Regulation of stem cell research in Estonia
By Tiina Titma
I- Research on human stem cells
In Estonia, there is no specific law on research on human stem cells.
A) Current legal position
Estonian law covers research on pluripotent stem cells derived from somatic cells only if the human stem cells are used in scientific research with the final purpose of medical use on human beings.
Thus, the Estonian rules covering research on human stem cells are covered by the Estonian legislation covering human stem cells used for medical uses.
Tissues and cells for human applications
In Estonia, the legislation covering aspects of tissues and cells being used as starting materials in a medicinal product is based on the Tissues and Cells Directive (2004/23/EC) on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells as in other European Union countries.
It has been transposed in Estonian law mainly by the Procurement, Handling and Transplantation of Cells, Tissues and Organs Act and the regulation on Criteria for the selection of cell, tissue, and organ donors, list of precluding circumstances for the donation of cells, tissues, or organs, list of mandatory laboratory studies established for a donor, and the conditions and procedure for carrying out these studies.
Indeed, requirements relating to quality and safety for the procurement and handling of cells, tissues and organs - including removal for transplantation purposes, coding, labelling, testing, preservation, processing, packaging, storage, release and distribution of human cells, tissues and organs for human application - are regulated under the Procurement, Handling and Transplantation of Cells, Tissues and Organs Act.
This Act does not regulate (§ 1(4) of Procurement, Handling and Transplantation of Cells, Tissues and Organs Act):
- the transplantation of gametes and embryos within the meaning of the Artificial Insemination and Embryo Protection Act;
- the handling of blood within the meaning of the Blood Act;
- the transplantation of cells, tissues and organs taken from a person to the person in the course of one surgical procedure;
- the use of cells, tissues and organs in scientific research if used for purposes other than medical use on human beings.
The consent of the person is mandatory (i) for removal cells, tissues or an organ from a living donor[1] (§§ 11, 12 of Procurement, Handling and Transplantation of Cells, Tissues and Organs Act ); (ii) for removal cells, tissues or an organ from a deceased donor in his or her lifetime or if no information is available that the person had objected to it[2]; (iii) for blood and blood components collected from a blood donor or a patient for the purpose of autologous transfusion for research purposes (§10 of Blood Act); (iv) for clinical trial of the medicinal product (§ 91 of Medicinal Products Act); (v) for donation of the gametes for using an embryo for scientific research (§ 32 (2) of Artificial Insemination and Embryo Protection Act).
The regulation on Criteria for the selection of cell, tissue, and organ donors, list of precluding circumstances for the donation of cells, tissues, or organs, list of mandatory laboratory studies established for a donor, and the conditions and procedure for carrying out these studies (https://www.riigiteataja.ee/en/eli/502112016002/consolide) stipulates the only conditions regarding particularly stem cells and differing from the regulations on general cell handling regulations as follows: for the procurement of bone marrow and peripheral blood stem cells, the blood sample for carrying out laboratory studies has to be collected within 30 days before the procurement (§ 8 (4) of the regulation).
Tissues and cells as parts of Advanced Therapy Medicinal Products (ATMPs)
ATMPs are evaluated via a centralised procedure as defined by European Union legislation (Article 8 of Regulation (EC) No 1394/2007). This process ensures that these medicinal products benefit from a single evaluation and authorisation procedure applicable across the European Union. In line with European Union legislation collection and testing must be done in accordance with an appropriate quality control system for which standards and specifications are set out within the legislation.
According to the Medicinal Products Act advanced therapy medicinal products that have been, by way of exception, made on the basis of a doctor’s prescription and subject to doctor’s professional liability for the purpose of use by a specific patient upon provision of in-patient health services in Estonia (§ (1.6) of Medicinal Products Act).
Blood stem cells as parts of blood medicinal products
Blood stem cells used for medicinal products are generally covered by the Blood Act. According to the Blood Act, the blood product is a medicinal product manufactured or produced from blood, packaged and labelled as required and containing one or several blood constituents. Whole blood, blood components and plasma-derived products are blood products. (§ 2 of the Blood Act)
Clinical trials involving human stem cells
The clinical trials are regulated by the Medicinal Products Act and in more detail by the regulation of the Minister of Social Affairs Conditions and Procedure for Conducting Clinical Trials of Medicinal Products.
For clinical trial the approval by one of the two Independent Ethics Committees and informed consent by the study subject, according to the international codes and Declaration of Helsinki, is mandatory. The two local committees are Tallinn Medical Research Ethics Committee at the National Institute for Health Development and Ethics Review Committee on Human Research of the University of Tartu.
Activity licence and registration
An activity licence must be present for (i) the procurement of cells, tissues and organs; and (ii) the handling of cells, tissues and organs. Activity licences for the procurement and handling of cells, tissues and organs shall be registered in the register of activity licences of the State Agency of Medicines. The State Agency of Medicines shall decide the issue or refusal to issue an activity licence for the procurement of cells, tissues and organs or for the handling of cells, tissues and organs. (§ 26 (1,5) and § 27 (1) of Procurement, Handling and Transplantation of Cells, Tissues and Organs Act)
The activity licence register of the State Agency of Medicines is to (i) keep account of the holders of activity licences for handling medicinal products, brokering of medicinal products, handling cells, tissues and organs, and (ii) keep account of their professional activities, (iii) exercising supervision over handling and brokering of medicinal products and over acquiring and handling cells, tissues and organs (§ 39 (1,2) of the Medicinal Products Act). There are nine licence holders in Estonia as of 10 October 2017.
B) Ethical and regulatory oversight
The Procurement, Handling and Transplantation of Cells, Tissues and Organs Act stipulates the transplantation competency as the national system of procurement, handling and transplantation of cells, tissues and organs shall be composed of:
- transplantation council
- national transplantation agency;
- transplantation centres;
- the procurers and handlers of cells, tissues and organs;
- Estonian Health Insurance Fund;
- State Agency of Medicines;
- Health Board;
- Ministry of Social Affairs (§ 5(2)).
The State Agency of Medicines (SAM) is the supervisory authority:
- for Estonian manufacturers and importers of centrally authorized ATMPs;
- for ATMPs which are prepared and used under the hospital exemption (HE) which are prepared on a non-routine basis and are used in a hospital with a prescription for a specific patient.
- for clinical trial authorisation for ATMPs, in the same way as for all other medicines.
- For decision on the issue or refusal to issue an activity licence for the procurement of cells, tissues and organs or for the handling of cells, tissues and organs.
- For registering the activity licences for the procurement and handling of cells, tissues and organs in its register of activity licences.
Two Independent Ethics Committees are in charge of approving clinical trials for medicinal products:
- The Tallinn Medical Research Ethics Committee at the National Institute for Health Development
- The Ethics Review Committee on Human Research of the University of Tartu
II- Research on human embryonic stem cells
Research on human embryonic stem cells is covered by Artificial Insemination and Embryo Protection Act.
A) Current legal and ethical position
According to the Artificial Insemination and Embryo Protection Act the provision of gametes, creation of embryos as well as the coding, labelling, research, preservation, processing, packaging, storage, release and issue of gametes and embryos are governed by the Procurement, Handling and Transplantation of Cells, Tissues and Organs Act unless otherwise provided by this Act.
The research on human embryonic stem cells is covered by Artificial Insemination and Embryo Protection Act.
It states:
- The provision of gametes, creation of embryos as well as the coding, labelling, research, preservation, processing, packaging, storage, release and issue of gametes and embryos are governed by the Handling and Transplantation of Cells, Tissues and Organs Act unless otherwise provided by this Act (§ 1 (2)).
- According to this Act, embryos which, in order to ensure the success of the artificial insemination or to protect the health of the child or the mother, are not transferred to a woman, and embryos which have remained unused may be used for scientific research (§ 32 (1)).
- Transfer of an embryo which has been used for scientific research to a woman is prohibited (§ 33).
- An embryo may be preserved or used for scientific research within fourteen days after fertilisation of the ovum. Preservation or use of embryos after expiry of the specified term is prohibited. The time during which the embryo is frozen pursuant to § 30 of this Act shall not be included in such term (§ 34).
- It is prohibited to perform the following acts in connection with artificial insemination of a woman:
(i) artificial fertilisation of an ovum with a sperm which has been selected on the basis of the sex chromosome contained therein, except in the cases where a gamete is selected in order to avoid transmission of a serious sex-related inheritable disease to the child; (ii) creation, by way of substitution of the nucleus of a fertilised ovum by a somatic cell of another embryo, foetus or living or dead person, of an embryo with genetic information identical to that of the embryo, foetus or living or dead person; (iii) fusion of embryos with different genetic information in order to create a cell fusion if at least one of the embryos is a human embryo, or fusion of a human embryo with a cell which contains genetic information different from that of the cells of the embryo and which may develop further together with the embryo; (iv) creation of an embryo capable of developing by fertilisation of a human ovum with animal sperm or animal ovum with human sperm (§ 35).
The consent of the person is mandatory for donation of the gametes for using an embryo for scientific research (§ 32 (2) of Artificial Insemination and Embryo Protection Act).
In addition, please see section I.
B) Ethical and regulatory oversight
Estonia has ratified the 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 and (i) 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; (ii) Additional Protocol to the Convention on Human Rights and Biomedicine concerning Transplantation of Organs and Tissues of Human Origin.
In addition, please, see section I.
III- Selected bibliography
A) Laws, regulations, guidelines
Artificial Insemination and Embryo Protection Act, 13 March 2011
Medicinal Products Act, 01 July 2017
Procurement, Handling and Transplantation of Cells, Tissues and Organs Act, 19 March 2017
Procurement, Handling and Transplantation of Cells, Tissues and Organs Act, 19 March 2017
Regulation (EC) No 1394/2007 on advanced therapy medicinal products, 13 November 2007
B) Literature
State Agency of Medicines (SAM)
[1] The distinction on persons with restricted active legal capacity are decreed in § 13 of Procurement, Handling and Transplantation of Cells, Tissues and Organs Act.
[2] If no information is available ... the procurer of cells, tissues and organs shall be required, if possible, to ascertain the declaration of intention of the deceased person expressed during his or her lifetime from the close person.