Regulation of stem cell research in Portugal
By Carla Barbosa and Andreia da Costa Andrade
I- Research on human stem cells
A) Current legal position
Currently, despite governmental efforts, there is no specific legislation in Portugal regulating research using stem cells.
In 2011, there was an attempt by the government to legislate this area of research. The Council of Ministers approved the regime for the use of stem cells intended to promote the use of stem cells of human origin for the purpose of scientific research with the "aim of preventing, diagnosing, detecting the origin and treating pathologies, degenerative type or resulting from the irresistible destruction of tissues and organs". This proposal did not continue and no legislation ever came into force.
With regard to the use of stem cells, we should first consider Law n.º 12/2009, of March 26, which establishes the legal regime of quality and safety related to the donation, collection, analysis, processing, preservation, storage, distribution and application of human tissues and cells, transposing into the domestic legal order Directive 2004/23/EC of the European Parliament and of the Council of 31 March Directive 2006/17/EC of the Commission, of 8 February and Directive 2006/86/EC of the European October. However, it is the legal provision itself that removes its application with regard to stem cell research.
Thus in all that refers to stem cell research questions, we must resort to the general laws that regulate clinical research in Portugal. The conduct of clinical trials of medicinal products for human use is regulated at national level by Law No. 21/2014, of April 16 (Clinical Investigation Law) as amended by Law no. 73/2015 of July 27 , and, in relation to Clinical Trials with medicinal products for human use, repealed Law no. 46/2004, of August 19 , transposing Directive 2001/20 / EC of the European Parliament and of the Council of 4 April on the approximation of the laws, regulations and administrative provisions of the Member States relating to the application of good clinical practice in the conduct of clinical trials on medicinal products for human use.
This law regulates clinical research, considered as any systematic study to discover or verify the distribution or effect of health factors, states or health outcomes, health processes or disease, performance, or safety of interventions or the provision of healthcare.
In addition to the above legislation there are a series of guidelines covering various matters related to clinical trials which can be found in Volume X of Eudralex. To that end, and as part of the harmonised European system, the conduct of clinical trials in Portugal requires authorisation from the INFARMED - National Authority of Medicines and Health Products, I.P. and a prior favorable opinion from the Ethics Committee for Clinical Research (CEIC).
For the purposes of the Clinical Investigation Law:
- The term "clinical studies" includes:
- "Non-interventional clinical studies" and
- "Interventional clinical studies"
2. The term "interventional clinical studies" includes (in addition to others not specified) as follows:
- "Clinical trials" and
- "Interventional clinical studies with medical devices" and "clinical studies with cosmetics products".
For the purpose of the Law the term "clinical trial" includes studies in which one or more investigational medicinal products are used.
The investigational medicinal products may or may not be authorized or marketed in Portugal. What defines them is that they are tested or used as a reference in a clinical trial (as defined in article 2 of the Law) that is transcribed:
"Investigational medicinal product", the pharmaceutical form of an active substance or placebo, being tested or used as a reference in a clinical study including medicinal products already with a marketing authorisation, but are used or prepared, as to the pharmaceutical form or package, in a different manner from the authorised one, or are used for a non authorised indication or intended to get more information on the authorised form.
At EU level, Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on the clinical trials of medicinal products for human use and repealing Directive 2001/20 / EC was adopted. This legislation will be directly applicable to the legal framework of the Member States 6 months after the publication in the Official Journal of the European Communities of the European Commission notice of operational compliance with the functional requirements of the EU Portal and the EU database provided for.
Also regarding the constitution of biobanks for research using stem cells (which exist in Portugal), it is worth mentioning the application of the Portuguese legislation on the constitution and functioning of biobanks whose regulation is found in Law n.º 12/2005, of January 26 and its regulation: Decree-Law n.º 131/2014, of August 29. These two laws defines “biological product bank” (biobank) as any repository of biological samples or their derivatives, whether or not with a defined storage period, whether using prospective or previously harvested material or has been obtained as a component of the provision of routine health care, either in screening programs or for research, and which includes samples that are identified, identifiable, anonymous or anonymous. No person may harvest or use human biological samples already collected or their derivatives, with a view to establishing a biological product bank, if they have not obtained prior authorization from an entity accredited by the department responsible for health protection, as well as the National Commission of Data Protection if the bank is associated with personal information. Biobanks shall be constituted only for the purpose of providing health care, including diagnosis and prevention of diseases, or basic or applied health research, and the biological samples should only be accepted in response to requests from doctors and not from individuals or their families. It is necessary for obtaining and using material for a biological product bank an Informed written consent. The consent form must include information on the purposes of the bank, its supervisor, the types of research to be developed, the risks and potential benefits, conditions and duration of storage, measures taken to guarantee the privacy and confidentiality of the participants and the prediction as to the possibility of communicating or not the results obtained with this material.
B) Ethical and regulatory oversight
The Portuguese National Council of Ethics for the Life Sciences (Conselho Nacional de Ética para as Ciências da Vida – CNECV ) was set up in 1990 to advise on and monitor ethical issues in science and technology that affect human health. It has issued many reports on stem cell research, and has recommended that therapeutic cloning and the use of surplus embryos for research should be permitted because of the potential therapeutic benefits for human beings.
With regard to the use of stem cells from an ethical point of view, we cannot fail to highlight the report 67/CNECV/12 – report on umbilical cord blood banks, umbilical cord tissue, and placenta. However, this report is based on the use of hematopoietic cells for therapeutic purposes at an experimental level - a technique dating back more than half a century. However, it was only in the late 1980s that it became a common clinical practice because of the very significant success achieved. It is in this context that the institution of "umbilical cord blood banks, umbilical cord tissue and placenta" is necessary. That is, an established capacity for the collection, storage and availability of stem cells obtained from umbilical cord blood but also from the cord and placenta itself, previously considered disposable biological material intended for incineration. Therefore, leaving aside the questions related to stem cell research.
II- Research on human embryonic stem cells
A) Current legal position
Firstly, with regard to embryonic stem cell research, we must take into account Law n.º 32/2006, of July 26, which regulates the use of medically assisted procreation. These regulations prohibit the creation of embryos through medically assisted procreation techniques with the deliberate purpose of their use in scientific research. However, it allows the scientific investigation in embryos with the aim of prevention, diagnosis or therapy of embryos, of perfecting the techniques of medically assisted procreation, as long as their realisation is controlled. According to the law, for purposes of scientific research can only be used:
(i) Cryopreserved, surplus embryos for which there is no parental project (depends on prior, express, informed and conscious consent of the intended beneficiaries);
(ii) Embryos whose condition does not allow the transfer or cryopreservation for procreation purposes;
(iii) Embryos that are carriers of a serious genetic abnormality, in the case of pre-implantation genetic diagnosis (depends on prior, express, informed and conscious consent of the beneficiaries to which they were intended);
(iv) Embryos obtained without fertilisation by spermatozoa.
Thus, the use of embryos for scientific research uses embryos produced for other purposes and subsequently the stem cells are withdrawn for research purposes. However, it always depends on the authorization of the experimentation by the National Council for Medically Assisted Procreation. In the same vein, the Oviedo Convention, ratified by Portugal in 2001, prohibits to "create human embryos for research purposes" in Article 18.
As mentioned above, we must also take into account Law n.º 12/2009 on the legal regime for quality and safety of the donation, collection, analysis, processing, preservation, storage, distribution and application of human tissues and cells, and the Law No. 21/2014, of April 16 (Clinical Investigation Law) where human embryonic stem cells are used for human applications and clinical studies
B) Ethical and regulatory oversight
The National Council for Medically Assisted Procreation (CNPMA), established by Law 32/2006, of 26 July, generally has the power to pronounce on the ethical, social and legal issues of the medically assisted procreation:
a) Update the scientific information on the medically assisted procreation and the techniques regulated by this legislation;
b) To establish the conditions of authorization of the centers where the techniques of medically assisted procreation are administered, as well as the centers where the gametes or embryos are preserved;
c) To monitor the activity of the centers referred to in the previous point, supervising compliance with this law, in articulation with the competent public entities;
d) Give an opinion on the authorization of new centers, as well as on situations of suspension or revocation of such authorization;
e) Give an opinion on the constitution of stem cell banks, as well as on the fate of the biological material resulting from the closure of these;
f) Establish guidelines related to the Pre-implantation Genetic Diagnosis, within the scope of articles 28 and 29 of this law;
g) Consider research projects involving embryos, approving or rejecting them, in accordance with Article 9;
h) To approve the document through which the beneficiaries of the medically assisted procreation techniques give their consent;
i) Provide information related to the donors, in the terms and within the limits set forth in article 15;
j) To pronounce on the implementation of the medically assisted procreation techniques in the National Health Service;
k) Gather the information referred to in Article 13 (2), carrying out its scientific treatment and evaluating the medical-sanitary and psycho-sociological results of the medically assisted procreation practice;
l) Define the model of the annual activity reports of the medically assisted procreation centers;
m) Receive and evaluate the reports provided for in the previous paragraph;
n) To contribute to the dissemination of available techniques and to the debate about their applicability;
o) To centralize all relevant information on the application of the medically assisted procreation techniques, namely registration of donors, beneficiaries and children born;
p) Deliberate on a case-by-case basis on the use of medically assisted procreation techniques for selection of HLA compatible group for the treatment of severe disease.
III- Selected bibliography
A) Laws, regulations, guidelines
- Lei n.º 21/2014, of 16 April, (Law on conduct of clinical trials on medicines for human use)
- Lei n.º 12/2009. (Law on the legal regime for quality and safety of the donation, collection, analysis, processing, preservation, storage, distribution and application of human tissues and cells (Diário da República, 1.ª série n.º 60. 2009:1876–1897) - (with the changes introduced by Law n.º 1/2015, of January 8 and Law n.º 99/2017, of 25 August)
- Lei n.º 32/2006 - Procriação medicamente assistida, Law N.º 32/2006, of 26 July, on medically assisted procreation. (with the amendments made by Law n.º 58/2017, de 25/07; Law n.º 25/2016, de 22/08; Law n.º 17/2016, de 20/06; and Law n.º 59/2007, de 04/09)
- Law n.º 12/2005, of 26 January and its regulation: Decree-Law n.º 131/2014, of 29 august
- 66/CNECV/2012, Opinion on proposals for Law N.º 266/2012 and N.º 323/2012 on clinical research and clinical trials, Conselho Nacional de Ética para as Ciências da Vida (CNECV) -The National Council of Ethics for the Life Sciences.
- 53/CNECV/07, Opinion on proposals N.º 126 / X and N.º 376 / X - Conselho Nacional de Ética para as Ciências da Vida (CNECV) -The National Council of Ethics for the Life Sciences.
- 47/CNECV/05, Opinion Nº 47: ‘Opinion on Stem Cell Research’, Conselho Nacional de Ética para as Ciências da Vida (CNECV),The National Council of Ethics for the Life Sciences.
- 25/CNECV/98, "Report on the draft bill regulating the therapeutic use of human-origin biological products and of biotechnology", Conselho Nacional de Ética para as Ciências da Vida (CNECV),The National Council of Ethics for the Life Sciences.
- 26/CNECV/99, Work Document: "Ethical Reflection on Human Dignity", Conselho Nacional de Ética para as Ciências da Vida (CNECV),The National Council of Ethics for the Life Sciences.
- 15/CNECV/95, Opinion Nº 15: "Report Opinion On Experimentation on the Human Embryo", Conselho Nacional de Ética para as Ciências da Vida (CNECV),The National Council of Ethics for the Life Sciences.
- Serrão D., Simpósio- Estatuto do embrião. Bioética. 2004;12:109–116.
- 35. Santos ADA, Renaud, Michel; Cabral RA. Relatório Procriação Medicamente Assistida. Cons. Nac. Ética para as Ciências da Vida- Presidência do Cons. Minist. 2004.
- Carvalho AS. Boa ética e boa ciência: o percurso da investigação em células estaminais. Rev. Interdiscip. sobre o Desenvolv. Hum. 2010;1:45–51.
- Pimentel JE. O estatuto jurídico do embrião humano. 2003.
- Regateiro F, Soares J, Antunes JL, Fevereiro P, Cabral RA, Renaud CM. Relatório sobre investigações em células estaminais. Cons. Nac. Ética para as Ciências da Vida- Presidência do Cons. Minist. 2005.
- Teixeira, Margarida; Oliveira CC. A Bioética e a investigação em células estaminais humanas - em Portugal e na Comunidade Europeia. Rev. Bras. Bioética. 2011;7(1- 4):32–46.
- Santos E. O estatuto jurídico-constitucional do embrião humano, com especial atenção para o concebido “in vitro.” Rev. Bras. Direito Const. RBDC. 2007;12:55–101.
- Silva S., Machado H. A compreensão jurídica , médica e “ leiga ” do embrião em Portugal : um alinhamento com a biologia ? Interface. 2009;13(30):31–43.
- Serrão D. Uso de embriões humanos em investigação científica. Livro Branco. 2003.
- Bragança J, Tavares Á, A. Belo J. Células estaminais e medicina regenerativa Um admirável mundo novo. Canal bq.4–17.