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