good manufacturing practices for blood establishments (gmp for plasma donations) dr a padilla blood...

Good Manufacturing Practices Good Manufacturing Practices for Blood Establishmentsfor Blood Establishments

(GMP for plasma donations)(GMP for plasma donations)

Dr A Padilla Blood Products & related Biologicals

Quality Assurance and Safety: MedicinesWorld Health Organization

EMP/QSM/Blood Products: Kuwait 30/11/122 |

OUTLINEOUTLINE

The GMP concept

Good Manufacturing Practices for BE

GMP compliance

Impact of QA/GMP approach

Website references

OUTLINE OUTLINE


GMP IN BLOOD ESTABLISHMENTSGMP 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


WHA63.12: "Blood Products" definitionWHA63.12: "Blood Products" definition

"Any therapeutic substances derived from human blood, including whole blood, labile blood components and plasma-derived medicinal products"


WHAT DO WE NEED TO ACHIEVE THROUGH GMP?

WHAT DO WE NEED TO ACHIEVE THROUGH GMP?

CONTROL INHERENT BIOLOGICAL VARIABILITY*

CONSISTENCY OF PRODUCTION/PROCESSES

TRACEABILITY DONOR RECIPIENT

*each individual donation is unique


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

HOW TO MANAGE THIS? HOW TO MANAGE THIS?


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

GMP: A TOOL TO CONTROL PROCESS VARIABILITY*

GMP: A TOOL TO CONTROL PROCESS VARIABILITY*

*human plasma has intrinsic biological variability


TRACEABILITYTRACEABILITY FROM DONOR TO PATIENTFROM DONOR TO PATIENT


COMPONENTS SEPARATION

DONORINFORMATION

FRACTIONATIONVIRAL INACTIVATION

TREATMENT

Good Manufacturing Practices

Blood donation

Plasma for Fractionation

Blood Components

Plasma-Derived Medicinal Product

PatientsPatients




Blood/Plasma donation


Blood Components


PatientsPatients

DONOR/DONATION • donor population• donor registration• donor selection• donor protection• collection process

COMPONENTS PREPARATION, e.g. • production process• testing• process control• release • storage & transport

FRACTIONATION, e.g. • fractionation process • viral inactivation• QC & release • distribution


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

TRACEABILITY IS KEY TRACEABILITY IS KEY


Plasma Contract Fractionation Programs- Need for GMP implementation in BE -

Plasma Contract Fractionation Programs- Need for GMP implementation in BE -

GM

PL

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ing GM

PL

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Quality Assurance Program

across countries

PLASMASUPPLIER FRACTIONATOR

Nat.Reg.Authority

Nat.Reg.Authority

GMP- common principles

Plasma Contract fractionation


FROM DONOR TO PATIENTFROM DONOR TO PATIENTFROM DONOR TO PATIENTFROM DONOR TO PATIENT

COMPONENTS PREPARATION

COLLECTIONPROCESS

FRACTIONATIONVIRAL INACTIVATION

TREATMENT

Blood/Plasma donation


Blood Components


PatientsPatients

TRACEABILITYLOOK BACK SYSTEM


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

Good Manufacturing Practices (GMP) for Blood establishments (BE): Definition

Good Manufacturing Practices (GMP) for Blood establishments (BE): Definition

GMP compliance: issues specific to the production of blood components, including plasma for fractionation


.. 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

WHO GMP Guidelines contain...WHO GMP Guidelines contain...


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

Structure of the DocumentStructure of the Document


- 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

- PersonnelOrganisation and responsibilities, Training, Personal hygiene

- DocumentationSOP and records, Documentation control

Chapters 3 – 8Chapters 3 – 8


- Premises and EquipementPremises, Equipment, Computerized-systems

- Qualification and ValidationQualification of equipment, Validation of manufacturing

processes, selection of an appropriate test system, Assay performence validation

- Management of Materials and ReagentsMaterials and reagents,

Receipt/Quarantine/Release/Storage/Traceability of material, Supplier/Vendor management

Chapters 3 – 8 (cont.)Chapters 3 – 8 (cont.)


- Process-specific guidanceDonor registration, Donor selection, Collection, Component preparation, Laboratory testing, Quality control, Labelling,

Release, Dispatch, Shipping, Returns

- Product characteristicsWhole blood, Red cells, Platelets, plasma for transfusion, plasma for fractionation, Cryoprecipitate/CPP

- Points to consider for validation of production stepsCentrifugation, Separation, Freezing, Leukocyte reduction,

Irradiation

Chapter 9: ManufacturingChapter 9: Manufacturing


GMP compliance....... the principleGMP 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


GMP compliance…… plasma variabilityGMP 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)


GMP compliance …the culture inside the organization

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

Suitability of plasma depends on meeting production standards for blood collection and component manufacturing

control of processes end-to-end required for production of all blood components

SUMMARY


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

IMPACT OF GMP IN BLOOD ESTABLISHMENTS (I)IMPACT OF GMP IN BLOOD ESTABLISHMENTS (I)


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

IMPACT OF GMP IN BLOOD ESTABLISHMENTS (III)IMPACT OF GMP IN BLOOD ESTABLISHMENTS (III)


• 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

WHO guidance documents: website addressedwww.who.int/bloodproducts


http:// www.who.int/bloodproductshttp:// www.who.int/bloodproducts

http:// www.who.int/bloodproductshttp:// www.who.int/bloodproducts


Web site addressesWeb site addresses

http://www.who.int/bloodproducts

http://www.who.int/bloodproducts/catalogue

good manufacturing practices for blood establishments (gmp for plasma donations) dr a padilla blood...

Documents

empqsmblood products

blood products definition

blood establishments

donor traceability

human blood

unique slide

labile blood components

human plasma