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)
Date: 2003-05-28
Institutions: European Commission
Subjects: bio-ethics, cytology, drafting of EU law, quality standard, safety standard

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 28.05.2003
COM(2003) 340 final

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

(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

2

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.

the 

legitimacy  of 

Most  of  the  amendments  proposed  by  the  EP  relate  to  the  addition  of  extensive
the
ethical  provisions.  Recognising 
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.

these  requirements, 

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/EC1, with respect to manufactured medicinal products derived from blood.

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

1 OJ L33, 8.2.2003, p.30.

3

                                                
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.

4

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:

5

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 Commission1,

Having regard to the Opinion of the European Economic and Social Committee2,

Having regard to the Opinion of the Committee of the Regions3,

Acting in accordance with the procedure laid down in Article 251 of the Treaty4,

Whereas:

(1) 

(2) 

(3) 

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.  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.

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.

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,

1

2

3

4

OJ C , , p. .
OJ C , , p. .
OJ C , , p. .
OJ C , , p. .

6

                                                
(4) 

(5) 

(6) 

(7) 

5

6

7

8

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,  and  testing,  processing,
preservation,  storage  and  distribution  of  all  sources  of  human  tissues  and  cells
intended for application in the human body. The processing, preservation, storage
and distribution of all human tissues and cells used for transplantation purposes should
also  be  regulated.  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  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  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.  The  further  manufacturing  steps  are
covered by the relevant legislation5.

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/EC6  and  Council  Recommendation  98/463/EC7,  and  a  the  new  in  Directive
2002/98/EC  which  is  based  on  public  health  principles  under  Article  152  is
currently under discussion in Council and the European Parliament8. 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.

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.

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

Directive  2001/83/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.67-128.
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.
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
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)

7

                                                
type of specific human cells or tissues, or of cells of a specific origin or type, use or
non-use of any specific type of human cells, 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’.

The donation, procurement, testing, processing, preservation, storage and distribution
of human tissues and cells for human application 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 application transplantation process.

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 transplantation application process.

(8) 

(9) 

(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  transplantation  application  programmes
should be founded on the philosophy of voluntary and unpaid donation, anonymity of
both donor and recipient, benevolence, altruism of the donor and solidarity between
donor  and  recipient  and  encouragement  of  the  absence  of  profit  by  establishments
involved in tissue and cell transplantation services. 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 Union9, and take fully into account the principles

9

OJ C 364, 18.12.2000, p.1.

8

                                                
of the Convention on Human Rights and  Biomedicine of the Council of Europe10, 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.

(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.

(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 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.

(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,

10

11

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
OJ L 281, 23.11.1995, p.31.

9

                                                
donor,  recipient,  tissue  establishment  bank,  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.

10

                                                
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  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, 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 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 In the case
of  such  industrially  manufactured  products  is  regulated  covered  by  other
Community  legislation  provisions  derived  from  tissues  and  cells,  this  Directive
shall apply 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  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.;

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.

11

Article 3

Definitions

For the purposes of this Directive:

a)

b)

c)

d)

e)

f)

g)

h)

i)

j)

k)

l)

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

‘Tissue’ shall mean all constituent parts of the human body formed by cells.

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

‘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.

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

‘Processing’  shall  mean  all  operations 
the  preparation,
manipulation,  preservation  and  packaging  of  tissues  or  cells  intended  for
human application transplantation.

involved 

in 

‘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.

‘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.

‘Distribution’  shall  mean  transportation  and  delivery  of  tissues  or  cells  for
storage, processing or human application use in recipients.

‘Transplantation’  shall  mean  the  process  of  reconstituting  a  function  by
transferring equivalent cells and/or tissues to a recipient. Human application:
shall  mean  the  use  of  human  tissues  and  cells  in  a  human  recipient
including the extracorporeal use

‘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.

‘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.

12

m)

n)

o)

p)

q)

‘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.

‘Tissue  establishment’  shall  mean  any  body,  public  or  private,  including
tissue bank or health care establishment that hosts a tissue procurement team 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.

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

‘Allogeneic  use’  shall  mean  cells  or  tissues  procured  transplanted  from  one
person and applied to another.

‘Autologous  use’  shall  mean  cells  or  tissues  removed  from  and  applied
transplanted back to the same person.

Article 4

Implementation

1. 

2. 

3. 

4. 

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  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.

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 will apply

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.

13

CHAPTER II

OBLIGATIONS ON MEMBER STATES AUTHORITIES

Article 5

Supervision of tissue and cell procurement

Member States shall ensure that tissue and cell procurement are 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. 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

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

Article 6

Accreditation of tissue establishments banks

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  transplantation  are  conducted  undertaken  have
been  accredited,  designated,  authorised  or  licensed  only  by  tissue  banks  by  a
competent authority or authorities for the purpose of these activities.

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

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

that 

the 

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

14

1. 

2. 

1. 

2. 

3. 

4. 

5. 

1. 

2. 

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

Article 7

Register of accredited tissue establishments banks and reporting obligations

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

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.  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
establishment registers.

Article 8

Inspection and control measures

1. 

2. 

3. 

4. 

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

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.

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  health  care  establishments  involved  in  procurement
accredited  tissue  banks  ,and  the  facilities  of  any  third  parties  as  specified  in
Article 24;

15

5. 

6. 

7. 

1. 

2. 

b)

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

c)

examine any documents relating to the subject of the inspection.

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.

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 banks, healthcare  establishment  or  the  facilities
of third parties and the conditions of procurement of tissues and cells .

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

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. 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.

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 The import/export of  human tissues and  cells for  transplantation  shall  be
undertaken only through accredited tissue banks.

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).

16

Article 10

Traceability

1. 

2. 

3. 

4. 

1. 

2. 

3. 

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

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)

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

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

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  and  transplantation  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.

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.

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

17

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 receive prior
approval  by  the  competent  authority.  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. 

2. 

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.

Member States shall take all necessary measures to ensure that the recipients, donors,
or 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

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)

b)

c)

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;

procedures are in place to resolve data discrepancies; and

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.

18

Article 15

Selection, evaluation, and procurement

1. 

2. 

3. 

4. 

5. 

6. 

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

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.

The  tissue  establishments  banks  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.

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.

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.

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
PROCESSING

Article 16

Quality management

1. 

2. 

3. 

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

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.

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

19

– 

– 

– 

– 

– 

– 

Standard Operating Procedures;

Guidelines;

Training and reference manuals;

Reporting forms;

Donor records.

information concerning the final destination of the tissues and cells

4. 

5. 

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

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

Article 17

Responsible person

1. 

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

a)

b)

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;

he / she shall have at least two three  years practical and relevant experience
in  the  relevant  fields.  in  one  or  more  tissue  banks  accredited  in  accordance
with Article 6.

2. 

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

a)

b)

c)

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 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;

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

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

3. 

Tissue establishments banks shall notify the competent authority or authorities of
the name of the responsible person referred to in paragraph 1. Where the responsible

20

person is  permanently or  temporarily  replaced,  the  tissue  establishment  bank  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. 

2. 

3. 

4. 

1. 

2. 

3. 

The  tissue  establishment  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  establishment  bank  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.

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

Tissue establishments 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.

Article 20

Tissue and cell processing

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

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

The  tissue  establishment  bank  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.

21

Article 21

Tissue and cell storage conditions

1. 

2. 

3. 

4. 

Tissue  establishments  banks  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.

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

Tissue establishments 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.

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  banks  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  bank  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 banks 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 tissue bank shall establish a written agreement with a third party in
the following circumstances:

a)

b)

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

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

22

c)

d)

where  a  tissue  establishment  bank  provide  services  to  another  tissue
establishment bank;

where a tissue establishment bank distributes tissue or cells processed by third
parties

e)       where a third party distributes tissues or cells.

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

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

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

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

Article 25

Access to human tissues and cells

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.

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

CHAPTER V

EXCHANGE OF INFORMATION, REPORTS, AND PENALTIES

Article 26

Coding of information

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.

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.

2. 

3. 

4. 

5. 

1.

2.

1. 

2. 

23

Article 27

Reports

1. 

2. 

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.

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

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

reference 

and  7  of
Where 
Decision 1999/468/EC  shall  apply,  having  regard  to  the  provisions  of  Article  8
thereof.

this  paragraph,  Articles 5 

is  made 

to 

1. 

2. 

24

3. 

4. 

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

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. 

2. 

3. 

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.

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 banks operating under national provisions before the entry into
force of this Directive.

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.

25

Article 34

Addressees

This Directive is addressed to the Member States.

Done at Brussels,

For the European Parliament
The President

for the Council
The President

26

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 bank.

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

27

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)

b)

c)

d)

e)

f)

g)

h)

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;

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;

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

Have a quality management system;

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

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

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

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
BANKS

In order to be accredited, tissue establishments 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.

28

b)

c)

d)

e)

f)

g)

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.

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

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;

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

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

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;

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.

29

ANNEX II

QUALITY MANAGEMENT SYSTEM

1. 

The basic elements of a quality system are:

a)

b)

c)

d)

e)

f)

A well-defined quality policy;

A clearly-defined organisational structure and accountability;

Clearly-defined and effective documentation;

Standard Operating Procedures (SOPs);

Correct maintenance of all registers; and

Process validation by the personnel directly involved.

2. 

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

a)

b)

c)

d)

e)

f)

g)

h)

Ensuring that all processes are correct, verified and documented;

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;

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

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

Establishing and maintaining an appropriate monitoring system;

Establishing and maintaining a records system;

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

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 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

30

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)

b)

c)

d)

e)

f)

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

Legal aspects;

Ethical aspects;

Organisational aspects;

Quality control programmes;

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 
establishmentbank’s activities;

the 

tissue

b) Management of registers and data analysis programmes;

c)

d)

e)

f)

Handling of the equipment used for each activity;

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

Knowledge of the personal safety guidelines; and

Bio-monitoring systems operating at the health care establishment.

31

ANNEX III

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

A. 

1. 

2. 

3. 

4. 

5. 

6. 

7. 

8. 

B. 

1. 

2. 

AUTOLOGOUS (AU) AND ALLOGENEIC (AL) LIVING DONORS

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.

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

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

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.

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.

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

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

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.

DECEASED DONOR

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.

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.

32

SELECTION CRITERIA FOR THE DONOR OF TISSUES AND/OR CELLS

ANNEX IV

1.

DECEASED DONOR

A. 

GENERAL CRITERIA FOR EXCLUSION

1.

2.

3.

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

Cause of death unknown.

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

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.

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

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).

People with a history of chronic haemodialysis.

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

5. 

6. 

7.

8. 

33

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. 

1. 

2. 

SPECIFIC EXCLUSION CRITERIA FOR CHILD DONORS

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

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)

b)

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;

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.

34

2. 

2.2

1. 

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.

ALLOGENEIC LIVING DONOR

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.

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.

35

LABORATORY TESTS REQUIRED FOR DONORS OF TISUES AND CELLS

ANNEX V

1.

Serology tests required for donors

Infection

HIV 1 and 2

Hepatitis B

Tissues and cells: recommendation
in case of positive result

Contraindication to donation

HBs  Ag  positive  is  a  contraindication  to
donation.

Anti 
complementary tests

HBc 

positive 

requires

Hepatitis C

Contraindication to donation

Treponema pallidum

tests 

Requires 
specific
to 
antibodies  for  T. pallidum.  A  positive
result contraindicates donation.

detect 

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

Contraindication to donation

General requirements to be met when determining serological markers

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

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.

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

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

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  +/(cid:1) 7  days  and  in  the  case  of  allogeneic
donors a repeat sample after 6 months.

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

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.

2.

1. 

2. 

3. 

4. 

5. 

6. 

7. 

36

ANNEX VI

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

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)

b)

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.

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. 

1. 

2. 

3. 

DONOR DOCUMENTATION

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.

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

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

37

4. 

5. 

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

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 bank includes:

a)

b)

c)

d)

e)

f)

g)

Consent;

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

Review of clinical data against donor selection criteria;

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

Date and time of the death/perfusion;

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

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)

j)

k)

l)

Degree of asepsis;

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

Grafts obtained and relevant characteristics;

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 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.

38

F. 

1. 

2. 

3. 

PACKAGING

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.

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.

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)

b)

Donor identification number or code; and

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)

b)

c)

d)

e)

f)

Identification of the tissue/cells;

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

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

Date and time of harvesting;

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

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.

39

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 bank. Each establishment bank shall have a
documented procedure for handling non-conforming consignments of tissues/cells.

40

CELL AND TISSUE PROCESSING, STORAGE, AND DISTRIBUTION

Annex VII

PROCESSING

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

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.

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

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

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

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  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.

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 guarantee an air quality of grade B in accordance
with  the  GMP  guideline.  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 5µm) is required.

STORAGE

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

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

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

A. 

1. 

2. 

3. 

4. 

5. 

6. 

7. 

B. 

1. 

2. 

3. 

41

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.

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.

DISTRIBUTION

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

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.

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.

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.

FINAL LABELLING FOR DISTRIBUTION

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

4. 

C. 

1. 

2. 

3. 

4. 

D. 

1. 

a)

b)

c)

d)

Identification number or code of the tissue /cells;

Characteristics of the tissue or cell;

Identification of the tissue establishment bank;

Lot number.

2. 

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

a) Morphology and functional data;

b)

c)

d)

e)

f)

g)

Date of distribution of the tissue /cell;

Serological determinations carried out on the donor and results;

Storage recommendations;

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

Expiry date after opening/manipulation; and

Instructions on reporting serious adverse reactions and /or events.

42

E. 

EXTERNAL LABELLING OF THE SHIPPING CONTAINER

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

a)

b)

c)

d)

e)

f)

Identification of the originating tissue establishment bank;

Identification of the health care establishment of destination;

A statement that the package contains human tissue/cells;

In  the  case  of  haematopoietic  progenitors,  the  following  shall  be  added:  ‘DO
NOT IRRADIATE’;

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

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.]

43

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.

2.1.

2.2.

OVERALL FIGURES

Total allocation for action (Part B): 12 € million for commitment

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 
intervention) (see point 6.1.1)

(financial

€ million ( to three decimal places)

Year

2004

2005

2006

2007

2008

Total

Commitments (1)

Payments (1)

2003

1.25

0.5

1.25

1.2

1.5

1.3

1.5

1.4

1.5

1.5

1.5

2.6

8.5

8.5

(b)

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

Commitments (1)

0.3

0.7

0.7

Payments (1)

0.15

0.55

0.65

0.6

0.6

0.6

0.6

0.6

0.95

3.5

3.5

44

Subtotal a+b

Commitments (1)

Payments (1)

1.55

0.65

1.95

1.75

2.2

1.95

2.1

2.0

2.1

2.1

2.1

3.55

12

12

(c)

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

Commitments/
payments (1)

TOTAL a+b+c

Commitments (1)

Payments (1)

0.22

0.22

0.22

0.22

0.22

0.22

1.32

1.77

2.17

2.42

2.32

2.32

2.32

13.32

0.87

1.97

2.17

2.22

2.32

3.77

13.32

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

programme

2.4.

[X]

Compatibility with financial programming and financial perspective

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:1

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

3.

BUDGET CHARACTERISTICS

Type of expenditure

New

EFTA
contribution

Contributions
form applicant
countries

Heading in
financial
perspective

Non-comp

Diff/

NO

YES

YES/

No 3

4.

LEGAL BASIS

Article 152 of the Treaty establishing the European Community

1

For further information, see separate explanatory note.

45

                                                
5.

5.1.

DESCRIPTION AND GROUNDS

Need for Community intervention 2

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
BankEstablishments  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 
beneficiaries of the actions being undertaken.

target  population  sub-groups  are 

the  ultimate

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.

2

For further information, see separate explanatory note.

46

                                                
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

Breakdown

Total

Commitments (in € million to three decimal places)

Year

2004

2005

2006

2007

2008

2003

Action  1  Enhance  the  safety

1.25

1.25

1.5

1.5

1.5

1.5

8.5

and  quality  of  organs  and

substances of human origin.

TOTAL 1.25

1.25

1.5

1.5

1.5

1.5

8.5

47

6.1.2.

Technical  and  administrative  assistance,  support  expenditure  and  IT  expenditure
(commitment appropriations)

Year

2004

2005

2006

2007

2008

2003

Total

1) 
administrative assistance

Technical 

and

Technical 

a) 
offices

assistance

b)  Other 
administrative assistance:

technical 

and

- intra muros:

- extra muros:

of  which  for  construction
and 
of
maintenance 
computerised  management
systems

0.3

0.3

0.3

0.3

0.3

1.5

Subtotal 1

0.3

0.3

0.3

0.3

0.3

1.5

2) Support expenditure

a) Studies

b) Meetings of experts

0.1

0.1

Information 

c) 
publications

and

0.1

Subtotal 2

0.3

TOTAL 0.3

0.2

0.1

0.1

0.4

0.7

0.2

0.1

0.1

0.4

0.7

0.1

0.1

0.1

0.3

0.6

0.1

0.1

0.1

0.3

0.6

0.1

0.1

0.1

0.3

0.6

0.8

0.6

0.6

2

3.5

6.2.

Calculation  of  costs  by  measure  envisaged  in  Part  B  (over  the  entire
programming period)1

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

1

For further information, see separate explanatory note.

48

                                                
7.

IMPACT ON STAFF AND ADMINISTRATIVE EXPENDITURE

7.1.

Impact on human resources

Staff to be assigned to management of the
action using existing

Description of tasks deriving from the
action

Types of post

Total

Number of
permanent posts

Number of
temporary posts

Officials 
temporary staff

or

A

B

C

0.5

0.5

Other human resources

1 (END)

Total

2

0.5

0

0.5

1

2

If necessary, a fuller description of the
tasks may be annexed.

7.2.

Overall financial impact of human resources

Type of human resources

Amount (€)

Method of calculation  *

Officials

Temporary staff

108000

0.5A (108000)+0.5C(108000)

Other human resources

43000

1 (END) 43000

A-7003

(specify budget line)

Total

151000

The amounts are total expenditure for twelve months.

49

7.3.

Other administrative expenditure deriving from the action

Amount €

Method of calculation

Budget line

(number and heading)

Overall allocation (Title A7)

A0701 

– 

Missions

13000

2000

24000

24000

A07030 – Meetings

A07031 – Compulsory committees 1

– Non-compulsory committees 1

A07040 – Conferences

A0705 – Studies and consultations

Other expenditure (specify)

Information systems (A-5001/A-4300)

Other expenditure - Part A (specify)

20 one day-missions to Brussels or
Strasbourg: EUR 4000
6 three days-missions to contractors
and institutes in Member States:
EUR 9000

Meeting (experts groups)

Compulsory Committees: Directive
Committee (article 30) 2 meeting a
year x 15x 800 =24000

No Compulsory Committee : Working
Group (1 x 2 meetings a year x 15 x
800 = 24000)

Total

63000

The amounts are total expenditure for twelve months.

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

I.

II.

Annual total (7.2 + 7.3)

Duration of action

III.

Total cost of action (I x II)

214000€

6 years

1284000€

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’

50

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

51

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.

52

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 bankestablishments(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

53

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  bankestablishments,  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.

54

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)

Donor 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

55