives in the different states. Protecting – mainly in vitro – human (embryonic) life serves as the main regulatory objective in most states, either explicitly (for example, Austria, Germany, Belgium and the Netherlands),
The differences between national regimes regulating matters that are directly relevant for stem cell procurement are most striking when the definitions provided in law for the human embryo are considered. These differences seem to have an impact on the particular orientation and overall character of national regulation.
3.1 Protecting rights and values
In Europe, the incorporation of the relevant bioethical considerations into biomedical technology regulation – often rather explicitly and through restrictive or prohibitive rules – is one of the dominant
The most pertinent regulatory distinctions concern the use of human biological material, including human embryos,
Table 2. The relevant restricted and prohibited activities in national measures.
Austria | ||||||||||
Purpose-bound procurement (of gametes and gonad tissues) (for a parental project). | Restriction, on the basis of a requirement of necessity, of the number of embryos (fertilised oocytes) created in a parental project. | Restricted, purpose-bound use of oocytes, viable cells and gametes (for a parental project) (to the benefit of the person involved). | Intervention with the germ line (prohibited). | |||||||
Belgium | ||||||||||
Purpose-bound procurement (of human bodily material) (for human use and therapy). | Purpose-bound use (of human bodily material) (for prevention, diagnosis, therapy and research). | Purpose-bound use of supernumerary human embryos (for the purpose of advancing human knowledge in health care). | Purpose-bound use of supernumerary human embryos (only for the purpose specified in advance in an agreement between the persons concerned). | Creating human embryos for research purposes (prohibited with an exception). | Commercialisation (the commercial use) of (supernumerary) human embryos, gametes and hESC (prohibited). | |||||
Reproductive human cloning (prohibited). | Creating hybrids and chimeras (prohibited). | Implanting research embryos into humans (prohibited with an exception). | ||||||||
France | ||||||||||
Purpose-bound use (of parts and products of the human body) (for medical or scientific research purposes). | Purpose-bound use (of parts and products of the human body) (the uses must be determined in advance at the time of procurement and other uses must be communicated to the persons concerned). | Procuring tissues and cells from minors or adult persons under legal guardianship (prohibited with strictly regulated exceptions). | Procurement (conservation and use) of embryonic and foetal tissues and cells in the context of the termination of a pregnancy from a woman, who is either a minor or an adult under legal guardianship (prohibited with an exception). | Transfer for reproduction purposes of research embryos (prohibited). | Creating and using human embryos for commercial or industrial purposes (prohibited). | |||||
Restriction, on the basis of a requirement of strict necessity, of the number of embryos (fertilised oocytes) created in a parental project. | Human reproductive cloning (prohibited) (Article 16-4, Code Civil). | Human cloning (the creation of human embryos) for research or therapeutic purposes (prohibited). | Creating human embryos by in vitro fertilisation for research purposes (prohibited). | Creating transgenic or chimeric embryos (prohibited). | Creating embryos in a parental project and their donation for research (permitted subject to conditions). | |||||
Procurement of tissues and cells (general) (permitted subject to conditions). | Procurement of hematopoietic cells from cord blood and the placenta (and cells from the umbilical cord and the placenta) (permitted subject to conditions). | Procurement, conservation and use of embryonic and foetal tissues and cells in the context of the termination of pregnancy (permitted subject to conditions). | Donation and use of gametes (permitted subject to conditions). | Research on human embryos and hES cells (permitted subject to conditions). | ||||||
Germany | ||||||||||
Purpose-bound fertilisation of the egg/placing of the sperm cell into the egg (for the purpose of a parental project). | Restriction, on the basis of a requirement of necessity, of the number of embryos (fertilised oocytes) created in a parental project. | Creating in vitro human embryos for purposes other than being used in a parental project (prohibited). | Purpose-bound use of in vitro human embryos. | Selling in vitro embryos or embryos removed from the uterus before nidation (prohibited). | Releasing, purchasing or using human embryos for purposes that do not serve their preservation (prohibited). | |||||
Trading donated organs and tissues (prohibited). | Changing the human germ line (with exceptions) (prohibited). | Creating chimeras and hybrids (prohibited). | Human cloning for any purposes (prohibited). | Import and uses of hESC, with the exception of importing hESC for research purposes and their subsequent use in research (prohibited). | ||||||
Purpose-bound procurement and use of tissues and cells (for therapeutic purposes) | Procurement of tissues and cells (general) (permitted subject to conditions). | Procurement of tissues and cells from deceased embryos and foetuses (permitted subject to conditions). | Use of blood stem cells (permitted subject to conditions). | |||||||
Hungary | ||||||||||
Purpose-bound donation of gametes and embryos (for parental project or biomedical research). | Purpose-bound use of gametes (for the purposes specified at the time of donation). | Creating human embryos for research purposes (prohibited). | Implanting a human embryo into an animal (prohibited). | Fertilisation of human and animal gametes (prohibited). | Using human embryos for the creation of multiple embryos or for the creation of human beings with characteristics unavailable through fertilisation (prohibited). | |||||
Donating gametes (permitted subject to conditions). | Donating in vitro human embryos (for parental project or for biomedical research (permitted subject to conditions). | Procurement of bone marrow, hematopoietic stem cells and other regenerative tissue (permitted subject to conditions). | Human cloning (reproductive and research) (prohibited). | Modifying the genome of the human offspring (prohibited). | ||||||
The Netherlands | ||||||||||
Purpose bound creation and use of human embryos. | Donating gametes (for parental project or research) (permitted subject to conditions). | Donating in vitro embryos (for parental project or research) (permitted subject to conditions). | Donating gametes for the creation of in vitro embryos (permitted subject to conditions). | Commercialisation (the offering of gametes and embryos for use for permitted purposes at a price higher than the cost of procuring and storing them)(prohibited). | Modifying germ line genetic identity (prohibited). | |||||
Using gametes and embryos for purposes other than those specified in legislation (prohibited). | Using cells procured from embryos for purposes other than those specified in legislation (prohibited). | Reproductive human cloning (prohibited). | Allowing the development of in vitro embryos beyond 2 weeks (prohibited). | Intentional modification of genetic material in the nucleus of gametes made available in a parental project (prohibited). | Creating hybrids and chimeras (prohibited). | |||||
Keeping of germ cells and other parts derived from a human foetus for the purposes of human reproduction or for other non-therapeutic purposes (prohibited). | Using cells derived from foetal tissue for other than the permitted purposes (prohibited). | Removing parts from a living born human fruit based on the prospective intended uses of foetal tissues (prohibited). | Using foetal tissue for the medical treatment of persons designated by the woman (prohibited). | |||||||
United Kingdom | ||||||||||
Creating, keeping and using (and procuring and distributing) in vitro human embryos (permitted subject to a license). | Creating, keeping and using in vitro human admixed embryos (permitted subject to a license). | Keeping or using gametes and embryos in circumstances in which regulations prohibit their keeping and use (prohibited). | Keeping and using of an embryo (and a human admixed embryo) after the appearance of the primitive streak (prohibited). | Altering the genetic structure of any cell while it forms part of a human embryo (prohibited). | Replacing a nucleus of a cell of an embryo with a nucleus taken from a cell of any person, embryo, or subsequent development of an embryo (prohibited). | |||||
The reliance on supernumerary human embryos as a source of hESC led in most regulatory regimes to targeted responses to the controversies raised by this technological development. The focus is on regulating their availability for the procurement of stem cells. The law in Belgium and in the Netherlands accepts their availability explicitly.
Where the use of supernumerary embryos for research purposes is permitted, national regulation resorts to the following means of introducing ethics-based boundaries for conduct. Belgian law uses a legal distinction between human embryos and foetuses at eight weeks of embryonic development, which needs to be interpreted together with the rule which prohibits research on embryos after the fourteenth day of their development.
The national measures contain further, predominantly ethics-based
There are other country-specific value-influenced restrictions in different areas of regulation, which may affect – as parts of the general regulatory framework – the availability of certain source-materials for stem cell procurement. As seen in Table 2, most national regimes include restrictions on the number of embryos created in a parental project, which rely, in one form or another, on a test of necessity. In connection with the earlier mentioned right of disposal over supernumerary embryos, Hungarian law recognises the possibility of refusing the donation of embryos in cases when their use for the declared purpose within the time available is unlikely and when it is likely that a human being will develop from the embryo.
3.2 Risk, quality and safety
The national measures governing tissue and cell procurement, partly as a consequence of the implementation of the EU Tissues and Cells Directive,
3.3 Institutionalisation and proceduralisation
The national regulatory systems examined all operate an institutional framework for the ethical and other expert (for example, biomedical or technological) supervision of stem cell related activities, including stem cell procurement, and they provide for regulated procedures governing particular aspects of those activities, such as securing research authorisation or obtaining informed consent. Again, in part, this is the outcome of the implementation of the relevant EU obligations which, in regulating risk, and quality and safety, place considerable emphasis on putting in place effective institutions and procedures.
3.4 Local diversity
Expressing local diversity in the regulation stem cell technologies provides an inevitable theme for national regulation.
4 Specific or generic? Analysing frames of stem cell procurement regulation
The national regulatory frameworks for stem cell procurement examined above, as reflected in the regulatory frames applied and their expression in legal rules, are essentially mixed regimes combining, although in a variety of ways, generic and stem cell technology-specific provisions. The different national regimes, although they operate with comparable rules serving similar objectives and find connection using technology-specific provisions with the technology regulated generally in a similar manner, are characterised by different approaches concerning the focal points of regulation, the details of the rules provided, and concerning the choice between generic and technology-specific provisions. Even though they tend to regulate stem cell technologies by way of introducing prohibitions and conditional permissions,
Regulatory unevenness was clearly an issue in most of the national regimes. On the one hand, there were issues which received prioritised regulatory attention (for example, the donation of supernumerary embryos). On the other, some issues which have similar importance from the perspective of the general objectives of regulatory intervention continue to suffer from under-regulation (for example, the non-commercialisation principle). Some of this unevenness is, necessarily, the result of uncertainty as to the future application of rules in a new technological context which can justify caution when introducing detailed rules. For example, it is uncertain how in the context of the procurement of hESC lines the restriction concerning the separation of the cells of the human embryo, introduced originally in a preimplantation genetic diagnosis context, will play out.
From the perspective of the core question of this article whether generic or technology-specific measures should be preferred in securing connection between regulation and the technology regulated, the variety exhibited in the earlier comparative overview made it clear that it would be difficult to identify a single best regulatory approach or regulatory solution. The national regimes all have better developed and less sophisticated components,
The current state of regulating stem cell procurement technologies in the different European countries as discussed here seems to correspond with what follows from the pitfalls and dilemmas of regulating emerging biotechnologies mentioned earlier.
The earlier comparison of national regimes also highlighted that, as a matter of the complications of connecting rules with the technology regulated, there is a fundamental difference between prohibitive and permissive regimes of stem cell procurement regulation.
Ultimately, as it follows from general dilemmas of technology regulation, the possibility offered by national regulatory variety for improving regulatory frameworks and their connection with technology through inter-systemic regulatory learning and borrowing, must be exploited with responsibility. Considering that the penultimate objective of regulatory intervention, as stated by the legal measures themselves, is the ensuring of public health protection through the development of novel biomedical therapies in regenerative medicine, the regulatory choices made have an impact on the access of patients to therapies to treat – often previously incurable – diseases. Regulation and its design are thought to influence the speed of therapeutic technologies moving from bench to bedside, thereby determining whether the best technologically possible therapies are available to patients in a way that justice and equity are ensured in the healthcare domain.
It is unlikely that hard and fast choices will be available to regulators. While generic measures are more likely to be sustainable on the longer term than technology-specific regulation, the overly extensive scope of such measures, their opaqueness and their lack of detail, especially when they are of low regulatory quality, may unjustifiably impede research and the development of new therapies. The main problem with technology-specific measures, which on the positive side enable a comprehensive and informed regulation of technology, is that they may not provide the flexibility necessary for accommodating scientific and technological change. They may also give rise to fragmentation in the regulatory space jeopardising regulatory accessibility and clarity, and creating boundaries between different aspects of the same technology. On this basis, the responsibility which comes with regulation in the biomedical domain, instead of diminishing, increases the need for learning from other regulatory regimes, wherever they may be located on the prohibitive-permissive scale. The experiences as well as the strengths and weaknesses of other regimes enable reflecting upon the operation and the broader impact of national rules, which is all the more necessary considering that conflict and resistance characterise the engagement of the law with the technology and that the choices in this regard must address the difficulties and the inherent contradictions of connecting rules with the technology regulated.
[1] EUCelLEX: Cell-based regenerative medicine: new challenges for EU legislation and governance (Grant agreement no.: 601806), available at http://www.eucellex.eu (accessed 5 May 2017). The countries included were Austria, Belgium, Canada, France, Germany, Hungary, the Netherlands, and the United Kingdom. They were selected with a view to securing sufficient diversity in the research of national regulatory regimes. The scope of the project consequently determines the scope of analysis in this article.
[2] It is important to note that we speak about stem cell technologies in plural, indicating that there are indeed multiple technologies in question which may raise very different issues requiring regulatory intervention. The emergence of human embryonic stem cell (hESC) technology meant that bioethical issues, which had no relevance for blood stem cells or adult stem cells, in particular the protection of human (embryonic) life, had to be addressed. The more recently discovered possibility of creating induced pluripotent stem cells (iPSC), which promises the replacement of hESC technology, was heralded as offering a way out from the moral dead end street of hESC technology. See, in this regard, Kristina Hug and Göran Hermerén, “Do We Still Need Human Embryonic Stem Cells for Stem Cell-based Therapies? Epistemic and Ethical Aspects” (2011) 7(4) Stem Cell Reviews 761-774.
[3] See the technological frames listed and the argument concerning a “fully inclusive approach” to regulating new health technologies, which means that regulation is effective and it is fully negotiated by all affected parties in Amanda Warren-Jones, “Mapping Science and New Health Technologies: in Search of a Definition” in Mark Flear, Anne-Maree Farrell, Tamara Hervey and Thérèse Murphy (eds.), European Law and New Health Technologies (Oxford: OUP, 2013) 70-102, pp. 70-71.
[4] For instance, on the basis of their risks or ethical implications, the law will distinguish between acceptable and prohibited sources of stem cells, the different types of stem cells, or between the different uses of stem cells.
[5] See also the Dutch proposal to allow the growing, under strict conditions, of human embryos beyond the generally applicable temporal restriction for the purposes of research on infertility, assisted reproduction and hereditary and congenital diseases available at https://www.theguardian.com/science/2016/may/28/netherlands-gives-green-light-for-growing-human-embryos (accessed 4 November 2016), which challenges the well-established and well-entrenched fourteen-day rule concerning the permissibility of research on human embryos, infra n. 53-56.
[6] See also the UK House of Lords’ judgment in Quintavalle, infra n. 91.
[7] Flynn v Holder, 684 F. 3d 852 (9th Circ. 2012).
[8] Brüstle v Greenpeace, Case C-34/10, ECLI:EU:C:2011:669. For an analysis, see Márton Varju and Judit Sándor, “Patenting Stem Cells in Europe: The Challenge of Diversity for EU Law” (2012) 49 Common Market Law Review 1007-1038.
[9] Durisotto v Italy, Decision of 6 May 2014, App. No. 62804/13, nyr. (ECtHR). For a commentary, see Emmanuelle Rial-Sebbag and Alessandro Blasimme, “The European Court of Human Rights’ Ruling on Unproven Stem Cell Therapies: A Missed Opportunity?” (2014) 23 Suppl 1 Stem Cells Dev 39-43.
[10] The focus is on the correspondence between the legal text and its purposes and the forms and uses of the technology. See R Brownsword, “So What does the World Need Now? Reflections on Regulating Technologies” in Roger Brownsword and Karen Yeung (eds.), Regulating Technologies: Legal Futures, Regulatory Frames and Technological Fixes (Oxford: Hart, 2008) 23-48, at 26-27. See also Jasanoff’s more general assessment of the “intersections” between law and science, especially the practices adopted by legal “experts” applying legal rules towards science and scientific development (in particular, the deference owed by law to science) in Sheila Jasanoff, Science and Public Reason (London: Routledge, 2012), pp. 15-18; Sheila Jasanoff, “Making Order: Law and Science in Action” in E J Hackett et al (eds.), The Handbook of Science and Technology Studies (Cambridge, MA: MIT Press, 2008) 761-786, pp. 761 and 768; and her work on the “co-production” of orders by law, science and technology in Sheila Jasanoff, “Ordering Life: Law and the Normalization of Biotechnology” (2001) 17(62) Notizie di Politeia 34-50.
[11] Brownsword and Yeung, Regulating Technologies, supra n. 10, p. 28.
[12] Ibid., pp. 26-27.
[13] See Sheila Jasanoff, “Serviceable Truths: Science for Action in Law and Policy” (2015) 93 Texas Law Review 1723-1749, pp. 1724-1725, concerning the ability of law to represent its inherent values, such as representation, order and stability, accountability, liberty and justice vis-à-vis science. For the broadest formulation of this problem, see the famous paradigm by Lessig that law’s contribution to regulation (to establishing “the optimal mix” of regulatory modes) cannot be contradictory to law’s specific ends in Lawrence Lessig, Code and Other Laws of Cyberspace (NY: Basic Books, 1999) pp. 222-223 and Lawrence Lessig, Code Version 2.0 (NY: Basic Books, 2006) pp. 325-326. See also Brownsword and Yeung, Regulating Technologies, supra n. 10, p. 31 on the rule of law as a consideration which needs to be taken into account in the analysis of regulatory connection and see Jasanoff, Science and Public Reason, supra n. 10, pp. 15-18 and Jasanoff, “Serviceable Truths”, supra n. 13, pp. 1724-1725 on her arguments concerning minimum deference in law towards science “where the law’s core concerns for representation, accountability, and justice, as defined by legal norms, should take precedence over science’s claims to higher authority”.
[14] See Hoppe’s argument concerning the impact of overregulation and generally of inadequate regulation on equity and justice in the health care context in Nils Hoppe, Bioequity – Property and the Human Body (Farnham: Ashgate, 2009) and Nils Hoppe “Innovative Tissue Engineering and its Regulation – the Search for Flexible Rules for Emerging Health Technologies” in Mark Flear et al (eds.), European Law and New Health Technologies (Oxford: OUP, 2013) 109-124, p. 113.
[15] Brownsword suggested that the pressure on regulators to connect regulation with technological developments, in a manner that ensures the effectiveness, efficiency, legitimacy and democratic nature of regulation, is likely to remain constant, in Brownsword and Yeung, Regulating Technologies, supra n. 10, p. 32.
[16] Ibid., p. 30.
[17] Ibid., p. 27. In this connection, see Brownsword discussing the dilemma of choosing between securing flexibility and ensuring consistency in regulation.
[18] Ibid., p. 30.
[19] Ibid., pp. 31-32. The synergies between the different factors must also be recognised. The effective regulation of the risks posed by the new technology may contribute significantly to the legitimacy of regulatory intervention. See in the EU context, where other sources of legitimacy, such as public trust, may be difficult to secure, Anne-Maree Farrell, “Risk, Legitimacy, and EU Regulation of Health Technologies” in Mark Flear et al (eds.), European Law and New Health Technologies (Oxford: OUP, 2013) 203-221, pp. 205-207.
[20] The key measure is the generic Tissues and Cells Directive (Directive 2004/23/EC on Setting the Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells, [2004] OJ L102/48), which regulates issues, such as risk, quality and safety, and the related institutional and procedural arrangements. The frames it introduced for regulation at the Member State level follow from its general objectives and from its dominant implementation paradigm (the market) aiming to secure the realisation of those objectives. These are public health protection, risk reduction and ensuring quality and safety, protecting rights and values, and maintaining national diversity. For the dominant regulatory frames in EU health technology regulation, which include markets, risk, and rights and ethics, see Gordon Bache, Mark Flear and Tamara Hervey, “The Defining Features of the European Union’s Approach to Regulating New Health Technologies” in Mark Flear et al (eds.), European Law and New Health Technologies (Oxford: OUP, 2013) 7-45, pp. 20-41.
[21] The legal measures adopted distinguish, either directly or indirectly, between the main types of cells and stem cells, such as adult cells, blood stem cells, totipotent and pluripotent stem cells, but they very rarely engage closer with stem cell technology, for instance by distinguishing between hESC and iPSC, and tend to keep their prohibitions and permissions at a more general regulatory level.
[22] Germany: the Stem Cell Act (on pluripotent human stem cells) and the Transfusions Act (on blood stem cells). See also the Dutch Embryo Act’s limited hESC-related provisions, and the provisions of the French Public Health Code and of the Belgian Act on the Procurement and Use of Human Bodily Material on hESC. The applicable Canadian measure, the CIHR Updated Guidelines for Human Pluripotent Stem Cell Research (2010), integrated into the 2nd Edition of the Tri-Council Policy Statement: Ethical Conduct of Research Involving Humans, distinguishes between hESC, iPSC and human embryonic germ cell (hEGC) lines and other pluripotent stem cell lines.
[23] Separate laws for the protection of human embryos were adopted in Belgium, Germany, and the Netherlands. This does not mean that human embryonic life would not be protected in more general legal measures in other countries. France represents a specific case as all relevant rules on medicine and biomedical research are regulated in the general Public Health Code, which has specific provisions on human embryos and hESC on human assisted reproduction and supernumerary embryos, and on the procurement and the donation of human biological material. The Hungarian Act on the Protection of Human Embryonic life (Act 1992:LXXIX) focuses solely on in vivo embryos and foetuses, and regulates the termination of pregnancies.
[24] This is most visible in the regulation of permitted sources of stem cells. There are restrictive regimes, such as Austria or Germany which strictly limit potential sources of stem cells, medium regimes, such as Hungary, the Netherlands, or France which exclude certain, ethically controversial sources of stem cells based on value-based considerations, or liberal regimes such as the UK or Belgium which recognise a broader spectrum of legitimate sources of stem cells. Other, more detailed (and issue specific) classifications are also available, see Human Stem Cell Research and Regenerative Medicine (Strasbourg: European Science Foundation, 2013).
[25] And the protection of the woman involved (Germany, the Embryo Protection Act). The Belgian rules have a strong focus on the regulation of the fate of supernumerary embryos created in a parental project. The Dutch Embryo Act also contains extensive provisions on biomedical research using human embryos. The Netherlands has a separate act for the protection of human foetal life (the life of the human fruit) and for the procurement of human foetal tissue. The Austrian Act on Medically Assisted Reproduction regulates this issue predominantly in the general technological context of human (assisted) reproduction.
[26] The UK: Human Fertilisation and Embryology Act 1990. Hungary: Act on Health Care.
[27] For example, Belgium, Germany and the Netherlands.
[28] The Belgian Act on the Procurement and Use of Human Bodily Material defines stem cells as cells of human origin capable of self-renewal and differentiation to one or multiple specialist human cells. The German regulatory framework relies on a distinction between totipotent and pluripotent (stem) cells when defining the human embryo and regulating stem cells. The Stem Cell Act defines pluripotent cells as all human cells which have the capacity for development through cell division and which can develop into different specialised cells, which, however, are unable to develop into a human being. hESC are defined as pluripotent cells harvested in vitro from a supernumerary human embryo. It also gives a definition to hESC lines as hESC which are maintained in a cell culture or stored in a cryoconserved state. The Transfusions Act defines blood stem cells.
[29] Which may include other overarching objectives, such as the protection of the rights and the dignity of persons in health care (see the French Public Health Code, arts. L1110-1 – L1110-3).
[30] See also the national particular regulatory concept of “Individuum” in Germany, the explicit German intention to protect embryos and women, or the focus of the French Public Health Code on the different groups of persons requiring special legal protection.
[31] “entwicklungsfähigen Zellen”, which covers fertilised egg cells and cells developed from them (Act on Medically Assisted Reproduction, art. 9(1)). It is unclear what “cells developed from them” stands for, especially whether it covers pluripotent stem cells, hESC in particular, procured in Austria or abroad, and whether it, thus, prevents their use for purposes other than assisted human reproduction. Since the concept does not distinguish between totipotent and pluripotent stem cells and does not recognise sources for “viable cells” other than the human body, it is unclear what legal status is available for iPSC in Austria. According to commentators, the breadth of the concept of “viable cells” indicates that the prohibition included in art. 9(1) goes beyond the aim of protecting human embryos and has the effect of preventing hESC and iPSC research in Austria, see Christian Kopetzki, “Zur Lage der embryonale Stammzellen in Österreich” in Hans-Jürgen Ahrens, Christian von Bahr, Gerfried Fischer, Andreas Spickhoff and Jochen Taupitz (eds.), Medizin und Haftung (Berlin: Springer, 2009) 297-315.
[32] Viability is also defined in the Embryo Protection Act: the fertilised human egg must be regarded as viable in the first 24 hours after the fusion of the nucleus, except when it is established that it is unable to develop beyond the single cell stage.
[33] In the Stem Cell Act, it is defined as every human totipotent cell. The Medicines Act states that human gametes, fertilised human eggs and human embryos are neither medicines nor tissue preparations.
[34] Potentiality refers to the ability of different cells to differentiate into different cell types. Curiously, potentiality and the distinction between different forms of potentiality, as a matter of producing clear and precise legal definitions, did not receive much attention in Europe neither at the national, nor at the European level.
[35] Supra n. 28.
[36] The Embryo Protection Act and the Stem Cell Act.
[37] Human Fertilisation and Embryology Act 1990.
[38] The definition applicable in law is that provided in art. 16-1 of the Civil Code which “guarantees the respect of every human being from the beginning of its life”.
[39] Act on Health Care. As an indication of achievable levels of regulatory detail, the Hungarian regime also regulates the fate of “unlawfully donated”, “refused” and “damaged” human embryos.
[40] In Belgium, in three separate measures regulating the procurement and use of human bodily material, regulating assisted human reproduction and regulating research on in vitro human embryos. In the Netherlands, in the Embryo Act.
[41] As it follows from the Oviedo Convention on Human Rights and Biomedicine (ETS No. 164). The Oviedo Convention includes rights and values, such as putting human dignity and integrity at the centre of biomedical regulation, balancing the interests and welfare of human beings against the interests of science, protecting the autonomy of the person through the informed consent rule, protecting privacy and confidentiality, protecting the integrity of the human genome, the protection of human embryos in research, protecting tissue and organ donors, prohibiting financial gain, or the prohibition of the use of human embryos for research purposes. See also the stem cell-relevant jurisprudence developed under the European Convention on Human Rights, such as Durisotto, supra n. 9, which rejected the violation of the right to private life by the refusal of access to an experimental stem cell therapy, the therapeutic value of which had not been established, and Parillo v Italy, Judgment of 27 August 2015, App. No. 46470/11, nyr. (ECtHR), which rejected the violation of the right to private life by the refusal to allow a woman to donate in vitro embryos for research purposes when that was not permitted by national law adopted to strike a balance between the relevant rights and interests.
[42] These could change over time as indicated by the 2013 modification of art. L2151-5 of the French Public Health Code by Act 2013-715 of 6 August 2013 which changed the original general rule prohibiting – subject to exceptions – research on human embryos, hESC and hESC lines to a general rule which permits research on human embryos and hESC provided that it has been duly authorised.
[43] The Oviedo Convention provides the common basis in Europe for such balancing exercises. See arts. 15 and 16 on the requirement of balancing between the risks and the benefits, the obligation to seek for alternative solutions, and the benchmark of ensuring the justifiability and the necessity of the intervention, which provisions also form part of the ethics- and human rights-based frame of technology regulation.
[44] In Germany, also hESC (Stem Cell Act).
[45] See the general distinction in Germany between the legitimate uses and misuses of biomedicine (Embryo Protection Act).
[46] The distinction in the Austrian Act on Medically Assisted Reproduction between uses of gametes and “viable cells” in assisted reproduction and for other purposes is responsible for the implied prohibition on the procurement of hESC from “viable cells”. It may also exclude the manipulation of the cells covered, especially the creation of embryos for research purposes through cloning. See Kopetzki, “Zur Lage”, supra n. 31.
[47] The UK also distinguishes between UK and imported human biological material.
[48] In Belgium, their availability, donation, storage and use as regulated in the Act on Medically Assisted Reproduction and on the Fate of Supernumerary Embryos and Gametes. The act, and the Act on Research on In Vitro Human Embryos, gives a specific definition for supernumerary embryos as human embryos created in a parental project which were not implanted into the female womb. It also defines supernumerary gametes as gametes which were procured in a parental project but were not used (the act distinguishes between gamete providers and donors, the former referring to a person from whom gametes are procured for research purposes and the latter to a person who donates gametes for a parental project). The Dutch Embryo Act mentions the procuring of hESC as one of the legitimate objectives of embryo donation.
[49] German law applies a distinction between human embryos and pluripotent stem cells, and prohibits the use of human embryos for research purposes under German jurisdiction. The Austrian concept of “viable cells”, because of its general scope and its failure to distinguish between the different stages and forms of human embryonic development, provides a controversial legal basis for the prohibitive regime established (supra n. 31, 46). Austrian law also lacks the concept “supernumerary embryos” which, read in light of the relevant strict legislative provisions, further supports the conclusion that under law human embryos are not available as sources of stem cells. The legal status of imported stem cells, including hESC – Austrian law lacking provisions for this purpose – is less certain, and they may be available for research.
[50] Public Health Code, art. L2151-5.
[51] Act on Health Care, ch. 9.
[52] Human Fertilisation and Embryology Act 1990, sch. 2.
[53] Act on the Procurement and Use of Human Bodily Material, art. 2 and Act on Research on In Vitro Human Embryos, art. 3(5).
[54] Human Fertilisation and Embryology Act 1990, art. 3(4).
[55] Act on Health Care, arts. 165, 181.
[56] The Embryo Act, art. 1 and the Foetal Tissue Act, art. 1.
[57] The balancing of conflicting interests, the regulation of technological possibilities and scientific appropriateness are other factors addressed in these rules.
[58] Austria: Act on Medically Assisted Reproduction, art. 16; Belgium: Act on the Procurement and Use of Human Bodily Material, art. 6 and Act on Medically Assisted Reproduction, art. 48; France: Public Health Code, arts. L1211-4, L1244-7; Germany: Stem Cell Act, art. 4 and Transplantations Act, art. 2; Hungary: Act on Health Care, art. 170; the Netherlands: Act on the Quality and Safety of Bodily Material, art. 3a.
[59] Austria: Act on Medically Assisted Reproduction, art. 8; Belgium: Act on the Procurement and Use of Human Bodily Material, art. 10, Act on Research on In Vitro Embryos, art. 8 and Act on Medically Assisted Reproduction arts. 12 and 41; Germany: Embryo Protection Act, art. 4 and Transplantations Act, art. 3; the Netherlands: Embryo Act, art. 5 and Foetal Tissue Act, art. 6; the UK: Human Fertilisation and Embryology Act 1990, sch. 3.
[60] Public Health Code, arts. L1211-2, L1221-5 and L1231-1.
[61] Act on Health Care, arts. 159, 176.
[62] Belgium: Act on Research on In Vitro Embryos, art. 3; France: Public Health Code, art. L2151-5; Germany: Embryo Protection Act, art. 4; the Netherlands: Embryo Act, art. 2.
[63] Act on Health Care, art. 159.
[64] Belgium: Act on Research on In Vitro Embryos, arts. 3, 4 and Act on the Procurement and Use of Human Bodily Material, art. 10; France: Public Health Code, art. L-1211-6; Germany: Embryo Protection Act, art. 4 and Transplantations Act, art. 8; Hungary: Act on Health Care, art. 164; the Netherlands: Embryo Act, art. 3; the UK: Human Fertilisation and Embryology Act 1990, sch. 2.
[65] Public Health Code, arts. L1211-2, L1244-7, L2141-4, L2151-1. See also in Germany Transplantations Act, art. 7.
[66] Act on Health Care, art. 176.
[67] Ibid.
[68] Act on Medically Assisted Reproduction, art. 16.
[69] Ibid.
[70] Act on the Procurement and Use of Human Bodily Material, art. 5.
[71] Public Health Code, art. L1211-4.
[72] Act on Health Care, art. 173(3).
[73] Act on Health Care, art. 164.
[74] Public Health Code, arts. L1244-5.
[75] Supra n. 20.
[76] See Act on Tissue Quality and Safety in Austria and Act on the Quality and Safety of Body Materials in the Netherlands.
[77] France: Public Health Code, Book 2. Germany: Transplantations Act.
[78] See Act on the Procurement and Use of Human Bodily Material in Belgium and Human Tissue Act 2004 in the UK.
[79] See A Mahalatchimy et al, “The Legal Landscape for Advanced Therapies: Material and Institutional Implementation of European Union Rules in France and the United Kingdom” (2012) 9 Journal of Law and Society 131-149.
[80] See the EU Tissues and Cells Directive, arts. 16-28.
[81] See, for example, the particular Dutch approach of framing the relevant prohibitions and permissions as institutional and procedural rules in the Embryo Act. See also supra n. 65 on the particular national examples for regulating information rights and the corresponding institutional obligations.
[82] See the specific provisions in France on obtaining informed consent, the Dutch rules on obtaining an authorisation for the “research protocol”, or the German approach of regulating the conditions of decision-making in the national institutional and procedural framework.
[83] For the EU level, this appears as the obligation to respect and accommodate local diversity, for example under the Tissues and Cells Directive, art. 4(3) recognises local discretion in deciding which specific type of human cells, especially which germ cells and embryonic stem cells may be used and which will be excluded from being used for human application.
[84] Decision of the Austrian Constitutional Court: VfSlg. 7400/1974 (Fristenlösung) on abortion.
[85] Supra n. 31, 46, 49.
[86] Decisions of the Belgian Constitutional Court 39/1991 and 146/2011.
[87] Decisions of the Constitutional Council 94-343/944 DC, 2001/446 and 647/2013.
[88] Decisions of the Constitutional Court 23/1990 (Capital punishment), 64/1991 (Abortion), and 48/1988 (Abortion).
[89] Decisions of the Constitutional Court BvF 2/90, 2 BvF 4/92 and 2 BvF 5/92.
[90] See the Report of the Committee of Inquiry into Human Fertilisation and Embryology (the Warnock report) (London: UK Department of Health and Social Security, 1984).
[91] Quintavalle v Human Fertilisation and Embryology Authority [2005] UKHL 28.
[92] On the generally prohibitive nature of regulation concerning the procurement of human biological material and on the reluctance to lift the restrictions on such activities, see Hoppe, Bioequity, supra n. 14.
[93] See the different range and variety of prohibitions and restrictions in the different national regimes as compiled in Table 2.
[94] Supra n. 10-14.
[95] The Canadian regime offers an interesting example. It combines hard legislation and soft governance. The detailed stem cell technology-specific rules are laid down in the non-binding soft instrument (the CIHR Guidelines), which rules, nonetheless, find their basis in the fundamental prohibitions laid down in legislation, the Assisted Human Reproduction Act. This solution seems to provide flexibility to regulation and it also pays attention to the demands of stakeholder compliance.
[96] See the classification introduced in supra n. 24.
[97] See the discussion by Hoppe on the regulatory strategy of erecting prohibitive “firewalls” first and introducing subsequently individual exceptions from the thereby introduced prohibitions, Hoppe, “Innovative Tissue Engineering”, supra n. 14, p. 121.
[98] See, for example, the provisions regulating the donation of supernumerary embryos for research purposes, or the regulation of the creation of research embryos, when that is permitted.
[99] See Hoppe, “Innovative Tissue Engineering”, supra n. 14, p. 124. He argued that on this basis better targeted measures offering multiple, specialised avenues of technological development should be put in place. He, nevertheless, conceded enforcing the earlier mentioned dilemmas of regulatory connection that the success of regulatory intervention assumes that regulation is able to interact with technology in a way that the concepts used in regulation actually correspond with the technology, regulation actually understands the technology itself, and that regulation is actually prepared to address typical and untypical developments in the technological domain.
[100] Supra n. 10, 13.