Linking Regulatory Decisions and PublicHealth Decisions for Vaccines:

the Indonesian Experience

Lucky S. SlametNational Agency of Drug and Food Control (NADFC),Rep.of Indonesia

Workshop D “Vaccines and Biological”14th International Conference of Drug Regulatory Authorities (ICDRA)

Singapore, 30 November 2010

Key Points

IntroductionMandate of NADFC as NRA in Indonesia with regards to Pre-Post Market of VaccinesNational Indonesian Technical Advisory Group (NITAG) mandate Model of Interaction among NITAG, NADFC as NRA and CDC - MOHCase studyConclusion

Introduction REGULATORY CHALLENGES ON AVAILABILITY OF

VACCINES IN INDONESIA

Demand for greater access to new vaccines which are affordable to support the Indonesian Immunization Program as to reduce mortality and morbidity caused by communicable diseases

Ensuring vaccine of assured safety, efficacy and quality as well as appropriateness of its use based on the real need of majority of population.

Ensuring consistency in Pre to Post Market Risk Assessment of vaccines by implementation of Good Regulatory Practices from development, production, importation, exportation and distribution to end-user (patient/consumer).

Mandate of NADFC as NRA in Indonesiawith regards to Pre-Post Market Control of

Vaccines

5

law enforcement with a high deterrent effect

Investigation and pro-justicia

Good Laboratory Practice (GLP)

Good Clinical Practice (GCP)

GDRP

Comprehensive Audit

Good Manufacturing Practices

(cGMP)

Specification and quality of substance, product, packaging (Pharmacopeia and non-compendial)

Good Manufacturing Practices (cGMP)

Good Distribution Practice(GDP)

Good Sampling Practice(GSmP)

Good Laboratory Practice(GLP)

Inspection

FUNCTION OF NADFC BASED ON 3 MAIN PILLARS OF GOOD DRUG REGULATORY PRACTICES (GDRP)

The Role of NADFC-Indonesia at Different Stages of Vaccine Development, Production and Evaluation

Research and Development of vaccines

Research and Development of vaccines

National regulatory systemClinical trial approvalReview of dossier/ Site Master File (SMF) as a part of MA procedureLot releaseLaboratory AccessSurveillance of vaccine field performance (AEFI)Regular inspections for GMP

The role of NRA in Vaccine Seven Regulatory Functions

Production and control of vaccines

Production and control of vaccines

Clinical trials Clinical trials

Licensing/Marketing Author Licensing/Marketing Author

Post marketing surveillance Post marketing surveillance

Preclinical testing Preclinical testing

7

Vaccine Regulatory PathwaysPre-Post Market

Registration-Pre Marketing Post Marketing

Product evaluation

Marketing Authorization

AEFIsLot release

GMP inspections

Market distribution

Lab.access

Lab.access

GMP inspections

Dossier

Overall Regulatory Frameworkin Vaccine Development, Production

and Evaluation in INDONESIA

Vaccine of Assured Q,S,E

Manufacturer

Pre- IND

Manufacturing process

development(batch trial)

Preclinical trial

IND

IND Regulatory

process

Regulatory consultation

GMPPhase 1

Safety

Immuno-genicity

Phase 2

Immuno-genicity

Safety

Dose ranging

Phase 3

Efficacy

Safety

Immuno-genicity

InspectionLot release

Pre-market Evaluation

MA Granted

PreRegistration

Preliminary review of full dossier

Process of Registration

Production

GMP

GMP

PMS / AEFI Monitoring

Communication with Sponsor / Manufacturer

during CTGCP

Inspection

• Global concern• Regional related data• Local data: incidence, prevalence, death rate, age

vulnerable group, sequelae Burden of disease

• Guideline : SAGE & WHO position paper • Pilot project • TAG’s recommendation

Guideline Recommendation

• Release/ registered to NRA• Cost benefit analysis • Vaccine sustainability

Vaccine availability

• MOH policy • Socialization /training• Operational cost GOI & local government• AEFI surveillance

Planning

New Vaccine Introduction into EPI Program in Indonesia

by NRA, CDC-MOH and NITAG

The National Indonesian Technical Advisory Group on Immunization (NITAG) mandate

to advise the national government on the formulation of strategies for the control of

vaccine preventable diseases through immunization

to guide national government on issue of vaccine quality and safety, immunization

choices and strategies, new vaccines and new delivery technologies

to assist the national authorities in evidence-based decision making

Mandate of NITAGA technical independent advisory group

MOH Decree, December 15th 2006 No.1418/Menkes/SK/XII/2006,revised in 2008&2010

To provide on immunization schedules, public & private sector

Review articles & recommendation on new vaccines

Standardize of AEFI reporting through the AEFI National Committee

Provide technical advise to help the government make decisions on immunization issues

The Role of NITAG

Sub committees of NITAG(Working group)

HepatitisMeaslesPolio eradicationAEFI National Committee

InfluenzaRotavirusPneumococcusHPV

Member of Working Group is also member of Regional CommitteeAPACHI, ASAP, ARSN, & other regional vaccine advisory

committee

Model of Interaction among NITAG, NADFC as NRA and CDC - MOH

CDC - MOH

NITAGNRA

CDC MOH ‐ TAG ‐ NRA  Interaction

Decree of Ministry of Health

Liaison members

Recommendation*Immunization schedules,*AEFI reporting*Technical advised fordecisions on immunization  issues 

*Pre‐market evaluation on clinical data of new vaccines* Introduction & evaluation of new vaccines*AEFI reporting

NADFC as NRA

NRA seeks scientific advice from NITAG’s with regards to• Decision making for vaccine’s Marketing Authorization• IND process for new vaccine• Post marketing surveillance

Involvement in NITAG’s meetings or discussions for developing guidance and scientific opinions

NRA advise on Marketing Authorization process and approval for vaccines used as EPI program

NADFC’s Role in the Networking of NRA – NITAG – CDC-MOH

Involvement in the stage of IND (investigational new drug/vaccine): • Evaluation of CT protocol• Advise for immunization schedule for CT and target population

Pre-market evaluation on clinical data of new vaccines

Introduction & evaluation of new vaccines

AEFI reporting

NITAG’s Role in the Networking of NRA – NITAG – CDC-MOH

Example of Case Study(Model of Interaction among NITAG,NADFC as NRA and CDC-MOH)

Replacement Tetanus Toxoid (TT) to Tetanus Diphteriae (adult type,Td) vaccination into School Children Immunisation Program

Year Diphteria Outbreak TotalcasesCases Freq Death CFR (&)

2003 5 5 - -2004 15 13 4 26.72005 52 42 4 7.7 13002006 44 38 4 9.1 1622007 86 66 6 6.9 1832008 77 73 11 14.3 2182009 140 135 8 5.7 121

Age(years)

Percent(%)

< I 41-4 315-9 36

10-14 16>14 13

6

5 25 140

1

77 (27 cases, 50 carriers)

6

64 2

Diph

teria

Out

brea

k20

03-2

009

20092010

Data : Sub-Directorate Surveilance, CDC, 2010

Age (years)

N Seroprotection(%)

> 1 1564 801-4 281 705-9 551 75

10-14 584 80

Data: National Institute Health Research Development, MOH, 2007

Protective titer of anti diphteria antibody ≥ 0,1 IU/ml

Year Coverage (%)2005 83.12006 90.62007 90.6*2008 93.52009 95.4

*Basic Health Research 2007 : 67.7%

DTP3 immunization coverage• High coverage of DTP-3• Not spread equally in all areas• No booster at 18-24 months

Seroprotection• 20%-30% children below 14

years of age did not reach protective level

CDCProblem:Diphteria

outbreak

NITAG*Review data

*Vaccine production capacity (BF)

NITAG Recommendation• Td use in school children• Outbreak response strategies

Bio Farma• Increase production

capacity of Td vaccine• Vaccine registration to

NRA

NRATd vaccine registration for

National Programme

Letter to NITAG

August 2008

November 2008

Registration November 2008

Registration Approval November 2009

Ask the capacity of vaccine production

Update

RecommendationApril 2010

Introduction of Td Vaccine in theNational Immunization Program

Lot Release & Lab Access

System on MA

CO

NT

RO

L B

Y N

AD

FC

IND

ON

ESI

A

Component ofNRA Function

CONCLUSION Linking Regulatory Decisions & Public Health Decisions for Vaccines

Clinical Trial

Monitoring PMS incl AEFI

Regulatory Inspection

VACCINE of assured

QUALITY, SAFETY &

EFFICACY, andaccording to the

actual need of the population

Model of Interaction among NITAG, NADFC as NRA & CDC- MOH

Borobudur-Budha’s Temple-Central Java Prambanan-Hindu’s Temple-Central Java

VISIT INDONESIA

Bali

Mt. Bromo-East Java

Bunaken –North

Sulawesi

Thank You