This work was supported by the EU grant HORIZON-WIDERA-2022, Project CREATIC Grant No. 101059788. The author would like to thank the editors for their constructive feedback and comments.

Scholarship in biomedical law has extensively analysed the impact of scientific innovation and social norms on the law.[1] Scientific advances in the fields of procreation,[2] transplantation,[3] and stem cells research,[4] among others, are challenging certain legal concepts, such as that of personhood, while also necessitating the creation of new legal concepts to regulate innovation and protect both our values and individual rights.[5] However, legal concepts also impact biomedical innovation or social norms. Exploring the real and potential effects of legal norms and concepts allows for a better understanding of the multidimensional interactions between innovation, society, and law. In particular, legal definitions are often shaped by compromises between a variety of interests that may affect their clarity and necessitate interpretation, resulting in multiple challenges in terms of biomedical innovation. Ultimately, these ambiguities can significantly impact patients’ rights and interests and society at large.

The recent adoption of a EU Regulation on substances of human origin (SoHO)[6] at the European Union level gives the opportunity to examine more broadly the legal approach to these body elements in Europe and provide an overview of the issues associated with defining them, knowing that they are regulated by several actors and in response to divergent regulatory aims. SoHO, encompassing a wide range of body materials, raise several ethical, safety, and traceability concerns, particularly regarding their collection, use and access.

This article seeks to examine the definition of SoHO (referred to in a broad sense, not restricted to the scope of the EU SoHO Regulation) and its impact on biomedical practices and innovation in Europe. While there is broad consensus on the etymological meaning of «definition» as to delimit, situate, and distinguish for the purpose of «individualisation»,[7] the concept of definition itself is subject to a range of definitions.[8] Considering the act of defining within its context, this study focuses both on the definition itself and on the rationale behind it, as they shape the act of defining and may provide insights for potential legal changes (a responsibility that falls ultimately to the legislator).

Concretely, exploring the definition of SoHO involves examining the issues surrounding it within a specific space, here that of EU law and the Council of Europe, to understand the legal constraints it must face, among other types of constraints. It also involves a discussion on the substance, criteria, and coherence of definitions within that space; before finally delving into its impacts on biomedical innovation. Providing an overview of the legal frameworks and definition(s) of SoHO contributes both to the acquisition of necessary legal knowledge and to the determination of a consistent basis for constructive dialogue with innovators and citizens, participating in responsible innovation, defined as a “transparent, iterative process by which societal actors and innovators become mutually responsible to each other with a view on the (ethical) acceptability, sustainability and societal desirability of the innovation process and its marketable products. . . .”[9]

This investigation shows the challenges posed by the conceptual uncertainty surrounding SoHO, which could affect biomedical practices and social acceptability.

Intertwined external and internal perspectives help explain how the legal frameworks and definitions of SoHO in Europe may influence innovation. The former, examining constraints shaping regulatory approaches, demonstrates that theoretical and institutional approaches partially explain fragmentation[10] and conflicting perspectives in delineating scope, which complicates navigating various laws (I). The latter, delving into definitions themselves, reveals that criteria recurrently lack clarity, leading to complexities in legal readability when using nested concepts (II). These elements may result in direct and indirect consequences on innovation (III).

I. Framing the access and use of SoHO: a fragmented European landscape

Despite recent regulatory initiatives, the European legal landscape of SoHO remains fragmented, resulting in complexity in navigating laws for innovators. The heterogeneity in legal classifications of SoHO in Europe (A) is partially explained by different practical and legal constraints playing on the respective scopes of legal instruments (B).

A) The Heterogeneity of European legal classifications of SoHO

When it comes to determining the object and scope of a legal instrument, there are different possible approaches of SoHO depending on what regulators consider to be at stake in accessing and using them. An essentialist regulatory approach could focus on the nature of the object to regulate, either on their biological characteristics or their human origin and the necessity to protect the person. Another possibility would be to approach SoHO according to their status, as incorporated or removed from the human body. This last hypothesis allows the protection of donors’ rights and interests when it comes to the donation of their body materials. Once removed, these same materials become objects of the market and change of legal regime. Besides, SoHO could also be defined by their use or function.

Although this approach interplays with the status-based approach, it shifts the focus from SoHO as mere objects of regulation to their concrete use or intended use. By differentiating between these uses from the outset, this approach reconciles competitive interests between market demands and patient rights, ensuring that consent aligns with the intended application of the substance. In contrast, the status-based approach often lacks clarity regarding rights related to human-derived elements as such.

These different approaches can be found in the current European landscape on SoHO, which shows a substantive fragmentation[11] depending on the different categories and types of substances, and their different types of use.

First, SoHO are classified according to some of their biological characteristics, although these gatherings differ depending on the norm and the normative body. At the Council of Europe, different norms regulate therapeutic SoHO on the one hand, and organs and tissues on the other hand (although these substances are all classified as SoHO by the European Directorate for the Quality of Medicines and Health Care)[12]. The first category, therapeutic SoHO, encapsulates human blood and its derivatives.[13] Organs and tissues are gathered as objects of regulation of Additional Protocol to the Oviedo Convention. This Protocol explicitly excludes reproductive organs and tissue, embryonic or foetal organs and tissues and blood and blood derivatives from its scope.[14] That is one difference with EU law, as two successive directives apply to, respectively, tissues and cells on the one hand and organs on the other hand,[15] in addition to another directive dedicated to the regulation of human blood and components.[16] The EU Tissue Directive explicitly includes the tissues excluded by the above-mentioned Council of Europe instruments.[17] In May 2024, the European Parliament approved a new EU SoHO Regulation that will cover substances that are currently unregulated or regulated differently: breast milk, faecal or intestinal microbiota transplants, bedside preparations of substitute by SoHO. The EU SoHO Regulation aims to address the shortcomings of the tissues and cells directives and adopt a common text covering both to facilitate the safety and quality of SoHO. Solid organs intended for transplantation and breast milk used exclusively for feeding the own child, without any processing carried out by a SoHO entity are excluded from its scope.[18] The EU SoHO Regulation will contribute to defragmenting the law on SoHO at the EU level, at least from a formal perspective, by gathering substances and by harmonizing laws as it will not need any transposition into EU Member states law, by contrast with the blood, tissues and cells directives.

Second, the European Protocol on Biomedical Research provides an example of a legal categorization that focuses more on the status of SoHO rather than their type. Indeed, the Protocol differentiates between embryos in vivo and in vitro, the latter being excluded from its scope.[19]

Finally, and in addition to these approaches by SoHO type or status, the legal scope of relevant norms depends on access to SoHO and their use, illustrating a functional approach. While some instruments only apply to SoHO intended to be used for therapeutic purposes,[20] and/or for research,[21] others focus on the market, either from a safety perspective[22] and/or from a practical/organisational standpoint (uniformizing practices with a laissez-passer for corpses).[23]

By applying to SoHO intended for human application, to SoHO donors and recipients and to SoHO activities, the EU SoHO Regulation aims to transcend the essentialist and functional approaches.[24] As a matter of fact, these approaches are not rigid or mutually exclusive as synergies are hardly evitable. Indeed, an exclusive essentialist approach would likely preclude finding a balance between the indispensable protection of donors and the necessary allowing of innovation. While focusing on the sole biological characteristics may dehumanize their source, setting aside any moral argument and potentially leading to the commodification of the human body, approaching these substances through the exclusive lens of their human source would result in an extended protection of SoHO in the name of the protection of the person. This protection, if derived from human dignity, would apply even to cases of deceased donors.

Normative approaches are more pragmatic, seeking to balance the safeguarding of human rights with the fostering of innovation. One example of merging an essentialist approach based on human origin with a functional approach (or according to status) is the specification in the Oviedo Convention of the prohibiting of making the human body source of financial gain “as such.”[25] This wording allows for necessary distinctions to be made, enabling innovation and the financing of SoHO-based research for example, while still prohibiting organ selling and the commodification of the human body. A similar formula has been incorporated into the EU Charter of Fundamental Rights.[26] In this regard, a clear-cut distinction based on SoHO status as incorporated/removed from the body, while showing an interesting balance,[27] does not reflect the post-removal effects that may exist on the use of these body materials. Living donors have a post-removal interest in the fate of organ or bone marrow donation for the therapeutic need of an identified recipient for example.[28] Similarly, European societies do afford objective protection to the human body after death, and corpses or body parts are not submitted to the rules of the market or nationalisation.[29] Another example of synergies between the essentialist approach and the functional approach in connection with certain uses is the fact that the quality and safety of the exchange of SoHO implies considering the conditions of their removals from a person’s body, thus including concerns for the respect of the donor and risks of organ trafficking.

Part A provided an overview of the heterogeneous classifications of SoHO in Europe, which vary particularly by substance type and use but are not impermeable, as there is some overlap in their underlying rationale. The heterogeneity in the classification of SoHO across Europe may be attributed to the existence of practical, legal, and political constraints playing on regulatory approaches. Part B is discussing some of these.

B) The Constrains Shaping Frameworks for SoHO

Constraints of different type explain these different, sometimes overlapping or potentially conflictied classifications of SoHO.

The first constraint is that the law follows innovation. Normative initiatives have followed the progress in biosciences, explaining time gaps between some instruments such as the directives on blood, tissues and cells, and the need to adopt a more adapted instrument.

A second constraint is that the removal of certain SoHO may be seen to involve specific challenges, requiring distinct or additional legal instruments. For example, a specific time constraint between organ removal and transplantation, due to ischemia,[30] partially explains why the EU SoHO Regulation explicitly excludes organs (unless these are removed for the purpose of separating tissues or cells for human application).[31] At the Council of Europe level, reproductive organs and substances have been excluded from the scope of the Additional Protocol to the Oviedo Convention on transplantation because of “different implications.”[32] Distinctions may also depend on the degree of risk associated with removal such as in the case of regenerating materials versus solid organs;[33] and/or following moral perceptions associated with certain substances in particular.

The specific challenges of certain SoHO may also persist despite attempts to defragment the law. While the EU SoHO Regulation, by contrast with the above-mentioned examples, aims to streamline and unify the legal framework by formally merging two directives into one single instrument, it ultimately acknowledges the specific characteristics of each type of substance. Thus, despite this formal defragmentation, the EU SoHO Regulation still confirms a substantive fragmentation, also explaining the heterogeneity of classifications.

Third, this substantive fragmentation playing on classifications is due to regulations from different branches of law, themselves partly explained by legal (institutional/constitutional) and political constraints. The history and legal foundations of the Council of Europe and the EU, especially the regulatory competences of the EU, explain why the Council of Europe’s main instruments relate to the protection of individual rights in biomedicine,[34] while most EU instruments organise their safe circulation on the market by establishing norms of quality and security.[35] Originally considered as a mere ground for derogation by Member States to the principles of free movement within the Community,[36] public health properly emerged in the Maastricht Treaty of 1992, which designated «health protection requirements» as «a constituent part of the Community’s other policies».[37] In 1999, the Amsterdam Treaty clarified that Community action «shall complement national policies,» particularly in «preventing human illness and diseases and obviating sources of danger to human health.”[38] In a context of crises regarding blood transfusion and mad cow disease, this treaty empowered the Council to adopt «high standards of quality and safety of human organs and substances of human origin, blood and blood derivatives.”[39] Therefore, the general competence granted to the EU in matters of health is a supporting competence, thus excluded from the scope of Article 4 related to shared competences with Member States. However, paragraph 2(k) of Article 4 TFEU, introduced by the Treaty of Lisbon, recognizes a specific shared competence concerning «common safety concerns in public health matters, for the aspects defined in this Treaty.»[40] Thus, in exception to the principle of supporting competence in the area of public health, some common security issues in health fall within the scope of shared competences. This is the case for high standards of quality and safety of organs and substances of human origin, blood and blood derivatives,» for which Article 168(4)(a) recognizes the Parliament and the Council’s power to adopt norms. This article is the legal basis of the EU SoHO Regulation. The specific competence in the field of quality and safety of SoHO can be explained by reference to the internal market, as health was subject to the internal market before a specific attribution of supportive competence in this matter.[41] The market and freedoms of movement of health services and goods apply to body materials and substances, and regulatory initiatives aim to favour innovation to the benefits of patients but also the economic interests of various stakeholders. Ethical principles in health, unless they had an impact on the internal market, should remain within the Member States’ powers.[42] By contrast, the creation of the Council of Europe in the aftermath of the atrocities of WWII aimed to affirm common European values and the principle of human dignity;[43] protected one year later by the European Convention on Human Rights,[44] a treaty later defined as the “instrument of European public order.”[45] Therefore, it is the more conducive organization to regulate SoHO through a human rights approach. The Oviedo Convention[46] and its protocols on transplantation,[47] biomedical research,[48] genetic testing[49] and clonage[50] are all grounded in human dignity, identity and the primacy of human beings over scientific interests. The Convention against Trafficking in Human Organs, which imposes Contracting States to establish as a criminal offence any removal “without the free, informed and specific consent of the living or deceased donor […]” but also in case of organ selling,[51] is also based on the Universal Declaration of Human Rights,[52] the law of Oviedo, human dignity and the right to life.

Despite these legal constraints shaping respective frameworks in the EU and the Council of Europe, this division needs to be nuanced. Indeed, there is some porosity between the two European organizations, giving way to various forms of institutional and normative interactions.[53] The most striking example of direct coordination comes from the EU acceptance or ratification of relevant instruments from the Council of Europe. Precisely, the EU is a contracting party to the European Agreement on the Exchange of Therapeutic Substances of Human Origin.[54] Other forms of interactions include the incorporation of the ethics and fundamental rights discourse into innovation law by the exclusion of “inventions the commercial exploitation of which would be contrary to «ordre public» or morality” from patentability;[55] including the affirmation by the Court of Justice of the EU of the non-patentability of embryos.[56] These alignments are favoured by the principle of equivalent human rights protection between the Council of Europe and the EU.[57] The EU Charter of Fundamental Rights adopted in 2000 and legally binding since 2009 recognized rights in biomedicine, with a particular provision on the right to integrity in the fields of medicine and biology.[58]

Nevertheless, despite these elements of coordination, legal and political constraints persist, manifesting as challenges in fostering constructive dialogue among judges[59] and ongoing debates regarding the impact of harmonization and the difficulties in balancing irreconcilable viewpoints. These constraints interfere with efforts to defragment the law.

In exploring the issues surrounding the definition of SoHO in Europe, Part I examined the various classifications they undergo according to different approaches, aiming to explain these classifications in relation to external constraints, that will partly play on definition themselves and on the capacity to change them. These constraints are various. In particular, legal aspects and political views on ethical principles and the market of SoHO are external elements that contribute to shaping the object and scope of respective norms, resulting in a remaining fragmented landscape and impact the very definitions of SoHO.

II. Defining SoHO: criteria and shortcomings

SoHO is an umbrella concept encompassing various types of substances depending on the legal or policy instrument in question. Within this broad category, the definitions of different types of SoHO highlight the challenge of achieving legal clarity and delineation within nested concepts. Indeed, some SoHO definitions are based on other SoHO types, and SoHO-based products are also built upon these nested concepts. This section explores this challenge, both in terms of defining certain SoHO-based products (B) and as one of the difficulties in determining, more broadly, the intrinsic and extrinsic elements of the definition of SoHO (A).

A) The Challenge in Determining SoHO’s Intrinsic and Extrinsic Elements of Definition

Within the above-mentioned constraints of respective frameworks, there are various options when it comes to defining SoHO. Naming SoHO or a specific type of SoHO is not neutral, and the choice of terminology for legal purposes has consequences beyond the mere discussion on the relevance of definitional criteria. As shown by Virginie Tournay et al, for instance, the notion of stem cell is polysemous and may entail different perceptions from a biological or legal perspective.[60] The definition serves as the tangible arena where the law fulfils its mission to arbitrate among diverse interests or to promote a politically oriented vision of the object to be regulated. In biolaw, the definition of death is a critical example of the challenges in defining a biological and progressive reality as a moment, the very moment where the legal status changes.[61] Any legal definition illustrates the difficulty of understanding and arguably drawing inspiration from the biological reality; while taking into account other social pressing needs such as preventing communicable diseases by allowing the burial of corpses, but also the need for organs and tissues for patients in need of transplant or for research. The definition of death falls within the jurisdiction of States, but the international community has generally agreed to legally define it with reference to two alternative criteria: cardio-respiratory death and brain death. However, these criteria are perceived differently by the deceased’s relatives, who more readily adhere to the former as the ‘true death’, and by doctors, who are more convinced by the latter.[62] The social questioning and increasing legal cases in the USA on the relevance of brain death[63] show the limits of the law to capture this reality, although agreeing on a definition remains critical beyond biomedical needs.

Regarding the above-mentioned classifications of SoHO, the classification as “organs, tissues, cells” has important consequences in terms of removals for therapeutic purposes for instance. For example, no removal of an organ may occur on a minor,[64] while tissue removals are possible under strict conditions.[65] The choice of terminology is paramount. The criterion of distinction between organs and tissues was traditionally based on the absence of regeneration of organs, by contrast with regenerating tissues. However, the feasibility of liver transplantation questioned the relevance of this distinction, as part of livers from living donors could be transplanted and then regenerate in the recipient’s body.[66] The criterion of vascularization came out as a more relevant way to define organs, differentiating from other types of SoHO. Similar reference to vascularization may be found in the definition of organs in the EU directive 2010/53.[67] Directive 2010/53 includes part of organs within the definition of organs providing they maintain these criteria of structure and vascularisation.[68] Additionally, the distinction with tissues is porous as bones, considered tissues, cannot regenerate.[69] The distinction between cells and tissues also raises the question of the difficulty of nested, intertwined concepts, tissues being defined as «all constituent parts of the human body formed by cells».[70] In this intricate task of choosing terminology and relevant criteria, linguistic specificities add to the difficulties in naming and defining Soho.[71]

The challenges of the law to adapt to scientific development and new understandings explain why certain definitions integrate that evolutive dimension. In certain cases, norms include broadly interpretable sub-concepts, such as the inclusion of blood’s derivatives into the definition of “therapeutic substances of human origin.”[72] Besides, norms may name the object without properly defining it, leaving the tasks of definition to States, and/or specifying the possible extension of the list of elements fitting in the definition of SoHO or categories of SoHO.[73] On its side, the EU SoHO Regulation opted for a broad definition as “any substance collected from the human body, whether it contains cells or not and whether those cells are living or not”, enabling to cover actual and future substances (with the exclusion of the organs intended for transplantation and breast milk when used exclusively for feeding one’s own child from its scope), including “SoHO preparations.”[74]

Challenges due to terminology and criteria of definition are not limited to the characteristics/components of SoHO, but also concern their different uses. There are debates surrounding the choice of the best terms to describe the overall transplantation process,[75] but also how different subprocesses such as conservation may change the legal classification of SoHO uses. In this regard, the EU SoHO Regulation’s incorporation of SoHO preparations into the definition of SoHO creates a unified regulatory framework centered on intended human use. However, some distinctions will still remain, particularly concerning donor consent.

Part A explored the challenges in defining SoHO, both in naming these body materials and in identifying the criteria that distinguish them from other types of SoHO or differentiate their uses. In addition to these challenges, these SoHO may also be the basis of other legal classifications such as medicinal products and medical devices, the use of which is regulated in EU law. In some cases discussed below, the nested definitions of SoHO-based products add an additional layer of complexity, challenging their interpretation and increasing the risk of legal uncertainty.

B) The Challenge in Interpreting the Definition Criteria of SoHO-based Products

The first step is the characterization of SoHO-based elements as “products.” The definition is crucial as it impacts the regulatory regime of these products, and consequently, shifts the balance between ethics and rights in access and use and innovation/market in favour of the latter. The category of medical products covers both medicinal products and medical devices.[76] The only definition of “product” in EU law comes from the Directive 2001/83/EC and has evolved.[77] Directive 2001/83/CE (as amended) relies on two alternate criteria to characterize a medicinal product: either its presentation as having properties for treating or preventing disease in human beings, or its function to restore, correct or modify physiological functions or to make a medical diagnosis.[78] A similar definition has been adopted in the Council of Europe Convention on Counterfeiting of Medical Products and similar crimes.[79]

The wording “presented as having properties for treating or preventing disease” is not very specific, giving some interpretative leeway to national and EU authorities who are both competent to determine if some substances/products are medicinal products.[80] In addition, the definition of medicinal product may partly overlap with other definitions such as medical device, which is the object of a separate Regulation.

The EU adopted a Regulation in 2017 on medical devices which entered into force in 2021.[81] This Regulation includes medical devices that incorporate SoHO.[82] More specifically, the regulation applies to devices that incorporate, “as an integral part”, substances that would be otherwise qualified as medicinal products, when they have an action ancillary to that device.”[83] Directive 2001/83/CE applies instead when the substance’s action is principal. According to guidelines from the Commission, the criterion of incorporation of medicinal substances as an “integral part” requires that the device and the substance are physically or chemically combined at the time of administration (i.e. use, implantation, application etc) to the patient.”[84] However, the concept of “ancillary” action is not defined.[85]

Products with features of medicinal products and other regulated products are called borderline products. For example, the classification of microbiome-based products remains uncertain in the EU and may alternatively be classified as medicinal products or medical devices depending “on their mechanism of action, characteristics, or claimed intended treatment.”[86] However, despite guidance documents, the classification of borderline products is a remaining challenge.[87] The introduction of a borderline mechanism by the EU Commission Proposal for the pharmaceutical Regulation in April 2023,[88] would permit developers or national authorities to request a scientific recommendation from the European Medicines Agency (EMA) regarding the characterization of a product under development. This mechanism should contribute to improving consistent legal classifications, although EU States will be able to request the EU Commission to decide in case they disagree with EMA’s characterisation. When it comes to SoHO-based products, EMA should consult a new structure, created by the EU SoHO Regulation: the SoHO Coordination Board.[89]

These challenges in classifying substances as medicinal products or medical devices persist when it comes to defining certain subtypes of medicinal products. SoHO-based medicinal products include biological medicines, such as blood or plasma-derived medicinal products, or advanced therapy medicinal products (ATMP).[90] ATMP are medicinal products based on genes, cells or tissues of human (or animal) origin. They are regulated by a specific Regulation from 2007: Regulation (EC) No 1394/2007.[91] In particular, Article 2 of the Regulation defines as ATMP engineered tissues or cells, i.e that have been subject to “substantial manipulation” or, that are “not intended to be used for the same essential function of functions in the recipient as in the donor.”[92] However, the concept of substantial manipulation is not defined by the Regulation and is subject to interpretation. Both the required elements and the threshold for a manipulation to be substantial are uncertain. The Regulation only includes a list of manipulations that are not considered substantial: cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilization, irradiation, cell separation, concentration or purification, filtering, lyophilization, freezing, cryopreservation, and vitrification.[93] Member States may have different interpretations of this criterion. Under Polish law for example, “most ordinary” cell culture in vitro is considered a substantial manipulation, resulting in the “unambiguous” classification of non-hematopoietic somatic cells in Graft-Versus-Host Disease therapy as ATMP.[94] The alternative EU definition of an ATMP for cell and tissue engineered products, i.e. when tissues or cells are “not intended to be used for the same essential function of functions in the recipient as in the donor”,[95] also engenders uncertainty. As shown by Cuende et al regarding bone marrow mononuclear cells for the treatment of ischemic syndromes, different interpretations of the “essential function” criterion may lead to opposite conclusions on how to classify these products.[96] While the autologous bone marrow derived mononuclear cells (BM-MNCs) and autologous bone marrow-derived CD133+cells (CD133 cells) intended for the promotion of new blood vessel growth and ischemic tissue repair would not be considered ATMP because of their physiological role in the processes of postnatal neovascularization, a restrictive interpretation of this criterion may lead to classifying allogeneic transplant as an ATMP as the graft is not only used for haematopoiesis restoration but also for its graft-versus leukaemia effect.[97] However, the authors have shown the inconsistency of this interpretation of the criterion: “It is evident that, in the donor, BM cells do not recognize foreign allogeneic antigens present in the residual tumor cells of the recipient; therefore, according to the EMA/CAT criteria, we would be dealing with an ATMP.”[98] As for the criterion of substantial manipulation, there is not a uniform approach on this due to multi-level regulations and divergent interpretations between Member States.[99]

By analysing the definitions of SoHO and SoHO-based products, Part II highlighted certain difficulties stemming in part from the overlap of defining criteria, which can lead to nested legal ambiguities. These definitional challenges are only partially explained by the practical and legal constraints in the European context that were discussed in Part I, as the definitional ambiguities raised here often occur within the same legal order, that of the EU. This suggests that there is some room for clarification and harmonization. This reflection is particularly important, as these ambiguities, along with the broader issue of multiple layers of regulation, can have various socio-economic impacts.

III. Socio-Economic Impacts on Responsible Innovation

The heterogeneity of legal classifications and uncertainties surrounding the definitions of SoHO have direct and potential impacts on innovation. While the primary focus often lies on economic and organizational consequences of legal classification (A), socio-ethical issues could result in a backlash against innovation and must be considered under a responsible research and innovation approach (B).

A) Direct Economic impacts

The classification of SoHO as ATMP or medical devices on the one hand, or transplant or transfusion, on the other hand, has significant regulatory implications in terms of production/manufacturing, nonclinical or clinical development, and accessibility to patients.[100]

Classifying SoHO-based products as ATMP leads to a specific procedure for marketing authorisation from the European Commission (unless a hospital exemption has been obtained),[101] and involves following guidelines on good manufacturing, resulting in higher costs in processing compared to products considered as transplants.[102] A classification of a product as a SoHO-based medical device triggers a procedure of CE declaration of conformity for marketing. Unlike cell-based products, cell-based therapies are covered by other frameworks and the active substance, i.e. human cells and tissues, cannot be commercialized or manufactured on an industrial scale, but are rather offered as a health service. Therefore, the uncertainties of legal concepts and definition criteria, as such, may have important economic consequences, including the risk of overclassification of novel SoHO-based products as ATMP.

In addition, the very inclusive definition of SoHO in the new EU SoHO Regulation is likely to have impacts on the European market. The EU SoHO Regulation, which addresses the above-mentioned risk of legal unclarity and insecurity due to current legal fragmentation, may inadvertently blur the distinction between different types or uses of SoHO. Gathering SoHO into a single text may lead to a reconsideration of where to place the slider between the market and altruism. This concern has been expressed by the Committee on Organ Transplantation which emphasized the importance of reaffirming the principle of “altruistic” donation of body elements.[103] The issue of preventing the body from becoming a source of profit (guaranteed by the Oviedo Convention) has also been broadly shared by stakeholders during the impact assessment of the revision of the 2002/98/EC and 2004/23/EC directives.[104] Thus, the EU SoHO Regulation explicitly refers to the principle of altruism when defining SoHO donation as “a process by which a person voluntarily and altruistically gives SoHO from their own body for persons in need, or authorises the use of such SoHO after their death.”[105] However, the willingness to reinforce donors’ protection and to reaffirm more broadly ethical principles may pose challenges in terms of self-sufficiency in certain SoHO in Europe. While the new EU SoHO Regulation explicitly aims to strengthen the continuity of supply of critical SoHO,[106] the generalization of ‘altruistic donations’ may increase Europe’s dependence on plasma imports from the United States.[107] This could potentially create imbalances in international SoHO trade. The EU currently imports 40% of its plasma needs[108] and the United States, together with other countries authorising payment for plasma donations (including CZ, Germany, Austria, Hungary in Europe) account for nearly 90% of the total world supply.[109] Some economists have raised fair concerns regarding the inconsistency in prohibiting the buying of plasma in Europe, while buying it from third countries.[110] This clearly illustrates the challenges of biolaw, between biopolitics and the concern to achieve self-sufficiency at the European level, and the protection of individuals. The legal categorizations of SoHO are closely linked to other concepts such as donation, and the explicit reference to the notion of altruism can rebalance in favour of values and to the detriment of meeting the demand.

This balance between conflicting viewpoints, from which the legal classification and definition of SoHO seem to result, inevitably raises ethical questions as well as concerns about acceptability by different groups, based on how the balance is struck, and by society as a whole.

B) Potential Socio-Ethical Impacts on Innovation

René Von Schomberg identified several deficits in approaches to innovation, among which an exclusive focus on risk and safety issues concerning new technologies, without taking into account their social desirability. The acceptability, sustainability and societal desirability of the innovation process and its marketable products are conditions of responsible research and innovation.[111] Acceptability can be sought by procedural guarantees of stakeholders’ engagement, with particular concern for citizens’ perspectives.[112] Acceptability has also a substantive dimension as, under a rights framework, it entails that “[a]ll health facilities, goods and services must be among other things, “respectful of medical ethics and culturally appropriate, [. . .] as well as being designed to respect confidentiality and improve the health status of those concerned.”[113]

Regulatory approaches and definitions may have an effect on acceptability, posing a range of ethical, legal, societal challenges for the development of SoHO-based innovations.

First, regulatory approaches based on the function/intent of use of SoHO may infringe upon donor autonomy. This assertion is based on the premise that the object of consent entails more than the mere SoHO removal procedure, encompassing the intended use of the donated body elements. In legal norms related to donation for the therapeutic needs of another person, the donor needs to be priorly informed about risks including the risk that unforeseen events prevent the transplantation from happening.[114] In the case of organ and tissue removals, the additional protocol to the Oviedo Convention related to transplantation also states that “[w]hen an organ or tissue is removed from a person for a purpose other than donation for implantation, it may only be implanted if the consequences and possible risks have been explained to that person and his/her informed consent, or appropriate authorisation in the case of a person not able to consent, has been obtained.”[115] These elements, which suggest that consent to donate is not strictly limited to removal but includes donors’ remaining interest in the fate of their removed body materials, support the need to dissociate the different uses. The EU SoHO Regulation’s objective to defragment the law by gathering (almost) all types of SoHO, and their different uses may appear, on its face, as insufficiently capturing the fundamental differences between these different purposes of donations. Writing on tissue donation, Alice Polomeni observes that “what circulates in donation is meaning.”[116] The particularity of organ and tissue donation calls for the examination of the persistence of this “meaning” when multiple uses of donated materials are possible, and the impact of commercialization of SoHO-based products based on willingness to donate. The EU SoHO Regulation requires to inform donors of intended and “any possible research or commercial uses of SoHO” and on their “right to revoke consent and any restrictions on that right after the collection.”[117] It would be interesting though to empirically study, if information on possible other uses may actually lead certain donors to withdraw their consent when informed the body materials they originally consented to give for the direct need of a recipient could be used for generating profits.[118] Beyond the sole possible different use than originally “intended”, the Committee on Organ Transplantation recommends a proportionate and appropriate disclosure of the commercial goal of these donations in order to preserve the altruistic donation of SoHO needed for patients’ survival.[119]

More broadly, both the definitions of SoHO and the differentiation criteria upon which various regulations rely raise questions regarding the adaptation of legal frameworks to accommodate diverse, at times conflicting, perspectives on the human body and SoHO-based innovations. Heterogeneity of perceptions between groups, for example citizens v. innovators, but also within groups (for example between different scientific societies)[120] are due to many factors, including ethical assessment of innovation or degree of understanding of technology, and perceptions on ownership of cells or other body materials. The uncertainties or lack of alignment of legal definitions can be seen as a compromise between these perceptions. However, they may lead to issues in terms of acceptability. First, unclarity generates legal insecurity and potential discomfort for donors, who in addition to a lack of scientific understanding have to face legal uncertainty. Second, the legal uncertainties surrounding the definition of SoHO as products may lead to overclassification, impacting fair access to treatment. Indeed, marketed ATMP are among the most expensive drugs worldwide, with prices ranging from several tens of thousands of euros to 3 million dollars per treatment.[121] Even though few ATMP have actually obtained marketing authorisation and they are usually aimed at treating rare diseases, their high prices may compromise the sustainability of healthcare systems for more prevalent diseases.[122] Lack of proportion between altruistic donation and considerable benefits may generate a loss of public confidence in the donation process.

Beyond playing on individuals’ consent, the uncertainties of definition, and the potential consequences of defragmentation as a decrease of differentiation between uses may generate broader consequences on the circulation of SoHO. While normative approaches still rely on SoHO “donors”, using a rhetoric of solidarity for the circulation of body materials, and while many donors are mainly willing to donate for the therapeutic benefit of another person,[123] there is a risk that this solidarity-based circulation may, if not supplanted, become entangled with commercial circulation of these products. Similarly, the substantial public investment in research on ATMP, primarily performed in academia, to the benefit of society and citizens and relying on some form of reciprocity, could be at risk of being overridden by commercial exchanges, which could lead to profit-driven entities dominating the field.

It is evident that not everything can be attributed to definitions and regulatory approaches. However, when it comes to social acceptability, the importance of perceptions, whether objectively founded or not, cannot be overstated. Overlooking ethical and social perceptions could potentially result in a loss of the hard-earned public confidence in the donation of bodily materials.[124] For instance, the modification of the French law regarding organ donation after death in 2016[125] sparked a surge in registrations on the register of opposition in the weeks following the adoption of the law, with nearly 300,000 new registrations (compared to approximately 90,000 in total since 1998).[126] Although the new decree reinforcing presumed consent[127] did not fundamentally change the law, as presumed consent to post-mortem organ removal was in force since 1976,[128] practices differed from strict legal requirements by associating more families to the point where close relatives had, de facto, a veto. Media attention and fears of organ harvesting without consent provoked, at least momentarily, a backlash. Such a type of backlash could happen when use of donated SoHO including profits ceases to be aligned with motivations for and values attached to SoHO donation. Demobilization of donors would inevitably play on innovation. It is essential to prioritize citizen engagement and empirical research on the impacts of terms and definitions.

Conclusion

The need to define SoHO stems from biomedical innovation, which enables access to the human body and its substances for various purposes. Without these advancements, legal definitions such as death, for example, which mark the possibility of accessing the human body, including its vital substances, could be left to individual subjectivity or to strict biological definitions. However, agreeing on a definition is necessary to protect the individual and to arbitrate between competing interests. It is precisely this compromise, alongside various constraints, that explains the fragmentation and imbrication of definitions of SoHO in Europe. It is clear that SoHO definitions, often evolving, are linked to the intended uses of these body elements. Thus, the categorizations of certain SoHO and the criteria for definition reflect an assessment of the risks associated with their procurement for donors. Additionally, definitions of SoHO uses and products are based on criteria whose interpretation is particularly porous. This uncertainty can accommodate the demands of innovation, given that science allows for new uses that continually challenge our legal categories. In addition to the above-mentioned substantive fragmentation, the territorial legal fragmentation within European law (Council of Europe law and EU law), or between the EU and its member states which keep a margin of interpretation, allows for the progressive adaptation of the law to evolving political, ethical, and social contexts,[129] inviting to consider the balance between market needs, fundamental values and societal concerns. However, definitional ambiguities can directly and indirectly impact biomedical innovation. A responsible approach to innovation involves studying the impact of—sometimes vague—definitions, and more broadly, regulatory approaches including defragmentation, on individuals’ willingness to donate their SoHO.

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^[1] For a transversal analysis of the legal adaptation to innovation in relation to the human body see C. Kuhn et C. Pomart (eds), Corps humain, technologies et Droit, IFJD, 2022, including a critical reflection on doctrinal approaches in the field of biolaw by C. Aubry de Maromont, “La discipline juridique à l’épreuve du biodroit,” pp. 213–226.

^[2] On the regulation of reproductive technologies in Europe see for instance E. Jackson, “The Right to Procreate and Assisted Reproductive Technologies in Europe,” in D. Orentlicher and T. K. Hervey (eds), The Oxford Handbook of Comparative Health Law, pp. 993–1008. For a comprehensive analysis on procreation see L. Marguet, Le droit de la procréation en France et en Allemagne. Étude sur la normalisation de la vie, PhD dissertation (Université Paris Nanterre 2018).

^[3] On xenotransplantation and the challenges of chimeric embryos, see a.o S. McLean and L. Williamson, Xenotransplantation: Law and Ethics, Routledge, 2005; S. Fovargue, Xenotransplantation and Risk. Regulating a Developing Technology, Cambridge Law, Medicine and Ethics, CUP, 2011; C. Saint‑Germain, “La ‘porcinification’ de la personne humaine. L’effacement médical de la frontière des espèces : le cas des xénogreffes,” in Cahiers de recherche sociologique, 2003, pp. 99–117.

^[4] S. Hennette-Vauchez, “Words Count. How interest in stem cells has made the embryo available – A look at the French law of bioethics,” Medical Law Review, Vol. 17, Issue 1, Spring 2009, p. 52–75.

^[5] See also the edited book from A. Mahalatchimy, and G. Nicolas (eds.), Transhumanisme : de nouveaux droits ?, Aix-en-Provence, DICE Éditions, 2024. DOI : 10.4000/11zci

^[6] Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on standards of quality and safety for substances of human origin intended for human application and repealing Directives 2002/98/EC and 2004/23/EC, OJ L, 2024/1938, 17.7.2024. Hereafter the “EU SoHO Regulation.”

^[7] C. Eisenmann, “Quelques problèmes de méthodologie des définitions et des classifications en science juridique,” p. 30, cited by V. Champeil-Desplats, Méthodologies du droit et des sciences du droit, Paris, Dalloz, 2014, p. 297.

^[8] V. Champeil-Desplats, ibid., p. 297–298.

^[9] R. Von Schomberg, “A vision of responsible research and innovation,” in R. Owen, J. Bessant, M. Heintz (eds), Responsible innovation: Managing the responsible emergence of science and innovation in society (2013): 51-74, p. 63.

^[10] See Introduction of this special issue.

^[11] A. Mahalatchimy and E. Rial-Sebbag, “Deciphering the Fragmentation of the Human Genome Editing Regulatory Landscape,” Front. Polit. Sci., vol. 3, Jan. 2022.

^[12] See EDQM webpage on “Substances of Human Origin” (blood, Organs, tissues and cells) (last accessed 30 Sept. 2024). The Council of Europe and EDQM recently concluded an agreement extending their cooperation in the field of SoHO, encapsulating all these substances.

^[13] European Agreement on the Exchange of Therapeutic Substances of Human origin and Protocol thereto, Paris, 15.XII.1958, art. 1.

^[14] Additional Protocol to the Convention on Human Rights and Biomedicine concerning Transplantation of Organs and Tissues of Human Origin (ETS No. 186), 24 January 2002, in force since 1 May 2006, Art.2(3). Similarly, res.CM 78(29) on harmonisation of legislations of member states relating to removal, grafting and transplantation of human substances from 11 May 1978 excludes from the scope of its rules the “transfer of embryos, the removal and transplantation of testicles and ovaries and utilisation of ova and sperm” (art1(2)).

^[15] Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells, OJ L 102, 7.4.2004, pp. 48–58.

^[16] Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC, OJ L 33, 8.2.2003, p. 30–40; Directive 2010/53/EU of the European Parliament and of the Council of 7 July 2010 on standards of quality and safety of human organs intended for transplantation, OJ L 207, 6.8.2010, p. 14 (consolidated text of Directive 2010/45/EU of the European Parliament and of the Council of 7 July 2010 on standards of quality and safety of human organs intended for transplantation).

^[17] Directive 2004.23.EC, op. cit.

^[18] Regulation (EU) 2024/1938, op. cit. (EU SoHO Regulation), art. 2(2)(a) and (b).

^[19] The Additional Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research (ETS 195).

^[20] Ex resolution 78(29) that applies to removal and transplantation; Recommendation R(79)5 CM COE concerning international exchanges and transportation of human substances, 1979: substances removed for transplantation or therapeutic need or diagnosis of somebody else than the donor and for research purposes; see also Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin, op. cit.

^[21] Recommendation R(79)5, op. cit. Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Biomedical Research (ETS No.195).

^[22] See EU directives. Directive 2004/23, op. cit.

^[23] Agreement on the Transfer of Corpses (ETS no.080), 26 October 1973.

^[24] EU SoHO Regulation, op. cit., Art. 1 and 2. The Regulation will cover all SoHO, including SoHO preparations, suggesting a functional approach based on intended human use. However, despite the broad classification of the Regulation, subclassifications will remain depending on use and SoHO type as other European norms and national legislations will articulate with the Regulation.

^[25] Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine (ETS 164, 1997), art. 21.

^[26] EU Charter of Fundamental Rights, art. 3(2)(c) prohibits the “making the human body and its parts as such a source of financial gain.”

^[27] See supra.

^[28] See infra.

^[29] On the protection of the human person and body after death see in particular D. Sperling, Posthumous Interests, Legal and ethical perspectives, CUP, Cambridge, 2008, J. Taylor, Death, Posthumous Harm and Bioethics, Routledge 2012, H. Young, “The right to Posthumous bodily integrity and implications of whose right it is,” in Marquette Elder’s Advisor, 2013, vol.14, pp. 197–26, in French see J. Mesmin d’Estienne, L’État et la mort, LGDJ thèses 2016, L. Carayon, La catégorisation des corps. Étude sur l’humain avant la naissance et après la mort, IRJS 2019. The case-law on the European Court of Human Rights in this regard is also instructive, through the protection of the rights of relatives: see, a.o., on organ/tissue removals see, a.o., Elberte v. Latvia, app. No. 61243/08 (2015), on mutilation after death see Akkum and others v. Turkey, app. No. 21894/93 (2005).

^[30] Ischemia is characterized by insufficient blood flow to an organ or tissue, leading to oxygen deficiency and potential tissue damage, impacting the feasibility of transplantation. There is a warm ischemic phase and a cold ischemic phrase, the latter referring to the phase where the removed organ is preserved in a hypothermic state prior to transplantation. Acceptable cold ischemic time limits vary from organ to organ from a few hours to a day. For more information see E. B: Finger, “Organ Preservation,” Medscape, 5 October 2023 (last accessed 29 September 2024).

^[31] See EU SoHO Regulation, op.cit., Recital 26.

^[32] Explanatory Report, §23-25. The Explanatory report does not, however, explain these different implications. It is worth noting, however, that despite these “different implications” uterus transplant is still covered by the protocol.

^[33] See in that sense the authorisation of tissue removals, by exception, on persons not able to consent and under 5 strict conditions, which may be partially unapplied in case of cell removals (art.14 and 15 Additional Protocol on Transplantation, op. cit.).

^[34] See Additional Protocol, art.1.

^[35] On the history and evolution of the EU competences in health see in particular T. K. Hervey and J.V. McHale, EU Health Law – Themes and Implications, CUP, 2015, see also E.Brosset, Manuel de droit de l’Union européenne de la santé, Bruylant et Strada lex, Coll. Droit de l’Union européenne (Manuels), 2024, 447 p., N. De Grove-Valdeyron, Santé publique, Annuaire de droit de l’Union européenne, 2024, pp. 847‑876 and from the same author Droit européen de la santé, LGDJ Coll. Systèmes, 2^e éd., 2018 ; see also V. Michel, Recherches sur les compétences de la Communauté européenne, L’Harmattan et Numilog, Logiques juridiques, 2003.

^[36] TFEU, art. 36 (ex-art. 30), art. 45(3) (ex-article 39 TEC) et article 52 (ex-art. 46 TEC).

^[37] TUE (92/C 191/01), art. 129(1), see now Art. 168 TFEU (ex-art. 152 TEC).

^[38] Treaty of Amsterdam, Art. 2(2)6, modifying Art. 129(1).

^[39] Id., Art. 129(4)(a); TUE, article 152.4.a.

^[40] Treaty of Lisbon, art 2(12).

^[41] The competence of the Union is not limited to the attribution of competence in health, as free movement of goods and services applies to the health sector. besides, there was already health regulation before competence in health was recognized, illustrating the classic subordination of health to the internal market. See Valérie Michel, “La compétence de la Communauté en matière de santé publique,” in Revue des affaires européennes, 2003-2004, pp. 157–184. As the author points out, health does not enjoy any specificity and has historically been approached from the angle of the internal market. Despite a specific title, health is also « scattered » throughout the treaty.

^[42] As a subset of health law, and even more subject to differences in ethical and moral perceptions, bioethics is a state power, although the EU has developed of EU biomedical law. For an analysis see S. Hennette-Vauchez, “EU Law and Bioethics,” in Marise Cremona (ed.), New Technologies and EU Law, Oxford, 2017; online edn, Oxford Academic, 20 July 2017 (accessed 27 Sept. 2024), arguing that the existing law is mostly about frames, procedures, and methods, more than it is about substance and content.

^[43] Statute of the Council of Europe, ETS No. 1, 5 May 1949, art.1 (a) and (b).

^[44] European Convention for the Protection of Human Rights and Fundamental Freedoms, ETS No.005, 1950 and its amending protocols (accessible here: Protocol No. 11, Protocol No. 14, Protocol No. 15, and Protocol No. 16.

^[45] ECtHR, Loizidou v. Turkey (preliminary objections), No. 15318/89, at 93.

^[46] Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine (ETS No. 164, 1997), op. cit.

^[47] Additional Protocol to the Convention on Human Rights and Biomedicine concerning Transplantation of Organs and Tissues of Human Origin (ETS No. 186), op. cit.

^[48] Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Biomedical Research (ETS No. 1959), 25 January 2005, in force since 01 September 2007.

^[49] Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Genetic Testing for Health Purposes (ETS No. 203), 27 November 2008, in force since 1 July 2018.

^[50] Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Beings (ETS No. 168), 12 January 2998, in force since 1 March 2001.

^[51] Council of Europe Convention against Trafficking in Human Organs (CETS No. 216), 25 March 2015, in force since 2018, art 4 (1) (a) and (b).

^[52]  Universal Declaration of Human Rights, UNGA res. 217A, Paris, 10 December 1948.

^[53] See a.o., B. Schumacher, “The Influence of the Council of Europe on the European Union: Resource Exchange and Domain Restriction as Venues for Inter-Institutional Influence,” in O. Costa, K.E. Jørgensen (eds), The Influence of International Institutions on the EU, Palgrave Studies in European Union Politics. Palgrave Macmillan, 2012, London ; F. Berrod et B. Wassenberg (eds), Les relations entre le Conseil de l’Europe et l’Union européenne. Complémentrité ou concurrence ?, Fare Cahiers no. 10, L’Harmattan, 2016. On Human Rights see S. Greer, J. Gerards and R. Slowe, Human Rights in the Council of Europe and the European Union, Achievments, Trends and Challenges, Cambridge Studies in European Law and Policy, CUP, 2018. On judicial dialogue see I. Pelin-Raducu, “Le dialogue entre les juges en matière de protection des droits de l’homme,” in S. Menétrey and B. Hess (eds), Les dialogues des juges en Europe, Larcier, 2014.

^[54] European Agreement on the Exchange of Therapeutic Substances of Human Origin (ETS No. 026), ratified on 30 March 1987; on the same day the EU also ratified the European Agreement on the Exchanges of Blood-Grouping Reagents (ETS No. 039), and the Convention on the Elaboration of a European Pharmacopoeia (ETS No. 050) in 1994.

^[55] European Patent Convention, art. 53(a).

^[56] Brüstle v Greenpeace, Case C-34/10 [2011] E.C.R.I-09821, at [53]; in which the Court provided an autonomous definition at the EU level of the human embryo, referring to the principle of human dignity.

^[57] On the presumption of equivalent protection see ECtHR, Bosphorus Hava Yolları Turizm ve Ticaret Anonim Şirketi v. Ireland, No. 45036/98 (2005). Other types of interactions include the fact that the EU shall accede to the ECHR. On equivalent protection, see P. de Hert and F. Korenica, “The doctrine of equivalent protection: its life and legitimacy before and after the European Union’s accession to the European Convention on Human Rights,” in German Law Journal, vol. 13 no. 7, 2012.

^[58] EU Charter of Fundamental Rights, Art 3§2.

^[59] For a discussion on the jurisprudence of the European Court of Human Rights on access to experimental treatments (regulated at the EU level), see E. Rial-Sebbag and A. Blassime, “The European Court of Human Rights’ Ruling on Unproven Stem Cell Therapies: A Missed Opportunity?,” Stem Cells and Development, 2014, Vol. 23(S1) (last accessed 25 March 2023).

^[60] V. Tournay, A. Leibing, A. Mahalatchimy, C. Mounet and G. Saez, “Ceci n’est pas une cellule souche. Du laboratoire au musée : le défi de la compréhension de la complexité biologique,” RDST, 17 | 2018, pp. 107–128.

^[61] Léon Kass argued in 1971 that dying was a process but death was a moment, the moment at which a point of no return is crossed and from which no effort at resuscitation will succeed in restoring the organism to a state of homeostasis see L. Kass, ‘Death as an Event: A Commentary on Robert Morison’ (1971) Science 173 (3998) pp. 699–700.

^[62] A. Lebret, Prélèvement d’organes et droits fondamentaux en Europe et aux États-Unis (Panthéon Assas University, 1 February 2019).

^[63] For an updated discussion on brain death cases in the USA, see Pr. Thaddeus Mason Pope’s website.

^[64] And more broadly persons that are not able to consent: Oviedo Convention, art. 20(1); Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin, art. 14(1).

^[65] Id., art 20(2), authorising States to allow this type of removal for regenerative tissue by exception providing the reunion of 5 cumulative conditions; see also art 14(2). Yet, the protocol on transplantation states that legislations may authorize cell removal from living donors on persons not able to consent in less strict conditions than for tissues in general: see art. 15.

^[66] Explanatory Report to Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin.

^[67] EU Directive 2010/53/EU, op. cit.

^[68] Ibid.; see also art. 2(2) Council of Europe Convention against organ trafficking, 2015, CETS 216.

^[69] See Explanatory Report to Protocol on Transplantation, op. cit.; EU Tissue directive2004/23, op. cit. For a discussion regarding organoids, see A. Bottacci, “Defining organoids in EU Law” in this special issue.

^[70] EU Tissue Directive, Art. 3(b). The Additional Protocol does not define tissues as such but states that “[t]he provisions of this Protocol applicable to tissues shall apply also to cells, including haematopoietic stem cells” (art. 2(2)).

^[71] For example, there is a recurrent distinction in some countries on solid/ liquid organs. On difficulties in naming see Explanatory report, Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin, § 28. See also a discussion on possible different linguistic interpretations (of qualified practitioner defined in Annex III of Directive 2004/33/EC) in the context of the adoption of the SoHO Regulation: European Commission, Directorate-General for Health and Food safety, Study supporting the evaluation of the EU legislation on Blood and Tissues and Cells (SANTE/2017/B4/010) – Final report, 2018, p. 88.

^[72] European Agreement on the Exchange of Therapeutic Substances of Human origin and Protocol thereto Paris, 15.XII.1958, Art.1.

^[73] Ibid., Art. 1 envisions these evolutions by allowing an extension of the scope of the Agreement to other therapeutic substances of human origin “by exchange or letters between two or more of the Contracting Parties.”

^[74] EU SoHO Regulation, op. cit., Art. 3(1), and art.2 (a) and (b). SoHO preparation being defined as.

^[75] See Explanatory Report, “the umbrella term ‘transplantation’ should also be considered applicable in relation to medically assisted reproduction treatments.”

^[76] CETS 211 – Counterfeiting of medical products and similar crimes, 28.X.2011, art.4(a).

^[77] See E. Lietzan, A. Mahalatchimy, P. Zettler, “Introduction to Medical Products Law,” in D. Orentlicher and T. Hervey (eds), The Oxford Handbook of Comparative Health Law, OUP, 2020, 10.1093/oxfordhb/9780190846756.013.57.

^[78] For a detailed presentation of the regulatory framework of Medicines in the EU and some comparative perspectives see A. Mahalatchimy, “Regulating Medicines in the European Union” in D. Orentlicher and T. Hervey (eds), The Oxford Handbook of Comparative Health Law, OUP 2020, 10.1093/oxfordhb/9780190846756.013.24. halshs-02943155.

^[79] CETS 211 – Counterfeiting of medical products and similar crimes, 28.X.2011, art.4 (b)(i) and (ii).

^[80] See also see A. Mahalatchimy, “Regulating Medicines in the European Union,” op. cit.

^[81] Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. European Union; 2017.

^[82] Ibid. Art.1 § 8.

^[83] Ibid.

^[84] European Commission, DG Enterprise and Industry, Medical Devices: Guidance Document Borderline products, drug-delivery products and medical devices incorporating, as an integral part, an ancillary medicinal substance or an ancillary human blood derivative, MEDDEC 2.1/3 rev 3, Ref. Ares(2015)2062695 – 18/05/2015, p. 13.

^[85] But see some information from the European Medicines Agency, Consultation procedure for ancillary medicinal substances in medical devices (last accessed 28 Sept 2024).

^[86] A. Mahalatchimy, “Regulating Medicines in the European Union,” op. cit., citing https://www.imi.europa.eu/sites/default/files/events/SF2017/microbiome_Mihokovic.pdf.

^[87] Ibid., p. 3.

^[88] Proposal for a Regulation laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, Brussels, 16 April 2023.

^[89] EU SoHO Regulation, op. cit., Art. 68 and 69.

^[90] For other examples and more details, see A. Mahalatchimy, “Regulating Medicines in the European Union,” op. cit., from p. 2.

^[91] Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004, OJ L 324 10.12.2007, p. 121.

^[92] Ibid., art. 2 (c).

^[93] Regulation (EU) 2017/745, op. cit, Annex I “Manipulations referred to in the first indent of Article 2(1)(c).”

^[94] I.A. Uhrynowska-Tyszkiewicz, E. Olender, A. Kaminski, “A Cell Graft or a Drug? Legal and Practical Aspects of Somatic Cells Application in Graft-Versus-Host Disease Experimental Treatment: The Polish Experience,” in Transplant Proc. 2016, vol. 48(5), pp. 1402–1406.

^[95] Regulation (EC) No 1394/2007, op. cit., art. 2(1)(c).

^[96] N. Cuende, L. Rico, C. Herrera, “Concise review: bone marrow mononuclear cells for the treatment of ischemic syndromes: medicinal product or cell transplantation?,” in Stem Cells Transl Med. 2012, vol. 1, pp. 403–408.

^[97] Ibid.

^[98] Ibid.

^[99] A. Mahalatchimy, E. Rial-Sebbag, V. Tournay, and A. Faulner, “The Legal Landscape for Advanced Therapies: Material and Institutional Implementation of European Union Rules in France and the United Kingdom,” Journal of Law and Society, 2012, vol. 39(1), pp. 131–149.

^[100] See also N. Cuende, “European and Spanish legal framework for the development of advanced therapies and regulatory and legal tools promoted at international level to facilitate patient access” in Rev Der Gen. 2018, vol. 48, pp. 201–231.

^[101] On hospital exemption see a.o. N. Cuende, C. Boniface, C. Bravery C, et al., “The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders’ concerns,” in Cytotherapy. 2014, vol. 16, pp. 1597–1600.

^[102] Guidelines on good manufacturing practice specific to advanced therapy medicinal products, European Commission, 2017.

^[103] European Committee on Organ Transplantation, Risk of Commodification of Substances of Human Origin – A position statement, 18 November 2022.

^[104] Study supporting the Impact Assessment of the Revision of Directive 2002/98/EC on safety and quality of human blood and blood components and of Directive 2004/23/EC on safety and quality of human tissues and cells and of their implementing acts Workshops – Summary notes, § 10.

^[105] EU SoHO Regulation, op. cit., art. 3(5).

^[106] Ibid., art. 1 and recitals.

^[107] Altruistic donations may still be compensated to achieve financial neutrality. In this regard and regarding import within the EU, see CJEU, Case C‑421/09, Humanplasma GmbH v Austria, ECR 2010 I-12869 (2010) finding that national rules prohibiting the importation of blood products provided from donations which were not entirely unpaid (even in case of sole compensation) was an unjustified restriction to freedom of goods as it was necessary to attain the objective to ensure the quality and safety of the blood and of the blood components.

^[108] See Data from 2020, Marketing Research Bureau, Data & Analysis of Immunoglobin Supply and Plasma Requirements in Europe 2020-2021, p. 12, revised May 19, 2023. Accessed 27 February 2024. See also p. 18, showing a huge difference between a country like Germany, which collects more plasma tant needed, enabling it to export (with a system of paid “donation”), while France, with a non-compensated system, has a huge deficit.

^[109] A. Ockenfels, A. Roth, “Consequences of unpaid blood plasma donations,” Vox EU CEPR, 4 nov 2023 (accessed Feb 2024).

^[110] Ibid.

^[111] R. Von Schomberg, op. cit., p. 63. In the particular field of biomedical innovation see É. Gennet, A. Mahalatchimy, “How does EU non-binding law contribute to the scientific concept of biomedical innovations?,” in this special issue, where the authors argue that “EU non-binding law reveals that main characteristics of innovation are to be found in its objective to promote societal values and market competitivity as improvements for the society which is seen as the beneficiary of innovation but also in its actual adoption by society where the society is seen as a player.”

^[112] Participation of these different groups in the legislative process contributes to this aim. In the context of revision of the BTC Directives and in the preparation of the SoHO Regulation, see for example European Commission Directorate General for Health and Food Safety, “Revision of the Union legislation on blood, tissues and cells – Public consultation factual summary report, Ref. Ares(2021)5131819 – 16/08/2021.

^[113] CESCR General Comment No. 14: The Right to the Highest Attainable Standard of Health (Art. 12), E/C.12/2000/4, § 12.

^[114] Oviedo Convention, op. cit., art. 5, see also Additional Protocol concerning Transplantation of Organs and Tissues of Human Origin, op. cit., art. 12.

^[115] Additional Protocol on Transplantation, op. cit., art. 20.

^[116] A. Polomeni, “Enjeux éthiques et cliniques des thérapies innovantes : l’exemple de l’allogreffe de cellules souches hématopoïétiques,” in Revue française d’éthique appliquée, 2017, vol. 2, pp. 91–103, p. 97.

^[117] EU SoHO Regulation, op. cit., Art. 55 §3 (b) and (e)“Standards concerning information to be provided prior to consent.”

^[118] This issue on the scope of SoHO donor’s consent regarding the different possible uses (as well as the form of consent -opt in/opt out) is comparable to the scope of patients’ consent regarding the secondary use of their health data. On consent to different uses in biomedicine and biomedical research see in particular J. Kaye, et al., “Dynamic consent: a solution to a perennial problem?,” in BMJ, 2011, 343. See also the Future EU Regulation on the European Health Data Space.

^[119] European Committee on Organ Transplantation, Risk of Commodification of Substances of Human Origin – A position statement, 18 November 2022, p. 3.

^[120] As shown by A. Blasimme, “Translating stem cells to the clinic: scientific societies and the making of regenerative medicine,” Quaderni [En ligne], 81 | Printemps 2013, mis en ligne le 5 juin 2015, consulté le 28 février 2024. Investigating guidance documents from the International Society for Stem cell Research (ISSCR) and the International Cellular Medicine (ICMS) proposing models of legitimate biotechnological innovation in the field of regenerative medicine, Blassime shows “disjunctive framings of clinical translation.” While the former frames cells as drugs, encouraging dedicated laws, the latter categorizes stem cells as natural parts of patient’s body, leading it to reject regulatory paternalism.

^[121] A. Liu, “A $3M gene therapy: bluebird bio breaks its own pricing record with FDA approval of Skysona,” Fierce Pharma, 2022, concerning Skysona, or eli-cel, for the rare neurological disorder cerebral adrenoleukodystrophy (CALD, Accessed 25 March 2024).

^[122] N. Cuende, et al., “Addressing Risks Derived From the Commodification of Substances of Human Origin: A European Proposal Applicable Worldwide,” Transplantation, 2023 Apr 1, vol. 107(4), pp. 867–877.

^[123] A study on determinants of blood donation willingness, conducted in EU countries, shows that donors valued more the direct therapeutic need of patients than the collective need to alleviate shortages. Interestingly, there was a lack of correlation between receiving incentives and willingness to donate. E.MJ Huis in’t Veld, WLAM de Kort and E.-M. Merz, “Determinants of blood donation willingness in the European Union: a cross-country perspective on perceived transfusion safety, concerns, and incentives,” in Transfusion 2019, vol. 59, pp. 1273–1282.

^[124] On the importance of subjective perceptions in blood donation behaviour, see Caroline Graf, Bianca Suanet, P. Wiepking and E.-M. Merz, “How public trust and healthcare quality relate to blood donation behavior: Cross-cultural evidence,” Journal of Health Psychology 2024, Vol. 29(1), pp. 3–14, showing the role of subjective perceptions of the quality of healthcare system, rather than the objective state of healthcare, for blood donation behaviour in Europe.

^[125] Décret n° 2016-1118 du 11 août 2016 relatif aux modalités d’expression du refus de prélèvement d’organes après le décès, JORF n° 0189 du 14 août 2016.

^[126] Assemblée nationale, Communication de J.-L. Touraine, “Mission ‘flash’ relative aux conditions de prélèvement d’organes et du refus de tells prélèvements,” 20 décembre 2017.

^[127] Décret n° 2016-1118 du 11 août 2016, op. cit.

^[128] Loi n° 76-1181 du 22 décembre 1976 relative aux prélèvements d’organes, dite « Loi Cavaillet », abrogated in 1994 (but presumed consent has been reaffirmed by successive bioethical legislations).

^[129] A. Mahalatchimy and E. Rial-Sebbag, “Deciphering the Fragmentation of the Human Genome Editing Regulatory Landscape,” Front. Polit. Sci., vol. 3, Jan. 2022, p. 10.

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Audrey Lebret, « Unravelling Challenges of European Legal Approaches and Definitions of SoHO in Shaping Biomedical Innovation », Définitions et concepts du biodroit [Dossier], Confluence des droits_La revue [En ligne], 07 | 2025, mis en ligne le 7 juillet 2025. URL : https://confluencedesdroits-larevue.com/?p=4176.