Transcript Norms and Standards Blood Products & in vitro Diagnostic Devices Dr Ana Padilla Department of Medicines Policy and Standards (PSM) Health Technology and Pharmaceuticals Cluster World.

Norms and Standards
Blood Products & in vitro
Diagnostic Devices
Dr Ana Padilla
Department of Medicines Policy and Standards (PSM)
Health Technology and Pharmaceuticals Cluster
World Health Organization
19 September 2006
Blood Products & IVDs
MEDICINES
Regulatory Authority
MEDICINES Regulations
BIOLOGICAL Products
BLOOD Derived Products
Human and animal
Blood derived medicinal products &
related in vitro diagnostic devices
Human blood derived products





Blood components (red cells, platelets, plasma)
Blood Coagulation Factors
Immunoglobulins
 Anti-hepatitis B
 Anti-rabies
 Anti-tetanus
 Anti-rhesus (anti-D)
Fibrin sealant
Albumin
Animal- derived sera





Anti-rabies
Anti-venoms (snake/scorpion)
Anti-tetanus toxins
Anti-diphteria toxins
Anti-botulism toxins
Other related products
 Anticoagulant & fibrinolysis
biological therapeutic products
 In vitro diagnostic devices for the control of quality and safety of
blood derived medicinal products including in vitro diagnostic devices
Quality and Safety: Biological Products
Starting material
Production Process
Final product
consistency
Blood collection &
Plasma quality & safety
Fractionation
Technology/ Viral
inactivation /Removal
Procedures
Product characteristics:
Bulk & Formulated Product
Quality Assurance and Safety of
Biological Products
WHO Norms and Standards
Biological Products
(Vaccines, blood products, other biologicals
and in vitro diagnostic devices)
NSB/IVB/FCH
(Vaccines, cell regulators)
(*) Expert Committee on Biological Standardization
QSD/PSM/HTP
(Blood products, in vitro diagnostic devices)
Quality Assurance and Safety:
Blood Products & related Diagnostics
WHO standard setting functions*:

WHO Biological Reference Preparations

WHO Guidelines on Quality Assurance & Control

Operational strategies to assure compliance of
international regulations at global level and to
improve access to quality medicines
(*) Expert Committee on Biological Standardization
I. WHO Biological Reference Preparations
Global Measurement Standards
(known as WHO International Standards)
WHO Biological Reference Preparations*
(Global measurement standards)
IMPACT

Tool for comparison of results between
different assays at global level
(biological measurement)

Support quality assurance regulations
of blood products & high risk in vitro
diagnostic devices

Facilitate development of diagnostic
and therapeutic products
Analytical
Sensitivity
Standards required by CTS
EU IVD Directive
WHO standards available
Screening and rapid assays
anti-HIV-1/2
none
none
anti-HTLV-I/II
none
none
anti-HCV
none
Planned
0.5 ng/ml (French or UK-standard)
HBsAg
2.6 IU (WHO HBsAg 2nd IS)
anti-HBc
none
2nd WHO International Standard
for HBsAg: 33 IU/ampoule
WHO dilutional reference panel
Planned
NAT assays (qualitative and quantitative)
HIV
HCV
HBV
Analytical sensitivity (IU/ml)
defined on WHO standards
HTLV I/II
HIV-1 RNA 1st IS (1999)
105IU/ml
HCV RNA 2st IS (2003)
105IU/ml
HBV DNA 1st IS (1999)
106IU/ml
none
Confirmatory assays
anti-HIV-1/2
none
none
anti-HTLV-I/II
none
none
anti-HCV
none
none
STREPTOKINASE:
Use of the International Standard in public health
MWT
11 12 13 14 15 16 17 18
Use of 3rd WHO IS for SK
Post marketing surveillance data
Alb
SK
120
60
40
20
Sample number
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
0
2
Longstaff et al J Thromb
Heamost 2005; 3, 1092
80
1
Potency estimates,
calibrated against the
WHO IS, for a range of
Streptokinase products
expressed as a
percentage of the
labeled potency. Two
different methods used.
100
% of label potency
STREPTOKINASE (SK):
Therapeutic preparations
II. WHO Guidelines and Recommendations
II. WHO Guidelines & Recommendations
IMPACT

Guidance for national regulatory authorities
and manufacturers: “how to control and
standardize production processes”

Promote global harmonization to secure
quality and safety of products

Used as the basis of national
regulations/worldwide regulations
WHO Requirements for the provision of safe blood, blood
components and plasma derivatives, TRS 840 Annex 2, 1994
New documents to fill the gaps:

WHO Recommendations for the Production,
Control and Regulation of Plasma for
Fractionation

WHO Guidelines on Viral Inactivation and
Removal Procedures for blood plasma
products

Tissue Infectivity Distribution in
Transmissible Spongiform Encephalopathies
III. WHO operational strategies to
assure compliance of international
regulations at global level and to
improve access to quality medicines
Blood Products and IVDs Regulations
Unless controlled, medicinal products derived from blood and
plasma can be a vehicle of transmission of infectious diseases
(HIV/Hepatitis) and/or emerging agents
Assured traceability
& quality
Stringent safety
regulations
Risk
34%
61%
Deficient regulatory
system
5%
Not tested
GDB: total of 77 million donations
WHO Regional Office for the Americas (AMRO)
Blood Products
Regional Network of NRAs:
promotion of appropriate
regulations for the control
of Blood Products & IVD
Legend
WHO GMP Workshops
North America
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the
part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full
agreement.
© WHO 2004. All rights reserved
Antivenom sera are essential to prevent
long-term disability & death
n
Courtesy Prof D Warrell, Nuffield Department of Clinical Medicine, Oxford
Production of animal derived sera
(antisera) for therapeutic use

Antisera are largely unavailable

Consequently, high degree of mortality & morbidity

No alternative specific treatment

Weak production systems in developing countries

Regulatory controls are poor

Potential risk of transmission of zoonosis
PRODUCTION OF ANTIVENOM SERA:
Technology in the public domain (not protected by intelectual property)
A - Collection of venoms
B – Horse Immunization
Protocols
C – Starting material of
animal derived sera
D – Fractionation &
Purification process
WHO Project
Enhance production and
availability of animal-derived
antisera at global level
*Endorsed by the WHO Expert Committee on Biological Standardization, 24 -28 Oct 2005
Snake bite is estimated to account for
a tenth as much mortality as malaria,
but there is no equivalent global
snakebite strategy
Cheng AC, Winkel K. Call for global snake-bite control and procurement
funding. Lancet 2001;357:1680
WHO Websites:
www.who.int/bloodproducts
www.who.int/medicines