GAP and Flu Vaccine Production iin Thailand n Thailand › influenza_vaccines_plan › news › GPO_9thPM.pdfMachine. 29 GPO Flu Vaccine Plant Prefilled Syringe line. 30 GPO Flu Vaccine

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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6

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


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Administration/QC


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BulkProduction

Administration/QC


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Filling


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Animal Building

Utility Building


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Utility Building


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Generator

Chiller Boiler

Electricity system


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Class

100K

Class 10KClass 100

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Vial

Washer

& Sterile

tunnel


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Vial

Capping

Machine

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Vial

Inspection

and

cartoning

Machine

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Prefilled

Syringe

line

30


Purified

Water

System


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Distillation

Machine &

Water

Storage

Tank


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Liquid Waste Water

Decontamination


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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

Documents

GAP and Flu Vaccine Production iin Thailand n Thailand › influenza_vaccines_plan › news › GPO_9thPM.pdfMachine. 29 GPO Flu Vaccine Plant Prefilled Syringe line. 30 GPO Flu Vaccine