Brussels, 21 June 2002
Proposal for a
DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
on setting standards of quality and safety for the donation, procurement, testing, processing, storage, and distribution of human tissues and cells Full Text
EXPLANATORY MEMORANDUM
INTRODUCTION
1. Each year in Europe, hundreds of thousands of patients undergo some form of therapeutic treatment based on the use of tissues and cells of human origin. Employment of these substances in the delivery of health care now goes beyond traditional transplants or implants into another human (allograft), to their incorporation into or combined with medical devices, and as the basis for services or products derived through biotechnology. While the therapeutic value of human allografts has been recognised for several decades, the increased number of implants as well as medical indications demands that requirements to ensure the quality and safety of human tissues and cells for clinical use be established in the European Union
2. Tissues are a functional group of cells, which may be transplanted or implanted as viable cells, or otherwise preserved, fixed, or altered. They include: bone and musculoskeletal elements (e.g. cartilage, tendons, fascias), cardiovascular tissues (e.g. arteries, veins, heart valves), ocular tissue (e.g. cornea, sclera), nerve cells, skin, brain cells, foetal tissue, reproductive cells (e.g. semen, sperm, ova) and stem cells (i.e. haematopoietic progenitor cells obtained from bone marrow, umbilical cord and peripheral circulation). As appropriate, these tissues and cells are used not only in reconstructive surgery such as corneal and hip replacement but also in the treatment of diseases such as cancer and diabetes, and increasingly in reproductive medicine. Advances in biotechnology have resulted in the production of tissue-derived products such as cultured allogeneic cells, engineered structural tissues, and constituent parts of medical devices. All these tissues or cells, which are frequently acquired through cross-border exchanges, come from donors who may be living or deceased.
3. Statistics related to the transplant of some of these human substances reflect their increasing importance to the health care delivery system. In the United States, the number of bone grafts increased 140% from 302,548 to 750,000 between 1992 and 1999. In Europe, the transplant of haematopoietic progenitors increased from less than 4,000 in 1990 to 18,720 in 1999. In 1998, the replacement of heart valves with human allografts numbered 3,412. Today, cornea transplantation in Spain amounts to more than 60 transplants per million population and more than 70 in France.
4. In order to increase public confidence in the use of human tissues and cells for application in the human body, it is essential, therefore, that EU provisions should ensure their quality and safety. Article 152 of the Treaty has provided the European Community (EC) with an opportunity, as well as an obligation, to implement binding measures laying down high standards of quality and safety for the use of blood, organs, and substances of human origin.
5. Increased therapeutic use of substances of human origin and the recognition that they can transmit diseases have led to extensive discussion not only on the need for increased safety measures but also on the associated ethical issues. This latter aspect was the subject of considerable debate during deliberations on the European
Commission's proposal for a Directive on in vitro diagnostic medical devices1. Opposition to the inclusion of human tissues, which are frequently an integral component of medical devices, in the Directive was based on lack of control, during procurement, of the tissues and cells used as starting material; lack of authorisation for and inspection of manufacturers or tissue banks; non-binding application of standards implied by the Directive without common compulsory specifications; and the existence of over 50 notified bodies in Europe expected to assess product conformity, without scientific level control. The Directive that was ultimately adopted2 was restricted to substances of human origin rendered non-viable, with most human products remaining unregulated.
6. In 1998, the European Group on Ethics in Science and New Technologies to the European Commission (EGE) confirmed that there was `the urgent need to regulate the conditions under which human tissues circulate within the European market'3. Four aspects were stressed in their report:
­ the ethical imperative to protect health. As no substance of human origin is free from the risk of disease transmission, `tissues, in particular those intended for transplantation to third parties or for the preparation of pharmaceutical specialities, must undergo advance testing to provide maximum health guarantees in accordance with the `state of the art'';
­ the integrity of the human body. This should be ensured when procuring tissues from an individual, whether living or dead;
­ the prior, informed, and free consent of the person concerned. Before procurement of human tissues, as a principle the donor's consent must have been given on the basis of information provided in as clear and precise lay terms as possible; and
­ The protection of identity. This requires that, in the interests of anonymity, any disclosure of information that could identify either the donor or recipient must be prohibited. In general, the donor should not know the identity of the recipient, nor vice versa ­ a requirement to prevent possible discrimination.
7. The EGE also noted that anonymous and free tissue donation basically remains a voluntary act of solidarity. People in each Member State should be encouraged to donate tissues in this spirit, thereby promoting shared aims and increasing the availability of substances of human origin in Europe. The EGE also discussed: the role and responsibilities of tissue banks and their profit or non-profit character; equitable access to the therapeutic opportunities afforded by the use of human tissues; and the need for tissue imports from third countries to be subject to at least equivalent ethical and health requirements. This proposal for a Directive reflects the recommendations put forth by the EGE.
8. While most Member States have adopted legislation to control the ethical aspects of donor protection (mainly in the area of organ transplantation), many have yet to agree upon rules covering quality, safety or the use of tissues and cells. An informal survey on existing regulations in the Member States carried out in 20004 confirmed that considerable discrepancies exist in the coverage with only those aspects related to donor protection addressed to date by nearly all of them. Specific rules for the authorisation for and inspection of tissue procurement and banking activities are lacking in the majority, as are regulations for determining donor suitability and the importation of human substances. The percentages of Member States that have regulations in place covering different topics are illustrated in Tables 1 to 3.
9. During a meeting convened under the Portuguese Presidency in Porto in June 2000, experts in the areas of tissues and cells analysed the regulatory situation in Europe and concluded that there is an urgent need for an EC Directive on the safety and quality of these human substances. Subsequently, experts and official representatives of the Member States arrived at a similar conclusion at a Conference co-organised by the European Commission and the Spanish Presidency in Malaga in February 2002. They supported the idea of developing an EC Directive setting high standards of safety and quality for the procurement, testing, processing, storage, and distribution of human tissues and cells in order to ensure a high level of human health protection in the European Union. They also provided specific orientations for the development of such an initiative, which received a general welcome in an EU Ministerial Seminar that immediately followed the Malaga Conference.
SCOPE AND OBJECTIVES
10. For the first three steps of their use (donation, procurement, and testing), this proposal for a Directive covers all tissues and cells of human origin for application to the human body, except blood and blood products, tissues and cells used as an autologous graft within the same surgical procedure and organs, but including starting materials for tissue and cell derived manufactured products. However, autologous cells used for medicinal products are not covered by this Directive. Tissues and cells used for research purposes would be covered when administered to the human body, but not when used for research in vitro or in animal models. The further steps of their use (processing, preservation, storage, and distribution) are covered if the tissues and cells are intended for transplantation.
Donation, procurement, and testing of all human tissues and cells for application to the human body.
11. This proposal for a Directive on human tissues and cells aims to cover all human cells and tissues, which are used for application to the human body, during the first phases of the process ­ donation, procurement and testing ­ in order to ensure their quality and safety.
12. The proposal, however, excludes blood and blood products (other than blood precursors), human organs, as well as organs, tissues, or cells of animal origin. Blood and blood products currently are regulated by Directive 2001/83/EC5, Directive 2000/70/EC6 and Council Recommendation 98/463/EC7, and a new directive based on public health principles is currently under discussion in Council and the European Parliament8.
13. The transplantation of human organs requires a different policy approach due to their specific nature and the severe shortages that result in many patients going untreated. The Commission will address this subject shortly by inviting national and international organisations involved in organ procurement for an exchange of information on the relevant issues.
14. Organs, tissues, and cells of animal origin for human therapy are still in the research phase, but nevertheless pose different regulatory problems that will need to be addressed in due course.
15. Tissues and cells used as an autologous graft (tissues removed and transplanted back to the same person), within the same surgical procedure and without being subjected to any banking process, are also excluded from this proposal. The quality and safety considerations associated with this process are completely different.
16. Autologous cells used for medicinal products require a completely different regulatory approach and therefore are completely excluded from this Directive.
17. This Directive does not intend to cover research using human tissues and cells, such as when used for purposes other than application to the human body, i.e. in vitro research or in animal models. Only those cells and tissues that in clinical trials are applied to the human body should comply with the quality and safety standards laid down in this Directive.
18. All other types of tissues and cells are covered. Some, however, in particular germ cells, foetal cells/tissues and embryonic stem cells, pose particular ethical concerns. To date, there is no consensus among Member States upon which basic harmonised decisions at EU level can be taken with regards to their use or prohibition. If, however, a particular application of these cells is accepted in a Member State, the relevant provisions of this Directive will apply.
Processing, preservation, storage, and distribution of tissues and cells to be used for human transplantation
19. When the tissues and cells are to be used for human transplantation, this proposal for a Directive applies to the processing, preservation, storage, and distribution phases.
Transplantation aims to recover a lost tissue or cell function by transferring to the human body equivalent tissues or cells. If their preparation includes steps that influence growth or differentiation of these cells, additional safety measures might need to be considered in the future.
20. The proposal excludes these phases of the process, however, when the tissues or cells are to be used for other purposes such anti-tumoral vaccines or therapies where the objective is not to recover a function by transplanting equivalent cells or tissues. These new therapeutic approaches require different, and very specific, processing standards, which cannot be established now since the associated risks are still under investigation. Furthermore in those cases they will fall under the legislation covering medicinal products or medical devices.
21. The Scientific Committee on Medicinal Products and Medical Devices (SCMPMD) concluded9 that the area of tissue engineering is not yet sufficiently developed, and clear boundaries cannot be drawn between it and other allied areas. Oversight for adequate control of the introduction and monitoring of tissue engineering processes in the European Union would require, in the opinion of the SCMPMD, specific legislation.
22. This proposal for a Directive, therefore, aims to ensure that tissues and cells used as source of these products should have the same level of quality and safety, compared with 'classical' transplantation. In this way, the Directive will help to facilitate indirectly their movement from one Member State to another. In addition, by establishing the same procurement, processing, and storage criteria, as well as the setting up of a Community register of accredited tissue banks, the Directive will help to remove uncalled-for restrictions on the exchange of tissues from one Member State to another.
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Brussels, 19.6.2002 COM(2002) 319 final 2002/0128(COD)