Vaccine Development & Deployment in Thailand

Thailand Science Park Convention Center (TSPCC), Jan 21, 2014

Charung Muangchana MD, MPH, PhD National Vaccine Institute(NVI), Ministry of Public Health

Outline  Vaccine introduction & immunization program  Vaccine development & production  TB problem & vaccine development plan

Thailand Selected Demographics Population

67 millions (est)*

Live Birth (2009)

733,014 /year

Total fertility rate

1.66* (est)

Infant Mortality

15.0/1,000 live births

(2006 estimate) GNI per capita

2,698 USD* (PPP 8,703 USD)**

* 2011, http://www.indexmundi.com/thailand/demographics_profile.html, http://www.tradingeconomics.com/thailand/gdp-per-capita ** 2011, http://www.tradingeconomics.com/thailand/gdp-per-capita-ppp

Thailand’s Perspective on Vaccines 

Modern & cost-effective public health tool for primary disease prevention & control, mostly having externality benefit

 Relatively

 Having

not difficult to implement & access

high risk for shortage of procurement

Vaccine Introduction & Immunization Program

Basic Immunization - EPI National Advisory Committee on Immunization Practice (NACIP) established since 1970

Target populations: - New born babies & children - Pregnant women - High–risk groups

Vaccine procurement, technical support, evaluation are organized at national level

EPI established since 1977 under technical & strategic advisory of NAICP

Nationwide coverage >90%, except in border areas & high terrains

All hospitals & HCs provide immunization service, free of charge

EPI Immunization Schedule of Thailand

Infants

Older children

Students Adults

Age

Vaccines (11 immunogens)

At birth

BCG, HB1

2 months

OPV1, DTP1, HB2

4 months

OPV2, DTP2

6 months

OPV3, DTP3, HB3

9 - 12 months

MMR1

1 ½ - 2 yrs

OPV4, DTP4, JE1, JE2

2 ½ - 3 yrs

JE3

4 yrs

OPV5, DTP5

4 - 7 yrs

MMR2

12-16 yrs

dT

Seasonal Flu in HCWs & High risk group 7

Timeline of vaccine introduction in Thai EPI since 1977 19771981

19821996

19871991

BCGBCG x 1 DTP x 3

DTP x 4

OPV OPVx 2

OPV x 3

OPV x 4

M

20022006

20072011 DTP-HB x 3

OPV x 5

M Rx1

M or MMR Rx2

MMR HB x 3

JE

20122016

BCG x 1

DTP x 5

HB TT

19972001

BCG x 2

DTP DTPx 2

R

19921996

JE x 2 TT x 2

HB x 4 JE x 3

TT x 3

dT x 3

Typhoid Typhoid

Influenza

Flu in HCW H1N1

Flu 2009in HR* Source: EPI / DDC / MOPH, 14 July 2011

(A)

HR* – High risk groups

Decision making process for introduction of new vaccines in Thai EPI 1

The disease is a major burden.

•Cases/ deaths/ disability

•Safe & efficacious vaccine

2

Vaccination is a priority intervention.

3

Vaccination is a good investment.

•Cost benefit /cost-effectiveness/cost saving

4

Vaccination is programmatically feasible.

5

Programmatic feasibility is proven in a pilot.

•Social & economic impacts

•Vaccine effectiveness

•Other interventions less promising

•Financing feasibility •Operation and logistic feasibility under existing health infrastructure •Public acceptance & political will •Pilot program conducted with the feasibility for sustenance if pilot outcome is promising. 18 June 2010

Practical steps in vaccine introduction Licensed or registered

Decision to introduce in EPI

Private sector

Promote / monitor vaccine use in private sector

Policy process

Pilot project

Expansion

Nationwide

Public sector • • • • •

Verify disease burden Establish CB / CE Ensure programmatic feasibility Ensure affordability & sustainability Obtain policymaker advocacy

Based on experience with introduction of HB (19851992), JE (1990’s), DTP-HB (since late 1990’s)

Practical steps in vaccine introduction Licensed or registered

Decision to introduce in EPI

Private sector

Hib, Pneumo, HPV, Rota, HA, Varicella,

Promote / monitor vaccine use in private sector

Policy process

Pilot project

Hib, Pneumo, HPV, Rota

• • • • • NA

Verify disease burden Establish CB / CE Ensure programmatic feasibility Ensure affordability & sustainability Obtain policymaker advocacy

Expansion Flu

Nationwide DTP-HB

JE

Public sector Based on experience with introduction of HB (19851992), JE (1990’s), DTP-HB (since late 1990’s)

Planning and budgeting for national immunization program Scrutinize

Budget Bureau

Propose

Cabinet Propose & defend

Review, prioritize & further put forward

MOPH & NHSO Prepare plans & budget proposal with justification

NACIP Advice

Scrutinize

EPI & DDC

Parliament Approval

Budget approved

EPI under UC • NHSO takes care of financing for vaccines and vaccine delivery, including procurement and supply of vaccines to all health care providers. • MOPH is responsible for: – Policy / strategy development and guidance, as well as technical support to health care providers – Vaccination service

Vaccine Development

Challenges on Vaccine Development in Thailand  Vaccine researches 

Depend on individual interest



Domestic vaccine candidate: in pre-clinic



Clinical testing— phase I-III & bridging studies 

Imported vaccine candidates

Current Vaccine R&D (Pre-clinical phase) in Thailand Dengue JE HIV

Influenza

Chikunguny a

 Live attenuated tetravalent; Chimeric Den-YF, tetravalent ; DNA  Inactivated cell culture; Live attenuated; Chimeric JE-YF, Dengue 2 PDK53  Candidate vaccines under development and clinical studies- phases I, II, III  Phase III (prime-boost, MOPH/ RTA/ Mahidol/ US)  R&D on seed virus (H5) initiated (Biotec & Mahidol)  Clinical trial on candidate H5 vaccines under preparation (DMS); Live-attenuated-product registered (GPO); Siriraj Hospital (Universal flu vac)  Inactivated cell-based GPO * Incomplete list

Current Vaccine Production in Thailand Producers

Vaccines

1. GPO

1. JE Vaccine

Status Upstream to downstream

(inactivated, MB derived)

2. Thai Red Cross

3. GPO-MBP

4. Livestock department

2. BCG

Upstream to downstream

3. ERIG

Upstream to downstream

4. Anti-venom

Upstream to downstream

5. Measles

Formulation & filling

6. OPV

Filling

7. MMR

Formulation & filling

8. Hepatitis B

Filling

9. Vero cell rabies

Formulation & filling

10. Influenza

Filling

13 animal vaccines

Upstream to downstream

Source: NVI, DDC, 2008

Challenges on Vaccine Development in Thailand  Vaccine researches 

Depend on individual interest



Domestic vaccine candidate: in pre-clinic



Clinical testing— phase I-III & bridging studies 

Imported vaccine candidates

 Vaccine production 

Number of human vaccines domestically produced has been decreased overtime

National Vaccine Committee (NVC) 2001 Cabinet National Vaccine Policy & Plan • NVC

• Subcommittees 

R&D



Production



QA/QC ACIP



Governmental Organizations

NVI

NGOs

R&D / Production / QA&QC / EPI

Private Sector

National Vaccine Policy & Strategies 2005

National Vaccine Policy & Strategies 2005 Aim: To promote development on specific vaccines for vaccine self-reliance, vaccine security, and capacity building on vaccine development  Promote development on vaccine science and technology : from research to production, QA/QC & immunization 

Promote the investment in domestic upstream vaccine production industry



Encourage collaboration between governmental and private sector



Establish the National Vaccine Institute (Public Organization)

National Vaccine Agenda 2011 10 projects in 10 years  Dengue vaccine development  BCG production & New TB vaccine development  DTP-HB production  Japanese encephalitis vaccine (JEV), cell-based, production  Acellular pertussis vaccine development & production  GMP pilot plant establishment  Bio-medical & vaccine resource center establishment  Human resource development  NVI Establishment as a center for policy driver on vaccine development and immunization of the country

Current Structure of National Vaccine Institute (NVI) Ministry of Public Health (MoPH) National Vaccine Committee (NVC) Executive Board

NVI Advisors

Gen Adm & Support

Strategic & KM

Director

Vaccine Policy Form

Networking

Tuberculosis

BCG Production Mahidolvongsanusorn Building

Queen Saovabha Memorial Institute

25

Queen Saovabha Memorial Institute

BCG culture (S2 culture) Harvesting Wash

Semi-dry mass Grinding Add solution

Conc. BCG Suspension Add solution

Final Bulk

0.5 ml of vials (half-closed stopper) Freeze-drying Capping Inspection

Freeze-dried BCG Vaccine Labelling / Packaging

Final Product

26

EPI Vaccine Coverage in Thai Children 1-year Old (%) 100

80

60

BCG DTP3

40

OPV3 M

20

T

0 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2003 Source: National vaccine coverage survey

Selected Thai EPI Vaccine Coverage and Disease Incidences Diptheria

Polio

6

12

2,5

100

2

80

100

5

80

Pertussis

100

10

80

8 60

4

60

1,5

60

40

1

40

4

1

20

0,5

20

2

0

0

6

3

40

2

1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999

DIPHTHERIA CASE RATE 100

0

DTP3 COVERAGE

Tetanus neo.

80

0

0 1977

1979

1981

1983

1985

1987

1989

1991

POLIO CASE RATE

100

100

1993

1995

1997

0 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999

1999

PERTUSSIS CASE RATE

OPV3 COVERAGE

Measles

20

DTP3 COVERAGE

HB

100

6

80

80

5

90 80

4 60

60

70 60

3 40

40

50 40

100

80

60

60

40

40

20

2

20

0

20

20

0

0

30 20

1

10 0

0 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999

1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999

NNT CASE RATE

TT2+ COVERAGE

0 2520 2522 2524 2526 2528 2530 2532 2534 2536 2538 2540 2542 2544

อัตราป่ วยโรคตับอักเสบ บี MEASLES CASE RATE

MEASLES COVERAGE

ความครอบคลุมของการได้รบั วัคซีนตับอักเสบบีครบ 3 ครัง้

TB Case notification from 2001-2012

Source : Bureau of TB, Dept.of Diseases Control, MOPH (updated 31 July 2013)

29

Trends in notified new smear-positive TB cases by age group among males, 2001-2012

Source : Bureau of TB, Dept.of Diseases Control, MOPH (updated 31 July 2013)

30

Drug resistance surveillance 2012 (prelim) Preliminary data of 4th Surveillance of Drug resistance in Tuberculosis: THAILAND 2012 Newly Treated Cases

Previously Treated Cases

Combined Drug resistance

Total tested Fully sensitive Any resistance

N 1456 1216 240

Pct 100.00% 83.52% 16.48%

N 175 110 65

Pct 100.00% 62.86% 37.14%

N 1631 1326 305

Pct 100.00% 81.30% 18.70%

H+R resistance (MDR-TB)

27

1.85%

29

16.57%

56

3.43%

Mono-resistance Two drugs resistance Three drugs resistance Four drugs resistance

164 47 2 3

11.26% 3.23% 0.14% 0.21%

32 3 1 4

18.29% 1.71% 0.57% 2.29%

196 50 3 7

12.02% 3.07% 0.18% 0.43%

Any H-resistance Any R-resistance

174 30

11.95% 2.06%

46 39

26.29% 22.29%

229 69

1.41% 4.23%

Mono H-resistance Mono R-resistance

99 2

6.80% 0.14%

16 7

9.14% 4%

115 9

7.05% 0.55%

ITEMS

Note: Total = 1747 cases, 116 cases are waiting for analysis, NTRL NTP-May2013

31

TB Burden สถานการณ์วณ ั โรคโลก Number of TB cases of 22 countries

32

National Vaccine Agenda 2011 10 projects in 10 years  Dengue vaccine development  BCG production & New TB vaccine development  DTP-HB production  Japanese encephalitis vaccine (JEV), cell-based, production  Acellular pertussis vaccine development & production  GMP pilot plant establishment  Bio-medical & vaccine resource center establishment  Human resource development  NVI Establishment as a center for policy driver on vaccine development and immunization of the country

New BCG & new TB vaccine plant

Conclusion  Thailand has a strong policy on immunization and

vaccine development for vaccine security and self-

& regional-reliance  New TB vaccine has been emphasized & included

in the national vaccine development agenda  Field trial & domestic production could be possible

ways of collaboration

Thank you