EU directive on tissue and cells

1
EU directive on tissue and cells

• Ineke Slaper-Cortenbach

2
Why a regulation on tissue and cells?

• Each year in Europe, hundreds of thousands of
  patients undergo some form of therapeutic
  treatment based on the use of tissues and cells
  of human origin. These tissues or cells are
  frequently acquired through cross-border
  exchange.
• Having a common set of high standards helps
  facilitate cooperation between healthcare
  systems. It also assures EU citizens that if they
  go for treatment in another EU country, they will
  benefit from the same protection from
  transmissible diseases as they would in their own
  Member State. Member States also have the option
  to apply stricter standards than those set down
  by the EU should they wish to do so.

3
EU Directive 2004/23/EC Setting standards of
quality and safety for the donation, procurement,
testing, processing, preservation, storage and
distribution of human tissues and cells

• This Directive should apply to tissues and cells
  including hematopoietic peripheral blood,
  umbilical-cord (blood) and bone marrow stem
  cells, reproductive cells (eggs, sperm), foetal
  tissues and cells, and adult and embryonic stem
  cells
• It was published in the Official Journal of the
  European Union on April 7, 2004 and entered into
  force
• Members States will have to implement it before
  April 7, 2006

4
EU Directive 2004/23/EC Setting standards of
quality and safety for the donation, procurement,
testing, processing, preservation, storage and
distribution of human tissues and cells
DLI?

• This Directive excludes
• blood and blood products (other than
  Hematopoietic progenitor cells) and human organs,
  as well as organs, tissues, or cells of animal
  origin. Blood and Blood products are currently
  regulated in other Directives
• Tissues and cells used as an autologous graft
  (tissues removed and transplanted back within the
  same surgical procedure and without being
  subjected to any banking
• Not applicable for research (animal studies)
• Organs or parts of organs if it is their function
  to be used for the same purpose as it functions
  in the human body.

5
EU Directive 2004/23/EC Setting standards of
quality and safety for the donation, procurement,
testing, processing, preservation, storage and
distribution of human tissues and cells

• Establishment of a register of entities operating
  in the field
• Designation of the competent authority (ies) in
  Member States
• Implementation of a quality system for tissue
  establishments, including specification of
  activities relating to a quality system (SOPs,
  guidelines, training reference manuals,
  reporting forms, donor records, information on
  final destination of tissues or cells, etc.)
• Introduction of a system of accreditation of
  tissue establishments by Member States and a
  system for notification of adverse events and
  reactions
• Organisation of inspections and control measures
  within Member States
• Ensurance of data protection and confidentiality.
  
• Assurance of traceability of tissues and cells
  through laboratory identification procedures,
  record maintenance and an appropriate labelling
  system
• Design of a single European coding system to
  provide information on the main characteristics
  and properties of tissues and cells

6
EU Directive 2004/23/EC Setting standards of
quality and safety for the donation, procurement,
testing, processing, preservation, storage and
distribution of human tissues and cells

• Chapter I General provisions (article 1-4)
• Chapter II Obligations on Member State
  Authorities (article 5-11)
• Chapter III Donor Selection and Evaluation (
  article 12-15 )
• Chapter IV Provisions on the quality and safety
  of cells (article 16-24)
• Chapter V Exchange of information, reports and
  penalties (article 24 - 30)
• Chapter VI Final provisions on the quality and
  safety of cells (article 31-33)
• Annexes Technical information.

7
EU Directive 2004/23/EC Setting standards of
quality and safety for the donation, procurement,
testing, processing, preservation, storage and
distribution of human tissues and cells

• EU Directive implementing EU Directive 2004/23/EC
  of the European Parliament and of the Council as
  regards certain technical requirements for
• the donation, procurement and testing of human
  tissues and cells
• JACIE part B and C
• coding, processing, preservation, storage and
  distribution of human tissues and cells
• JACIE part D
• Aim In order to prevent the transmission of
  diseases by human tissues and cells for human
  application to ensure an equivalent level of
  quality and safety

8
Technical requirements of 2004/23/EC

For further information, see http//europa.eu.in
t/comm/health/ph_threats/human_substance/tissues_e
n.htm
9
Time frame technical requirements

• The implementing Directive adopted on February 8,
  2006 covers the first phase of the donation and
  procurement process.
• This will be followed up with a proposal for a
  second Directive in the 2nd half of 2006, which
  will cover the second phase, including storage,
  processing and preservation criteria for tissues
  and cells.

Member States have until November 2006 to put in
place national measures implementing the new rules
10
Technical requirements of 2004/23/ECdonation,
procurement and testing of tissues and cells

• Article 2 Requirements for the procurement of
  human tissues and cells
• Article 3 Selection criteria for donors of
  tissue and cells (Annex I)
• Article 4 Laboratory tests required for donors
  (Annex III)
• Article 5 Procurement procedures
• Article 6 requirements for distribution
• Article 7/8 transposition entry into force

• staff must be properly trained
• the facilities must be maintained to prevent
  contamination
• proper, sterile instruments must be used for
  procurement
• SOPs for
• the donation and testing process
• during transport
• at the point of reception in tissue
  establishments
• selection of tissue and cell donors (live or
  deceased)
• A unique identifier code for proper
  identification and traceability.

11
Technical requirements of 2004/23/ECdonation,
procurement and testing of tissues and cells

12
Technical requirements of 2004/23/ECcoding,
processing, preservation, storage and
distribution of tissues and cells

• Article 3 Requirements for the accreditation,
  designation, authorisation or licensing of
  Tissues establishments (Annex I)
• Article 4 Criteria for accreditation,
  designation, authorisation, licensing of tissue
  and cell preparation processes at the tissue
  establishments (Annex II)
• Article 5/6 Notification and serious adverse
  reactions/events (Annexes III)
• Article 7 Annual reports
• Article 8Communication between competent
  authoristies
• Article 9 Tracability
• Article 10 European Coding System

13
Technical requirements of 2004/23/ECcoding,
processing, preservation, storage and
distribution of tissues and cells

Licensing of Tissues establishments (Annex I) A.
Organisation and management B. Personnel C.
Equipment and materials D. Facility and
premises E. Documentation and registry F. Quality
review
14
Technical requirements of 2004/23/ECcoding,
processing, preservation, storage and
distribution, procurement and testing

Tissue and cell preparation processes (Annex
II) A. Reception at tissue establishment B.
Processing C. Storage and release of products D.
Distribution and recall E. Final labelling for
distribution F. External labelling of the
shipping container
15
Technical requirements of 2004/23/ECbottle-neck
I

• The air quality standard is a key factor for
  risk of tissue or cell contamination
• Unless otherwise specified, where tissues or
  cells are exposed to the environment during
  processing, without a subsequent microbial
  inactivation process, an air quality of Grade A
  as defined in the current European Guide to Good
  Manufacturing Practice, Annex 1 (Commission
  Directive 2003/94/EC) is required with a
  background environment appropriate for the
  processing of the tissue/cell concerned.

16
Technical requirements of 2004/23/ECbottle-neck
II

• Storage facilities must be provided that clearly
  separate and distinguish tissues and cells prior
  to release/in quarantine from those that are
  released and from those that are rejected, in
  order to prevent mix up and cross-contamination
  between them. Physically separate areas or
  storage devices must be allocated in both
  quarantine and released storage locations for
  holding certain tissue and cells collected in
  compliance with special criteria (e.g
  Autologous/allogeneic directed donations or known
  infective material).

17
JACIE /EC directives
18
Modifications to Standards

• Members of JACIE Exc. Board currently working
  with FACT Sub-committees developing 3rd edition
  of standards and manual
• Part B Diana Samson
• Part C Derwood Pamphilon
• Part D Ineke Slaper-Cortenbach

Available to the membership
Membership review
Publisher
Crosswalk with cGTP and EU Directive New edition
standards and manual
Consistency and Legal review
Changes review
1
5/ 6 8
9 10
11 12
19
Technical requirements of 2004/23/EC
Crosswalks between JACIE and EU directives

• Diana Samson performed crosswalks on the
  2004/23/EC directive and the 2 technical
  directives with JACIE standards and WMDA
  standards (collection).
• No major differences
• JACIE is specifying the issues for cellular
  therapy products in depth

20
Advanced Therapies

More information http//pharmacos.eudra.org/F2/adv
therapies/index.htm
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
More general information www.cytotherapy.org
european LRA committee www.jacie.org JACIE
standards