52003PC0340

Amended 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 (presented by the Commission pursuant to Article 250 (2) of the EC Treaty)

EXPLANATORY MEMORANDUM

A. Procedure

In June 2001, the Commission submitted a proposal for a Directive on setting standards of quality and safety for the donation, procurement, testing, processing, storage, and distribution of human tissues and cells for adoption by the co-decision procedure laid down in Article 251 of the Treaty establishing the European Community - (COM (2002) 319 final of 19.06.2002) - 2002/0128(COD).

On 10 May 2002, the European Parliament adopted its report in first reading. The Commission gave its opinion on each of the 76 Amendments adopted by Parliament and accepted 35, 16 in whole (amendments 11,13, 21, 22, 23, 26, 40, 53, 54, 58, 63, 64, 66, 72, 74 and 76) and 19 in part, conditionally or after reformulation (amendments 2, 12, 16, 20, 32, 33, 34, 35, 38, 49, 52, 55, 56, 57, 69, 75, 78, 80 and 85).

In the light of these developments, the Commission has drafted this amended proposal. The amendments, where added or modified, are in 'bold' and 'underlined', and where deleted, in 'bold' and 'strikeout'. Only extensive linguistic changes are mentioned below.

B. Purpose of the Proposal

This Proposal attempts to close the existing gap in Community legislation related to ensuring a high level of quality and safety of human tissues and cells and takes fully into account existing provisions in these areas. It seeks to ensure a comparable level of quality and safety of human tissues and cells in all Member States, bearing in mind the freedom of movement of citizens within Community territory.

The aims of this proposal are to:

- establish European Community legislation setting standards for the quality and safety of tissues and cells of human origin used for application in the human body;

- strengthen requirements related to the suitability of donors of tissues and cells and the screening of these donated substances of human origin in the European Union;

- establish at Member State level requirements for establishments involved in the procurement, testing, processing, storage, and distribution of tissues and cells of human origin, as well as national accreditation and monitoring structures;

- lay down provisions at Community level for the formulation of a register of accredited establishments;

- lay down provisions at Community level for the formulation of a quality system for tissues and cells in related establishments;

- lay down common provisions at Community level for the training of staff directly involved in the procurement, testing, processing, storage, and distribution of tissues and cells of human origin, without prejudice to existing legislation;

- establish rules for ensuring the traceability of tissues and cells of human origin from donor to patient and vice versa, which are valid throughout the European Union;

- establish a system for the regulation of imports of human tissues and cells from third countries that ensure equivalent standards of quality and safety.

C. Explanation of the Amendments

The Commission has made a number of amendments to its original proposal, reflecting those modifications introduced by the European Parliament and accepted by the Commission. In addition, the Commission has made some revisions as a direct consequence of the Parliament's amendments, and in order to clarify the text. In this amended proposal, the Commission has also taken into account the current status of the dossier in the Council. Reflecting the key concerns of the European Parliament, the main amendments to the original proposal can be grouped as follows:

1. Ethical provisions.

Most of the amendments proposed by the EP relate to the addition of extensive ethical provisions. Recognising the legitimacy of these requirements, the Commission, therefore, has given them careful consideration and can accept those related to the anonymity of donors and/or non-profit procurement (amendments 11, 12, and 13), therefore recitals 13 and 14 have been modified accordingly. Other proposed ethical provisions cannot be accepted, however, as they fall outside the scope of Article 152, that provides for public health protection and not the implementation of ethical objectives as such.

2. Scope of the Directive:

In order to address EP amendments 20, 21 and 22, the scope of the Directive (Article 2) has been extended to include the donation, procurement and testing of autologous cells to be used for the manufacturing of medicinal products. This will facilitate a consistent approach to quality and safety measures for all substances of human origin, and is consistent with the approach already adopted in the Directive 2002/98/EC [1], with respect to manufactured medicinal products derived from blood.

[1] OJ L33, 8.2.2003, p.30.

The scope has been also widened to cover further steps in the process. The term 'transplantation' has been changed to 'human application', in order to clarify that other therapies, such as reproductive medicine (reproductive cells), are also covered for the processing, preservation, storage and distribution steps. This modification of the scope has implications for the definition of transplantation in Article 3, and consequently for other provisions of the text.

Two clarifications have also been introduced in Article 2. The first concerns the reference to the Blood Directive (2002/98/EC) and the second to the wording of the exclusion of manufactured products for the processing, preservation, storage and distribution steps, which are covered by other Directives.

In order for consistency with the new scope, the definition of tissue establishment has been modified in Article 3 (Definitions) and throughout the text, in keeping with amendment 12 of the European Parliament. This is in order to clarify that the range of establishments covered by this Directive includes not only traditional tissue banks, but also all establishments where activities related to the human application of human tissues and cells are undertaken.

Other amendments proposed by the European Parliament cannot be accepted as they fall substantially outside the scope of the Directive. Two of these amendments (6 and 62) require the Commission to submit in the short term a legislative proposal in the field of organ transplantation. This requirement is difficult to accept, because the shortage of available organs and the urgent nature of their use requires organisational aspects that are difficult to address under Article 152, therefore a Proposal on this field needs to be examined carefully.

The Commission cannot support the Parliament's amendments, which go in the direction of introducing 'in vitro' research on tissues and cells into the scope of the Directive, an area outside the scope of Article 152.

3. Use of any specific type of tissues and cells

Amendments 29 and 78 of the Parliament strengthen the principle that this Directive should not interfere with Member State's decisions with respect to prohibition on the use of any specific tissue or cell. The Commission has introduced partially these amendments in recital 7 and article 4. The amendments improve the proposal from a technical and editorial point of view and are globally in line with the developments in the Council.

4. Accreditation

Article 6 has been modified as a consequence of the new scope (Article 2) and the new concept of a tissue establishment (Article 3).

Article 6 covers the accreditation of tissue establishments, clarifying that with the new definition these establishments could also undertake the procurement of tissues and cells. A direct consequence of this, which is in keeping with the orientations of the Council, is the importance of the authorisation of the procurement conditions and the staff involved - both key elements of the process. This amended proposal has introduced some modifications in Article 5 - supervision of tissue and cell procurement. Consequently, Article 6.2 has also been modified, particularly in cases where a patient's condition means that any delay is unacceptable.

5. Import and export

European Parliament Amendments 34 and 35 on import and export provide certain flexibility with regard to compliance with third country legislation. The Commission has redrafted Article 9 taking into account the principles of these amendments and on the basis that it is equally important to ensure that no 'sub-standard' tissues and cells are exported to third countries.

6. Anonymity and traceability

Amendments 16, 38, 40, 49, 53 and 54 refer to anonymity and/or traceability.

The amendments strengthen the provisions on traceability, extending it to materials in close contact with the tissues and cells, ensuring a minimum period of thirty years for keeping the data and including the final destination in the quality system. The Commission has amended its proposal as a consequence in Articles 10 and 16.

The principle that tissue and cell donation should respect the anonymity of the donors and recipients is also respected in these amendments. However, the EP would like an exemption in the case of specific types of cells. The Commission proposal already introduces the possibility for Member States to keep or adopt different legislation in case of donors closely related to the recipient, however a modification in Article 14 has been introduced..

The Commission would also like to differentiate clearly between these two concepts. Therefore, instead of a modification of the recital on traceability, a new recital for anonymity, recital 18, is proposed.

7. Others

Amendment 32 on publicly accessible records in tissue establishments (Article 7), amendment 33 on establishing guidance for consistent inspections in all MS (Article 8), amendment 57 clarifying the relationship of tissue establishments with third parties (Article 24), amendment 55 on the requirements for the responsible persons (Article 17), and amendment 56 transferring the provisions of reconstruction of the body from the annexes to an Article, are all accepted at least partially, and the corresponding Articles have been amended.

8. Establishment of technical standards:

The European Parliament has suggested a different solution for the establishment of technical implementing provisions. The Parliament's amendment establishes that any update or modification to Annexes III, IV and V should be through a new proposal to Parliament and Council. The rest of the annexes should be amended by a Committee composed of Member State representatives, in accordance with Decision 1999/468/EC. The Commission cannot support the Parliament's amendment.

Amendments 63 (exceptions on the requirement for operating on a 24-hour basis), 64 and 66 (information to the donor), 69, 71 and 72 (testing), 75 (environment conditions in the processing of tissues and cells) and 76 (storage) are useful for strengthening the standards and have been taken into account in this amended proposal.

D. Amended proposal:

Having regard to Article 250, paragraph 2, of the EC treaty, the Commission modifies its proposal as follows:

2002/0128 (COD)

Amended 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

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community, and in particular Article 152(4)(a) thereof,

Having regard to the proposal from the Commission [2],

[2] OJ C , , p. .

Having regard to the Opinion of the European Economic and Social Committee [3],

[3] OJ C , , p. .

Having regard to the Opinion of the Committee of the Regions [4],

[4] OJ C , , p. .

Acting in accordance with the procedure laid down in Article 251 of the Treaty [5],

[5] OJ C , , p. .

Whereas:

(1) The transplantation of tissues and cells of human origin is an expanding field of medicine offering potential opportunities for the treatment of as yet incurable diseases. The aim of this Directive is to further the opportunities offered by tissue and cell therapy without causing unacceptable risks for donors and recipients. The quality and safety of these substances must be ensured, particularly in order to prevent the transmission of diseases. .

(2) The availability of tissues and cells of human origin used for therapeutic purposes is dependent on Community citizens who are prepared to donate them. In order to safeguard public health and to prevent the transmission of infectious diseases by these tissues and cells, all precautionary measures need to be taken during their procurement, testing, processing, storage, distribution and use.

(3) There is an urgent need for a unified framework in order to ensure high standards of quality and safety with respect to the procurement, testing, processing, storage and distribution of tissues and cells across the Community and to facilitate exchanges for the thousand of patients receiving this type of therapy each year. It is essential, therefore, that whatever their intended use, Community provisions should ensure that tissues and cells of human origin are of comparable quality and safety. The establishment of such standards, therefore, will help to reassure the public that human tissues and cells that are procured in another Member State, nonetheless, carry the same guarantees as those in their own country.

It is necessary to regulate the donation, procurement, testing, processing, preservation, storage and distribution of all sources of human tissues and cells intended for application in the human body. . This Directive will also apply to haematopoietic peripheral blood, placenta and bone marrow stem cells; reproductive cells (eggs, sperm); foetal tissues and cells, adult and embryonic stem cells . Tissues and cells intended to be used for industrially manufactured products, including medicinal products and medical devices, should be covered only as far as donation, procurement and testing are concerned where the processing, preservation, storage and distribution is regulated by other community legislation. (5) The proposal excludes blood and blood products (other than haematopoietic progenitor cells), 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/EC [6] and Council Recommendation 98/463/EC [7], and in Directive 2002/98/EC which is based on public health principles under Article 152 [8]. 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.

[6] Directive 2000/70/EC of the European Parliament and of the Council of 16 November 2000 amending Council Directive 93/42/EEC as regards medical devices incorporating stable derivates of human blood or human plasma. OJ L 313, 13.12.2000, p.22.

[7] Council Recommendation of 29 June 1998 on the Suitability of blood and plasma donors and the screening of donated blood in the European Community. OJ No L 203, 21.07.1998, p.14

[8] Proposal for a Directive 2002/98/EC of the European Parliament and of the Council setting standards of quality and safety for the collection, testing, processing, storage, and distribution of human blood and blood components and amending Council Directive 2001/83/EC 89/381/EEC. COM(2000)816 final. 13.12.2000. 2000/0323 (COD)

(6) This Directive does not 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.

(7) This Directive does not interfere with decisions made by Member States concerning the right of Member States to take decisions to prohibit the donation of, experimentation with, processing, storage, distribution and use or not-use of any type of specific human cells or tissues, or of cells of a specific origin or type, including germ cells and embryonic stem cells. If any Member State takes such a decision, the reason for which must be made publicly available, the ban may also be extended to imports of cells or tissues of such kinds. If, however, any particular use of such cells is authorised in a Member State, this Directive will require the application of all provisions necessary to protect public health and guarantee respect for fundamental rights. Moreover, this Directive does not interfere with provisions of Member States defining the legal term 'person' or 'individual'.

(8) The donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells for human application should comply with high standards of quality and safety in order to ensure a high level of health protection in the Community. This Directive should establish standards for each one of the steps in the human tissues and cells application process.

(9) It is necessary to increase confidence among the Member States in the quality and safety of donated tissues and cells, in the health protection of living donors and respect for deceased donors, and in the safety of the application process.

(10) As there is a need to ensure the availability of tissues and cells for medical treatments Member States should promote the donation of high quality and safety tissues and cells in the Community

(11) Tissues and cells used for allogeneic therapeutic purposes can be procured from both living and deceased donors. In order to ensure that the health status of a living donor is not affected by the donation, a prior medical examination is required. The dignity of the deceased donor has to be respected.

(12) The use of tissues and cells for application in the human body can cause diseases and unwanted effects. Most of these can be prevented by careful donor evaluation and the testing of each donation in accordance with rules established and updated according to the best available scientific advice.

(13) As a matter of principle, tissue and cell application programmes should be founded on the philosophy of voluntary and unpaid donation, anonymity of both donor and recipient, altruism of the donor and solidarity between donor and recipient . Member States are urged to take steps to encourage a strong public and non-profit sector involvement in the provision of tissue and cell application services and the related research development.

(14) Commercial establishments may also be accredited as cell and tissue establishments provided they comply with the standards.

(15) The procurement of human tissues and cells must fully respect the Charter of Fundamental Rights of the European Union [9], and take fully into account the principles of the Convention on Human Rights and Biomedicine of the Council of Europe [10], in particular in relation to donor consent, including the protocols thereto. However, both the Charter of Fundamental Rights and the Council of Europe Convention lay down minimum requirements only, beyond which both the European Union as a whole and the individual Member States may go in their legislation. Neither text makes express provision for harmonisation but lays down minimum standards.

[9] OJ C 364, 18.12.2000, p.1.

[10] Council of Europe. 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. European Treaty Series - No. 164. Oviedo, 4.IV.1997. p.11

(16) All necessary measures need to be taken in order to provide prospective donors of tissues and cells with assurances regarding the confidentiality of any health related information provided to the authorised personnel, the results of tests on their donations, as well as any future traceability of their donation.

(17) Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and the free movement of such data [11], applies to personal data processed in application of the present directive. Article 8 of this Directive prohibits in principle the processing of data concerning health. Limited exemptions to this prohibition principle are foreseen. Directive 95/46/EC provides also that the controller must implement appropriate technical and organisational measures to protect personal data against accidental or unlawful destruction or accidental loss, alteration, unauthorised disclosure or access and against all other unlawful forms of processing.

[11] OJ L 281, 23.11.1995, p.31.

(18) As a general principle the identity of the recipient(s) should not be disclosed to the donor or his family and vice versa, without prejudice to legislation in force in Members States on the conditions of disclosure.

(19) An accreditation system for tissue establishments and a system for notification of adverse events and reactions linked to the procurement, processing, testing, storage, and distribution of tissues and cells of human origin should be established in Member States.

(20) Member States should organise inspections on conditions of procurement, tissue establishment and any third party, to be carried out by officials representing the competent authority or authorities , and ensure that appropriate control measures are in place to ensure compliance of the tissue establishments and the procurement of tissues and cells with the provisions of this Directive.

(21) Personnel directly involved in the donation, procurement, testing, processing, preservation, storage and distribution of tissues and cells of human origin should be appropriately qualified and provided with timely and relevant training The provisions laid down in this Directive as regards training should be applicable without prejudice to existing Community legislation on the recognition of professional qualifications.

(22) An adequate system to ensure the traceability of tissues and cells of human origin should be established; traceability should be enforced through accurate substance, donor, recipient, tissue establishment , and laboratory identification procedures as well as record maintenance and an appropriate labelling system.

(23) In order to increase the effective implementation of the provisions adopted under this Directive, it is appropriate to provide for penalties to be applied by Member States.

(24) Since the objectives of the proposed action, namely to set high standards of quality and safety for human tissues and cells throughout the Community cannot be sufficiently achieved by the Member States alone and can therefore, by reason of scale and effects, be better achieved at Community level, the Community may adopt measures in accordance with the principles of subsidiarity as set out in Article 5 of the Treaty. In accordance with the principle of proportionality, as set out in that Article, this Directive does not go beyond what is necessary for this purpose.

(25) It is necessary that the best possible scientific advice is available to the Community in relation to the safety of tissues and cells; in particular in order to assist the Commission in adapting the provisions of this Directive to scientific and technical progress.

(26) The opinions of the Scientific Committee for Medicinal Products and Medical Devices and that of the European Group on Ethics in Science and New Technologies, have been taken into account as well as international experience in this field, and will be sought in the future whenever necessary.

(27) Since the measures necessary for the implementation of this Directive are measures of general scope within the meaning of Article 2 of Council Decision 1999/468/EC of 28 June 1999 laying down the procedures for the exercise of implementing powers conferred on the Commission [12], they should be adopted by use of the Regulatory Procedure provided for in Article 5 of that Decision.

[12] OJ L 184, 17.7.1999, p.23.

HAVE ADOPTED THIS DIRECTIVE:

CHAPTER I

GENERAL PROVISIONS

Article 1

Objective

This Directive lays down standards of quality and safety of human tissues and cells intended for human application, in order to ensure a high level of protection of human health

Article 2

Scope

1. The provisions of this Directive shall apply to the donation, procurement, testing processing, preservation, storage and distribution of human tissues and cells intended for human application and of manufactured products intended for human application derived from human tissues and cells.

Where the processing, preservation, storage and distribution of those manufactured products is regulated by other Community legislation , this Directive shall apply only to donation, procurement and testing.

2. This Directive does not apply to:

a) tissues and cells used as an autologous graft within the same surgical procedure;

;

c) blood and blood components as defined by Directive 2002/98/EC of the European Parliament and of the Council setting standards of quality and safety for the collection, testing, processing, storage, and distribution of human blood and blood components and amending Council Directive 2001/83/EC .;

d) organs or parts of organs if their function is to be used for the same purpose as the entire organ on or in the human body.

Article 3

Definitions

For the purposes of this Directive:

a) 'Cells' shall mean individual cells or a collection of cells of human origin when not bound by any form of connective tissue.

b) 'Tissue' shall mean all constituent parts of the human body formed by cells.

c) 'Donor' shall mean a living or deceased individual, including non-natus, who is the source of cells or tissues.

d) 'Organ' shall mean a differentiated and vital part of the human body, formed by different tissues, that maintains its structure, vascularisation, and capacity to develop physiological functions with an important level of autonomy.

e) 'Procurement' shall mean a process by which the donated tissue or cells become available.

f) 'Processing' shall mean all operations involved in the preparation, manipulation, preservation and packaging of tissues or cells intended for human application .

g) 'Preservation' shall mean the use of chemical agents, alterations in environmental conditions or other means during processing to prevent or retard biological or physical deterioration of cells or tissues.

h) 'Quarantine' shall mean the status of retrieved tissue or cells or packaging material, or tissue isolated physically or by other effective means whilst awaiting a decision on their release or rejection.

i) 'Distribution' shall mean transportation and delivery of tissues or cells for storage, processing or human application .

j) Human application: shall mean the use of human tissues and cells in a human recipient including the extracorporeal use

k) 'Serious adverse event' shall mean any untoward occurrence associated with the procurement, testing, processing, storage and distribution of tissues and cells that might lead to the transmission of a communicable disease, to death or life-threatening, disabling, or incapacitating conditions for patients or which results in, or prolongs, hospitalisation or morbidity.

l) 'Serious adverse reaction' shall mean an unintended response, including a communicable disease, in the donor or in the recipient associated with the procurement or transplantation of tissues and cells that is fatal, life-threatening, disabling, incapacitating, or which results in, or prolongs, hospitalisation or morbidity.

m) 'Tissue bank' shall mean the establishment, public or private, that is responsible for the activities of processing, preservation, storage, and distribution of tissue and cells. It may also be responsible for the procurement of tissues and cells.

n) 'Tissue establishment' shall mean any body, public or private, including tissue bank or any part of a hospital or other health care establishment where activities relating to the processing, preservation, storage or distribution of human tissues and cells are conducted. It may also be responsible for procurement and testing of tissues and cells.

o) 'Tissue procurement team' shall mean the health care professionals involved in any of the activities necessary for tissue and cell procurement.

p) 'Allogeneic use' shall mean cells or tissues procured from one person and applied to another.

q) 'Autologous use' shall mean cells or tissues removed from and applied back to the same person.

Article 4

Implementation

1. Member States shall designate the competent authority or authorities responsible for implementing the requirements of this Directive.

2. This Directive shall not prevent a Member State from maintaining or introducing more stringent protective measures that comply with the provisions of the Treaty. In particular, a Member State may introduce requirements for voluntary and unpaid donation, which include the prohibition or restriction of imports of human tissues and cells to ensure a high level of health protection, provided that the conditions of the treaty are met.

3. This Directive shall not interfere with Member States' decisions prohibiting or restricting the donation, procurement, testing, processing, preservation, storage, distribution or use of any specific type of human tissues or cells or cells from any specified source, including where those decisions also concern imports of the same type of human tissues or cells. Where a Member State decides on such a prohibition, the reason for the prohibition must be made publicly available. If, however, any particular use of such cells is authorised in a Member State, the provisions of this Directive shall apply

4. In carrying out the activities covered by this Directive, the Commission may have recourse to technical and/or administrative assistance to the mutual benefit of the Commission and of the beneficiaries, relating to identification, preparation, management, monitoring, audit and control, as well as to support expenditure.

CHAPTER II

OBLIGATIONS ON MEMBER STATES AUTHORITIES

Article 5

Supervision of tissue and cell procurement

Member States shall ensure that tissue and cell procurement is carried out by persons with appropriate training and experience and that they take place in circumstances accredited, designated, authorised or licensed for that purpose by the competent authority or authorities. 2. The competent authority or authorities shall take all necessary measures to ensure that tissue and cell procurementd, complies with the requirements listed in Part A of Annex I.

Article 6

Accreditation of tissue establishments

1. Member States shall ensure that all tissue establishments where activities relating to the processing, preservation, storage, and distribution of human tissues and cells intended for human application are conducted have been accredited, designated, authorised or licensed by a competent authority or authorities for the purpose of these activities.

2. Haematopoietic progenitor cells from peripheral blood, umbilical cord and bone marrow, however, may be distributed directly for immediate transplantation from where the procurement is carried out, to a health care establishment, provided that the persons and conditions for that purposes are regulated by the competent authority or authorities in conformity with the provisions of Article 5. The same applies to cases where the patient's state of health is such that any delay of transplantation is unacceptable.

3. The competent authority or authorities, having verified that the tissue establishments complies with the requirements set out in Annex I, shall accredit the tissue establishment and indicate which activities it may undertake and which conditions apply.

4. The tissue establishment shall not undertake any substantial changes to its activities without the prior written approval of the competent authority or authorities .

5. The competent authority or authorities may suspend or revoke the accreditation of a tissue establishment if inspection or control measures demonstrate that it does not comply with the requirements of this Directive.

Article 7

Register of accredited tissue establishments and reporting obligations

1. The competent authority or authorities shall establish and maintain a publicly accessible register of tissue establishments specifying the activities for which they have been accredited.

2. Tissue establishments shall maintain a record of their activities, including the types and quantities of tissues and/or cells procured, preserved, processed, stored and distributed, or otherwise disposed of and on the origin and destination of the tissues and cells processed for application in the human body, in accordance with Annex VI. They shall submit to the competent authority or authorities an annual report on these activities. This report shall be available to the public. .

3. Member States and the Commission shall establish a network of the national tissue establishment registers.

Article 8

Inspection and control measures

1. Member States shall ensure that the competent authority or authorities organise inspections and that tissue establishments, as well as establishments of third parties as specified in Article 24 carry out appropriate control measures in order to ensure compliance with the requirements of this Directive.

The competent authority or authorities shall also organise inspections and ensure that appropriate control measures are in place are in place for the procurement of human tissues and cells. 3. Inspections and control measures shall be organised by the competent authority or authorities on a regular basis. The interval between two inspections and control measures shall not exceed two years.

4. Inspections and control measures shall be carried out by officials representing the competent authority or authorities who must be empowered to:

a) inspect accredited tissue establishments and the facilities of any third parties as specified in Article 24;

b) evaluate the procedures and the activities carried out by the tissue establishments and the facilities of third parties;

c) examine any documents relating to the subject of the inspection.

5. The competent authority or authorities shall organise inspections and other control measures as appropriate in the event of any serious adverse reaction or serious adverse event.

6. Member States shall, upon the request of another Member State or the Commission, provide information about the results of inspections and control measures carried out in individual tissue establishments , the facilities of third parties and the conditions of procurement of tissues and cells .

7. Member States in collaboration with the Commission shall prepare guidelines concerning the conditions of the inspections and control measures, and on the training and qualification of the officials involved, in order to reach a consistent level of competence and performance.

Article 9

Import/Export of human tissues and cells

1. Member States shall take all necessary measures to ensure that all imports of tissues and cells from third countries are undertaken by accredited, designated, authorised or licensed tissue establishments. Those that receive such imports from third countries shall ensure that they meet the equivalent standards of quality and safety to the ones laid down in this Directive.

2. Member States shall take all necessary measures to ensure that all exports of tissues and cells to third countries are undertaken by accredited, designated, authorised or licensed tissue establishments. Those that send such exports to third countries shall ensure that they comply with the requirements of this Directive .

3. The import or export of certain specific tissues and cells referred to in Article 6.2 may be authorised directly by the competent authority or authorities.

The competent authority or authorities shall take all necessary measures to ensure that exports of tissues and cells meet quality and safety standards laid down in this Directive. The competent authority or authorities shall approve imports of human tissues and cells from third countries only when equivalent standards of quality and safety to the ones laid down in this Directive are ensured.

4. The procedures for verifying the equivalent standards of quality and safety in accordance with paragraph 3 shall be established by the Commission in accordance with the procedure referred to in Article 30(2).

Article 10

Traceability

1. Member States shall ensure that tissue establishments take all necessary measures to ensure that all tissues and cells procured, processed, stored and distributed on their territory can be traced from the donor to recipient and vice versa. This traceability also applies to all relevant data for quality and safety relating to products and materials coming into contact with these tissues and cells

2. The procedures for ensuring traceability at the Community level shall be established by the Commission according to the procedure referred to in Article 30(2)

3. Tissue establishments shall implement a donor identification system and assign a code to each donation and its products.

4. All tissues and cells must be identified with a label that contains the information listed in Annexes VI and VII.

Article 11

Notification of serious adverse events and reactions

1. The Member States shall ensure that there is a system in place to report, register, and transmit information about serious adverse events and reactions related to the procurement, testing, processing, storage and distribution of tissues and cells, as well as any serious adverse reaction observed during or after clinical application which may be linked to the quality and safety of tissues and cells.

2. The responsible person referred to in Article 17 shall notify the competent authority or authorities of any serious adverse events and reactions referred to in paragraph 1 and provide a report analysing the cause and the ensuing outcome.

3. The procedure for notifying adverse events and reactions shall be established by the Commission in accordance with the procedure referred to in Article 30(2).

CHAPTER III

DONOR SELECTION AND EVALUATION

Article 12

Principles for tissue and cell donation

1. Member States shall take any necessary measures to encourage voluntary and unpaid donations of tissues and cells with a view to ensuring that they are in so far as possible provided from such donations

Member States shall report to the Commission on these measures two years after the entry into force of this Directive, and thereafter every three years. On the basis of these reports the Commission shall inform the European Parliament and the Council of any necessary further measures it intends to take at Community level.

2. Member States shall take all necessary measures to ensure that any promotion and publicity activities in support of the donation of human tissues and cells conform to guidelines or legislative provisions laid down by the Member States . Advertising the need for, or availability of, human tissues and cells, with a view to offering or seeking financial gain or comparable advantage shall be prohibited.

3. Member States shall encourage that the procurement of tissues and cells is carried out on a non-profit basis.

Article 13

Consent

1. The procurement of human tissues or cells shall be carried out only after all mandatory consent requirements in force in the Member State are met.

2. Member States shall take all necessary measures to ensure that the donors, their families or any person granting authorisation on behalf of the donors, are provided with the information listed in Annex III.

Article 14

Data protection and confidentiality

1. Member States shall take all necessary measures to ensure that all data, including genetic information, collated within the scope of this Directive and to which third parties have access have been rendered anonymous so that the donor and the recipient are no longer identifiable.

2. For that purpose, they shall ensure that:

a) data security measures are in place as well as safeguards against any unauthorised data additions, deletions, or modifications to donor files or deferral records, as well as any transfer of information;

b) procedures are in place to resolve data discrepancies; and

c) no unauthorised disclosure of information occurs, whilst guaranteeing the traceability of donations.

3. Member States shall take all necessary measures to ensure that the identity of the recipient(s) is not disclosed to the donor or his family and vice versa, without prejudice to legislation in force in Members States on the conditions of disclosure .

Article 15

Selection, evaluation, and procurement

1. The activities related to tissue procurement shall be carried out in such a way as to ensure that the donor evaluation and selection is carried out according to the requirements specified in Annex IV and that tissues and cells are procured, packaged and transported to the tissue establishments in accordance with Annex VI.

2. In the case of an autologous donation, the suitability criteria shall be established and documented by the physician responsible for the patient, according to the clinical record, the therapeutic indication, and in accordance with the requirements listed in point 2.1 of Annex IV.

3. The tissue establishments shall ensure that the selection and acceptance of tissues and cells comply with the requirements of Annex VI. They shall also ensure that all donations are tested in accordance with Annex V.

4. The results of the donor evaluation and testing procedures shall be documented and any relevant abnormal findings shall be reported in accordance with Annex III.

5. The competent authority or authorities shall ensure that all the activities related to tissue procurement shall be carried out in accordance with the conditions specified in Annex VI.

6. Once the tissues have been retrieved, the deceased donor body should be constructed so that it is as similar as possible to its original anatomical shape. Reconstruction methods should minimise any impact on normal funeral procedures.

CHAPTER IV

PROVISIONS FOR QUALITY AND SAFETY ON TISSUE AND CELLS

Article 16

Quality management

1. Member States shall take all necessary measures to ensure that each tissue establishment sets up and maintains a quality system on the principles of good practice.

2. The Commission shall establish in accordance with the procedure laid down in Art 30(2) the Community standards and specifications, referred to in Annex II, for the activities relating to a quality management system.

3. Tissue establishments shall take all necessary measures in order to ensure that the quality management system includes at least the following documentation:

- Standard Operating Procedures;

- Guidelines;

- Training and reference manuals;

- Reporting forms;

- Donor records.

- information concerning the final destination of the tissues and cells

4. Tissue establishments shall take all necessary measures to ensure that this documentation is available for official inspections.

5. Tissue establishments shall keep the data required for full traceability according to Article 10, for a minimum of 30 years after the confirmed clinical use of the respective tissue/cell. Storage may also be in electronic form.

Article 17

Responsible person

1. Tissue establishments shall designate a responsible person. This person shall fulfil the following minimum conditions and qualifications:

a) he / she shall possess a diploma, certificate or other evidence of formal qualifications in the field of medical or biological sciences awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned;

b) he / she shall have at least three years practical and relevant experience in the relevant fields.

2. The designated person referred to in paragraph 1 shall be responsible for:

a) ensuring that human tissues and cells intended for human application in the establishment for which that person is responsible are procured, tested, processed, stored and distributed in accordance with this Directive and the laws in force in the Member State ;

b) providing information to the competent authority or authorities as required in Article 6;

c) implementing the requirements of Articles 7, 10, 11, 15, 16, and 18 to 25 in the tissue establishment .

3. Tissue establishments shall notify the competent authority or authorities of the name of the responsible person referred to in paragraph 1. Where the responsible person is permanently or temporarily replaced, the tissue establishment shall provide immediately to the competent authority or authorities the name of the new responsible person and his or her date of commencement.

Article 18

Personnel

Personnel directly involved in activities related to the procurement, processing, preservation, storage and distribution of tissues and cells in a tissue establishment shall be qualified to perform such tasks and shall be provided with the relevant training specified in Annex II.

Article 19

Tissue and cell reception

1. The tissue establishment shall ensure that human tissue and cells and associated documentation comply with the requirements listed in Annex VI. The documentation to be verified for each tissue or cell is listed in Parts D and E of Annex VI.

2. The tissue establishment shall ensure and record the fact that the packaging conditions of the human tissue and cells received comply with the provisions listed in Annex VI. Any tissues and cells that do not comply with these provisions should be discarded in accordance with Annex VI.

3. The acceptance or rejection of the incoming tissues/cells shall be documented.

4. Tissue establishments shall ensure that human tissues and cells are correctly identified at all times. Each delivery or batch of tissues or cells must be assigned an identifying code, in accordance with Article 10.

Article 20

Tissue and cell processing

1. The tissue establishment shall include in its Standard Operating Procedures all the processing that directly affect quality and safety, and shall ensure that they are carried out under controlled conditions. The tissue establishment shall ensure that the equipment used, the working environment, process design, validation, and control conditions are in compliance with Annex VII.

2. Any modifications to the processes used in the preparation of the tissues and cells shall also meet the criteria laid down in paragraph 1.

3. The tissue establishment must make special provisions in its Standard Operating Procedures for the handling of tissues and cells to be discarded in order to prevent the contamination of other tissues or cells, the processing environment, or personnel.

Article 21

Tissue and cell storage conditions

1. Tissue establishments shall ensure that all procedures associated with the storage of tissues and cells are documented in the Standard Operating Procedures and that the storage conditions comply with requirements listed in Annex VII.

2. Tissue establishments shall ensure that all storage processes are carried out under controlled conditions.

3. Tissue establishments shall establish and maintain procedures for the control of packaging and storage areas, in order to prevent any condition that might adversely affect the function or integrity of tissue and cells.

4. Processed tissues or cells must be held in quarantine until released by the responsible person referred to in Article 17. Tissues or cells must not be released from quarantine for preservation and storage until all the requirements laid down in the Standard Operating Procedures have been met.

Article 22

Labelling, user information and packaging

Tissue establishments shall ensure that labelling, documentation, and packaging conform to the requirements listed in Annex VII Parts D and E.

Article 23

Transport and distribution

The tissue establishment shall guarantee the quality of tissues or cells until delivery. Distribution conditions shall comply with the requirements listed in Annex VII.

Article 24

Relationship of tissue establishments with third parties

1. Tissue establishments shall establish written agreements each time an external activity takes place which influences the quality and safety of tissues and cells processed in cooperation with a third party, and in particular in the following circumstances :

a) where a third party take responsibility in one phase of tissue or cell processing on behalf of the tissue establishment ;

b) where a third party provides goods and services that affect tissue or cell quality and safety assurance;

c) where a tissue establishment provide services to another tissue establishment ;

d) where a tissue establishment distributes tissue or cells processed by third parties

e) where a third party distributes tissues or cells.

2. The tissue establishments shall evaluate and select third parties on the basis of their ability to meet the standards laid down in this Directive.

3. Tissue establishments shall notify to the competent authority or authorities the complete list of agreements that they have established with third parties.

4. The agreements between tissue establishment and third parties shall specify responsibilities to be carried out by the third party and detailed procedures.

5. Tissue establishments shall provide copies of agreements with third parties when required by the competent authority or authorities .

Article 25Access to human tissues and cells

1. Member States, with due regard for the principle of transparency, shall ensure that public and private establishments involved in health care, and establishments authorised to manufacture medicinal products or medical devices, have access to human tissue and cells, without prejudice to the provisions in force in Member States on the use of certain tissues and cells.

2. Such establishments shall report relevant information to the tissue establishments in order to facilitate traceability, and ensure quality control and safety.

CHAPTER V

EXCHANGE OF INFORMATION, REPORTS, AND PENALTIES

Article 26

Coding of information

1. Member States shall establish a system for the identification of human tissues and cells, in order to ensure the traceability of all human tissues and cells, as indicated in Article 10.

2. The Commission, in co-operation with Member States, shall design a single European coding system that will provide the basic description and properties of tissues and cells.

Article 27

Reports

1. Member States shall send the Commission, three years after the implementation date indicated in Article 32 (1), and every three years thereafter, a report on the activities undertaken in relation to the provisions of this Directive, including an account of the measures taken in relation to inspection and control.

2. The Commission shall transmit to the European Parliament, the Council, the Economic and Social Committee, and the Committee of the Regions, the reports submitted by the Member States on the experience gained in implementing this Directive.

Article 28

Penalties

Member States shall lay down the rules on penalties applicable to infringements of the national provisions adopted pursuant to this Directive and shall take all measures necessary to ensure that they are implemented. The penalties provided for must be effective, proportionate, and dissuasive. Member States shall notify those provisions to the Commission by the date specified in Article 33(1) at the latest and shall notify it without delay of any subsequent amendments affecting them.

CHAPTER VI

CONSULTATION OF COMMITTEES

Article 29

Adaptation to technical and scientific progress

The adaptation of the technical requirements set out in Annexes I to VII to technical and scientific progress shall be decided by the Commission in accordance with the procedure referred to in Article 30(2).

Article 30

Regulatory procedure

1. The Commission shall be assisted by a Committee, composed of representatives of the Member States and chaired by the representative of the Commission.

2. Where reference is made to this paragraph, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof.

3. The period referred to in Article 5(6) of Decision 1999/468/EC shall be set at three months.

4. The Committee shall adopt its rules of procedure.

Article 31

Consultation of scientific committee (s)

The Commission may consult the relevant scientific committee(s) when adapting the Annexes of this Directive to scientific and technical progress.

CHAPTER VII

FINAL PROVISIONS

Article 32

Transposition

1. Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive not later than .... They shall forthwith inform the Commission thereof.

When Member States adopt these measures they shall contain a reference to this Directive or shall be accompanied by such reference on the occasion of their official publication. Member States shall determine how such reference is to be made.

2. Member States may decide for one year after the date laid down in the first subparagraph of paragraph (1), not to apply the requirements of this Directive to tissue establishments operating under national provisions before the entry into force of this Directive.

3. Member States shall communicate to the Commission the texts of the provisions of national law that they have already adopted or which they adopt in the field governed by this Directive.

Article 33

Entry into force

This Directive shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

Article 34

Addressees

This Directive is addressed to the Member States.

Done at Brussels,

For the European Parliament for the Council

The President The President

ANNEXES

Annex I. - Requirements for the procurement of human tissues and cells.

Annex II. - Quality management system.

Annex III. - Information to be provided on the donation of cells and/or tissues.

Annex IV. - Selection criteria for the donor of tissues and/or cells.

Annex V. - Laboratory tests required for donors

Annex VI. - Cell and/or tissue procurement procedures and reception at the tissue establishment .

Annex VII. - Tissues and cell processing, preservation and distribution.

ANNEX I

A. REQUIREMENTS FOR THE PROCUREMENT OF HUMAN TISSUES OR CELLS

The establishment responsible for tissue and cells procurement has to ensure certain minimum requirements and other conditions. It must:

a) Have links with a medical/surgical team that specialises in cell/tissues procurement, and has the staff with the necessary training and experience required to do this work;

b) Have a co-operation agreement with the team responsible for donations. The written contractual documents will specify the terms of the relationship as well as the protocols to be followed;

c) Have Standard Operation Procedures (SOPs) for the procurement, packaging, and transportation of the cells and / or tissues until the moment they are processed;

d) Have a quality management system;

e) Ensure that, in addition to the tests described in Annex V, appropriate investigations are carried out to prevent the presence of known transmissible diseases;

f) Have the facilities and material resources needed for the procurement and packaging of the cells and/or tissues;

g) Have the staff and services needed for body reconstruction and other mortuary procedures when cell / tissue are retrieved from a deceased person;

h) Ensure that the procedures for the procurement or collection of the cells and / or tissues are carried out according to Annex VI;

i) Maintain a register to ensure adequate traceability of the cells / tissues obtained and delivered. Details must be maintained on the procurement procedures, the donor (donor identification, consent and clinical data), the tissues donated, the intended use or destination of the tissues, the date of removal and the tests carried out. Access to this register will be restricted to persons, authorised by the responsible person, who will be required to comply with the confidentiality requirements laid down in the Directive.

B. CRITERIA FOR ACCREDITATION OF TISSUE ESTABLISHMENTS

In order to be accredited, tissue establishments must:

a) Have an organisational structure and operational procedures appropriate to the activities for which accreditation is sought, ensuring that it is able to receive, distribute, and allocate tissues and cells for transplantation on a 24 hour basis. Member States shall make exemptions to the requirement on operating on a 24 hour basis in the event that the tissue establishment provides only tissues and cells for which no urgency is required.

b) Have documentation showing the links that will be maintained with third parties (medical and non-medical institutions) with which the establishment will collaborate. Third party agreements will specify the terms of the relationship as well as the protocols to be followed;

c) Have staff with adequate training and suitable facilities to carry out the activities for which accreditation is sought, in accordance with the standards laid down in this Directive;

d) Have a quality assurance programme relating to the activities for which accreditation is sought, in accordance with the standards laid down in this Directive;

e) Ensure, in accordance with scientific knowledge, that the risks inherent in the use and handling of biological material are minimised;

f) Have access to a serum bank that maintains at least one sample from each allogeneic donor for a minimum period of 2 years from the distribution of the last anatomical piece of the donor, so that required tests can be performed after grafting;

g) Have a register with access restricted to persons authorised by the responsible person in order to ensure adequate traceability of the cells / tissues received and distributed. These records should contain information on all donors, anatomical pieces, and tissues and cells with the data required for their identification. The register must meet the confidentiality requirements laid down in the Directive; and

h) Work according to Standard Operation Procedures, which shall conform to the standards laid down in this Directive.

ANNEX II

QUALITY MANAGEMENT SYSTEM

1. The basic elements of a quality system are:

a) A well-defined quality policy;

b) A clearly-defined organisational structure and accountability;

c) Clearly-defined and effective documentation;

d) Standard Operating Procedures (SOPs);

e) Correct maintenance of all registers; and

f) Process validation by the personnel directly involved.

2. The main functions of a quality system include but are not limited to:

a) Ensuring that all processes are correct, verified and documented;

b) Ensuring the appropriate analysis and the communication of results to the competent authorities in those cases where: the integrity and function of a human cellular or tissue-based product could be affected, the product could possibly be contaminated, or the product could potentially transmit a communicable disease;

c) Ensuring that, if needed, appropriate corrective actions are taken and registered;

d) Ensuring that the proper training and education are provided to the staff for each of the activities in which they are involved;

e) Establishing and maintaining an appropriate monitoring system;

f) Establishing and maintaining a records system;

g) Investigating and documenting product deviations and the corrective actions taken; and

h) Conducting evaluations, investigations, audits, and other actions necessary to ensure the quality of tissues / cells, products and processes.

3. The basic and on-going training for staff in charge of tissue / cell procurement and staff of the tissue establishments shall be:

a) Carried out within two months of their joining the tissue establishment and after intervals no longer than two years;

b) Carried out when a new activity or a new technology is introduced; and

c) Controlled, reviewed and updated periodically, but at least every two years, and be adequate to their needs.

4. The on going training shall cover at least the following subjects:

4.1. General topics:

a) General review of the procedures for obtaining and / or processing human cells and tissues for transplant purposes;

b) Legal aspects;

c) Ethical aspects;

d) Organisational aspects;

e) Quality control programmes;

f) Quality and safety criteria for the evaluation, procurement, processing and monitoring of cells and tissues for transplantation; and

g) Safety at work.

4.2. Specific topics:

a) Technical knowledge and specific protocols for each of the tissue establishment's activities;

b) Management of registers and data analysis programmes;

c) Handling of the equipment used for each activity;

d) Knowledge of the quality control guidelines and general operation of the health care establishment;

e) Knowledge of the personal safety guidelines; and

f) Bio-monitoring systems operating at the health care establishment.

ANNEX III

INFORMATION TO BE PROVIDED ON THE DONATION OF CELLS AND/OR TISSUES

A. AUTOLOGOUS (AU) AND ALLOGENEIC (AL) LIVING DONORS

1. The person in charge of the donation process shall ensure that the donor has been properly informed of at least those aspects relating to the donation and procurement process outlined in paragraph 4.

2. The information must be given in an appropriate and clear manner, using terms that are easily understood by the donor.

3. The person providing the information must be required and able to answer any questions asked by the donor.

4. The information must cover: the purpose and nature of the procurement, its consequences and risks; analytical tests, if they are performed; recording and protection of donor data, medical confidentiality; and therapeutic purpose.

5. For the allogeneic living donor (AL), information must be provided to the donor on the evaluation procedure: i.e. the reasons for requiring the donor's medical and personal history, a physical examination, and analytical tests.

6. Information must be given to donors on the applicable safeguards that are intended to protect them.

7. The donor should be informed that he has the right to receive the confirmed results of the analytical tests clearly explained. He shall be free to exercise this right or not.

8. Information must be given on the necessity for requiring the applicable mandatory consent, certification, and authorisation in order that the tissue and / or cell procurement can be carried out.

B. DECEASED DONOR

1. All information must be given to the donor's relatives and all necessary consents and authorisations must be obtained prior to the procurement of cells / tissues in accordance with the applicable legislation.

2. The confirmed results of the donor's evaluation must be communicated, and clearly explained, to the donor's relatives when these results have relevance for their health or for public health in accordance with the legislation in Member States.

ANNEX IV

SELECTION CRITERIA FOR THE DONOR OF TISSUES AND/OR CELLS

1. DECEASED DONOR

A. GENERAL CRITERIA FOR EXCLUSION

Deceased donors shall be excluded from donation if any of the following conditions are met:

1. Cause of death unknown.

2. Ingestion of, or exposure to, a toxic substance that may be transmitted in a toxic dose to the tissue recipients.

3. Presence or previous history of malignant disease, except for primary basal cell carcinoma, carcinoma in situ of the uterine cervix, and some primary tumours of the central nervous system that have to be evaluated according to the current consensus document of the Council of Europe 'Standardisation of organ donor screening to prevent transmission of neoplasic diseases'. Donors with malignant diseases could be evaluated and considered for cornea donation, except for those with retinoblastoma, melanoma of the anterior pole, haematological neoplasm, and malignant tumours that could affect the anterior pole of the eye.

4. Risk of transmission of diseases caused by prions. This includes:

- specific selection criteria for people diagnosed with Creutzfeldt-Jakob Disease or having family history of non-iatrogenic Creutzfeldt-Jakob Disease;

- people with a history of rapid progressive dementia or degenerative neurological diseases of unknown origin;

- recipients of hormones derived from the human pituitary gland (e.g. growth hormones) and recipients of dura mater.

5. Infection which is not controlled at the time of the donation, including bacterial diseases, systemic viral and fungal infections.

6. History, clinical evidence, or confirmed positive laboratory tests of HIV infection, acute or chronic hepatitis B or hepatitis C infection. (For haematopoietic progenitor cells donors, Annex V about the donors with positive tests for HBV and HCH shall be applied).

7. People with a history of chronic haemodialysis.

8. Haemodilution of donor samples:

With potential donors who have received blood, blood components, colloids within the 48 hours preceding death, or crystalloids within the 1 hour preceding death, a sample of blood taken before the transfusion will have to be available if calculations using the algorithm set out below indicate a haemodilution of over 50%. If a sample is not available, the donor must be excluded owing to the effect of the haemodilution on the results of the serology tests.

9. Evidence of any other risk factors.

B. SPECIFIC EXCLUSION CRITERIA FOR CHILD DONORS

1. Any child who may present with any of criteria listed in part A will be excluded as a donor.

2. Any children born from mothers with HIV infection or that meet any of the exclusion criteria described in part A must be excluded as donors until the risk of transmission of infection can be definitely ruled out.

a) Children aged less than 18 months born from mothers with HIV, hepatitis B or hepatitis C infection or at risk of such infection, or who have been breastfed by their mothers during the previous 12 months, cannot be considered as donors regardless of the results of the analytical tests;

b) Children who have not been breastfed by their mothers during the previous 12 months, and for whom analytical tests, physical examinations, and reviews of medical records do not provide evidence of HIV, hepatitis B or hepatitis C infection, can be accepted as donors.

C. EXTERNAL PHYSICAL INSPECTION

A physical examination of the body shall be performed to detect any signs that may be sufficient in themselves to exclude the donor, or which may be assessed in the light of the donor's medical and personal history. Attention should be given to the following: tumours (e.g. melanoma), infections (e.g. genital ulcers, anal condylomas), risk factors for transmissible diseases (e.g. vessel puncture, tattoos, piercing), traumas to the donor's body, and scars from recent or old operations.

D. SPECIFIC SELECTION CRITERIA

Specific selection criteria for tissues from deceased donors shall be taken into account case by case on the basis of current scientific knowledge.

2. LIVING DONOR

2.1. AUTOLOGOUS LIVING DONOR

1. The medical doctor responsible for the patient-donor must determine, based on the patient's medical history and therapeutic indications, and document the viability of the transplant.

2. If the removed cells or tissues are stored or cultured, the same serology tests must be carried out as for an allogeneic living donor. Positive results will not rule out the person undergoing the treatment.

2.2 ALLOGENEIC LIVING DONOR

1. The selection criteria for the allogeneic living donor shall be established and documented by the responsible physician based on the donor's physical status, clinical and personal record, the results of clinical analyses, and other laboratory tests establishing the donor's health.

2. The same exclusion criteria as for deceased donors have to be followed, but others may need to be added: e.g. pregnancy (except for donors of haematopoietic progenitors cells and amniotic membrane) and breastfeeding. The specific exclusion criteria for each tissue/cells shall also need to be taken into account.

ANNEX V

LABORATORY TESTS REQUIRED FOR DONORS OF TISUES AND CELLS

1. Serology tests required for donors

Infection // Tissues and cells: recommendation in case of positive result

HIV 1 and 2 // Contraindication to donation

Hepatitis B // HBs Ag positive is a contraindication to donation.

Anti HBc positive requires complementary tests

Hepatitis C // Contraindication to donation

Treponema pallidum // Requires tests to detect specific antibodies for T. pallidum. A positive result contraindicates donation.

HTLV-I and II in donors living or coming from high incidence areas, or their sexual partners or children. // Contraindication to donation

2. General requirements to be met when determining serological markers

1. The tests should be carried out by a qualified laboratory, authorised by the competent authority or authorities in the Member State.

2. The serological tests will be carried out on the donor's serum or plasma; they should not be performed on other fluids or secretions such as the aqueous or vitreous humour.

3. The type of test used shall be in agreement with the scientific knowledge.

4. All blood samples should be obtained immediately prior or after the tissue procurement in case of a deceased donor.

5. In the case of living donors (except allogeneic bone marrow and peripheral blood cells donors, for practical reasons), blood samples should be obtained at the time of donation, with an admitted margin of +/- 7 days and in the case of allogeneic donors a repeat sample after 6 months.

6. In case of an allogeneic haematopoietic progenitor cell transplantation, blood samples shall be tested within 30 days prior to donation.

7. If in a living donor (except allogeneic haematopoietic progenitor cell donors) the blood sample is drawn 6 days after procurement and tested by nucleic acid amplification technique (NAT), a repeat blood sample is not necessary for HIV, HBV and HCV.

ANNEX VI

CELL AND/OR TISSUE PROCUREMENT PROCEDURES, AND RECEPTION AT THE TISSUE ESTABLISHMENT

A. VERIFICATION PROCEDURE

Consent

Before the procurement of tissues or cells, the person responsible from the procurement team shall confirm that the consent for the procurement has been obtained according with the legislation in place on the Member State.

Donor identification

a) Donor and donation data shall be registered and maintained in a manner that ensures correct donor identification and traceability of each individual tissue and cell.

b) The data registration system has to be validated to ensure that the recorded information ensures correct identification and traceability.

B. FACILITIES AND PROCEDURES FOR THE PROCUREMENT OF TISSUES AND CELLS

Donations shall be retrieved in appropriate facilities that minimise bacterial contamination of procured tissues or cells. For living donors, the procurement environment must also ensure their health and safety.

C. PROCUREMENT PROCEDURES FOR TISSUES AND CELLS

The procurement procedures shall be appropriate for the type of donor and the type of tissue/cells donated. They should also protect those properties of the tissue/cells that are required for their ultimate clinical use, and at the same time avoid microbiological contamination during the process. In the case of deceased donations, the time interval from death to procurement shall be specified so as to ensure the protection of the required biological properties.

D. DONOR DOCUMENTATION

1. For each donor, there should be a dossier that contains: donor identification, the consent form, clinical data, laboratory test results, and results of other tests carried out. Data related with the procurement process shall also be registered.

2. In case an autopsy was carried out, the results shall be included in the dossier.

3. All the records must be legible and permanent and shall be in compliance with data protection legislation.

4. Donor clinical records shall be maintained for at least 30 years in the registry of the procurement establishment.

5. The date and time of procurement (start and end) must be recorded.

E. DATA TO BE REGISTERED

The data that must be registered in the tissue establishment includes:

a) Consent;

b) Donor identification and characteristics: type of donor, age, sex, cause of death, and presence of risk factors;

c) Review of clinical data against donor selection criteria;

d) Results of physical examination, of laboratory tests and of other tests (autopsy report when one was conducted);

e) Date and time of the death/perfusion;

f) Date and time of the procurement, and health care establishment where the procurement is carried out;

g) Conditions under which the cadaver is kept: refrigerated (or not), time of start of refrigeration and time of transfer to procurement site;

h) Place of procurement, procurement team, and person in charge of procurement;

i) Degree of asepsis;

j) Details about the preservation solutions used during procurement, including composition, lot, date of expiry, temperature, amount, concentration and preparation method;

k) Grafts obtained and relevant characteristics;

l) Relevant incidents that have occurred before, during, and after procurement;

m) Destination of the cells/tissues procured;

n) Method of preservation until arrival of tissues/cells at the establishment ;

o) In the case of cellular cultures, it is necessary also to document:

- Characteristics of the lesion to be treated;

- Medicinal allergies (e.g. antibiotics) of the recipient.

F. PACKAGING

1. Following procurement, all donations shall be packed individually in a manner that minimises the risk of contamination and preserves the required characteristics and biological function of the cells/tissues.

2. The packaged cells/tissues shall be shipped in a rigid container suitable for transport, which maintains the integrity of the contents and the specified temperature.

3. Any accompanying tissue or blood samples for testing shall be correctly labelled and identified.

G. Labelling of the retrieved tissue /cells

Every package containing tissues or cells must be labelled at least with:

a) Donor identification number or code; and

b) Type of tissue/cells.

H. Labelling of the shipping container

When tissues/cells are shipped, every shipping container must be labelled at least with:

a) Identification of the tissue/cells;

b) Identification of the procurement establishment (address and phone number) and the person in charge of the delivery;

c) Identification of the tissue establishment of destination (address and phone number) and the person in charge of the reception at the destination;

d) Date and time of harvesting;

e) In the cases of haematopoietic progenitors, the following shall be added: DO NOT IRRADIATE; and

f) In the case of 'autologous' donors, the following shall be added: 'for autologous use only'.

I. Reconstruction of cadaver

Once the tissues have been retrieved, the deceased donor body should be reconstructed so that it is as similar as possible to its original anatomical shape. Reconstruction methods should minimise any impact on normal funeral procedures.

J. Receipt of the tissue/cells at the processing/storage establishment

When the retrieved tissues/cells arrive at the processing/storage establishment, there shall be a documented verification that the consignment, including, transport conditions, packaging, labelling and associated documentation and samples, meet the requirements of this Annex and the specifications of the receiving establishment . Each establishment shall have a documented procedure for handling non-conforming consignments of tissues/cells.

Annex VII

CELL AND TISSUE PROCESSING, STORAGE, AND DISTRIBUTION

A. PROCESSING

1. Every tissue and cell processing facility must have an adequate system of process control.

2. When technical procedures cannot be verified at any particular time throughout the process, they must be continuously monitored to ensure that the established Standard Operating Procedures are met.

3. Where a microbial inactivation procedure is applied to the tissue or cells, it must be specified, documented, and validated.

4. Where any processing step is carried out by a third party, an agreement must be documented to demonstrate the required performance specification and validation.

5. The processes should undergo regular critical evaluation to ensure that they continue to achieve the intended results.

6. Before new processes are implemented, they must be validated to demonstrate that they will consistently result in tissues that comply with the SOPs of the tissue establishment . Where any significant change in processing occurs, involving new or modified equipment, major overhauls or change of location, these validation steps must be repeated and documented.

7. Environments in which tissues are processed must be adequately controlled to minimise or avoid the potential for tissue contamination. Where tissues or cells are exposed to the environment during processing, without a subsequent microbial inactivation process, an air quality of Grade A (< 3,500 particles per m3 of minimum 0.5 ìm) is required, usually by using a laminar air flow (LAF) cabinet. The background environment must guarantee an air quality of grade B in accordance with the GMP guideline. .

B. STORAGE

1. Storage conditions, including relevant parameters such as temperature, must be defined to maintain the required tissue and cell properties.

2. Critical parameters (e.g. temperature, humidity, sterility) must be controlled, monitored, and recorded continuously to demonstrate compliance with the specified conditions.

3. Maximum storage time must be specified for each type of storage condition. If the maximum storage time has been reached, the cells and tissues have not yet been used up and it can be guaranteed through validated tests that the cells and tissues are still capable of functioning, the storage time may be extended.

4. The selected period must reflect possible deterioration of the required tissue and cell properties, changing donor selection and testing criteria over time and the availability of alternative treatments.

C. DISTRIBUTION

1. Transport conditions, including relevant parameters such as temperature, must be defined to maintain the required tissue and cell properties.

2. Packaging must ensure that the tissue is maintained in the condition established in the Standard Operating Procedures. If the packaging has not received market validation for this purpose, then critical parameters, such as temperature and humidity must be continuously controlled during the delivery process.

3. Where distribution is carried out by a contracted third party, a documented agreement must be in place to ensure that the required conditions are maintained.

4. A documented system must in place for the recall of tissue or cells in the event that a potential risk to the recipient(s) is identified following distribution.

D. FINAL LABELLING FOR DISTRIBUTION

1. Every unit of tissue / cells distributed has to be accompanied by a label with at least the following information:

a) Identification number or code of the tissue /cells;

b) Characteristics of the tissue or cell;

c) Identification of the tissue establishment ;

d) Lot number.

2. The following information shall be provided either on the label or in accompanying documentation:

a) Morphology and functional data;

b) Date of distribution of the tissue /cell;

c) Serological determinations carried out on the donor and results;

d) Storage recommendations;

e) Instructions for opening the container, package, and any required manipulation;

f) Expiry date after opening/manipulation; and

g) Instructions on reporting serious adverse reactions and /or events.

E. EXTERNAL LABELLING OF THE SHIPPING CONTAINER

Every container shall be labelled with at least the following information:

a) Identification of the originating tissue establishment ;

b) Identification of the health care establishment of destination;

c) A statement that the package contains human tissue/cells;

d) In the case of haematopoietic progenitors, the following shall be added: 'DO NOT IRRADIATE';

e) Recommended transport conditions (e.g. keep cool, in upright position, etc.); and

f) Safety instructions / method of cooling (when applicable) [for instance: liquid N2 poses a hazard for transport, manipulation of dry ice with bare hands also, etc.]

LEGISLATIVE FINANCIAL STATEMENT

Policy area(s): Health and Consumer Protection.

Activit(y/ies): Public Health. Quality and safety on the use of substances of human origin

Title of action: proposal for a directive of the european parliament and of the council setting high standards of quality and safety for the donation, procurement, testing, processing, storage, and distribution of human tissues and cells

1. BUDGET LINE(S) + HEADING(S)

B3-4308, B3-4308A (partially; amounts already included in the financial statement of the Public Health Programme)

2. OVERALL FIGURES

2.1. Total allocation for action (Part B): 12 EUR million for commitment

2.2. Period of application:

(2003-2008)

2.3. Overall multiannual estimate of expenditure:

The figures shown are indicative. The actual amounts will be set in the annual budgetary procedures.

a) Schedule of commitment appropriations/payment appropriations (financial intervention) (see point 6.1.1)

EUR million (to three decimal places)

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(b) Technical and administrative assistance and support expenditure (see point 6.1.2)

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(c) Overall financial impact of human resources and other administrative expenditure (see points 7.2 and 7.3)

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(1) All the expenses will be taken on the financial budget of the new public health programme

2.4. Compatibility with financial programming and financial perspective

[X] Proposal is compatible with existing financial programming.

Proposal will entail reprogramming of the relevant heading in the financial perspective.

Proposal may require application of the provisions of the Interinstitutional Agreement.

2.5. Financial impact on revenue: [13]

[13] For further information, see separate explanatory note.

[X] Proposal has no financial implications (involves technical aspects regarding implementation of a measure)

3. BUDGET CHARACTERISTICS

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4. LEGAL BASIS

Article 152 of the Treaty establishing the European Community

5. DESCRIPTION AND GROUNDS

5.1. Need for Community intervention [14]

[14] For further information, see separate explanatory note.

5.1.1. Objectives pursued

The objective is to permit the funding of activities aiming at implementing certain provisions of this Directive, once adopted.

- Standards and specifications to be included in the Quality System for Tissue Establishments and Health Care Establishments where the procurement of human tissues and cells is carried out ;

- Preparation of a notification system for adverse reactions and events;

- Preparation of a traceability System for Tissues and cells;

- Adaptation of the Annexes to technical progress

5.1.2. Measures taken in connection with ex ante evaluation

No applicable

5.2. Action envisaged and budget intervention arrangements

- General objectives: links with the overall aim

The overall aim of the Directive is to make a contribution towards the attainment of a high level of health protection by directing action towards improving public health, preventing human illness and diseases, and obviating sources of danger to health.

- Specific and quantifiable objectives

Complete and implement the framework on high standards of quality and safety for the donation, procurement, processing, storage and distribution and use of human tissues and cells;

Develop and operate a tissues and cells traceability system.

- Target population:

The general population and target population sub-groups are the ultimate beneficiaries of the actions being undertaken.

The direct beneficiaries of the Community's financial contribution are governmental or quasi-governmental agencies and institutes competent in the area of tissues and cells, associations of health professionals and learned institutions, and representative NGOs active in the field of health information, prevention of diseases and health promotion.

5.3. Methods of implementation

Not applicable. Implementation under the responsibility of the Member States.

6. FINANCIAL IMPACT

Service contracts following the call for tenders procedures and grants for joint financing of studies and reports with other sources in the public and/or private sector. As regards grants, the level of financial assistance by the Commission may not exceed, as a general rule, the 70% of the expenditure actually incurred by the recipient

6.1. Total financial impact on Part B - (over the entire programming period)

6.1.1. Financial intervention

Commitments (in EUR million to three decimal places)

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6.2. Calculation of costs by measure envisaged in Part B (over the entire programming period) [15]

[15] For further information, see separate explanatory note.

A Detailed calculation will be defined in the framework of the new programme for community action on the field of public health.

7. IMPACT ON STAFF AND ADMINISTRATIVE EXPENDITURE

7.1. Impact on human resources

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7.2. Overall financial impact of human resources

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The amounts are total expenditure for twelve months.

7.3. Other administrative expenditure deriving from the action

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The amounts are total expenditure for twelve months.

1 Specify the type of committee and the group to which it belongs.

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The need for human and administrative resources will be covered within the allocation granted to the managing DG in the framework of the annual allocation procedures.

8. FOLLOW-UP AND EVALUATION

8.1. Follow-up arrangements

This Directive is under the objectives of the new programme of community action in the field of public health. The Strand two of this programme ' responding rapidly to health threats' states as objectives 'enhance the safety and quality of organs and substances of human origin including blood' and the 'implementation vigilance networks and human products'.

Performance indicators selected

*output indicators (measurement of resources employed and efficiency)

The programme provides for annual work plans which will determine quantifiable deliverables, and on-going monitoring of actions will be undertaken. Relevant indicators will include reports and analyses undertaken, development of guidelines and establishment of effective networks, together with up-take and multiplier effects in Member States by competent authorities and local groups and associations.

*impact indicators (measurement of performance against objectives)

The impact and performance of the programme, including effectiveness against objectives of the actions, will be subject to detailed evaluation arrangement, using direct, i.e. health-related indicators and indirect measurements (e.g. setting up and proper operation of mechanisms and procedures for health monitoring and rapid response).

Specific indicators will be included in the contractual framework to be developed for outsourcing arrangements.

To facilitate the evaluation process, measurable quantitative and qualitative benchmarks are being identified for the three strands of the programme. These will be finalised before the programme comes into effect so that they are available for the development of the annual work plans and the establishment of the monitoring process, the assessments and the evaluations foreseen in Article 12.1 and 12.3 of the Common Position.

In addition these benchmarks will be used in relation to the submission of information by the Member States to the Commission on the implementation and impact of the programme (see Art 12.2 of the Common Position).

8.2. Arrangements and schedule for the planned evaluation

The Commission will have an external assessment of the implementation and achievements during the four first years of the programme. It will also assess the impact achieved on health and the efficiency of the use of resources, as well as consistency and complementarity with other Community programmes and initiatives. The Commission will communicate these conclusions with its comments, to the European Parliament, the Council, the Economic and Social Committee and the Committee of the Regions. The Commission will also submit to them a final report on the implementation of the programme. The evaluation reports will be made publicly available.

9. ANTI-FRAUD MEASURES

All proposals for subsidies will be assessed for technical content and financial criteria which include adequacy of own resources, sound finances and financial management, past record of performance or reliability as regards the capability of fulfilling the terms of subsidy, relationship between partners in a given project and potential for effective accounting and control. These also apply in cases of service contracts. Specific rules governing the characteristics and monitoring of outsourcing contracts will be implemented, following the Commission guide and model contract.

Requests for final payment must be accompanied by an evaluation of the operational and financial status of the project concerned.

All measures will take account of Article 3(4) of the financial regulation, as well as SANCO international audit recommendations, in conformity with the International Control Standards of the Commission, including the UCLAF 'Guide to testing for vulnerability to fraud' of 18.4.1997.

- Specific control measures envisaged

Checks in situ will be carried out using appropriate selection criteria (scale of subsidy, interim report, results of on-going monitoring, information on progress with the execution of the relevant work-plan). In cases of service contracts, the Commission will regularly monitor that the contractors comply with the rules laid down in the contracts. In cases where there are reasons to believe that the performance of a project that has received a subsidy, or that of a service contract, is seriously being compromised, an urgent check will be carried out and, if there are remaining suspicions, the service concerned will refer the matter to the relevant audit services and the Anti-Fraud Office.

IMPACT ASSESSMENT FORM

THE IMPACT OF THE PROPOSAL ON BUSINESS WITH SPECIAL REFERENCE TO SMALL AND MEDIUM-SIZED ENTERPRISES (SMEs)

Title of proposal

Proposal for a Directive of the European Parliament and of the Council setting standards of quality and safety for the donation, procurement, testing, processing, storage, and distribution of human tissues and cells.

Document reference number

No 2000/191

The proposal

Taking account of the principle of subsidiarity, why is Community legislation necessary in this area and what are its main aims?

The aims of this proposal are to:

- close existing gaps in Community legislation with regard to the setting of standards for the quality and safety of human tissues and cells used for the application in the human body;

- strengthen requirements related to the suitability of tissues and cells donors and the screening of donated tissues and cells in the European Community;

- establish at Member State level requirements for establishments involved in the donation, procurement, testing, processing, storage and distribution of human tissues and cells, as well as national accreditation and monitoring structures;

- lay down provisions at Community level for the formulation of a quality system for tissue establishments(QSTB);

- lay down common provisions at Community level for the training of staff directly involved in the donation, procurement, testing, processing, storage and distribution of human tissues and cells, without prejudice to existing legislation;

- establish rules for ensuring the traceability of human tissues and cells from donor to recipient, which are valid throughout the Community.

The impact on business

Who will be affected by the Proposal?

This proposal will have an impact on the activities carried out within the framework of the human and tissues transplantation process, particularly those extending from prospective tissues and cells donors to the distribution of the tissues and cells for therapeutic use. The tissue and cell establishments directly concerned by the provision of this proposal vary from tissue establishments, to health centres where procurement is carried out, to third parties which can be responsible for some step of the process. The proposal will have indirect implications on the tissue engineering products industry.

What will business have to do to comply with the Proposal?

In most Member States, responsibility for the provision of tissues and cells transplantation services is overseen by a national authority. This proposal will not add any further administrative constraints on these institutions and, in certain cases, will lead to their simplification. For those that will have to set up such a national system, an administrative burden will be imposed on tissue establishments.

The requirements of this Directive may increase the cost for starting materials used by business.

What economic effects is the Proposal likely to have?

In establishing a notification system for tissue establishments as well as an inspection and control system, this proposal may introduce an administrative burden on those establishments in the Member States where such systems are not already in place. On the other hand, common high standards for the quality and safety of human tissues and cells that are set up under this proposal may help to reduce costs associated with adverse events and effects related to transplantation, facilitate the circulation of human tissues and cells across the borders, and encourage advancement of the goal of Community self-sufficiency, and lead to positive economic effects.

Does the Proposal contain measures to take account of the specific situation of small and medium-sized firms (reduced or different requirements etc.)?

No specific provision is envisaged for small and medium sized firms in this proposal.

Consultation

List the organisations which have been consulted about the proposal and outline their main views.

Organisations invited to Stakeholders meeting.

European Association of Tissue Banks (EATB)

European Eye Bank Association (EEBA)

European Association of Musculoeskeletal Transplantation

British Association of Tissue Banks (BATB)

Spanish Association of Tissue Banks (AEBT)

Spanish Registry of Bone Marrow (REDMO)

European Group for Bone Marrow Transplantation (EBMT)

World Bone Marrow Association (WBMA)

Europdonor Foundation

International association of patients associations (IAPO)

EUCOMED medical technology

European Federation of Pharmaceutical Industry Associations (EFPIA)

BAXTER Bioscience