ROLE OF THE INDONESIA DRUG

REGULATORY AUTHORITY ON
MARKETING AUTHORIZATION

Dra. Farida Anwar, M.Si

 OUTLINE

Introduction

Pre and Post Market Control

PIC/s Membership

ASEAN Harmonization
 HEAD OF THE NATIONAL AGENCY
OF DRUG AND FOOD CONTROL
INSPECTORATE
ORGANIZATION
OF NADFC
PERMANENT SECRETARY
1. Bureau of Planning and Financing
2. Bureau of International Cooperation
3. Bureau of Legal and Public Relation
4. Bureau of General Affairs

National Centre of Drug Centre of Drug Centre of Drug

Laboratory of Drug and Food and Food and Food
and Food Control Investigation Research Information

Deputy I Deputy II Deputy III

Therapeutic Product, Narcotics,
Psychotropic and Addictive
Control
1. Directorate of Drug and
Biological Product
Evaluation
2. Directorate of Therapeutic
Product Standardization
3. Directorate of Therapeutic
Product and Consumer Good
Production Control
4. Directorate of Therapeutic
Product and Consumer Goods
Distribution Control
5. Directorate of Narcotics,
Psychotropic and Addictive
Substance Control
Traditional Medicines,
Cosmetics and Compliment
Products Control
1. Directorate of Traditional
Medicines, Food Supplement
and Cosmetics Evaluation
2. Directorate of Traditional
Medicines, Cosmetics and
Compliment Product
Standardization
3. Directorate of Traditional
Medicines, Cosmetics and
Compliment Product Control
and Certification
4. Directorate of Indonesian
Traditional Medicines
Food Safety and Hazardous
Substance Control
1. Directorate of Food Product
Evaluation
2. Directorate of Food
Standardization
3. Directorate of Food Control
and Certification
4. Directorate of Product and
Hazardous Substance Control
5. Directorate of Surveillance and
Food Safety

Drug and Food Control

Regional Offices 33 Technical Units in Indonesia
 VISION AND MISSION

Vision
Safe Food and Medicine to Improve Public
Health and National Competitiveness

• Protecting public health by strengthening

Mission risk-based food and drug control system
• Ensuring the resilience of business operator
to provide medicine and food safety
assurance, strengthening partnerships with
stakeholders
• Improving institutional capacity of Badan
POM
 CATCHMENT AREA
OF INDONESIAN DRUG AND FOOD CONTROL
Regulatory Framework of Quality Assurance

components

Assured Q,S,E of medicinal product

Documentation, Monitoring, and Evaluation

Pre Regulatory Technical Post-marketing

Marketing Elements Elements authorization
(full spectrum/ (quality surveillance
Assessment
comprehensive specifications, (for quality and
(marketing Basic tests, adverse events,
functions incl,
authorization/ inspection, GMP, GLP, and product
licensing and recall, central & GPP, GDP, information/
registration) provincial lab) GSP, GCP) promotion)

Adequate legislation and law enforcement

 Core of Regulatory Function
Pre-Market
 Review and approval of
medicinal products for clinical
trials  Clinical Trial
Authorization (CTA) ; import
permit
 GMP (Good Manufacturing
Practices) inspections of
medicinal products
manufacturers, including
biologicals
 Benefit-risk assessment and
approval of medicinal
products, including
biologicals  Marketing
Authorization
Post-Market
 Safety monitoring & risk-benefit
assessment of marketed products
 Risk communication & provision of
unbiased information to healthcare
professionals & consumers
 Quality surveillance of marketed
products
 GMP and GDP (Good Distribution
Practice) inspections
 Investigation & enforcement of
legislation administered by NADFC
(BPOM)
 Prosecution of offenders
 LINKAGE OF REGULATORY FUNCTION ON DRUG
CONTROL (Pre and Post Market)

PRE MARKET POST MARKET

Product Quality Consistency

Development Data :  Production facility and
Formulation, GMP Data
Distribution Inspection
Stability, BA, BE
 Sampling and testing

Safety Consistency
Admin Safety &
Dossier Efficacy  Sampling and testing
Data
Data  Monitoring of ADR

Evaluation Information Consistency

 Labeling Monitoring
 Advertising Control
Marketing Authorization
 Concept of Pre-Market Evaluation
CRITERIA AND REQUIREMENTS

Scientifically Within time

Sound target

GOOD GOOD
DOSSIER Procedurally Legally & DOSSIER
PRACTICES predictable scientifically PRACTICES
consistent

1. Good, clear & defined 3. Well trained people

process Good Quality 4. Good Management
2. Consistent application Decision Review Practices

PRODUCTS WITH REGISTRATION NUMBER

 DOSSIER Format- ACTD

Country-specific
administrative data.
Not part of ACTD
Part I
Administrative Data
& Product Information
ACTD
Part II Part III Part IV
Quality Non-clinical
Clinical
Overview,
Overall Summary Overview,
Summary,
& Reports Summary Assessment
Drug substance & Study Reports* Reports,
Drug product & Study Reports*
* Upon Request
 QUALITY DOCUMENT
QUALITY OVERALL SUMMARY
S. DRUG SUBSTANCE
S.1 General information (Nomenclature,
Structural formula, General
properties)
S.2 Manufacturing process and
Manufacturer(s) (manufacturer,
description of manufacturing process
and process control, control of
material, controls of critical steps and
intermediates)
S.3 Characterisation
S.4 Control of drug substances :
specification & analytical procedures
include validation of analytical
procedures, batch analyses, and
justification of specification
S.5 Reference standards or material
S.6 Container closure system
S.7 Stability
P. DRUG PRODUCT
P.1 Description and composition
P.2 Pharmaceutical development
Information on development studies;
Component of drug product; Finished
product; Manufacturing process
development; Container closure system;
Microbiological attributes; Compatibility
P.3 Manufacture : Batch formula; Manufacturing
process and process control; Controls of;
critical steps and intermediates; Process
validation and/or evaluation
P.4 Control excipients
Specification and analytical procedures
P.5 Control of finished product Specification,
analytical procedures, validation of analytical
procedures, batch analyses, characterization
of impurities, justification of specification
P.6 Reference standards or materials
P.7 Container closure system
P.8 Stability On Site
P.9 Product interchangeability/
equivalence evidence 11
 WHO SHOULD
APPLY?

Pharmaceutical Industries
located in Indonesia
How to apply
Pre-registration (timeline 40 WD) registration for
* Determination of the registration category MA?
and evaluation path/timeline
* Consultation on completeness of
registration dossier/document
* Registration Fee

Registration (150 WD)

* Submit registration dossier
according to the registration
category, completed with bank
receipt of registration fee
 REGISTRATION CATEGORY

NEW REGISTRATION VARIATION RENEWAL

Category 1 Category 4 Category 7

New Drug and Biological Major Variation(VaMa)
Products, including
Similar Biotherapeutic
Product (SBP) Category 5
Minor variation with
Category 2
approval (VaMi-B)
Copy Drug/Generics
Category 6
Category 3 Minor variation with
Others notification (VaMi-A)
 TIMELINES for EVALUATION
• Minor variation which need approval
40 WD • Application for Export only

• Life saving drugs

• Orphan drugs
• Drugs for National Program
100 WD • Drug development and all Clinical Trials in Indonesia
• Major Variation( i.e New Indication/posology) for the above
products included in path 100 WD

• Drug which has been marketed in the countries which have

implemented harmonized evaluation system or established
150 WD evaluation system
• Major Variation (i.e New Indication/posology)for the above products
including in path 150 WD).
• Copy/Generic drug

• New drugs, Biological Products, Similar Biotherapeutic

300 WD Products, Major Variation (New indication / posology) which
are not included in path 100 WD and 150 WD
 Criteria On Drug Evaluation
(Risk Based Assessment)

Efficacy Product Information/ Specific

and Safety Quality Labelling Criteria

- Non - Manufacturing Product - According to

Clinical Process Information public health
Studies according to should need
GMP correct and
- Clinical - Psychotropics :
- Product objective to
Studies advantage of
Specification ensure
(phase E&S over
rational use
I,II,III) marketed
- Stability Study of drug.
products
- BE Study (for
generic - National Program:
products) local clinical trial,
(if requested)
 NATIONAL COMMITTEE ON DRUG EVALUATION

• Consist of experts in the field of clinical

pharmacology, pharmacy, biology and relevant
clinicians
• Recruited from Universities and other relevant
institutions
• Sign statement of independency (not to have a
conflict of interest)
• Conducting meeting regularly to discuss the
result of evaluation on the safety, efficacy and
quality of drugs
16
 Risk Base Review
Safety and Efficacy Aspect : Implementation of GRP
• Scientific and Evidence based:
Pre-clinical studies, product (Good Review Practices):
development, clinical protocol • Transparancy and
design
• Risk versus benefit risk. profesionalism
• Special case : identify and evaluate • Standardize general review
safety process
Quality Aspect: • Avoid inconsistent decision
Standardization and Control on
specification and Method of Analysis making
of active ingredients and finished • Strengthen review
products
Control of production process:
management
 according to GMP : ensure safety • Accelerate review time
and consistency • Communication with
Control on promotion and labelling
• According to approved Product
stakeholder
Information
• Rational
 CRITERIA FOR IMPORTED DRUG
 Drugs for public health program
 Based on decision by Health program

 New innovated drugs

 Under patent protection
 Originator drugs

 Drugs which are needed but not feasible to be

produced locally
 Manufacturing technology & facility not available in Indonesia
 Manufacturing capacities insufficient to fulfill national need
 Economically not feasible to be produced in Indonesia due to
low need (i.e Orphan drugs)
 Produced through centralized system by foreign
pharmaceutical industry which has invesment in Indonesia,
supported by balance of import and export activity
 REQUIREMENT FOR IMPORTED DRUG

 Applicant
 Pharmaceutical Industries in Indonesia having written
authorization from the manufacturer abroad.

 Manufacturer
 Have manufacturing Licence and meet GMP requirement as
proven by : - Valid GMP Certificate
- Data of last inspection within the last 2 years
 Submit latest Site Master File (SMF) document, if :
• The manufacturer has not had any product with the same
dosage form authorized to be marketed in Indonesia
• The manufacturer has product with the same dosage form
authorized to be marketed in Indonesia, but there is a change
of production facilities.

 Site Inspection
 If SMF evaluation results requires evidence of compliance to
GMP, site inspection will be conducted.
 Requirement on Equivalence Study
(Decree of the Head of The NADFC dated 30 December 2011)

 Equivalence Study:
 Comparative Dissolution Test
 Bioequivalence Study
 Required for : 10 therapeutic classes (89
active substances) + modified release drug
 Implementation :
Copy/generic drugs:
 In registration process
 New registration
 Renewal
 POSTMARKET CONTROL
Safety aspects :
Monitoring of Adverse Drug Reactions /Pharmacovigilance

Quality aspect:
• Inspection on GMP:
to ensure that the drug products are consistently
manufactured according to standard of Q requirement.
• Inspection on GDP :
to ensure that the drug products are distributed in
expedited manner to provide its accessibility for the
patients.
• Sampling, Laboratory testing

Monitoring of labelling, adverstising and other promotional

activities 21
 PHARMACOVIGILLANCE PROGRAM
MoH Decree No. 1010/Menkes/Per/XI/2008
on Drug Registration, Article No. 22
Re – evaluation of marketed drug is done under following
circumstances:
– Post-market surveillance reveals that the risk
outweighs its benefit
– The effectiveness is not better than its placebo
– Not met bioequivalence requirements
– Need to improving composition and reformulation
MoH Decree No. 1799/Menkes/Per/XII/2010
on Pharmaceutical Industry, Article No. 9
Pharmaceutical Industry (Marketing Authorization
Holder) must perform Pharmacovigillance
 PHARMACOVIGILLANCE PROGRAM

Head of NADFC Regulation No. HK.03.1.23.12.11.10690

of 2011 on Pharmacovigilance Implementation for
Pharmaceutical Industry and its Technical Guidelines

Pharmaceutical Industry (MAH) must report:

- ADEs/ADRs/AEFI as Spontaneous Reports of their marketed
drug/vaccines
- PSUR for the products that meet the criteria and as required by
NADFC
- Post Market Study for certain products as required by NADFC
- Scientific Journal and or publication relating with safety issue of
their respective product
- Regulatory Action by other DRAs relating with their respective
product
- Action by Global Company in other country
- Risk Management Plan as required by NADFC
 PIC/S MEMBERSHIP

PIC/S

An international organization established as a

forum for cooperation among regulatory GMP
Inspectorate

Mission PIC/S

Leading in the development, implementation

and maintenance of harmonized GMP standards
and quality system implementation of GMP
Inspectorate
 PIC/S Objective
• Harmonization of inspection procedures by
establishing standard for GMP
• Provide training opportunities to the GMP inspectors.
• Facilitating collaboration and networking between
authorities and International Organizations to
increase mutual trust (mutual confidence)
• Mutual recognition of inspection reports.

PIC/S members
Indonesia become a PIC/S member No.41,
efective since 1 July 2012
(ASEAN member: Singapore, Malaysia, Indonesia)
 Benefit of Becoming PIC/S Member
Consumers:
Government:
 Obtain high quality
drug
product according to the  NADFC position is aligned with
quality standards other PIC/S participating
authorities.
 Improve NADFC performance
 Facilitating collaboration and
networking between authorities
and International Organizations
to increase mutual trust (mutual
confidence)
 Harmonization of inspection
procedures by establishing
Industry : standard for GMP
 Increase the Pharmaceutical Industry  Fast information access through
competitiveness Rapid Alert System.
 Increase the potency of export  Become an expert team
 Increase the level of confidence of the members in writing guidelines
manufacturer.
 Mutual recognition of GMP Certificate
Sources: www.picscheme.org
ASEAN Harmonization on Pharmaceuticals

ASEAN Members Countries :

Brunei Darussalam Myanmar

Cambodia Philippines

Indonesia Singapore

Lao PDR Thailand

Malaysia Vietnam
 Objective of PPWG

“To develop harmonization schemes of

pharmaceutical regulations of the ASEAN
member countries to complement and
facilitate the objective of AFTA, particularly
the elimination of technical barriers to trade
posed by regulations,
without compromising product quality,
efficacy and safety”
 SCOPE of PPWG
• Exchange of information on existing
requirements and regulations
• Review existing pharmaceutical requirements
and regulations, and conduct comparative
studies
• Study other harmonized procedures and
regulatory system
• Develop technical requirements
• Establish common technical documents
towards achieving MRA
 Strategies
• Comparison of existing product registration
requirements for pharmaceuticals
• Development of common technical requirements
(CTR) for pharmaceutical product registration
• Development of common technical dossier (CTD)
towards MRA
• Implementation of harmonized ASEAN
Pharmaceutical Product Dossier

ACTD implementation by 31 December 2008 at the latest: full

acceptance of dossier format taking into account ACTR and its
relevant GLs
30
 DEFINITIONS of ACTR and ACTD
 ASEAN COMMON TECHNICAL REQUIREMENT
(ACTR):
A set of written materials, intended to guide
applicant(s) to prepare application dossier in a
way that is consistent with the expectations of
all ASEAN Drug Regulatory Authorities (DRA)

 ASEAN COMMON TECHNICAL DOSSIER (ACTD):

The part of the marketing authorization
application dossier that is common to all
ASEAN member countries
 ASEAN HARMONIZED PRODUCT

ACTR GUIDELINES
(ASEAN COMMON ACTD
TECHNICAL (ASEAN COMMON and Q&A
REQUIREMENT) TECHNICAL DOSSIER)

• GL on Stability Study
• GL on Analytical
• Technical • Standard document Validation
Requirements on Q, for drug registration • GL on Process
E, S, Labeling / PI Validation
• Submission of
Admin. • GL on BA/BE Study
documents is
• Relationship to according to ACTR • GL on Efficacy and
GMP Safety (refer to some
implementation parts of ICH GL)
 TECHNICAL WORKING GROUP (TWG)

 QUALITY:
 ACTR/ACTD QUALITY : Indonesia
 ASEAN Guideline on Stability Study : Indonesia
 ASEAN Guideline on Process Validation : Singapore
 ASEAN Guideline on Analytical Method Validation : Thailand
 ASEAN Guideline on BA/BE Study : Malaysia

 NON CLINICAL/CLINICAL :
 ACTR/ACTD Non-clinical/safety: Philippines
 ACTR/ACTD Clinical/Efficacy : Thailand

 OTHER TWG:
 Biologics : Indonesia and Singapore
 Variation Guideline : Malaysia
 Thank you
Thank you
Gamsa
34