Medical genetic technologies in the biosafety system: a risk-based approach

Yudin Egor Vital'evich ORCID: 0000-0002-3511-9752 Junior Research Fellow, The Department of Labor and Social Law, the Faculty of Law of Saint Petersburg State University 199106, Russia, Sankt-Peterburg, g. Saint Petersburg, ul. 22-Ya liniya v. o., 7, of. 400 yudinegorv@gmail.com

April 2019 was marked for Russia by the adoption of the Federal Scientific and Technical Program for the Development of Genetic Technologies (hereinafter referred to as the 2019 Program) ^[1], which identified the key frontiers within which it is planned to actively broadcast (introduce) genetic technologies. By Decree of the President of the Russian Federation No. 160 dated March 28, 2022, from March 28, 2022, the 2019 Program period was extended until 2030 ^[2]. One of such frontiers in the 2019 Program is the healthcare sector, medicine. The main work on the development of genetic technologies in the field of medicine is associated, among other things, with the editing of genetic variants and genome defects that determine the occurrence of diseases with the described genetic etiology; with cellular modifications in multigenic pathologies, etc. Also, the 2019 Program established that the work on the transition to personalized medicine ^[3] will provide, among other things, regulatory legal support for the use of genetic technologies in the medical field.

The creation of conditions (including legal ones) for the provision of high-quality and safe medical care is a social obligation of the state, named social in the Constitution of Russia, to ensure the rights of citizens to health protection and medical care (Articles 7, 41 of the Constitution of Russia) ^[4]. Moreover, by ensuring the right of citizens to medical care (social right), the state thereby ensures the right to life (personal right) (Article 20 of the Constitution of Russia). Thus, social rights are closely intertwined with personal rights and act as guarantors of the protection of the latter ^[5]. Moreover, as K. V. Aranovsky, S. D. Knyazev, E. B. Khokhlov draw attention, personal and social rights are characterized by the presence of a common subject, for example, health, human life ^[6]. We share this view of scientists. Consequently, medical provision and medical activity are socially significant activities in which the population, firstly, realizes their social (right to medical care) and personal (right to health, life) rights inextricably linked with them and, secondly, satisfies needs that are of a socially significant nature ^[7].

The above is of particular importance when using medical genetic technologies (hereinafter referred to as MGT), because they have a special specificity. In this connection, they (MGT) transform the medical activity itself, giving it new features that affect, among other things, the building of effective mechanisms for the legal regulation of emerging social relations.

The concept of MGT as a separate type of genetic technology

Systematically considering the phenomenon of MGT, first of all it is necessary to determine the concept of genetic technologies in general, of which MGT is a separate type. The disadvantages of the current domestic legislation include the fact that the concept of genetic technologies is not disclosed in it. In legal science, the author's definitions of genetic technologies are presented in a very small number ^[8].

Taking into account the absence of a legal definition of genetic technologies and without detracting from the heuristic significance of their definitions proposed by various scientists, in the framework of this study we understand genetic technologies as a tool(s), method(s) and process(s) (their totality), which are developed on the basis of knowledge about the genome (genes, other molecules) and are aimed at to interact with genetic material containing genetic information in order to solve individual tasks in various fields of human activity. Such interaction can be realized in the forms of research of genes, deoxyribonucleic acid, ribonucleic acid, proteins, other molecules and structures; manipulations with them; as well as research of other genetic information. It should be noted that despite the presence of the concept of "genetic technologies" in the legal material, the use of the term "genomic" seems to us more preferable due to the fact that genomics as a branch of molecular genetics (which in turn is a branch of molecular biology) is engaged in the study of the genome, i.e. the totality of genes, their mutual functioning, expression and interaction with each other and with environmental factors. Consequently, genetic technologies are included in genomic technologies and correlate with each other as general and particular, where it is genetic technologies that are a special case of a more general phenomenon – genomic technologies. Nevertheless, within the framework of this work, taking into account the approach already chosen by the legislator, the concepts of "genetic technologies", "genomic technologies", "gene technologies" will be synonymous.

In turn, by MGT we mean genetic technologies used in medical activities. In this context, we define medical activity as professional activity related to the provision of medical care, conducting medical examinations, medical examinations and medical examinations, sanitary and anti-epidemic (preventive) measures (i.e. in the meaning that is normatively designated in Article 2 of Federal Law No. 323-FZ of November 21, 2011 "On fundamentals of public health protection in the Russian Federation" (hereinafter – Law No. 323-FZ) ^[9]).

The social significance of MGT

MGT are socially significant genetic technologies. Their social significance is manifested, in particular, in the following. MGT is used for preventive, research, diagnostic, therapeutic and rehabilitation purposes, i.e. within the framework of medical provision of the population, the purpose of which is to meet the needs of the population of a socially significant nature (maintaining their health). In this regard, MGT is distinguished by universal coverage of an unlimited number of people (i.e. all those who need these technologies). The development of MGT and the expansion of the scope of their use contributes to an increase in human life expectancy and its quality ^[10]. The active translation of MGT into clinical practice is aimed, among other things, at improving the effectiveness of countering various infections, pandemics (which is especially relevant) and reducing losses from diseases. Consequently, in the end, the successful translation of MGT into the healthcare sector will contribute to solving problems of a socially significant nature and more effective treatment of socially significant ^[11] and other diseases that pose a threat to national health (oncological, cardiovascular, neurodegenerative, metabolic diseases, hereditary, etc. ^[12]).

MGT in the biological safety system of Russia

The social significance of MGT outlined above allows us to conclude that MGT can be considered as an element of the biosafety system, which in turn is a component of national security. The role of genetic technologies in the field of biological safety draws the attention of many researchers in the legal doctrine ^{[13],[14],[15],[16],[17],[18],[19],[20]}. MGT showed a special socially significant role in ensuring the biological safety of the inhabitants of our state during the spread of a new coronavirus infection caused by the SARS-CoV-2 virus. A genetic study was successfully carried out with respect to this virus ^[21]. Based on the results obtained, it became possible in the future to carry out work on the development of a vaccine (for example, a domestic vaccine based on the adenovirus vector "Gam-COVID-Vac" ("Sputnik V") ^[22]).

The domestic regulatory framework contains a legal definition of biological safety since relatively recently. In accordance with Article 1 of Federal Law No. 492-FZ of December 30, 2020 "On Biological Safety in the Russian Federation" (hereinafter referred to as Law No. 492–FZ), biological safety is a state of "protection of the population and the environment from the effects of hazardous biological factors, which ensures an acceptable level of biological risk" ^[23]. The legislative definition of biological safety proposed in this normative act is very similar in its content to the definition of biological safety enshrined in the Recommendations of the Interparliamentary Assembly of the CIS Member States on the Harmonization and Unification of the Legislation of the CIS Member States in the field of chemical and biological safety of October 28, 2010, except that in this definition It has been established that the effect is realized not by dangerous biological factors, but by pathogenic biological agents ^[24]. Moreover, the substantive component of this legal category is broader than that of a dangerous biological factor. However, if evaluated in aggregate, then the attempt of the legislator to normalize the field of biosafety through the adoption of Law No. 492-FZ can only be welcomed.

In accordance with paragraph 2 of Article 4 of Federal Law No. 390-FZ of December 28, 2010 "On Safety", the definition of the main directions of state policy in the field of safety is the competence of the President of Russia ^[25], which defines these directions in the field of chemical and biological safety ^[26]. According to sub-item 10, item 15 of Decree No. 97 of the President of Russia dated March 11, 2019, as part of solving the problem of resource provision of the national system of chemical and biological safety, it is necessary to create conditions for the implementation of genetic certification of the population, the development of technologies for screening human gene pools. In accordance with sub-item 8, paragraph 13 of the same regulatory document, in terms of solving the task of monitoring chemical and biological risks, it is necessary to carry out genetic certification of the population, taking into account the legal basis for protecting data on the personal genome of a person and to form a genetic profile of the population.

Returning to the 2019 Program, we note that it focuses on the need to predict the risks of uncontrolled spread and use of genetic technologies ^[1]. In turn, Law No. 492-FZ in Article 9 refers to measures aimed at protecting the population and the environment from the effects of dangerous biological factors and preventing biological threats (hazards), a set of measures to prevent and prevent dangerous man-made activities, which also includes the possible uncontrolled use of genetic materials and synthetic biology technologies ^[23].

Consequently, MGTS are an element of the biological security system of the Russian state. Violations related to the use of MGT (including their unjustified and uncontrolled use) can lead not only to harm to the health/life of citizens (private interest), but also pose a threat to national security (public interest), and can also cause harm to an indefinite circle of people and society as a whole.

Rationing the use of MGT as an integral part of biosafety using a risk-based approach

Based on the positions formulated above, we believe that building effective mechanisms for regulating MGT as an element of biosafety and their dissemination should be carried out on the basis of a risk-oriented approach. The specificity of MGT (social significance) determined by us, the high risk nature of such technologies for specific individuals, society and the state as a whole are factors determining this need. Moreover, the risk-oriented approach allows determining the parameters of legal regulation (risk management ^[27]). With the help of a risk-oriented approach, it is possible to build objectively existing risks in a certain hierarchy when using MGT by identifying them (risks), understanding their essence and probability of occurrence.

The high-risk nature of MGT is manifested in the actual intervention in the extremely delicate genetic integrity of people, and in the application of some MGT and in physiological integrity (for example, in invasive prenatal diagnosis). In addition, the genetic information generated by the results of the use of MGT may not always be characterized by a sufficient degree of unambiguity to use it as a basis on which clinically important decisions are made that are of direct importance, firstly, for the health or life of the patient, and, secondly, for the effective performance of professional duties by medical workers.

In connection with the above, it seems possible to identify some of the risks associated with the use of MGT, and to attribute to them the following: the possibility of harm to the health / life of patients; the commission of actions by medical workers that entail adverse consequences for them; unreasonable and uncontrolled use of MGT; the creation of other situations that threaten biological safety and, as a consequence, national security.

Using a risk-based approach, it is possible to classify MGT based on the possibility of occurrence of the risks identified above as a classifying criterion. According to the degree of probability of occurrence of risks associated with the use of MGT, we distinguish the following MGT:

1) MGT, characterized by a low degree of risk occurrence;

2) MGT, characterized by an average degree of risk occurrence;

3) MGT, characterized by a high degree of risk.

The attribution of certain MGTS to the selected types must be justified, in our opinion, based on certain parameters that take into account the social essence of MGT, which will affect the features of the regulatory mediation of the use of MGT of certain types, based on the likelihood of risks. Among such parameters, we highlight the parameters related to:

a) the duration of MGT use^[1];

b) the invasiveness/noninvasiveness of MGT^[2];

c) diseases for which prevention, diagnosis, treatment and rehabilitation are carried out using MGT^[3];

d) subjects in respect of which MGT is applied^[4];

e) the role of MGT in the general process of medical provision^[5].

It is on the basis of the parameters presented above that we believe that uniform legal regulation of all genetic technologies in general using a risk-based approach and classifying them into categories of low, medium and high probability of occurrence of risks will not meet the main purpose of such regulation – effective regulation of social relations arising in connection with various genetic technologies.  More preferable for the purposes of building effective legal regulatory mechanisms, we see the development of similar attribution parameters for each individual type of genetic technologies (for those used in agriculture, in the food industry, etc.). Only in this case will it be possible to take into account their social essence and social significance, which differ, necessary for effective legal regulation depending on the type of genetic technologies and which will influence the choice of the optimal legal tools that form the basis of an effective legal mechanism for their regulation.

In our opinion, the attribution of certain MGT to the types allocated based on the probability of occurrence of risks on the basis of the criteria proposed by us should not, in our opinion, be an exclusive advantage of the legislator (including the Ministry of Health of Russia). For a more effective and adequate correlation of MGT with the probability of occurrence of risks, it seems to us necessary to conduct joint work between the regulatory regulator and the professional medical community, represented by specialists in MGT and the specifics of their application in various branches of medical activity. Only with the bilateral interaction, on the one hand, of the community of medical professionals and, on the other hand, of the legislator, it will be truly possible to effectively regulate this aspect. 

It is also important to emphasize that the classification of MGT and the attribution parameters we have identified will allow us to more reasonably analyze their (MGT) clinical significance and identify the overall role in medical activity as a whole. In this regard, the application of this classification and its normative formalization through consolidation in, for example, Law No. 323-FZ will minimize the risks of uncontrolled spread and use of genetic technologies in the field of medical activity. And the latter, in turn, will ensure the necessary level of biosafety, an element of which MGT are.

Conclusion

Summarizing all of the above, we note that MGT is a separate type of genetic technology. They are characterized by their specificity and social significance, which, in our opinion, do not allow us to build effective mechanisms for their legal regulation on common grounds with genetic technologies in general. The characteristic features, social significance and high-risk nature of MGT identified by us in this work allow us to approach the legal analysis of MGT as an integral element of the biological safety system of Russia. In order to design effective mechanisms for rationing the use of MGT, taking into account the risks of their use identified by us, we consider it necessary to correlate existing MGT with the species we have identified based on the proposed attribution parameters. This proposal will make it possible to comply with the regulatory (Law No. 492-FZ) permissible level of biological safety in Russia when using MGT and minimize the likelihood of risks, some of which are already reflected in domestic legal material (Law No. 492-FZ, Program 2019).

^[1] In the field of healthcare, there are: MGT, which have been used in medical activities for a long time and have proven to be effective (for example, MGT, used in neonatal screening of newborns for hereditary and congenital diseases); MGT, which are used for a relatively short time and which do not have unambiguous effectiveness (for example, assisted reproductive technologies, namely, their direction as an IVF procedure); MGT, which are new to medical practice, their effectiveness and the need for use in medical activities have yet to be established by accumulating information about the effectiveness of their use in various clinical trials (for example, the CRISPR/Cas9 gene editing technology).

^[2] Whether the use of MGT is carried out through violation of bodily integrity (for example, carrying out gene therapy by introducing a genetic construct into the body) of a person or not.

^[3] There is no doubt that MGT used in the provision of medical care to persons with possible/confirmed socially significant diseases and diseases that pose a danger to others should belong to the category of MGT characterized by a medium/high degree of risk. Examples of socially significant diseases are diabetes mellitus, HIV, and diseases that pose a danger to others – tuberculosis, some viral fevers and infectious diseases.

^[4] In our opinion, MGT, which are used in relation to patients who are socially vulnerable and unprotected groups of the population (disabled people, children, etc.), should belong to the category of MGT, characterized by a medium/high degree of risk.

^[5] In many cases, MGT act only as a separate component of preventive, diagnostic, therapeutic and rehabilitation measures (primarily in relation to the medical provision of persons with possible/confirmed multifactorial polygenic diseases (for example, rheumatoid arthritis)). In other situations, MGT plays a key role in preventive, diagnostic, therapeutic and rehabilitation activities (for example, in the diagnosis of proximal spinal muscular atrophy 5q (SMA)) (see: Clinical recommendations "Proximal spinal muscular atrophy 5q" (approved by the Ministry of Health of the Russian Federation, 2021) // URL: https://cr.minzdrav.gov.ru/schema/593_2 (accessed: 10.07.2022)).