Transcript Guidelines

The ‘Achilles’ project:
a WHO initiative to support quality in
the manufacturing of plasma for
fractionation
Dr Ana Padilla,
Blood Products & related Biologicals
Essential Medicines and Pharmaceutical Policies Department
Health Services and Systems Cluster
World Health Organization
WHO Norms and Standards:
Blood Products & related Biologicals
WHO Expert Committee on Biological Standardization
WHO Blood Regulators Network
OUTLINE

WHO Essential Medicines List

Plasma for Fractionation

The "Achilles" Project:
 Rationale and scope
 Project goals
 WHO action plan
 Expected outcomes
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Blood Plasma: a valuable human resource
Medicinal products derived from
human donations of blood and
plasma play a critical role in health
care
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Human
Plasma
Human
Blood
Plasma

Complex mixture of (glyco)proteins

Therapeutic product (plasma for transfusion = fresh
frozen plasma)

Pooled plasma = starting material for fractionation to
medicinal products:
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Albumin
Blood Coagulation Factors (e.g. F VIII, FIX)
Immunoglobulins (IV, IM)
Serine proteases
Fibrin sealants
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WHO Essential Medicines List
 Human derived blood plasma products
– Plasma for Fractionation
•
•
•
•
Blood Coagulation Factors: FVIII, PCC
Human Normal Immunoglobulin (IV and IM)
Anti-D immunoglobulin
Anti-tetanus immunoglobulin
Blood-derived medicinal products for the treatment of
haemophilia and immune diseases are included in the WHO
Model List of Essential Medicines
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What is of
the
global
situation
?
Availability
blood
plasma
products
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The global need for blood plasma products exceeds by far available supply
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Plasma for fractionation available in industrialized countries to cover their
needs

Alternatives to plasma products are not sufficiently available, or even not
existent
 hemophilia: recombinant products are expensive; gene therapy still
experimental
 normal immunoglobulin should cover the wide range of antigens (e.g.
pathogens) prevailing in a population;
 specific immunoglobulins can be sourced only in immunized populations
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Plasma safety and availability:
Plasma Safety in highly regulated countries
highly regulated countries

Commitment of health politicians, strong regulation,
reinforcement and continuous surveillance by authorities
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Commitment of blood services and plasma fractionators
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GMP implementation in manufacture of all blood plasma
derived products
No documented virus transmission by plasma products
licensed within this regulatory framework > 10 years
Blood plasma products needs covered
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Plasma ««unused»
Plasma
unused »for
forfractionation:
fractionation
countries with poor or limited regulations
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Quality criteria for plasma for fractionation not met
GMP has not been a natural background for blood transfusion
Sensitivity of blood transfusion services to independent
regulatory control
Need to strengthen experience & regulation of plasma and
plasma products
Lack of government awareness: rationale for regulation
Lack of technical capacity of regulatory authorities
 5.8 million liters not recovered in developing countries
(Burnouf, 2007)
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Achilles Project:
Project: Rationale
Achilles
Rationale
Blood plasma products in the WHO Essential Medicines List but
no access to these products by developing countries because
of:
1. Poor quality and safety of plasma (destroyed)
2. Need for introduction of blood products regulations
3. The Achilles project considers upgrading of plasma quality as
the driving force for implementation of a safe blood program.
4. The project includes elements of quality, safety and
economical benefits.
5. May attract more efficiently the attention of the authorities
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AchillesConclusion:
Project: Rationale

Use of local plasma to improve supply of plasma products in developing
countries, a legitimate option
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Compliance with GMP, a key issue for successful PCF
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Build-up technical expertise of local NRA and plasma supplier is a need
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Common GMP standards, a basis for mutual recognition of quality
standards and inspections results between NRA's
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Independent regulatory systems for blood products regulation need to
be established or strengthened in developing countries
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Adoption of a Regional/International GMP standard facilitates regional
collaboration between NRAs and implementation of PCF
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Good Manufacturing Practices (GMP):
an essential tool for improvement of safety
GMP implementation in Blood/Plasma
Establishments: a key element to
Quality and safety of plasma for fractionation
Plasma contract fractionation programs
Supporting access to blood plasma products
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TRACEABILITY
FROM DONOR TO PATIENT
Blood/Plasma
donation
Blood
Components
DONATION
INFORMATION
Patients
Plasma for
Fractionation
Plasma-Derived
Medicinal Product
COMPONENTS
PREPARATION
FRACTIONATION
VIRAL
INACTIVATION
GMP
LOOK BACK SYSTEM
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TREATMENT
Plasma
for
Fractionation*
WHO and Plasma for Fractionation
a biological product inherent variability
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Quality of blood/ plasma is
dependent on collection,
preparation, testing , storage
and transport
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Quality of plasma for
fractionation influences the
range, quantity, quality, and
safety of plasma derivatives
WHO Recommendations
for the Production,
Control and Regulation of
Human Plasma for
Fractionation
(adopted in November
2005)
www.who.int/medicines
* WHO Technical Report Series 941, Annex 4: 56th WHO Expert Committee on
www.who.int/bloodproducts
Biological Standardization, 24-28 October 2005.
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Assuring Blood/Plasma Safety:
“Layers of Safety”
1. Donor selection criteria (epidemiological data)
2. Deferral procedures: national registries to avoid use of
collections from previously unsuitable donors
3. Laboratory testing for infectious disease markers:
selection of kits and validation
4. Implementation of GMPs in blood/plasma
collection establishments
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Plasma Contract Fractionation Programs
(Need for GMP implementation)
GMP- common principles
Quality Assurance Program
PLASMA
SUPPLIER
FRACTIONATOR
across countries
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GMP
Licensing
Nat.Reg.
Authority
Licensing
GMP
Nat.Reg.
Authority
Pathogen Threats
Spain 2005
Canada 2001
>1 million
Legal 640,000
Europe 1985-1992
216,975
250,000
Japan 1
150,000
Japan 1
250,000
USA
Up 1989:2,459,000
90s: legal 7,036,000
Up 2005: legal 7,486,643
Undocumented
2000: 5,6 million
2006: 8,9 million
Australia 1990
80,000
Australia 2005/2006
24 Aug 07
65,707
Migration Flows from Latin America Chagas disease
Over 2.0 billion airline passengers are traveling each year.
The battle against infections and the struggle for blood
safety are closely interrelated !
Infections are a global problem necessitating global
collaboration!
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Pathogen Threats
Pathogen
Threats

Impact of migrations: health safety/security
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Standardization of in vitro biological diagnostic
technologies
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Convergence of regulatory policies
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Track and monitor blood safety
Need to strengthen blood products regulations worldwide to ensure
availability of safe blood and blood products in the face of known
and emerging threats, including emerging infectious diseases
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WHO “Achilles”
“Achilles” project:
WHO
project:
Expected
ProjectOutcomes
Goals
Increase availability of safe blood derived products by:
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Supporting implementation of national validated quality
and safety standards for blood establishments
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Using expertise and experience from developed
countries
WHO Guidelines for good manufacturing practices (GMP) in
blood establishments are being developed to support
implementation.

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WHO
project
WHO“Achilles”
“Achilles” project
ActionPlan
Plan(demonstration
(demonstration project)
Action
project)

Development of comprehensive GMP guidelines to support
training and inspection activities: GMP Guidelines for
Blood Establishments (high priority project, ECBS 2009)

Upgrading quality assurance systems and regulatory
expertise initially in 2 pilot countries.

Development of specific and measurable health care
outcomes to monitor success and progress (e.g. plasma
available, reduction of infectious disease markers in blood
donors, decrease of GMP failures, economic benefit)
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WHO “Achilles”
“Achilles” project:
WHO
project:
Expected Outcomes
Outcomes
Expected
 Sustainable and affordable blood plasma derived essential medicines
 Optimal use and benefit from donated blood plasma
 Increased quality and safety of all blood products in blood establishments
 Substantial contribution to public health programs
 International agreed standards for blood establishments
 Potential application of QA and GMP principles to other medical disciplines
 Involvement of developing countries in international BT activities
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International
Conference
of Drugblood
Regulatory
Emerging
Diseases:
regulating
products
Authorities
(ICDRA):
Recommendations,
(ICDRA:
Recommendations,
BernBern
08) 2008
 Recognizing the need worldwide for blood products regulation to
ensure availability of safe blood and blood products in the face of
known and emerging threats, including emerging infectious diseases,
WHO should:
» Take steps to further develop and strengthen national/regional blood regulatory
authorities and to promote cooperation
» Provide harmonized "assessment criteria for blood regulatory systems" (BRN):
convene a consultation of NRAs to review Draft assessment tool
» Prioritize development of Guidelines on GMP for Blood Establishments
» Promote introduction of WHO recommended plasma standards by NRAs
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Relevant
site addresses
Web siteWeb
addresses
www.who.int/bloodproducts
www.who.int/biologicals
www.who.int/medicines
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