Ponthip Wirachwong, PhD
GOVERNMENT PHARMACEUTICAL ORGANIZATION 17 Nov 2016
GAP and Flu Vaccine Production in Thailand
GAP and Flu Vaccine Production in Thailand
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Presentation utline
GPO’s ProfileGPO’s Profile
Development of GPO’s Influenza Vaccine Project
Achievement and Progress
(Pilot & Industrial Plants)
� Sustainability for Influenza Vaccine manufacturing
� Remaining Challenges
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“To be a leader in pharmaceutical
product and medical supply business
sustainably beneficial and essential to
the Thai society and ASEAN Community.”
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State Enterprise under the Ministry of Public Health established in 1966
Pharmaceutical products• 300 items
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Biological Products
• Tetanus antitoxin• In-progress Development
• DTP-HB vaccine• Live Chimeric JE vaccine• Influenza vaccine
State Enterprise under the Ministry of Public Health established in 1966
ARV/
Infectious
38%
CVS
11%
CNS
24%
Others
25%
Diabetes2%
2004: H5N1 outbreak
2005: MOPH working group on pandemic influenza vaccine preparedness
2007: Thai Government approved 42 million USD for industrial-scale influenza vaccine plant.
2007: 1st WHO Grant for development of Lab-scale Seasonal IIV
2009: Development of Pandemic Live Attenuated Influenza Vaccine
2010:Technical Assistance from KAKETSUKEN on pilot-scale Seasonal IIV
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To build and sustain capacity to manufacture up to 10 million doses of
seasonal IIV with WHO PQ
Ability to convert manufacturing capacity to 60 millions doses of IIV/LAIV pandemic flu vaccine
To support country and regional flu pandemic preparedness through
stockpile of pre-pandemic vaccine
H1N1 2009 LAIV (Fluvac)
approved for Pandemic Use
H5N2 LAIV
(Fluvac H5) approved for Pandemic Use
♦♦♦♦Inactivated Influenza Vaccine Production Process established
♦♦♦♦Clinical study Phase I/II completed 7
Study Profile
Cases with Adverse Events
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HAI Day Study group
GMT95%CI
Sero-
conversionN (%)
FLU A
H1N1
Antibody Titer
21 Vaccine 392.60(337.59-456.59)
176
(88.00%)
Placebo 20(15.79-25.33)
0(0.00%)
60 Vaccine 253.1(218.31-293.42)
166(83.00%)
Placebo 20(15.82-25.29)
0(0.00%)
90 Vaccine 221.21(189.48-258.25)
163(81.50%)
Placebo 20.85(16.45-26.42)
1(1.00%)
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HAI Day Study group
GMT95%CI
Sero-
conversionN (%)
FLU A
H3N2
Antibody Titer
21 Vaccine 214.81(183.77-251.09)
107
(53.50%)
Placebo 43.17(34.20-54.49)
0(0.00%)
60 Vaccine 165.12(143.17-190.43)
93.00(46.50%)
Placebo 43.17(34.20-54.49)
1(1.00%)
90 Vaccine 155.06(135.47-177.48)
92(46.00%)
Placebo 45.00(35.77-56.62)
2(2.00%)
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HAI Day Study group
GMT95%CI
Sero-
conversionN (%)
FLU B
Antibody Titer
21 Vaccine 115.92(97.60-137.66)
173
(86.50%)
Placebo 9.40(7.83-11.28)
1(1.00%)
60 Vaccine 83.72(70.39-99.58)
153(76.50%)
Placebo 9.33(7.82-11.13)
1(1.00%)
90 Vaccine 73.33(61.15-87.94)
146(73.00%)
Placebo 9.40(7.89-11.19)
1(1.00%)
� The results have indicated that the vaccine is safe.
� There were no major problems in local and
systemic reactions, and atypical adverse events
occurred during the study.
� The vaccine group showed significantly higher
immunogenicity than the placebo group.
� Clinical Trial Phase III is being planned.
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GPO
เทศบาลทับกวาง
GPO Flu Vaccine Plant: Located in Saraburi Province
GPO Flu Vaccine Plant: Plant Layout
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Utility
Administration/QC
Filling
BulkProduction
AnimalBuilding
GPO Flu Vaccine Plant
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Egg Hatching Building
GPO Flu Vaccine Plant
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Administration/QC
GPO Flu Vaccine Plant
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BulkProduction
Administration/QC
GPO Flu Vaccine Plant
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Filling
GPO Flu Vaccine Plant
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Animal Building
Utility Building
GPO Flu Vaccine Plant
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Utility Building
GPO Flu Vaccine Plant
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GPO Flu Vaccine Plant
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Generator
Chiller Boiler
Electricity system
GPO Flu Vaccine Plant
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Class
100K
Class 10KClass 100
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Vial
Washer
& Sterile
tunnel
GPO Flu Vaccine Plant
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GPO Flu Vaccine Plant
Vial
Capping
Machine
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GPO Flu Vaccine Plant
Vial
Inspection
and
cartoning
Machine
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GPO Flu Vaccine Plant
Prefilled
Syringe
line
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GPO Flu Vaccine Plant
Purified
Water
System
GPO Flu Vaccine Plant
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Distillation
Machine &
Water
Storage
Tank
GPO Flu Vaccine Plant
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Liquid Waste Water
Decontamination
GPO Flu Vaccine Plant
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GeneratorSolid Waste
Decontamination
2016
Complete plant
construction
2017
Complete commissioning and
qualification of utilities, cleanrooms,
machines
Scaling-up production
2018
Process Performance
Qualification Lots
Clinical lots production
Start clinical trial (immunological
bridging 18 -49 yrs)
2019
Complete clinical trial
Dossier submission
for licensure
2020
Vaccine licensure
GMP Approval
Start commercial production
Political leadership/commitments
Financial support ($US 42 million) for industrial-
scaled flu plant
Policy environment and healthcare system
Annual vaccination of seasonal flu vaccine (~3.5
millions doses/year)
Commitment from international partners under WHO
GAP framework and collaborative supports from all
technical partners
Need for guaranteed supply of SPF eggs/Vaccine quality
eggs
Imported SPF eggs from Germany, US, France, Mexico
A few domestic supply of SPF eggs/VQE by private
producers
Further technical development to strengthen R&D and
production capabilities
Process transfer from pilot to industrial production
WHO-pre-qualified seasonal/pandemic flu vaccine
Cell-based, universal flu vaccines
WHO: Dr. Marie-Paule Kieny, Dr. Martin Friede, Mr. Guido Torreli,
Ms. Erin Sparrow, Ms. Florence Barthelemy
IEM: Prof. Larisa Rudenko
US Government, BARDA, US CDC
Government of Japan, KAKETSUKEN
NIBSC
NVI
Thai Partners:
MOPH: Dr. Suwit Wibulpolprasert, TFDA, DMSC
Mahidol University
Silpakorn University