Good Manufacturing Practices
for Blood Establishments
(GMP for plasma donations)
Dr A Padilla
Blood Products & related Biologicals
Quality Assurance and Safety: Medicines
World Health Organization
OUTLINE

The GMP concept

Good Manufacturing Practices for BE

GMP compliance

Impact of QA/GMP approach

Website references
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GMP IN BLOOD ESTABLISHMENTS
 GMP* addresses the manufacturing activities
(collection, testing, process, storage, labelling,
distribution) of the blood establishment
 Implementation of GMP requires to separate
medical functions from manufacturing activities (e.g.
plasma) in blood establishments
*GMP applies to products and processes
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WHA63.12: "Blood Products" definition
"Any therapeutic substances derived
from human blood, including whole
blood, labile blood components and
plasma-derived
medicinal
products"
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EMP/QSM/Blood
Products:
Kuwait
30/11/12
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WHAT DO WE NEED TO ACHIEVE
THROUGH GMP?
 CONTROL INHERENT BIOLOGICAL VARIABILITY*
 CONSISTENCY OF PRODUCTION/PROCESSES
 TRACEABILITY DONOR RECIPIENT
* each individual donation is unique
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HOW TO MANAGE THIS?
 To control the high variability, we need proof of a robust
collection and production process
 To control the process, we need a systematic approach
(the QA/GMP approach) to ensure compliance at all steps
involved
 To apply the systematic production approach, each
intermediate and final product must fulfil defined quality
requirements: pre-defined validated specifications
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GMP: A TOOL TO CONTROL PROCESS
VARIABILITY*
important to understand which characteristics
are most relevant, and their impact, on products
and processes
measurable characteristics
trend analysis to observe processes
effective change control mechanisms
* human plasma has intrinsic biological variability
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TRACEABILITY
FROM DONOR TO PATIENT
Blood
donation
DONOR
INFORMATION
Blood
Components
Patients
Plasma for
Fractionation
Plasma-Derived
Medicinal Product
COMPONENTS
SEPARATION
FRACTIONATION
VIRAL
INACTIVATION
8
Good
Manufacturing Practices
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TREATMENT
TRACEABILITY
FROM DONOR TO PATIENT
Blood/Plasma
donation
Blood
Components
Plasma for
Fractionation
DONOR/DONATION
• donor population
• donor registration
• donor selection
• donor protection
• collection process
COMPONENTS
PREPARATION, e.g.
• production process
• testing
• process control
• release
• storage & transport
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Patients
Plasma-Derived
Medicinal Product
FRACTIONATION, e.g.
• fractionation process
• viral inactivation
• QC & release
• distribution
TRACEABILITY IS KEY




unique donor/donation number
clear identification of donor, donation, products
post donation information
effective information system between blood
establishment, testing lab, hospital or plasma
supplier and fractionation plant
 must work in both ways donor-patient-donor
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Plasma Contract Fractionation Programs
- Need for GMP implementation in BE GMP- common principles
Quality Assurance Program
PLASMA
SUPPLIER
Plasma Contract
fractionation
FRACTIONATOR
across countries
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GMP
Licensing
Nat.Reg.
Authority
Licensing
GMP
Nat.Reg.
Authority
FROM DONOR TO PATIENT
Blood/Plasma
donation
COLLECTION
PROCESS
Blood
Components
Patients
Plasma for
Fractionation
Plasma-Derived
Medicinal Product
COMPONENTS
PREPARATION
FRACTIONATION
VIRAL
INACTIVATION
TRACEABILITY
LOOK BACK SYSTEM
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TREATMENT
Good Manufacturing Practices (GMP) for
Blood establishments (BE): Definition
GMP is that part of QUALITY ASSURANCE that ensures that
products are consistently produced to the quality standards
appropriate to their intended use, as required by predefined
specifications and, if applicable, by the marketing authorisation.
GMP is concerned with both production and quality control.
WHO Guidelines for Blood Establishments (TRS 961, Annex 4):
http://www.who.int/entity/bloodproducts/publications/GMP_Bloodestablishments.pdf
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GMP compliance:
issues specific to
the production of
blood
components,
including plasma
for fractionation
WHO GMP Guidelines contain...
.. general GMP topics, e.g. quality management
.. specific topics to manufacturing of blood
components, from donor selection through
distribution of final product
.. newer GMP concepts, e.g. risk management,
product quality reviews
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Structure of the Document
Chapters 1 – 2:
Introduction, Glossary/Abbrev.
Chapters 3 – 8:
Quality Management
Chapter 9:
Manufacturing
Chapters 10:
Contract manufacturing,
analysis and services
Chapters 11 - 12:
Acknowledgements/References
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Chapters 3 – 8
- Quality Management
Principles, Product Quality Review, Quality risk management,
Change control, Deviation evaluation and reporting, Corrective and
preventive actions, Internal audits, Complaints and product recall,
Process Improvement, Look back
- Personnel
Organisation and responsibilities, Training, Personal hygiene
- Documentation
SOP and records, Documentation control
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Chapters 3 – 8 (cont.)
- Premises and Equipement
Premises, Equipment, Computerized-systems
- Qualification and Validation
Qualification of equipment, Validation of manufacturing
processes, selection of an appropriate test system, Assay
performence validation
- Management of Materials and Reagents
Materials and reagents,
Receipt/Quarantine/Release/Storage/Traceability of
material, Supplier/Vendor management
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Chapter 9: Manufacturing
- Process-specific guidance
Donor registration, Donor selection, Collection, Component
preparation, Laboratory testing, Quality control, Labelling, Release,
Dispatch, Shipping, Returns
- Product characteristics
Whole blood, Red cells, Platelets, plasma for transfusion, plasma
for fractionation, Cryoprecipitate/CPP
- Points to consider for validation of production steps
Centrifugation, Separation, Freezing, Leukocyte reduction,
Irradiation
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GMP compliance....... the principle
 The production process must
–
–
–
–
Be validated
Be reproducible
Be clearly specified and documented
Be in accordance with the licensed process (at all times)
 Change must be managed
– Planned change(s) should be controlled
– Unplanned changes (deviations) should be
• Recorded
• Reviewed for impact on product Safety, Quality and Efficacy
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GMP compliance…… plasma variability
 A robust (standardized) process required
 Knowledge of the production process competence needed:
– Knowledge of the plasma characteristics
– Knowledge of impact on processes and products
 Process optimization for those characteristics
 Process documentation: change control to manage
modifications
 Trend analysis to monitor the process (behaviour over time)
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GMP compliance …
the culture inside the organization
The culture of the organisation should encourage:
 respect for the defined process
 respect for the planned change mechanism
 openness in timely reporting of deviations
 commitment to determine variation cause
 recognition of the benefits of trend analysis
 determination to learn from past mistakes
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SUMMARY
Suitability of plasma depends on
meeting production standards for
blood collection and component
manufacturing
control of
processes end-toend required for
production of all
blood
components
IMPACT OF GMP IN BLOOD ESTABLISHMENTS (I)
 In blood establishments, GMP introduces the application
of quality assurance principles in all steps involved in
the collection, production and testing of blood
components
 GMP supports systematic application of donor selection
criteria for each donation
 GMP reduces errors and technical problems in
collection, production, testing, and distribution
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IMPACT OF GMP IN BLOOD ESTABLISHMENTS (III)
 Implementation of GMP in blood establishments has
shown to be a beneficial tool to help countries in
improving plasma quality
 GMP in blood establishments will increase availability of
plasma and is one of the key issues for a successful
plasma contract fractionation program and/or domestic
fractionation
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WHO guidance documents: website addressed
www.who.int/bloodproducts
• Reference on GMP for blood establishments (2011):
http://www.who.int/entity/bloodproducts/publications/GMP_Bloodestablishments.pdf
• Reference on production, control and regulation of plasma for fractionation (2007):
http://www.who.int/entity/bloodproducts/publications/TRS941Annex4blood.pdf
• Reference on viral inactivation and removal procedures (2005):
http://www.who.int/entity/bloodproducts/publications/GMP_Bloodestablishments.pdf
• Catalogue of blood products and blood safety related reference materials:
http://www.who.int/bloodproducts/catalogue/en/index.html
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http://
www.who.int/bloodproducts
Web site addresses
http://www.who.int/bloodproducts
http://www.who.int/bloodproducts/catalogue
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