The ‘Achilles’ project: a WHO initiative to support quality in the manufacturing of plasma for...

$: The ‘Achilles’ project: a WHO initiative to support quality in the manufacturing of plasma for fractionation Dr Ana Padilla, Blood Products & related Biologicals.$
The ‘Achilles’ project: The ‘Achilles’ project:

a WHO initiative to support quality in a WHO initiative to support quality in the manufacturing of plasma for the manufacturing of plasma for

fractionationfractionation

Dr Ana Padilla ,Blood Products & related Biologicals

Essential Medicines and Pharmaceutical Policies DepartmentHealth Services and Systems Cluster

World Health Organization

WHO Norms and Standards: WHO Norms and Standards:

Blood Products & related BiologicalsBlood Products & related Biologicals

WHO Expert Committee on Biological Standardization

WHO Blood Regulators Network

HSS/EMP/BPB: Teheran, Oct 083 |

OUTLINEOUTLINE

WHO Essential Medicines List

Plasma for Fractionation

The "Achilles" Project: Rationale and scope Project goals WHO action plan Expected outcomes

OUTLINE OUTLINE


Blood Plasma: a valuable human resourceBlood Plasma: a valuable human resource

Medicinal products derived from human donations of blood and plasma play a critical role in health care


Human Blood PlasmaHuman Blood Plasma

Complex mixture of (glyco)proteins

Therapeutic product (plasma for transfusion = fresh frozen plasma)

Pooled plasma = starting material for fractionation to medicinal products:

Albumin Blood Coagulation Factors (e.g. F VIII, FIX) Immunoglobulins (IV, IM) Serine proteases Fibrin sealants

Human Plasma Human Plasma


WHO Essential Medicines List 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


What is the global situation ?What is the global situation ?

The global need for blood plasma products exceeds by far available supply

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

Availability of blood plasma products Availability of blood plasma products


Plasma Safety in highly regulated countriesPlasma Safety in highly regulated countries

Commitment of health politicians, strong regulation, reinforcement and continuous surveillance by authorities

Commitment of blood services and plasma fractionators

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

Plasma safety and availability: highly regulated countries

Plasma safety and availability: highly regulated countries


Plasma « unused » for fractionationPlasma « unused » for fractionation

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

Plasma «unused» for fractionation:countries with poor or limited regulations

Plasma «unused» for fractionation:countries with poor or limited regulations

5.8 million liters not recovered in developing countries (Burnouf, 2007)


Achilles Project: Rationale Achilles Project: 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

Achilles Project: Rationale Achilles Project: Rationale


Conclusion: Conclusion:

Use of local plasma to improve supply of plasma products in developing countries, a legitimate option

Compliance with GMP, a key issue for successful PCF

Build-up technical expertise of local NRA and plasma supplier is a need

Common GMP standards, a basis for mutual recognition of quality standards and inspections results between NRA's

Independent regulatory systems for blood products regulation need to be established or strengthened in developing countries

Adoption of a Regional/International GMP standard facilitates regional collaboration between NRAs and implementation of PCF

Achilles Project: Rationale

Achilles Project: Rationale


GMP implementation in Blood/Plasma Establishments: a key element to

Quality and safety of plasma for fractionationPlasma contract fractionation programs

Supporting access to blood plasma products

Good Manufacturing Practices (GMP): an essential tool for improvement of safety


TRACEABILITYTRACEABILITY FROM DONOR TO PATIENTFROM DONOR TO PATIENT

TRACEABILITYTRACEABILITY FROM DONOR TO PATIENTFROM DONOR TO PATIENT

COMPONENTS PREPARATION

DONATIONINFORMATION

FRACTIONATIONVIRAL INACTIVATION

TREATMENT

GMPLOOK BACK SYSTEM

Blood/Plasma donation

Plasma for Fractionation

Blood Components

Plasma-Derived Medicinal Product

PatientsPatients


WHO and Plasma for FractionationWHO and Plasma for Fractionation

Quality of blood/ plasma is dependent on collection, preparation, testing , storage and transport

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 www.who.int/bloodproducts

Plasma for Fractionation* a biological product inherent variability

Plasma for Fractionation* a biological product inherent variability

* WHO Technical Report Series 941, Annex 4: 56th WHO Expert Committee on Biological Standardization, 24-28 October 2005.


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




Plasma Contract Fractionation Programs(Need for GMP implementation)

Plasma Contract Fractionation Programs(Need for GMP implementation)

GM

PL

ice

ns

ing GM

PL

ice

ns

ing

Quality Assurance Program

across countries

PLASMASUPPLIER FRACTIONATOR

Nat.Reg.Authority

Nat.Reg.Authority

GMP- common principles


Pathogen ThreatsPathogen Threats

24 Aug 07

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!

ource:

Europe 1985-1992250,000

Australia 199080,000

Australia 2005/200665,707

Spain 2005>1 million

Legal 640,000Canada 2001216,975

USAUp 1989:2,459,000

90s: legal 7,036,000

Up 2005: legal 7,486,643

Undocumented2000: 5,6 million2006: 8,9 million

Japan 1990 150,000

Japan 1994 250,000

Migration Flows from Latin America Chagas disease


Pathogen ThreatsPathogen Threats

Impact of migrations: health safety/security

Standardization of in vitro biological diagnostic technologies

Convergence of regulatory policies

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

Pathogen Threats Pathogen Threats


Increase availability of safe blood derived products by:

Supporting implementation of national validated quality and safety standards for blood establishments

Using expertise and experience from developed countries

WHO Guidelines for good manufacturing practices (GMP) in blood establishments are being developed to support implementation.

WHO “Achilles” project: Expected Outcomes


WHO “Achilles” project: Project Goals

WHO “Achilles” project: Project Goals


WHO “Achilles” projectAction Plan (demonstration 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)




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






International Conference of Drug Regulatory International Conference of Drug Regulatory AuthoritiesAuthorities (ICDRA): Recommendations, Bern 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

Emerging Diseases: regulating blood products

(ICDRA: Recommendations, Bern 08)

Emerging Diseases: regulating blood products

(ICDRA: Recommendations, Bern 08)


www.who.int/bloodproductswww.who.int/biologicalswww.who.int/medicines

Web site addressesRelevant Web site addresses Relevant Web site addresses

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