Post on 18-Feb-2021
Paola Di Ciaccio
Vanja Nikolac
Directive 2004/23/ECof the European Parliament and of the Council of
31 March 2004 on setting standards of quality and
safety for the donation, procurement, testing,
processing, preservation, storage and distribution of
human tissues and cells
LAW DECREE November 6 2007, n.191
Transposition of Directive2004/23/EC on setting
standards of quality and safety for the donation,
procurement, testing, processing, preservation, storage
and distribution of human tissues and cells
Directive 2006/17/ECimplementing 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
LAW DECREE January 25 2010, n.16
Transposition of Directives 2006/17/EC and 2006/86/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, as
well as regards traceability requirements, notification of
serious adverse reactions and events and certain
technical requirements for the coding, processing,
preservation, storage and distribution of human tissues
and cells
Directive 2006/86/ECof 24 October 2006 implementing Directive 2004/23/EC
of the European Parliament and of the Council as
regards traceability requirements, notification of
serious adverse reactions and events and certain
technical requirements for the coding, processing,
preservation, storage and distribution of human tissues
and cells
ITALY in the HSC field: HOW IS THIS RULED?
STANDARD REQUIREMENTS FOR TISSUE ESTABLISHMENTS(RESPONSIBILITY OF CENTRES)
RESPONSIBILITIES OF COMPETENT AUTHORITIES
IN SINGLE MEMBER STATES
FOR CHECK ON APPLICATION OF TE STANDARDS
IDENTIFICATION OF RESPONSIBILITIES
BLOOD CELLS
ORGANS TISSUES
DONATORE
Competent Authorities in Italy: Health Minister and
Regions act through technical bodies, CNT and CNS
They are technical and organizational structures thatcoordinate the national transplant network (for organs,
tissues and cells) and the national blood donationnetwork, respectively
They are both located in Romeat the ITALIAN NATIONAL INSTITUTE OF HEALTH
A ROLE INBETWEEN HEALTH MINISTRY AND REGIONAL AUTHORITIES
Law n. 91, Aprile 1, 1999Art.7
ITALIAN NATIONAL TRANSPLANT CENTRE
ITALIAN NATIONAL BLOOD CENTRE
Law n.219. October 21, 2005
Article 4 – implementation of requirements foreseen by Directives
Article 6 – authorization and accreditation of tissue establishments
Article 7 – adoption by CAs of adequate control measures and inspection
system (every two years) to ensure adherence to Directive requirements
Article 8 – guarantee traceability
Article 9 – vigilance on import/export
Article 10 – data and activity registry and compulsory annual public report
Article 11 – notification and investigations of serious adverse events and
reactions
DIRECTIVE 23/2004/EC
ACTIVITIES IN HSC FIELD
� Data collection and processing
� National coordinating and
supporting body
� Training of professionals and
inspectors
� Issuing of protocols and guidelines
� Inspections
� Vigilance and surveillance (SAERs)
HSC Donor identification issues and registries
Pat Don
• need for high degree ofcompatibility;
• about one third of patientsrequiring HSCT finds acompatible donor withinhis/her family;
• patients without a familycompatible donor rely thenon unrelated donors frominternational registry .
International bone marrow registry (I)
Bone Marrow Donors Worldwide (BMDW) is the continuing effort to collect the HLA phenotypes and other relevant data of volunteer stem cell donors and cord blood units, and is responsible for the co-ordination of their worldwide distribution. Participants are 73 stem cell donor registries from 52 countries, and 47 cord blood banks from 32 countries.
23,853,648(23,246,742 donors
and 606,906 CBU's)
BMDW started as an initiative of the Immunobiology Working Party of the European Group of Blood and Marrow Transplantation (EBMT) in 1988. In February 1989 the first edition was distributed, which contained the donor files of eight registries with a total of 155,000 volunteer stem cell donors.
International bone marrow registry (II)
Adults Unrelated Donors
- Bone Marrow
- Peripheral Blood Stem Cells
Unrelated
Cord Blood Units
Registries
HLA typing Laboratories
(Biological identity profile)
Cord Blood
Banks
Patients
Transplant Centre
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Cord bloodPeripheral bloodBone marrow
10.493
12.227
13.305
15.399
16.876
18.302
19.265Top five countries in 2012:
Germany 6,247 41%
USA 3,374 22%
Japan 1,332 9%
China 639 4%
UK-ANT 405 3%
4.126
10.989
4.150
MATCHED UNRELATED DONORS in the world
WHY THIS ISSUE IN ARTHIQS (I)
• Increased transplant activity;• increase the clinical indications;• improvement of supportive care;• increasing age of the patients;• increasing age of donors.
• Risks related to HSC donation are generally considered as non-existent.
• However, over the years various reports from individualtransplantation centers and donor registries have shown thatthe collection procedure can be related to theonset of anumber of symptoms, with changes in vital signs and/orexaminations, in the majority of cases of moderate andtransient entity.
• Some serious adverse events/reactions(including death) havebeen reported.
• HSC donor follow-up is widely recognized to beinsufficient,especially regardingrelated donors.
WHY THIS ISSUE IN ARTHIQS (II)
HOW WE ARE GOING TO TACKLE THIS …
⇒Revision of existing standards and their
harmonization with EU directives, in close
collaboration with international registry and
professionals scientific societies;
⇒Definition of European guidelines to assure high
level donors safety in all MS.
CROATIA - Competent Authority
Population
2011 census 4,284,889
Area
56,594 km2
Capital
Zagreb
Competent Authority
Ministry of Health
Croatian Ministry of Health- organisational chart
Competent authority forblood
tissues and cells
organs
assisted reproductive technologies
Institute for transplantation and biomedicine
Data collection
Authorisation
Regulatory issues
Organisational and financial issues
Service for Inspection of Blood, Tissues and Cells
Inspection
Supervision of the implementation of acts and other regulations
Vigilance (adverse reaction and event reporting system)
Croatian Ministry of Health
CROATIAN
LEGISLATION IN THE FIELD OF HSC
Directive 2004/23/EC
of the European Parliament and of the
Council of 31 March 2004 on setting
standards of quality and safety for the
donation, procurement, testing,
processing, preservation, storage and
distribution of human tissues and cells
ACT ON THE APPLICATION OF HUMAN
TISSUES AND CELLS
December 14 2012
2nd, improved set of legislation transposing EUTCDs
CROATIAN
LEGISLATION IN THE FIELD OF HSC
Directive 2006/17/ECimplementing 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
Ordinance
On the conditions in terms of premises, personnel,
medical and technical equipment and quality system
for the performance of the activities of collection,
procurement, testing, processing, preservation,
storage and distribution of human tissues and cells
June 17 2013
Directive 2006/86/ECof 24 October 2006 implementing Directive 2004/23/EC
of the European Parliament and of the Council as
regards traceability requirements, notification of
serious adverse reactions and events and certain
technical requirements for the coding, processing,
preservation, storage and distribution of human tissues
and cells
Ordinance
On the method of monitoring serious adverse events
and serious adverse reactions in the field of
application of human tissues and cells, the method of
keeping records, the notification time limits and the
content and format of the annual report
April 17 2013
Commission Decision 2010/453/EU
of 3 August 2010 establishing guidelines concerning the
conditions of inspections and control measures, and on
the training and qualification of officials, in the field of
human tissues and cells provided for in Directive
2004/23/EC of the European Parliament and of the
Council
Ordinance
On the requirements concerning professional
qualifications and professional training and on the
method of conducting supervision in the field of
application of human tissues and cells
April 30 2013
CBB : deserves special attention
Umbilical Cord Blood• First transplantation in 1988., in Paris, in a patient with Fanconi anemia
• First unrelated cord blood transplant in adult in 1996.
• In 1997. International NetCord Foundation, a non-profit association of umbilical cord blood banks was established - today aprox. 35 banks and
registries are members
• In the global network of CBB there are aprox. 600 000 UCB units (Eliane Gluckman, Annalisa Ruggeri, Fernanda Volt, Renato Cunha, Karim Boudjedir and Vanderson Rocha: Milestones in umbilical cord blood transplantation, 2011 Blackwell
Publishing Ltd, British Journal of Haematology, 154, 441–447)
• More than 20 000 units have been distributed (Ibid.)
CBB deserves special attention
Umbilical Cord Blood
mobility source
CBB deserves special attention
Umbilical Cord Blood
• Long term leukaemia-free survival in children (Wagner et al, 1996; Locatelli et al, 1999) and adults(Cairo & Wagner, 1997; Rubinstein et al, 1998; Laughlin et al, 2001; Sanz et al, 2001) is similar for cord blood transplant
recipients and matched unrelated bone marrow transplant recipients
• Improved results, mostly in adults, with the use of double cord blood transplants (Barker et al, 2005; Brunstein et al, 2007; Rocha et al, 2010)
• Notch-mediated expansion resulting in rapid engraftment (Colleen Delaney, Shelly Heimfeld, Carolyn Brashem-Stein, Howard Voorhies, Ronald L. Manger, and Irwin D. Bernstein1; Notch-mediated expansion of Human Cord Blood Progenitor Cells
Capable of Rapid Myeloid Reconstitution , Nat Med. 2010 February ; 16(2): 232. doi:10.1038/nm.2080)
Shows that storing of high quality units
is not only worth but essential
CBB deserves special attention
Umbilical Cord Blood- advantages• Simple collection procedure
• Has to be risk for donor - a mother or a newborn• No donor attrition• Low risk of viral transmitting• Immediate availability in emergency• Easy delivery • Grater proportion of rare haplotypes present in UCB banks then in BMT
registries
(Anfisa Stanevsky a, Gal Goldstein b, Arnon Nagler: Umbilical cord blood transplantation: Pros, cons and beyond)
Targets
• Developing guidelines for CB banking establishing commongood practice for the field in MS
• Setting guide for CBB inspection leading to harmonisation ininspection practice (including inspectors’ education and
skills, inspection documentation, performance) and mutual
recognition of EU inspection bodies