EU directive on tissue and cells

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EU directive on tissue and cells

• Ineke Slaper-Cortenbach

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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

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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) These products
  are regulated in 2002/98/EC and 2004/33/EC
• 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) or
  for organs, tissues and cells of animal origin
• Organs or parts of organs if it is their function
  to be used for the same purpose as it functions
  in the human body.

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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 (SOPs, guidelines, training
  reference manuals, reporting forms, donor records
  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

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Meeting with the European Commission on March 9,
2006 in Brussels

• Representation of WMDA, EBMT, ISCT-Europe and
  JACIE.
• Import and export of cells
• position of DLI
• Air quality
• European coding system

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Article 9 Import/export of human tissues and
cells

• 3.
• a. The import or export of tissues and cells
  referred to in Article 6(5) (directly
  distributed) may be authorised directly by the
  competent authority
• b. In case of emergency, the import or export of
  certain tissues and cells may be authorised
  directly by the competent authorities
• c. The competent authority or authories shall
  take all necessary measures to ensure that
  imports and exports of tissues and cells referred
  to in subparagraphs (a) and (b) meet quality and
  safety standards equivalent to those laid down in
  this Directive

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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
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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

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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
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2006/17/EC technical requirements for donation,
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.

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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
  authorities
• Article 9 Traceability
• Article 10 European Coding System

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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

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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
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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
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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 but at
  least equivalent to GMP grade D in terms of
  particles and microbial counts!!

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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 or secured segregation within the
  device 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).

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European Coding System International Cellular
Therapy Coding and Labelling Advisory Group

• AABB, ASBMT, EBMT, FACT, ICCBBA Inc, ISBT,
  ISCT, ISCT Europe, JACIE, NMDP and WMDA for the
  international use of ISBT 128 in the coding of
  hematopoietic progenitor cell and other
  therapeutic cell products
• review existing regulation regarding labeling
• design product label templates that satisfy
  regulatory requirements
• provide a focus for the standardization of
  terminology and product naming
• promote the adoption of the ISBT 128 standard in
  cellular therapy facilities around the world
• provide advice and support to facilities
  introducing the standard
• advise on the ongoing development of the ISBT
  128 standard to support new developments in
  cellular therapy.

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More general information www.celltherapysociety.o
rg european LRA committee www.jacie.org JACIE
standards