Innovation within the framework of legality

How will the law "On Biomedical Cell Products" affect Russian innovations

Anton Buzdin, Forbes, 22.03.2017

The law regulating the use of cellular technologies in Russia: the beginning of a new industry, simplification of interaction between the medical and business communities, or complication of joint work?

Law (Federal Law No. 180 "On Biomedical Cell Products") it will directly affect the medical industry, for example, aesthetic medicine. In order to rejuvenate the face and skin in Russia, SPRS therapy (Service for Personal Regeneration of Skin) was created. This is a personalized set of procedures for the natural restoration of the skin with the help of the patient's own fibroblast cells. The technology consists in isolating and growing fibroblasts (cells that produce collagen, elastin and other important skin components) from a small fragment of skin obtained from the patient's ear region, where the cells are maximally protected from ultraviolet radiation and other adverse environmental factors. A sufficient number of fibroblasts for therapy are delivered to clinics, where certified cosmetologists inject them into the patient's skin using a special technique. Some of the obtained fibroblasts of the patient's skin are placed in a cryobank, where they can be stored in liquid nitrogen in individual cells for an unlimited time and used during the patient's life. Since fibroblasts are obtained from the skin of the patient undergoing therapy, many risks associated with the use of cellular technologies are removed.

Vadim Zorin, the developer of SPRS therapy, is the only one in Russia who has passed all the stages of developing a cellular drug from the first (preclinical trials) to the final (post-marketing clinical trials) stage and received official permission from Roszdravnadzor to use the technology. According to him, the successful experience of using the technology for thousands of patients allows us to speak confidently about its safety and effectiveness.

However, not all technologies can be said so confidently.

What are Biomedical cell products

The document includes products containing grown living human cells. They are used in various studies and in medicine. It is important that technologies related to reproduction (for example, artificial insemination) and transplantology (for example, transplantation of bone marrow, skin, liver, kidneys and other organs and tissues) do not fall under the law. The use of cellular technologies for purely scientific or educational purposes is also not subject to the law.

We are talking about technologies that allow you to isolate your own or someone else's cells and use them to treat a patient. Cellular products can be used in regenerative medicine – to accelerate wound healing and tissue repair after surgery, as well as in aesthetic medicine, for example, to rejuvenate the skin or prevent scarring. Ilya Eremin, head of the Center for Biomedical Technologies of the Central Clinical Hospital of the Presidential Administration of the Russian Federation, mentioned in a conversation that the use of cellular products in medicine has long been the present, not the future, including in Russian clinics. Some Russian medical organizations have accumulated quite a lot of experience in the use of cellular products. With the adoption of the law, real rules appeared that determine the process of legitimizing the development of regenerative medicine.

For example, all manipulations with cell cultures intended for administration to the patient will be regulated. Previously, such serious actions as genetic modification of cells, changes in the conditions and duration of their cultivation, were practically not controlled. This led to the fact that there was an increased risk of side effects such as oncological transformation of cells and their uncontrolled growth. Well, the therapeutic effect of the whole procedure itself was also questioned, since it is the thoroughness of compliance with regulations that determines the success of using cellular technologies.

The essence of the document

First of all, the law will "open" the biomedical field for state regulation. In order to determine the object of regulation of the law, such concepts as "cell line", "donor of biological material", "cell differentiation" and many others are introduced for the first time. The law prohibits the use of biomaterial obtained from human embryos or fetuses for the production of biomedical cell products. This forces researchers and businesses to focus on developing products based on postnatal cells, that is, taken after birth. In many ways, this allows minimizing the risk of malignant transformation of cells (which has been repeatedly noted earlier for embryonic stem cells), as well as reducing ethical and criminal risks.

The law states that the donation of biological material is based on the principles of voluntariness and gratuitousness. The purchase and sale of biological material and such odious approaches as artificial creation of a human embryo, interruption or disruption of the development process of a human embryo or fetus for the production of biomedical cell products are prohibited. The voluntary nature of donation is documented either by the donor himself, if we are talking about lifetime donation, or, if we are talking about posthumous donation, by his closest relatives. In the latter case, relatives confirm that during his lifetime he did not refuse a potential donation of this kind.

It is established that medical care with the use of cellular products can be provided only by medical workers who have been trained in a specialized additional professional program. Independent use of biomedical cell products by a patient is not permitted by law.

It also introduces a requirement for mandatory registration of "cell products to be put into circulation in the Russian Federation for the first time" for use in medicine. The registration certificate is issued with a validity period of five years, and then extended. For registration, the rules of ethical expertise, preclinical and clinical studies, as well as the procedure for interaction with government agencies are regulated. Ultimately, the decision on registration is made on the basis of an examination of the ratio of the expected benefit to the possible risk of using the product.

At the same time, the law is not retroactive, and products previously registered in one form or another are not subject to mandatory re-registration. This rule was initially tougher, but edited in cooperation with representatives of the business community.

A special state register and a special authorized federal body are being created for the registration of biomedical cell products, which causes discussion in the relevant expert community – after all, the relevant market is extremely small in Russia today, and the creation of a new bureaucratic body seems redundant to many. Perhaps it would be more effective to transfer the relevant powers to an already existing structure.

Another very important provision of the law, which is welcomed by my colleagues, is a set of measures to protect a patient who has fallen into the group of clinical trials of a cellular product. The patient should be informed in writing about the product itself and its expected effectiveness, as well as about the goals and duration of the study, as well as the degree of risk to which he may be exposed in connection with participation in the study.

The life and health of the subject are subject to compulsory insurance at the expense of the organization testing the technology. At the same time, in the event of an insured event, payments, according to the law, should vary in the range from 500 thousand to 2 million rubles, if we are talking about the disability of the patient or his death in the course of ongoing research.

International perspective

According to Artur Isaev, director of the Human Stem Cell Institute (ISCH) and one of the Russian captains of the cellular technology industry, the adopted bill roughly reflects the situation in this industry in the United States and the European Union several years ago. The fact is that even under J. Bush Jr. passed legislation strictly restricting the use of cellular medical technologies, in much the same way as it was done in Federal Law No. 180. Following the United States, similar bills began to be adopted by the EU countries. At the same time, such a conservative interpretation did not allow the industry to develop quickly, in accordance with the progress in related fields of fundamental research. Therefore, first the UK, then the USA, and then the rest of the EU countries began to lift restrictions on the use of natural or artificial embryonic tissues as a source of biomaterial. Of course, this is a very controversial issue from an ethical point of view, but, apparently, it can give a new impetus to innovative developments, especially in the field of regenerative medicine.

The impact of the law on innovation in Russia

Almost all my colleagues agree on some positive features of the document: finally, an important area of medical technology is being removed from the "gray" area. Sergey Larin, Deputy Director of the Higher School of Molecular and Experimental Medicine of the Center for Pediatric Hematology, Oncology and Immunology. Dima Rogacheva, the creator of Russia's first preparations of gene-cell antitumor vaccines for immunogenotherapy of malignant tumors, believes that the procedure prescribed in the law for registering new products will give confidence to investors investing in their development. This will strengthen the pool of domestic high-tech industries in this area and accelerate the pace of implementation of new developments. Accordingly, prerequisites are being created for the creation of products that are competitive on the world market.

The law does not regulate scientific developments, so it probably will not affect the situation with fundamental research. At the same time, the procedure prescribed in the law for passing preclinical and clinical trials implies significantly large amounts of investment in each product. This will certainly increase the cost of developing and bringing each product to market. Other scientists agree with this. Thus, the laboratories of Vadim Zorin, Ilya Eremin and Pavel Kopnin from the Blokhin Cancer Center for the first time established that the mobile part of the gum is the best source of stem cells capable of differentiation (transformation), including into muscle tissue, which has long been an unsolved problem. The work of scientists was published in 2016 in the prestigious journal Cell Cycle. According to Eremin, this is a huge potential for the introduction of technology into the clinic, now, thanks to the law, all the stages necessary for the introduction of a new product into clinical practice have become clear.

The law is a good initiative. However, unfortunately, it does not yet have any provisions stimulating investment in the industry, does not imply the possibility of accelerated registration for a number of products, where appropriate, does not have simplified requirements for minimally manipulated products and contains a number of apparently unnecessary restrictions on xenogenic cells and embryonic cell lines. Artur Isaev believes that long-term and substantial investments are needed to register cellular products under this law. In general, the law has more advantages than disadvantages for the industry. Most likely, the regulator will finalize everything else in the future.

Portal "Eternal youth" http://vechnayamolodost.ru  22.03.2017