Harmonizing a national system with the CE, PIC/S and EMEA

1
Harmonizing a national system with the CE, PIC/S
and EMEA

• G Andreu
• Etablissement Français du Sang

2
Harmonizing a national system with the CE, PIC/S
and EMEA

• Where are we coming from ?

3
Blood Transfusion Organization in France - 1

• 1952 Blood Transfusions first law, founded
  on the principles of
• voluntary donor services,
• anonymity of both donor and recipient,
• Non remuneration of the donor,
• absence of profit on the part of the
  establishments involved in blood transfusion
  services.
• Resulting in the creation of up to 150 Blood
  Transfusion Centers (BTC)
• Including 7 BTC preparing plasma-derived products
• 5 different status, and ca 100 hospital-based BTC

4
Blood Transfusion Organization in France - 2

• Regulation and control between 1952 and 1993
• Regulation for
• donor testing,
• donor selection,
• Blood collection
• Blood components specifications (minimal)
• Few inspections (no dedicated inspection service)
• No haemovigilance organization

5
Blood Transfusion Organization in France - 3

• 1993 Blood transfusions second law,
• Affirmation of ethical issues
• voluntary donations, anonymity of both donor and
  recipient, non remuneration of the donor, absence
  of profit
• Separation of BTC and plasma industry
• French Blood Agency (AFS) in charge of regulation
  and inspection
• Publication of BT good practices (1993 to 2000)
• Publication of a list and specifications of Blood
  components,
• Creation of the haemovigilance network
• Merging BTC from 150 to 43
• Organization of inspections

6
Blood Transfusion Organization in France - 4

• 1998 Blood transfusions third law,
• Reaffirmation of ethical issues
• Creation of the Agence Française de Sécurité
  Sanitaire des Produits de Santé (AFSSAPS) French
  Agency of Medical Safety of Health Products in
  charge, inter allia, of regulation and inspection
  of BT services
• Creation of the Etablissement Français du Sang
  (EFS), single civil BT operator in France
• 2000 to 2003
• New set of BT good practices and list of blood
  components
• Organization of EFS in 18 regional BTC (including
  4 overseas)

7
Europe Council of Europe (CoE) and European
Union

• Lichtenstein
• Lithuania
• Luxemburg
• Malta
• Moldavia
• Netherland
• Norway
• Poland
• Portugal
• Romania
• Russia

• Albany
• Andorra
• Armenia
• Austria
• Azerbaidjan
• Belgium
• Bulgaria
• Croatia
• Chyprus
• Tchequie
• Denmark

• Estonia
• Finland
• France
• Germany
• Georgia
• Greece
• Hungary
• Iceland
• Ireland
• Italy
• Lettonia

• San Marino
• Slovaquia
• Slovenia
• Spain
• Sweden
• Suitzerland
• Macedonia
• Turky
• Ukraine
• United Kingdom

8
Europe Council of Europe (CoE) - 1

• Created in 1949
• Early involvement of Council of Europe in Blood
  Transfusion
• Main concern in ethical aspects, i.e. the non
  commercialization of products of human origin as
  blood, organs and tissues
• 1958 agreement on rules for exchange of
  therapeutic products of human origin
• 1962 agreement on rules for exchange of
  blood grouping reagents

9
Europe Council of Europe (CoE) - 2

• 1978 resolution about organ and tissues
  collection and transplantation
• 1983 recommendation about prevention of AIDS
  transmission by blood transfusion
• 1995
• Recommendation N14 on ethics and technical
  principles for Blood Transfusion
• Recommendation N15 on preparation, use and
  quality assurance of blood components
• regularly updated since (11th edition)
• considered as a reference text for member states,
  and some other countries

10
EU documents related to blood transfusion - 1

• 1965 Directive 65/65/EEC
• common measures related to pharmaceutical
  industry
• 1975 Directive 75/319/EEC
• norms of analytic, toxico-pharmacologic and
  clinical protocols for pharmaceutical industry
• 1989 Directive 89/381/EECs
• Specific measures related to medicinal products
  derived from blood or plasma, and clear
  separation with labile blood components
• 1993 Directive 1993/42/EC
• About Medical Devices

11
EU documents related to blood transfusion - 2

• 1998 Directive 1998/79/EC
• About In Vitro diagnostic Medical Devices
• 2003 Directive 2002/98/EC
• Setting standards of quality and safety in BT
• 2004 Directive 2004/33/EC
• Technical requirements in BT
• 2004 EMEA/CPMP/BWP/3794/03 Guideline
• on the scientific data requirements for a plasma
  masterfile
• 2005 EMEA/CPMP/BWP/125/04 Guideline
• on epidemiological data on blood transmissible
  infections

12
EU documents related to blood transfusion - 3

• Regulation from EU in the next future in the
  Blood tranfusion field
• 2005-2006
• Directive on Quality system
• Directive on Haemovigilance
• 2007
• ?

13
European Blood Transfusion Agenda
14
Harmonizing a national system with the CE, PIC/S
and EMEA

• Where are we ?
• Significant examples
• Donors signature
• Pre-donation Hb control
• Reagents for BTC labs

15
Process leading to the signature of the donor
(directive 2004/33/EC, annex II)
16
Perception of EU Directives by the French Blood
Donors Associations - 1

• In the present french regulation, there is no
  requirement for donors to sign an informed
  consent before donation
• The concept of informed consent is poorly known
  in France, and frequently misunderstood in the
  general population

17
Perception of EU Directives by the French Blood
Donors Associations - 2

• The signature of donor has been considered as a
  strong sign of donors liability, leading to a
  complete rejection of signature by a vast
  majority of the french blood donors associations
  during their national meeting in may, 2004.

18
Donors signature conclusion

• Introduction of a cultural change led to major
  difficulties
• 18 months later, these difficulties have been
  overcome by intensive dialog with
• Blood donors associations
• AFFSaPS and Health Ministry
• the introduction of donors signature in routine
  blood donor sessions is scheduled for january 2006

19
Pre-donation Hb Control - 1

• At present, there is no systematic pre-donation
  Hb control in France, which is required by
  Directive EU 2004/33
• Hb is controlled on a donation sample, and donors
  below 12 (F) /13 (M) are excluded until Hb
  normalization
• There is no policy of donors iron
  supplementation
• Two different problems have to be faced
• Choice of a well adapted procedure
• Organize a specific donor management to avoid a
  dramatic exclusion rate at the time the measure
  is adopted.

20
Pre-donation Hb control 2

• Is Hemocue (fingerstick) adapted to select
  anemia in blood donors ?
• Sensibility 48,7
• Specificity 96,8
• positive predictive value 52,1
• Negative predictive value 96,4
• False negative 3,6
• False positive 47,9

21
Pre-donation Hb control action plan for
2005-2006

• Venous pre-donation Hb control on every new donor
  (Hemocue)
• Thresholds of 12 g/100 mL (F) and 13 g/100 mL(M)
• Systematic blood count on every donation
• Elaboration of a national logigram to manage
  donors found below the threshold
• Proposition to delay the adoption of 12.5 /13.5
  threshold

22
Reagents used in BT labs - 1

• Before the EU Directive on in vitro diagnostic
  medical devices,  in-house  reagents were
  frequently prepared and used in BTC
• Red cells for ABO grouping and Ab screening
• MoAbs and human sera for immuno-hematology
  (donors and recipients)
• IQC for immuno-hematology and virology

23
Reagents used in BT labs - 2

• EFS created a special division dedicated to the
  production of reagents (Reagents Production Unit)
  
• Organized in 4 different locations
• Registered as a reagent manufacturer
• Present catalog of 19 reagents
• Reagents for internal use at the present time
• Leading project for Harmonization in EFS BT labs

24
Where are we going ?In Harmonization, be
realistic

• Despite EU directives and other international
  recommendations, Blood Transfusion remains highly
  heterogenous among countries, because of
• different understandings of EU texts
• Definition of the  responsible person 
• subsidiarity
• Leucodepletion specifications (cellular and
  plasma components)
• Medical practice
• Quantitative use of blood components (varies by a
  factor 3)
• Choice of blood components (as BC vs apheresis
  PCs)

25
Harmonization in Blood Transfusion Lessons from
the last 10 years

• Anticipation
• Development of scientific expertise
• Cooperation with related medical specialties
• Cooperation with industry
• Participation
• In EU, CoE and other international expert groups
• Be a force of proposition
• As a single country is OK
• As a group of countries, (as EBA), is far better

26
Harmonization Lessons from the last 400 years
Marin Mersenne 1588-1648

• Mathematician, physicist, philosopher
• Friend of Fermat Descartes
• Author of many best-sellers
• Questions harmoniques
• Harmonicorum libri
• lHarmonie Universelle
• 1644 Cogita physico-mathematica