Quality standards for human tissues and cells
The transplantation of human tissues and cells is a strongly expanding field of medicine offering excellent opportunities for the treatment of as yet incurable diseases. In order to minimise the infection risk involved in transplant operations, it is essential to ensure the quality and safety of the substances concerned. This directive therefore aims to establish high standards of quality and safety for tissues and cells of human origin for human therapeutic uses.
Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells [See amending act(s)].
Article 152 of the EC Treaty (henceforth Article 168 TFEU), requires the European Union to establish high quality and safety standards for the use of blood, organs and other substances of human origin.
In 1998, the European Group on Ethics in Sciences and New Technologies (EGE) confirmed the urgency of monitoring the conditions under which human cells and tissues circulate, the donation of which, anonymous and free, should remain basically a voluntary act. Moreover, the growing use of human tissues * and cells * in therapeutic treatment (reconstructive surgery, cancer and diabetes treatment) and the development of intra-Community trade in these substances make it necessary to define a minimum regulatory basis.
Tissues are groups of cells, which may be transplanted or implanted as viable cells, or otherwise preserved, fixed or altered. Originating from a live or dead donor *, they include: bone and musculo-skeletal elements (e.g. cartilage, tendons), cardiovascular tissues (e.g. arteries, veins, and heart valves), ocular tissue (e.g. cornea), nerve and brain cells, skin, foetal tissue, reproductive cells (e.g. semen, sperm, and ova) and stem cells.
SCOPE AND IMPLEMENTATION
This directive applies to the donation, procurement, testing, preservation, storage * and distribution * of human tissues and cells intended for human use. It also relates to manufactured products derived from human tissues and cells intended for human use. In the case of products made industrially from tissues and cells, the directive applies merely to donation, procurement and testing.
Blood and blood constituents, organs, tissues and cells used as an autologous graft * within the same surgical procedure and autologous cells for the manufacture of pharmaceuticals are excluded from the scope.
Member States must designate the competent authorities responsible for implementing the directive. They must keep the option of maintaining or introducing more stringent protective measures.
OBLIGATIONS ON MEMBER STATES’ AUTHORITIES
Supervision of human tissue and cell procurement
Member States must ensure that tissue and cell procurement and testing are carried out by persons with appropriate training and experience and that they take place in conditions approved by the competent authorities.
Accreditation, designation or authorisation of tissue establishments
All tissue establishments * must be accredited, designated or authorised by a competent authority, which may suspend or revoke such accreditation, designation or authorisation if, following inspections, it is shown that the establishment does not meet the requirements of the directive.
Inspection and control measures
The competent authorities must organise inspections and checks at tissue establishments at least every two years. The Member States, at the request of the Commission or another Member State, must provide information with information on the results of these inspections and checks.
Member States must ensure traceability from the donor to the recipient and vice versa, of all tissues and cells procured, processed, stored or distributed on their territory. The traceability requirement also applies to all products and materials coming into contact with tissues and cells. To this end Member States shall ensure the implementation of a donor identification system which assigns a unique code to each donation and to each of the products associated with it. All tissues and cells must be identified with a label that contains information on the procedures for procurement and receipt, processing, storage and distribution.
The data necessary to ensure traceability must be kept for at least thirty years after clinical use.
Import/export of human tissues and cells
Member States must ensure that all imports and exports of human tissues and cells from and to third countries comply with the directive’s quality and safety requirements and are undertaken by accredited, designated and authorised tissue establishments so as to ensure the traceability of tissues and cells.
Register of tissue establishments and reporting obligations
The competent authorities must maintain a publicly accessible register of tissue establishments specifying the activities for which they have been accredited, designated or authorised. For their part, tissue establishments must keep a record of their activities and submit an annual report, which is also publicly accessible, to the competent authorities.
Notification of serious adverse events and reactions
Member States must provide for the creation of a system for the notification, registration and transmission of information on any incident linked to the procurement, testing, processing, storage, distribution and transplantation of tissues and cells.
DONOR SELECTION AND EVALUATION
Principles governing tissue and cell donation
Member States must encourage voluntary and unpaid donations of tissues and cells. However, donors may receive compensation strictly limited to making good the expenses and inconveniences related to the donation (e.g. travel expenses). No promotion and publicity activities are allowed in support of the donation of human tissues and cells with a view to offering or seeking financial gain or comparable advantage. The general rule is that Member States must endeavour to ensure that the procurement of tissues and cells is carried out on a non-profit basis.
The consent of donors, recipients or their next of kin is obligatory. They must receive information on the purpose and nature of the procurement, the associated risks, the analytical examinations, the recording and protection of donor details and medical confidentiality. In the case of a dead donor, all this information must be provided to the next of kin and all the necessary authorisations and consent must be obtained from the next of kin before any operation takes place.
Member States must take all necessary measures to ensure that all data collected and to which third parties have access are rendered anonymous. The recipient’s identity must never be divulged to the donor or his or her family, or vice versa. To this end, measures must be adopted to ensure data security and prevent unauthorised modifications to files and records.
Selection, evaluation and procurement
Donors must be evaluated and selected in accordance with strict standards, depending on the nature of the donor (dead or alive, specific case of children) and the type of operation.
QUALITY AND SAFETY OF TISSUES AND CELLS
Each tissue centre must put in place a quality control system, which must include at least the following information: guidelines; operating procedures; training and reference manuals; donor records (to be kept for at least 30 years); information on the final destination of tissues or cells. These documents must be available for official inspections by agents of the competent authority.
Tissue and cell reception
Tissue and cell donations must be subjected to tests relating to specific requirements. The same applies in respect of selection, acceptance and packaging of tissues and cells.
Tissue and cell processing
Tissue establishments must include in their operating procedures all the processes that affect quality and safety. They must ensure that the equipment used, the working environment and process monitoring conditions comply with the requirements regarding the processing, storage and distribution of tissues and cells.
Tissue and cell storage conditions
Storage conditions must comply with specific requirements. Storage processes must be carried out under controlled conditions.
EXCHANGE OF INFORMATION, REPORTS AND PENALTIES
Member States must create a system for identifying human tissues and cells in order to ensure their traceability. With their collaboration, the Commission must devise a single European codification system in order to provide information on the main features and properties of the tissues and cells.
Member States must send the Commission, three years after the implementation date for this directive and every three years thereafter, a report on the activities undertaken, with reference to the provisions of this directive, and including an account of the inspection and monitoring measures taken.
Member States must lay down the rules on penalties applicable to infringements of the national provisions and notify those penalties to the Commission by the date when this directive enters into force at the latest.
Ethical considerations remain the responsibility of the Member States
In the course of the adoption process for the directive, many MEPs, concerned by the ethical aspects of the subject, advocated the inclusion of minimum requirements covering, in particular, a ban on human cloning and a guarantee that no abortions could take place with a view to obtaining foetal tissue. The outcome was that ethical considerations did not come under the scope of the directive and would therefore be left to the appreciation of the Member States. On the subject of cloning, the directive does not interfere with decisions made by Member States concerning the use or non-use of any specific type of human cells, including germ cells and embryonic stem cells.
|Act||Entry into force||Deadline for transposition in the Member States||Official Journal|
OJ L 102 of 7.4.2004
|Amending act(s)||Entry into force||Deadline for transposition in the Member States||Official Journal|
Regulation (EC) No 596/2009
OJ L 188 of 18.7.2009