The article explores whether the broader regulatory framework applicable to the member states of the EU contains suitable tools to react to the rapid advances in science, especially as to the question of germline editing technologies. From the perspective of EU member states, the regulatory framework is fragmented between norms of international law, secondary EU law and national legislation. The rules and their interpretation are strongly influenced by the concept of precaution, which reflects the concern that there is not enough knowledge to assess the impact of genome editing technology on individuals, society and future populations. However, the argument of precaution loses its strength with every new scientific discovery. The expanding knowledge in the field creates the need to replace regulation, which is based on the lack of knowledge (such as precautionary moratoriums) by the regulation that is based on the actual knowledge. The article reaches a conclusion that the EU framework for advanced treatments and medicinal products is in a state where it can, in principle, address the questions associated with the safety and efficacy of germline editing technologies. The EU framework is, however, not suitable to assess the moral and societal impacts of new technology, which should be left for member states.
The debate on the regulation of gene editing is driven by three central concerns. The first concern is the concern for societal order. It is driven by fear that the technology might be abused for non-healthcare purposes and thus undermine the fundamental moral values of society and change the society irreversibly. The most notable demonstration of this concern is the fear of overuse in editing the human genome for nonmedical reasons, for example designing children (known as “designer babies”) and the resulting social conflicts.1 On a more general level, this concern is reflected in the complex debate on determining the line between the treatment of disease and enhancement of a human.2 The second concern is the fear that the technology is not safe enough. Concerns are raised about technology’s technical limitations, such as possibilities of unexpected mutations after gene editing,3 apprehension whether modified organisms will be affected indefinitely, and whether the edited genes will be transferred to future generations, potentially affecting them in unexpected ways.4 The gene-editing technology also raises concerns that it could be weaponised,5 even if this concern is mostly discussed in the context of genetic engineering of biological pathogens or species.6
The focus of this paper is the regulatory framework for using gene-editing technology in healthcare. From the perspective of EU member states, the debate on how the clinical application of gene editing should be regulated is shaped by the three above mentioned concerns and framed by the complex framework of international treaties, EU legislation, national rules, and rules of soft law, most of which were not drafted with the gene-editing technology in mind. The discussion on the appropriate regulatory model for genome editing has two dimensions. The first dimension is whether the technology should be regulated by the tools of international, EU or national law. The second dimension is whether the regulation should focus on the object, such as the device or product or on the process, such as the course of treatment and the conduct of the healthcare provider.
The advantage of the object-based approach is the concentration of expertise. The products are assessed by experts who have better knowledge than the workers who use them. The disadvantage of this approach is that it does not focus on how the healthcare workers or laypersons actually use the regulated products. To ensure safety and tackle the ethical concerns of gene therapies, the “object-based” regulation needs to be complemented by “process-based regulation” that focuses on the conduct of healthcare providers. Whereas the “object-based” regulation is focused on alleviating doubts on the safety of a technology (“how the technology should look like”), the “process-based” regulation is focused on the protection of societal values from negative impacts of a newly developed technology (“how the technology should be used”).
The precautionary principle could be applied as a strategy to deal with the concern of unforeseen consequences for both societal orders, public safety or individual safety. According to this principle, if there is a potential for harm from the activity and if there is uncertainty about the magnitude of impacts or causality, then anticipatory action should be taken to avoid harm.7 The precautionary principle is a variation of the ethical non-maleficence principle.8 In practice, however, this can lead to a consequence called an ‘uncertainty paradox’, which is a situation where there is a discrepancy between a promise of scientific knowledge and the lack thereof in a specific case.9 This principle is applied mainly in environmental law, where it is even considered fundamental,10 but it can also be used in the application of new technology or product.
The article seeks to assess whether the international, supranational and national rules relevant for the EU area are prepared for the rapid advancement of technology in the field of genome editing, especially as to the question of germline editing technologies. The article also discusses which regulatory levels are suitable for object-based regulation and which are more suitable towards regulating the processes of gene therapy.
2 Rapid Development Induced by CRISPR
The discovery of methods for programming CRISPR to edit genomic DNA was made in 201211,12 and started a new era in biology and in related fields. The intensive research eventually leads to practical applications. Genome editing technologies have already taken over the field of plant breeding.13 The deployment of genome editing in the production of eggs, poultry and livestock is foreseen in the near future.14 At the time of writing, the US Patent Collection database contains 6745 CRISPR related patents15 and European Patent Register contains 777 patents or applications that contain CRISPR as keyword.16 The Core collection of the Web of Science17 contains 30523 documents mentioning CRISPR between years 2012–2021.
Arguably, CRISPR has started a new era in the field of healthcare. Figure 1 shows the proportion of peer-reviewed articles indexed in the Web of Science database that contained CRISPR as a keyword between 2012 and 2020 categorised into respective research fields.
The tree bar chart demonstrates that the research activity in cell biology and biochemistry has spilled over towards research in clinical medicine. The first discoveries associated with CRISPR brought hopes to treat both communicable as well as non-communicable diseases, which gave impulse to frenetic research activity searching for potential clinical applications. Less than three years after its discovery, the CRISPR methods were used to successfully modify human embryos.18 In the immediate reaction to this experiment, the research community generally accepted that mankind needed a moratorium on clinical applications of CRISPR until “the ethical and safety concerns of human-embryo editing are worked out.”19 The international summit was held in 2015 with a concluding statement: “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.”20 At the time of the conference, these criteria had not been met for any proposed clinical use.
Three years later, in 2018, the first genetically engineered babies were born, which was met with “universal condemnation by scientists and international organizations.”21 Fast forward further three years to 2021, and we are witnessing an abundance of CRISPR related research that is aimed for clinical application. According to a summary article published by innovative genomics institute in 2020, there were ongoing successful clinical trials for using genome editing technologies for treating cancer, eye diseases, chronic infections and rare ‘protein-folding’ disease.22 The first use of CRISPR technology injected into the blood of a patient was reported in June 2021.23 Private and public institutions dedicate significant amounts of resources to clinical applications of genome editing, and regulators all over the world are currently allowing clinical trials involving gene editing to happen.24 It can be observed that the moratorium on any clinical applications of genome editing technologies is coming to its de facto end if it ever factually existed. The genie of genome editing therapies is out of the bottle. The calls for a global moratorium on heritable genome editing from the science community are still vocal and prevalent.25 However, the conclusions of the Second International Summit on Human Genome Editing acknowledge the transition towards regulated heritable human genome editing26 and formulate eleven recommendations for countries that intend to permit its clinical use.27
3 The Reactive Approach to Genome Editing in the EU
Due to the rapid progress in science, the EU and its member states are now in a position where they need to react to the actual development in genome editing rather than anticipating it and using regulation as an incentive to reach policy objectives. The question of whether there should be a moratorium on at least some of the clinical applications of gene editing technologies has not been resolved in a systematic way across the EU. Currently, each member state can make its own decision whether to put in place the moratorium or specific regulation on clinical applications of somatic or germline genome editing. The compatibility of “object-based” and “process-based” regulations is an issue. The rules on market access of medicinal products and medical devices are centralised or harmonised,28 but the rules on the actual provision of healthcare remain in the competence of the member states.29 Part of “process-based” regulation often has the form of non-binding guidelines issued by professional organisations.
The international human rights treaties play an important role in Europe. Yotova observes that international law already plays a role in regulating genome editing through more general treaties and soft law instruments30 and identifies main limits of international law’s regulation, which can be summarised as (1) use of genome editing for medical purposes only; (2) respect for the dignity and human rights; (3) management of risks and their proportionality to benefits; (4) patient autonomy; and (5) rights of future generations,31 with a lack of international consensus concerning the particularities of genome editing. Whilst current international law sets out common minimum standards, the decisive part of the process-based regulation currently lies at the national level.
Seventeen EU countries are bound by the Article 13 of the Oviedo Convention,32 which prohibits interventions that aim to introduce any modification in the genome of any descendants. Other member states where the intensity of biomedical research is high (such as Germany, Italy, Netherlands, Belgium and Sweden) did not ratify this convention.33 This does not necessarily mean, that the countries which did not ratify Oviedo Convention have a liberal stance towards human germline editing.
A specific form of germline editing moratorium is contained in Article 90 of the Clinical trials regulation,34 which says “no gene therapy clinical trials may be carried out which result in modifications to the subject’s germ line genetic identity.” This provision does not offer a complex solution because it regulates only clinical trials and does not cover the registration of medicinal product or the actual application of medicinal product in case its clinical trials proceeded outside the EU. The Clinical trials regulation also contains very little reasoning of why this provision is included, as it only refers to the similar provision in the revoked Clinical trials directive.35
European Union and the Member states are yet to create a workable legislative framework that will balance the safety and ethical concerns with the benefits of the new technology with a wide scope of practical application. In its “horizon scan report,” the EMEA called for stakeholder dialogue to address the new challenges of new technologies upfront.36
4 The Transition from Moratoriums Based on Precaution
The concept of the legal moratorium on the new technology based on precaution is not alien to EU law. The EU rules on genetically modified organisms,37 genetically modified food and genetically modified feeds38 are put in place with the objective to protect human health, animal health and the environment in accordance with the precautionary principle. The precautionary principle is explicitly mentioned in the first paragraph of the Cartagena Protocol on Biosafety to the Convention on Biological Diversity to which the EU is a member.39 The precautionary principle is explicitly mentioned in the first recital of the Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms as well as in the recital no. 22 of the Regulation (EC) No 1946/2003 on transboundary movements of genetically modified organisms. The GMO framework is also applicable to modern biotechnological methods, including CRISPR.40 It is important to stress that the GMO legislative framework does not apply to humans.41
When it comes to the regulation of human genome editing, the application of the precautionary principle is more nuanced. The strictness of the regulation depends on the criterion, whether the induced genetic changes are heritable or non-heritable. There is a distinction between somatic gene editing, which targets only some of the cells of a patient and is believed not to affect future generations and germline editing, which affects all cells in an organism, including eggs and sperm, and so is passed on to future generations.42
A significant degree of precaution is required for both kinds of genome editing. Whereas somatic editing brings risks of adverse events to a single patient, germline editing brings risks also to the future population. As a result, somatic gene editing for medical purposes is in general accepted, albeit strongly regulated, whereas germline editing is in general prohibited as a measure of precaution by EU law43 as well as laws of individual member states, especially the states that transposed the Article 1344 of the Oviedo Convention45 into their national legislation.
The precautionary approach that puts emphasis on the general prohibition of a certain technology loses its validity over time as science advances. The underlying argument for the precautionary approach is based on the lack of knowledge46 about the implications of new technology. Therefore, it loses strength with every new piece of information brought by science. We argue that any potential general prohibition based on a precautionary approach must be perceived as a temporary moratorium, where the rules based on lack of knowledge on the implications of new technology are inevitably going to be replaced by the rules based on the knowledge of beneficial and harmful implications of the technology.
The advance of science, however, does not weaken only the regulation underlined by a precautionary approach. We agree with the argument raised by Schleidigen et al.47 that the parties to the European Convention of Human Rights are under the obligation to revisit their rules in accordance with the development of science. Even if a moratorium on any technology is based on moral and ethical values, these values will have to be balanced by a right of individuals to enjoy the benefits of scientific progress and its applications granted by Article 15(1)(b) of the International Covenant on Economic, Social and Cultural Rights.
Any argument for a precautionary moratorium of any form of genome editing within the EU also loses validity in time when considering the global perspective. If a state enforces a moratorium on the development of new technology, knowledge and discoveries will arise in different parts of the world. There are already 11 countries in the world that explicitly permit germline editing for other purposes than reproduction.48 These include research-intensive countries like China, the UK and the USA49 It can be argued that countries that stick to the precautionary moratorium relinquish the opportunity to have a say on research priorities and policy in the field of genome editing. In the end, the countries that preserve the moratorium may end up having too little expertise to formulate their own rules and will most likely copy the regulatory mechanisms of the countries that made further progress in adopting new technology once the technology becomes too advanced to be ignored.
5 Object-Based Regulation as the First Step out of the Moratorium
The regulatory approach of the EU is predominantly object-based and focuses on the efficiency and safety of medicinal products and medical devices. The first possible step out of the precautionary moratorium is the regulation of market access for individual products, where it is up to the manufacturer to put forward scientific evidence on the safety of the new product. This approach respects the principle of precaution because no product is considered safe to use unless proven otherwise. A good example of this approach is a clinical trial of a medicinal product. The precaution, which is based on a lack of knowledge on the effects of a given product, is eased when the manufacturer brings convincing information on the risks and benefits of a new product or its new application.50 The manufacturer’s reward for creating new knowledge is the right to access the market with the newly developed product.
The approach based on the market authorisation of individual products, such as medicinal products or medical devices, emphasises the safety of the consumer or patient. The objective is not to introduce products with zero risks to patients or end users because this is, in most cases, impossible. The approach is based on risk management51 where the benefits and risks of each product introduced to a market must be known and transparently documented so that only products where there is scientific evidence that benefits outweigh the risks are made available for use. The most common tool for object-based regulation is standardisation. The standards are documented agreements containing technical specifications or other precise criteria to be used consistently to ensure that products are fit for their purpose.52
The EU utilizes this approach for marketing authorisation of new medicines, medical devices and diagnostic methods to incentivise investments in research and development. Furthermore, this approach can be paired with other legal tools which follow further societal, political, or environmental objectives. The most notable of these tools are research policy, research subsidies, rules for state aid in research,53 clinical trials regulation, IP rights, design standards and performative rules for manufacturers of medical devices. Policymakers can use this toolbox to channel the flow of innovation in the direction needed by society. The approach of incentivising innovation towards societal objectives is in general preferable to the precautionary moratorium.
5.1 Clinical Trials and Medicinal Products Policy
The EU legislation on clinical trials distinguishes between somatic and germline gene editing. The clinical trials directive from the year 200154 anticipated the need for clinical trials involving medicinal products for gene therapy, somatic cell therapy, xenogenic cell therapy and the development of medicinal products containing genetically modified organisms. However, the directive explicitly excluded the option of trials that may result in modifications to the subject’s germ line genetic identity. The current Clinical trials Regulation55, which replaces the Clinical trials Directive in 2022, preserves this policy.56 The prohibition of clinical trials which result in modifications to the subject’s germ line genetic identity is contained in Article 90 of the Clinical trials Regulation.
The legislative framework of secondary law that impacts somatic gene therapies contains the Regulation on advanced therapy medicinal products57 and the Directive on the Community code relating to medicinal products for human use.58 This is further developed by overarching and specific guidelines published by the European Medicines Agency59 that cover practical aspects of safety, efficiency, quality and pharmacovigilance. The complexity of the framework and systematic expert work of the European Medicines Agency demonstrates that EU institutions are capable of developing rules that manage the safety, efficacy and risks of advanced medicinal products.
5.2 Design Standards and Performative Rules in MDR
The products that are delivered into the body of patients to change their genes would, in most cases, fall outside the scope of Medical Device Regulation, as they would most likely fall under the definition of advanced therapy medicinal products. However, this may happen in connection with the parallel use of a medical device. For example, intravitreal injection of medicinal product can be combined with special optronic goggles to enhance effects.60
Medical Device Regulation61 is an example of regulation where the policymaker anticipates that the new products will be developed in accordance with predefined standards62 and specifications.63 Another useful tool used by Medical Device Regulation is the application of so-called performative rules, where the manufacturer is not bound by a certain predefined standard but is asked to achieve a generally defined objective. A good example is an obligation to have measures in place to provide sufficient financial coverage in respect of their potential liability.64
5.3 Patent Rules and Morality Exception Article 53 of the European Patent Convention
Another form of object-based regulation are intellectual property rights. Intellectual property policy can incentivise or de-incentivise investment into the research and development of new technologies. The EU law is framed by the European patent convention,65 which has broader geographical coverage. Article 53 of the European patent convention denies patent rights to inventions that would be contrary to ‘ordre public’ or morality. Guidelines for Examination in the European Patent Office explain that the purpose of this provision is “to deny protection to inventions likely to induce riot or public disorder, or to lead to criminal or other generally offensive behaviour.”66 This provision is based on moral concerns only. The precaution and individual safety are not mentioned in Article 53 or in guidelines.67 The secondary EU legislation provides a further specification of what is considered to be contrary to ordre public or morality in the Directive on the legal protection of biotechnological inventions.68 Article 6 of the Directive explicitly includes processes for modifying the germ line genetic identity of human beings.69
The concept where the patent offices serve as guardians of public order and morality is broadly criticised. The research of Plomer showed that the panels of the European patent office are, in practice, not well equipped to tackle questions of dignity and morality70 and that they have questionable legitimacy as opposed to governments and courts.71 Sherkow goes even further with criticism of limitations of “ordre public” when he claims that the removal of “ordre public” exception will be more appropriate since the patent holder could step in and prevent unethical use or exploitation of a biotechnological patent by private action.72 Keeping certain technology out of patent protection frees the inventor from accountability for the actual use and abuse of the invention. Feeney at all observed the current trend of ethical licensing, where the patent holder controls the ethical use of potentially exploitable technology and reached a conclusion that this tool is a commendable albeit insufficient solution to a problem, which can be solved only by international legislation.73 On the other hand, Pila argues against the approach where the responsibility for ethical use is given to the hands of patent owners.74 Instead, she calls for a more elaborate form of risk assessments aimed at “recognising and confronting the uncertain consequences of new technologies and their implications for society.”75
Even if the abovementioned authors propose different solutions, they all agree that the current regulation of patent exceptions based on morality is problematic. All authors propose the shift of focus from assessing whether a certain technology is moral or immoral per se towards the consideration of how such technology will be actually used in society.
6 Process-Based Regulation
The regulation of genome editing technologies needs to go beyond answering the question of whether the individual product or procedure is reasonably safe to use or whether a certain object or technology is per se moral or immoral. The regulation needs to keep perspective on the whole process of treatment, not only on the object that is used to treat a patient. Every application of genome-editing technology needs to be embedded into the broader regulatory framework, which protects various societal values, such as human dignity, equity, the welfare of an individual, patients’ autonomy or public health. These values are, in general, shared across all member states, declared in Charter of Fundamental Rights of the European Union and reinforced by commitments to international treaties.76 However, the examples of euthanasia, abortions and in-vitro fertilisation of single parents demonstrate that shared values do not lead to unanimous answers to questions whether a specific treatment is morally acceptable and legal. De Ruijter observes that “the EU is de facto balancing fundamental rights and values relating to health, implicitly taking on obligations for safeguarding fundamental rights in the field of health and affecting individuals’ rights sometimes without an explicit legal competence to do so,”77 but also observes that the decision at what level these values and rights should be protected is ultimately political.78 As a consequence, it remains the competence of the member states to determine which forms of treatment are considered acceptable and ultimately legal. It is still up to the Member states to determine under what circumstances will the actual healthcare be provided, how the rights of a patient will be protected and how the oversight over individual healthcare providers will be exercised. The regulation on national level may take form of binding legislation as well as the form of soft law in the form of clinical guidelines and good practices.
As we mentioned above, the debate on the regulation of gene editing is driven by three concerns, which are fears for public safety, individual (patient) safety and moral values. These concerns can be addressed on the international level, EU level and national level. The current regulatory framework that affects EU member states is based on the state of professional knowledge (or better said, lack of it) from the late 20th and early 21st century. While the basic principles79 and mechanics80 of the regulatory framework are sound, the rapid advancements of technology brought by the use of CRISPR pose a challenge. We argue that adaptations of the regulatory framework are needed.
The existing instruments of international law remain relevant for addressing certain concerns in the field of public safety81 and moral values, especially in the area of so-called first-generation human rights.82 Considering the global perspective, where individual states took very different approaches in regulation of gene-editing technology, it seems that the only globally shared position is the prohibition of germline genome editing for the purposes of mere reproduction where no treatment is involved.83 There is little hope for a global international treaty that would address other issues, such as germline genome editing for treatment purposes, standards for somatic treatments or ethical guidance and transparency of research.
The member states of EU share basic values codified in CFREU, but the political decision must be made on which levels should be these values protected when it comes to practical questions connected with patient safety and morality. We suggest that the division line between the competence of the EU and member states should be based on object-based versus process-based regulations. The EU should focus on object-based regulation, and process-based regulation should be left in the competence of member states. The division of competencies on core issues on gene editing can be summarized in Table 1. We analysed two cases where secondary EU law attempts to assess technologies on other criteria than their technical function and efficiency. The first case is the moratorium on clinical trials that involve germline editing,84 and the second case is the ordre public exception on the patentability of processes for modifying the germ line genetic identity of human beings.85 The former provision creates a moratorium based on precaution. The latter penalises certain technologies on the basis of a moral principle. We demonstrated that both provisions are problematic. The rationale of these provisions is based on the presumption that there is a lack of knowledge on the potential safety or moral consequences of the technology. Paradoxically, they work against creating better knowledge by putting a moratorium on research activities and disincentivising investments into the development of technology, but they are not suitable to prevent the development of germline editing treatments outside of EU borders and their subsequent deployment in Europe.
We suggest, that in the case of genome editing, the secondary EU law should not address the questions of morality and ethics, as these questions can be adequately addressed by the international fundamental rights treaties and national law. The EU law should focus on the scientifically backed efficiency and safety of new technology and developing standards that will shape the future technology. The policy that removes obstacles in research and incentivises new knowledge progress does not lead to the regulatory race to the bottom. Moral and ethical reservations against certain applications of genome editing technologies are certainly legitimate, and as our research showed, some of them are shared globally. More profound knowledge will, however, lead to better arguments for ethical constraints and better regulation based on societal values. It can be also assumed, that better understanding of the technology will lead to its greater social acceptance, as it was in similar cases, like dispensing Human Growth Hormone (HGH) to the children, that used to be controversial from a moral and ethical points of view,86 but is currently considered as common treatment.
Somatic genome editing is widely accepted as a legitimate treatment across the EU states, whereas germline editing is prohibited mainly on the grounds of precaution and morality. The legal basis of the moratorium on germline genome editing differs among the individual member states, depending on the ratification status of the Oviedo Convention. As the countries outside the EU are becoming more open to human germline editing (albeit not for reproduction purposes), it is important to discuss whether the EU and its member states should adapt their current policy.
The increasing amount of knowledge on genome editing, including human germline editing, erodes regulation based on the precautionary principle and can even change the moral perspective on specific therapies. The current regulatory framework, which is based on the lack of knowledge on future implications of the technology, needs to be replaced by the regulation based on knowledge and risk-based approach. The regulatory framework on the EU level should acknowledge the possibility of using germline editing technology in treatment in case it is proven safe and efficient. This will create further incentives to research activity and create knowledge, which can be used as a basis for political decisions on the moral acceptability of individual treatments.
We, therefore, suggest that the member states of EU should pool their resources to expertly assess the efficiency and safety of germline editing procedures similarly as they do with medicinal products, medical devices and innovative therapies and focus on the products (objects) that are used for the treatment. On the other hand, the member states should keep the competence to decide on the acceptability of individual treatments (processes) within their borders and on conditions under which these treatments will be provided.
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Most notably within the framework of Regulation (EU) 2017/745 on medical devices (OJ L 117 5 May 2017, p. 1), http://data.europa.eu/eli/reg/2017/745/2020-04-24 and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (OJ L 117 5 May 2017, p. 176) http://data.europa.eu/eli/reg/2017/746/2017-05-05 Regulation (EC) No 1394/2007 on advanced therapy medicinal products (OJ L 324, 10 December 2007, pp. 121–137) Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (OJ L 158, 27 May 2014, pp. 1–76) http://data.europa.eu/eli/reg/2014/536/oj OJ L 117 of 5 May 2017.
In accordance with the Article 168 on the Treaty on the Functioning of the European Union the health policy and the organisation and delivery of health services and medical care, the management of health services and medical care and the allocation of the resources remains within the competence of Member states.
Yotova, supra note 21, p. 658.
Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine Oviedo 04/04/1997.
The largest European states (including states outside EU) that did not ratify the Oviedo convention are the Russian Federation, Germany, United Kingdom, Italy, Ukraine, Poland, The Netherlands, Belgium and Sweden.
Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (OJ L 158, 27 May 2014, pp. 1–76), available online at http://data.europa.eu/eli/reg/2014/536/oj.
Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (OJ L 121, 1 May 2001, p. 34).
European Medicines Agency, Genome Editing EU-IN Horizon Scanning Report (2021), available online at https://www.ema.europa.eu/en/documents/report/genome-editing-eu-horizon-scanning-report_en.pdf.
Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC OJ L 106, 17 April 2001, pp. 1–39; Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms OJ L 125, 21 May 2009, pp. 75–97; Regulation (EC) No 1946/2003 of the European Parliament and of the Council of 15 July 2003 on transboundary movements of genetically modified organisms OJ L 287, 5 November 2003, pp. 1–10.
Regulation (EC) No 1829/2003 on genetically modified food and feed OJ L 268, 18 October 2003, p. 1.; Regulation (EC) No 1830/2003 concerning the traceability and labelling of genetically modified organisms and the traceability of food and feed products produced from genetically modified organisms OJ L 268, 18 October 2003, p. 24.
See Judgment in Case C-528/16 Confédération paysanne and Others v Premier ministre and Ministre de l’Agriculture, de l’Agroalimentaire et de la Forêt.
See CJEU Article 2(2) of Directive 2001/18/EC, on the deliberate release into the environment of genetically modified organisms which defines genetically modified organism (GMO) as ‘an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination.’
M.T. Bergman, Perspectives on gene editing (9 January 2019), available online at https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/ (accessed 22 October 2021).
The clinical trials in germ line gene therapy are allowed to be carried out under the provisions of Article 90 of the regulation no. 536/2004 on medicinal products.
Article 13: “An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants.”
Supra note 32.
See, for example, Articles 10.6 and 11.8 of the Cartagena Protocol on Biosafety which mention “lack of scientific certainty due to insufficient relevant scientific information and knowledge” on potential adverse effects.
S. Schleidgen, H.G. Dederer, S. Sgodda, S. Cravcisin, L. Lüneburg, T. Cantz and T. Heinemann, ‘Human germline editing in the era of CRISPR-Cas: Risk and uncertainty, inter-generational responsibility, therapeutic legitimacy’, BMC Medical Ethics 21 (1) (2020) 87, doi: 10.1186/S12910-020-00487-1/METRICS.
See: F. Baylis, M. Darnovsky, K. Hasson and T.M. Krahn, ‘Human Germline and Heritable Genome Editing: The Global Policy Landscape’, The CRISPR Journal 3 (5) (2020) 365–377, doi: 10.1089/crispr.2020.0082.
The list of 11 countries according to Baylis et al. (supra note 48) includes: Burundi, China, Congo, India, Iran, Ireland, Japan, Norway, Thailand, United Kingdom, United States.
Under EU law, a good example of this may be the provisions of Article 8 of the Directive 2001/83/EC on the Community code relating to medicinal products for human use (OJ L 311 28 November 2001, p. 67), available online at http://data.europa.eu/eli/dir/2001/83/2019-07-26.
See, for example, World Health Organization, Medical device regulations: global overview and guiding principles (Geneva: World Health Organization, 2003).
European Commission, Joint Research Centre, H. Kebapci, B. Wendland and S. Kaymaktchiyski, ‘State aid rules in research, development & innovation: addressing knowledge and awareness gaps among research and knowledge dissemination organisations: decision tree’, Publications Office (2020), available online at https://data.europa.eu/doi/10.2760/675525.
Article 9, para. 6 of the Clinical regulations directive.
Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC.
Recital no. 75 of the Clinical trials regulation states “Directive 2001/20/EC provides that no gene therapy trials may be carried out which result in modifications to the subject’s germ line genetic identity. It is appropriate to maintain that provision,” without any further elaboration.
Regulation 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 December 2007.
Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use OJ L 311, 28 November 2001.
Such as the “Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products (EMA/CAT/80183/2014)” or “Guideline on safety and efficacy follow-up and risk management of Advanced Therapy Medicinal Products (EMEA/149995/2008).”
See ‘Gene therapy with new medical device’, EuroTimes (n.d.), available online at https://www.eurotimes.org/gene-therapy-with-new-medical-device/ (accessed 25 October 2021).
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 OJ L 117, 5 May 2017, pp. 1–175.
See Article 8 of the Medical Device Regulation.
See Article 9 of the Medical Device Regulation.
See Article 10, para. 16 of the Medical Device Regulation.
Convention on the Grant of European Patents (European Patent Convention) of 5 October 1973 as revised by the Act revising Article 63 EPC of 17 December 1991 and the Act revising the EPC of 29 November 2000.
Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions OJ L 213, 30 July 1998, pp. 13–21.
The list is non exhaustive and contains processes for cloning human beings; processes for modifying the germ line genetic identity of human beings; uses of human embryos for industrial or commercial purposes; processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes.
A. Plomer, ‘Human Dignity and Patents’, SSRN Electronic Journal (2013) doi: 10.2139/SSRN.2360999.
J.S. Sherkow, E.Y. Adashi and I.G. Cohen ‘Governing Human Germline Editing Through Patent Law’, Journal of the American Medical Association 326 (12) (2021) 1149–1150. DOI: 10.1001/JAMA.2021.13824.
O. Feeney, J. Cockbain and S. Sterckx, ‘Ethics, Patents and Genome Editing: A Critical Assessment of Three Options of Technology Governance’, Frontiers in Political Science (2021) 731505, doi: 10.3389/FPOS.2021.731505.
J. Pila, ‘Adapting the ordre public and morality exclusion of European patent law to accommodate emerging technologies’, Nature Biotechnology 38 (2020) 555–557, doi: https://doi.org/10.1038/s41587-020-0504-5.
For broader analysis how societal values and health values interact with international treaties and the of Charter of Fundamental Rights of the European Union we refer to A. De Ruijter, EU Health Law & Policy: The Expansion of EU Power in Public Health and Health Care (Oxford: Oxford University Press, 2019), especially pp. 37–38.
Ibid., p. 15.
Ibid., p. 225.
Such as respect to human life, dignity, access to healthcare and social security.
Such as mechanisms to ensure safety and efficiency of medicinal products.
For the analysis on the applicability of the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction see M.E. Kosal, ‘Emerging life sciences and possible threats to international security’, Orbis 64 (4) (2020) 599–614.
See Yotova, supra note 21, p. 658.
Baylis et al., supra note 48.
Article 9, para. 6 of the Clinical Regulations Directive.
Article 6 of the directive on legal protection of biotechnological inventions.
J. Lantos, M. Siegler and L. Cuttler, ‘Ethical Issues in Growth Hormone Therapy’, Journal of the American Medical Association 261 (7) (1989) 1020–1024. doi:10.1001/jama.1989.03420070070033.