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
Date: 2002-06-19
Institutions: European Commission
Subjects: EU law, cytology, export, health care, health control, import, management, organ transplantation, product quality, product safety, public health, therapeutics

24.9.2002

EN

Official Journal of the European Communities

C 227 E/505

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

(2002/C 227 E/28)

COM(2002) 319 final — 2002/0128(COD)

(Submitted by the Commission on 19 June 2002)

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,

Having regard to the opinion of the Economic and Social
Committee,

Having regard to the opinion of the Committee of the Regions,

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

Whereas:

(1) The extensive therapeutic use of human tissues and cells
for application in the human body demands that their
quality and safety be ensured 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, processing, storage, distribution and use.

therefore, that whatever their intended use, Community
provisions should ensure that tissues and cells of human
origin are of comparable quality and safety. The estab-
lishment of
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.

such standards,

(4) It is necessary to regulate the donation, procurement, and
testing of all sources of human tissues and cells intended
for application in the human body. The processing, pres-
ervation, storage and distribution of all human tissues and
cells used for transplantation purposes should also be
regulated. However, cells for autologous use should be
excluded from the scope if they are to be used for the
manufacturing of medicinal products. Tissues
and
allogeneic cells intended to be used for industrially manu-
including medical devices, should be
factured products,
covered only as
far as donation, procurement and
testing are concerned. The further manufacturing steps
are covered by the relevant legislation (1).

(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/EC (1), Directive 2000/70/EC (2) and Council
Recommendation 98/463/EC (3), and a new directive
based on public health principles
is currently under
discussion in Council and the European Parliament (4).
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.

(1) Directive 2001/83/EC of

(2) Directive 2000/70/EC of

the European Parliament and of

the
Council of 6 November 2001 on the Community code relating to
medicinal products for human use (OJ L 311, 28.11.2001, p. 67).
the
Council of 16 November 2000 amending Council Directive
stable
93/42/EEC as
derivates of human blood or human plasma (OJ L 313, 13.12.2000,
p. 22).

the European Parliament and of

regards medical devices

incorporating

(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,
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,

testing, processing,

(3) 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 L 203, 21.7.1998, p. 14).

(4) Proposal for a Directive 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 89/381/EEC.
COM(2000) 816 final — 2000/0323(COD).

C 227 E/506

EN

Official Journal of the European Communities

24.9.2002

(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
trials are applied to the human body should
clinical
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 use or non-use of any
specific type of human cells,
including germ cells and
embryonic stem cells. 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 funda-
mental rights. Moreover, this Directive does not interfere
with provisions of Member States defining the legal term
‘person’ or ‘individual’.

(8) The donation, procurement, processing, preservation,
storage and distribution of human tissues and cells for
transplantation 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 transplantation process.

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

in the health protection of

the Charter of Fundamental Rights of

(13) The procurement of human tissues and cells must fully
respect
the
European Union (1), and take fully into account the prin-
and
ciples of
Biomedicine of the Council of Europe (2),
in particular
in relation to donor consent.

the Convention on Human Rights

(14) 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.

(15) Directive 95/46/EC of the European Parliament and of the
Council of 24 October 1995 on the protection of indi-
viduals with regard to the processing of personal data and
the free movement of such data (3), applies to personal
data processed in application of
the present directive.
this Directive prohibits in principle the
Article 8 of
processing of data concerning health. Limited exemptions
foreseen. Directive
to this prohibition principle are
controller must
95/46/EC provides
implement
and organisational
measures to protect personal data against accidental or
unlawful destruction or accidental loss, alteration, unauth-
orised disclosure or access and against all other unlawful
forms of processing.

appropriate

also that

technical

the

(16) An accreditation system for tissue banks 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.

(10) 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.

(17) Member States should organise inspection and control
measures, to be carried out by officials representing the
competent authority, to ensure compliance of the tissue
establishments with the provisions of this Directive.

(11) 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.

(18) Personnel directly involved in the donation, procurement,
testing, processing, preservation, storage and distribution
of tissues and cells of human origin should be appro-
priately 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.

(12) As a matter of principle, tissue and cell transplantation
programmes should be founded on the philosophy of
voluntary and unpaid donation, anonymity of both
donor and recipient, benevolence of
the donor and
encouragement of the absence of profit by establishments
involved in tissue and cell transplantation services.

(1) OJ C 364, 18.12.2000, p. 1.
(2) Council of Europe. Convention for the protection of human rights
and dignity of the human being with regard to the application of
biology
and
biomedicine. European Treaty
Series — No 164. Oviedo,
4.4.1997, p. 11.

and medicine: Convention on human rights

(3) OJ L 281, 23.11.1995, p. 31.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/507

(19) An adequate system to ensure the traceability of tissues
and cells of human origin should be established; tracea-
bility should be enforced through accurate substance,
donor, recipient, tissue bank, and laboratory identification
procedures as well as record maintenance and an appro-
priate labelling system.

(20) 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.

(21) 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.

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

in particular in order to assist

(23) 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
international
been taken into account
experience in this field, and will be sought in the future
whenever necessary.

as well

as

(24) 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 (1),
they should be adopted by use of
the Regulatory
Procedure provided for in Article 5 of that Decision,

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 used for application to the human

body, in order to ensure a high level of protection of human
health

Article 2

Scope

The provisions of

1.
this Directive shall apply to the
donation, procurement, and testing of human tissues and
cells for application to the human body. The provisions of
this Directive shall also apply to the processing, preservation,
storage and distribution of human tissues and cells when they
are to be used for human transplantation.

In the case of industrially manufactured products derived from
tissues and cells,
this Directive applies 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;

(b) autologous cells to be used for the manufacturing of

medicinal products;

(c) blood and blood components as defined by [Directive of
the European Parliament and of
setting
standards of quality and safety for the collection, testing,
processing, storage, and distribution of human blood and
blood components
and amending Council Directive
89/381/EEC];

the Council

(d) organs.

Article 3

Definitions

For the purposes of this Directive:

(a)

‘Cells’: shall mean individual cells or a collection of cells
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
structure, vascularisation, and capacity to develop
its
level of
functions with an important
physiological
autonomy.

(1) OJ L 184, 17.7.1999, p. 23.

(e)

‘Procurement’: shall mean a process by which the donated
tissue or cells become available.

C 227 E/508

EN

Official Journal of the European Communities

24.9.2002

(f)

‘Processing’: shall mean all operations involved in the prep-
aration, manipulation, preservation and packaging of
tissues or cells for transplantation.

Article 4

Implementation

(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 use in recipients.

(j)

‘Transplantation’: shall mean the process of reconstituting a
function by transferring equivalent cells and/or tissues to a
recipient.

(k) ‘Serious

event’:

adverse

shall mean any

associated with the procurement,

untoward
testing,
occurrence
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 incapaci-
tating conditions for patients or which results in, or
prolongs, hospitalisation or morbidity.

(l)

reaction’:

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

fatal,

is

(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 a tissue bank or health
care establishment that hosts a tissue procurement team.

(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 transplanted

from one person to another.

(q) ‘Autologous use’: shall mean cells or tissues removed from

and transplanted back to the same person.

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

This Directive shall not prevent a Member State from
protective

2.
maintaining
introducing more
measures that comply with the provisions of the Treaty.

stringent

or

3.
In carrying out the activities covered by this Directive, the
Commission may have recourse to technical and/or adminis-
trative assistance to the mutual benefit of the Commission and
of
relating to identification, preparation,
management, monitoring, audit and control, as well as to
support expenditure.

the beneficiaries,

CHAPTER II

OBLIGATIONS ON MEMBER STATES AUTHORITIES

Article 5

Supervision of tissue procurement

1. Member States shall take all necessary measures to ensure
that tissue procurement teams are either part of a tissue bank
or a health care establishment duly accredited and inspected.

2. Member States shall take all necessary measures to ensure
that tissue procurement teams are notified to the competent
including the staff
the procurement,
authority and that
involved, complies with the requirements listed in Part A of
Annex I.

Article 6

Accreditation of tissue banks

1. Member States shall ensure that all activities relating to
storage, and distribution of
the processing, preservation,
human tissues and cells
for human transplantation are
undertaken only by tissue banks that have been accredited by
a competent authority for that purpose.

2.
Haematopoietic progenitor cells from peripheral blood,
umbilical cord and bone marrow, however, may be distributed
the
directly from the health care
procurement is carried out, which could not be accredited as
a tissue bank, to a health care establishment for immediate
transplantation.

establishment where

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

24.9.2002

EN

Official Journal of the European Communities

C 227 E/509

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

(c) examine any documents relating to the subject of

the

inspection.

The competent authority may suspend or revoke the
inspection or
control
it does not comply with the

5.
accreditation of a tissue bank if
measures demonstrate that
requirements of this Directive.

Article 7

Register of accredited tissue banks and reporting obli-
gations

The competent authority shall establish and maintain a
specifying the

1.
publicly accessible register of
tissue banks
activities for which they have been accredited.

2.
Tissue banks shall maintain an official record on the
origin and destination of the tissues and cells processed for
application in the human body. An annual report of these
activities shall be submitted to the competent authority.

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

Article 8

Inspection and control measures

1. Member States shall ensure that the competent authority
organises inspections and that tissue banks carry out appro-
priate
the
requirements of this Directive are complied with.

control measures

to ensure

in order

that

2.
The competent authority shall also organise inspections
and ensure that appropriate control measures are in place in
health care establishments where the procurement of human
tissues and cells is carried out, as well as in establishments of
third parties as specified in Article 24.

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

shall, upon the request of another
6. Member States
Member State or the Commission, provide information about
the results of inspections and control measures carried out in
individual tissue banks, healthcare establishment or the facilities
of third parties.

Article 9

Import/export of human tissues and cells

1. Member States shall take all necessary measures to ensure
that all imports of human tissues or cells from third countries
are approved by the competent authority. All tissues and cells
that are exported to third countries shall comply with the
requirements of this Directive.

2.
The import/export of human tissues and cells for trans-
plantation shall be undertaken only through accredited tissue
banks.

The competent authority shall approve imports of human
3.
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

3.
Inspections and control measures shall be organised by
the competent authority on a regular basis. The interval
between two inspections and control measures
shall not
exceed two years.

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.

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

(a)

inspect health care establishments involved in procurement,
accredited tissue banks, as well as the facilities of any third
parties;

The

procedures

2.
the
Community level shall be established by the Commission
according to the procedure referred to in Article 30(2).

traceability

ensuring

for

at

Tissue establishments shall

3.
implement a donor identifi-
cation system and assign a code to each donation and its
products.

(b) evaluate the procedures and the activities carried out by the
health care establishments, tissue banks and the facilities of
third parties;

All tissues and cells must be identified with a label that

4.
contains the information listed in Annexes VI and VII.

C 227 E/510

EN

Official Journal of the European Communities

24.9.2002

Article 11

Article 14

Notification of serious adverse events and reactions

Data protection and confidentiality

The Member States shall ensure that there is a system in
information about
the
related
storage, distribution and

1.
place to report,
serious
adverse
procurement,
testing, processing,
transplantation of tissues and cells.

register, and transmit
reactions
and
events

to

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

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;

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

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

CHAPTER III

DONOR SELECTION AND EVALUATION

Article 12

Principles for tissue and cell donation

1. Member States shall 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

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 receive prior approval by
the competent authority. Advertising the need for, or avail-
ability 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

(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 if the
donor is closely related to the recipient.

Article 15

Selection, evaluation, and procurement

1.
The tissue procurement team shall ensure that the donor
evaluation and selection is carried out according to the
requirements specified in Annex IV.

2.
The tissue procurement team shall ensure that tissues and
cells are procured, packaged and transported to the tissue
banks in accordance with Annex VI.

3.
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
the
requirements listed in point 2.1 of Annex IV.

accordance with

indication,

and

in

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.

The tissue banks shall ensure that

4.
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.

2. Member States shall take all necessary measures to ensure
that the recipients, donors or their families are provided with
the information listed in Annex III.

The

results of

5.
evaluation and testing
procedures shall be documented and any relevant abnormal
findings shall be reported in accordance with Annex III.

the donor

24.9.2002

EN

Official Journal of the European Communities

C 227 E/511

The competent authority shall ensure that all the activities
6.
related to tissue procurement shall be carried out in accordance
with the conditions specified in Annex VI.

(b) he/she shall have at least two years practical experience, in
one or more tissue banks accredited in accordance with
Article 6.

CHAPTER IV

PROVISIONS FOR QUALITY AND SAFETY IN TISSUE
PROCESSING

Article 16

Quality management

1. Member States shall take all necessary measures to ensure
that each tissue establishment sets up and maintains a quality
management system.

The Commission shall establish in accordance with the
2.
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.

Tissue establishments shall take all necessary measures to
for official

this documentation is

available

4.
ensure
that
inspections.

5.
Tissue establishments shall keep donor records for a
minimum of 30 years after the confirmed clinical use of the
last tissue/cell.

Article 17

Responsible person

Tissue banks shall designate a responsible person. This
the following minimum conditions and

fulfil

1.
person shall
qualifications:

The designated person referred to in paragraph 1 shall be

2.
responsible for:

(a) ensuring that every unit of tissues and cells of human
origin has been procured and tested for application in
the human body and processed, stored, and distributed,
when intended for transplantation,
in compliance with
the laws in force in the Member State;

(b) providing information to the competent authority as

required in Article 6;

(c)

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

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

Article 18

Personnel

involved in activities

Personnel directly
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 bank 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.

The tissue bank shall ensure and record the fact that the
2.
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.

The acceptance or rejection of the incoming tissues/cells

3.
shall be documented.

(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;

4.
Tissue banks 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.

C 227 E/512

EN

Official Journal of the European Communities

24.9.2002

Article 20

Article 24

Tissue and cell processing

Relationship of tissue banks with third parties

1.
The tissue bank 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 bank shall ensure that the
equipment used,
the working environment, process design,
validation, and control conditions are in compliance with
Annex VII.

A tissue bank shall establish a written agreement with a

1.
third party in the following circumstances:

(a) where a third party takes responsibility in one phase of
tissue or cell processing on behalf of the tissue bank;

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

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

tissues or cells,

Article 21

Tissue and cell storage conditions

Tissue banks shall ensure that all procedures associated
1.
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.

Tissue banks shall ensure that all storage processes are

2.
carried out under controlled conditions.

3.
Tissue banks 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.

(b) where a third party provides goods and services that affect

tissue or cell quality and safety assurance;

(c) where a tissue bank provide services to another tissue bank;

(d) where a tissue bank distributes tissue or cells processed by

third parties.

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

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

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

Tissue banks shall provide copies of agreements with

5.
third parties when required by the competent authority.

Article 25

Access to human tissues 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 pres-
ervation and storage until all the requirements laid down in the
Standard Operating Procedures have been met.

1. Member States shall ensure that public and private estab-
lishments involved in health care, and establishments auth-
orised 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.

Article 22

Labelling, user information and packaging

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

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

CHAPTER V

EXCHANGE OF INFORMATION, REPORTS, AND PENALTIES

Article 23

Transport and distribution

Article 26

Coding of information

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

1. Member States shall establish a system for the identifi-
cation of human tissues and cells, in order to ensure the tracea-
bility of all human tissues and cells, as indicated in Article 10.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/513

The Commission,

in cooperation with Member States,
2.
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
report on the activities
every three years
undertaken in relation to the provisions of
this Directive,
including an account of the measures taken in relation to
inspection and control.

thereafter,

a

The Commission shall

European
2.
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.

transmit

to the

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
to the Commission by the date
notify those provisions
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 technical

The adaptation of
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).

requirements

set out

Article 30

Regulatory procedure

The Commission shall be assisted by a Committee,
the Member States and

1.
composed of
representatives of
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.

The period referred to in Article 5(6) of Decision

3.
1999/468/EC shall be set at three months.

4.

The Committee shall adopt its rules of procedure.

Article 31

Consultation of scientific committee

The Commission may consult the relevant scientific committee
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 banks 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 Communities.

Article 34

Addressees

This Directive is addressed to the Member States.

C 227 E/514

EN

Official Journal of the European Communities

24.9.2002

A. REQUIREMENTS FOR THE PROCUREMENT OF HUMAN TISSUES OR CELLS

ANNEX I

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 cooperation 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 BANKS

In order to be accredited, tissue banks 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;

(b) Have documentation showing the links that will be maintained with third parties (medical and non-medical
institutions) with which the bank 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.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/515

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 banks 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 bank'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.

C 227 E/516

EN

Official Journal of the European Communities

24.9.2002

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

ANNEX III

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 confirmed results of the analytical tests must be communicated, and clearly explained, to the donor.

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.

SELECTION CRITERIA FOR THE DONOR OF TISSUES AND/OR CELLS

ANNEX IV

A. GENERAL CRITERIA FOR EXCLUSION

1. Deceased donor

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.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/517

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.

2.1. Autologous living donor

2. 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.

C 227 E/518

EN

Official Journal of the European Communities

24.9.2002

ANNEX V

LABORATORY TESTS REQUIRED FOR DONORS

1. Serology tests required for donors

HIV 1 and 2

Hepatitis B

Hepatitis C

Treponema pallidum

Infection

Tissues and cells: recommendation in case of positive result

Contraindication to donation

HBs Ag positive is a contraindication to donation
Anti HBc positive requires complementary tests

Contraindication to donation

Requires
pallidum. A positive result contraindicates donation

specific antibodies

to detect

tests

for T.

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 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 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.

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

ANNEX VI

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 in the Member State.

Donor identification

(a) Donor and donation data shall be registered and maintained in a manner that ensures correct donor identifi-

cation 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.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/519

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 bank 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 bank;

(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.

C 227 E/520

EN

Official Journal of the European Communities

24.9.2002

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 bank 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 verifi-
cation 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 bank. Each bank 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 bank. 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 µm) is required, usually by using a laminar air flow (LAF) cabinet. The background environment must be
suitable to maintain a Grade A in the LAF. Where tissues or cells are exposed to the environment during
processing with a subsequent microbial inactivation process, a Grade C environment (< 350 000 particles per
m3 of minimum 0,5 µm and < 2 000 particles per m3 of 5 µm) is required.

24.9.2002

EN

Official Journal of the European Communities

C 227 E/521

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.

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 be 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 bank;

(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 bank;

(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.].