ThaiFDA

byYuppadee JAVROONGRIT, Ph.D.

Assistant Director, Drug Control Division, FDA, ThailandThe 14th ICDRA

Raffles City Convention Centre, Singapore29 November 2010

Workshop K-Regulatory functions/marketing“Current Status and Future Perspective

for Mutual Recognitionin the context of ASEAN Collaboration”

ThaiFDA

• the ASEAN• collaboration• Mutual Recognition on Pharmaceuticals

Topics

ThaiFDA

• the ASEAN• collaboration• Mutual Recognition on Pharmaceuticals

Topics

ThaiFDA

total population ~ 580 million

- Brunei Darussalam- Cambodia- Indonesia- Lao PDR- Malaysia- Myanmar- Phillippines- Singapore- Thailand- Vietnam

AMSASEAN = Association of Southeast Asian Nations

Established --> 8 Aug. 1967Area --> 4.5 mill.Km2

ThaiFDA

The ASEAN- major Collaboration

ASEAN Summit

- Economic Cooperation-AEM - Political & Security Cooperation- Socio-cultural Cooperation

The Leader (Presidents, Prime Minister)

Minister of Economic/Trade MinistryMinister of Foreign Affairs Ministry

ThaiFDA

• the ASEAN• collaboration• Mutual Recognition on Pharmaceuticals

Topics

ThaiFDA

The ASEAN- CollaborationASEAN Summit

Economic Cooperation-AEM - Political & Security Cooperation- Socio-cultural Cooperation

WG1 - Mutual Recognition Arrangements (MRAs) & StandardsWG2 - Accreditation and Conformity Assessment Sub-WG - Scientific/Industrial Metrology

ACCSQ

ACC - ASEAN Committee on CosmeticPPWG - Pharmaceutical PWGEE PWG- Electrical and Electronic PWGPf PWG - Prepared Foodstuff PWGTMHS PWG - Traditional Medicine & Health Supplement PWGMedical Devices&Equipment PWGA PWG - Automotives PWGRB PWG - Rubber-based PWG…….

AWGPD – ASEAN Working Gr. on Pharmaceuticals Dev.…..

ThaiFDA

The ASEAN- CollaborationASEAN Summit

Economic Cooperation-AEM - Political & Security Cooperation- Socio-cultural Cooperation

WG1 - Mutual Recognition Arrangements (MRAs) & StandardsWG2 - Accreditation and Conformity Assessment Sub-WG - Scientific/Industrial Metrology

ACCSQ

ACC - ASEAN Committee on CosmeticPPWG - Pharmaceuticals PWGEE PWG- Electrical and Electronic PWGPf PWG - Prepared Foodstuff PWGTMHS PWG - Traditional Medicine & Health Supplement PWGMedical Devices&Equipment PWGA PWG - Automotives PWGRB PWG - Rubber-based PWG…….

AWGPD – ASEAN Working Gr. on Pharmaceuticals Dev.…..Mutual

Recognition

ThaiFDA

• the ASEAN• collaboration• Mutual Recognition on Pharmaceuticals

Topics

ThaiFDA

The ASEAN- CollaborationASEAN Summit

Economic Cooperation-AEM - Political & Security Cooperation- Socio-cultural Cooperation

WG1 - Mutual Recognition Arrangements (MRAs) & StandardsWG2 - Accreditation and Conformity Assessment Sub-WG - Scientific/Industrial Metrology

ACCSQ

ACC - ASEAN Committee on Cosmetic

PPWG - Pharmaceuticals PWGEE PWG- Electrical and Electronic PWGPf PWG - Prepared Foodstuff PWGTMHS PWG - Traditional Medicine & Health Supplement PWGMedical Devices&Equipment PWGA PWG - Automotives PWGRB PWG - Rubber-based PWG…….

AWGPD – ASEAN Working Gr. on Pharmaceuticals Dev.…..Mutual

Recognition

ThaiFDA

ACCSQ/PPWG (1999-now)ASEAN Consultative Committee

for Standards and Quality / Pharmaceutical Product Working Group

Objective:to develop harmonization scheme of Pharmaceuticals regulations of the ASEAN member countries, to complement and facilitate the objective of AFTA, particularly, the elimination of Technical Barriers to Trade posed by the regulations, without compromising on drug quality, efficacy, and safety”

ThaiFDA

BA/BE Studies Malaysia

• ACTR : Quality IndonesiaSafety PhilippinesEfficacy Thailand

• ACTR-Guidelines : Analytical Validation Thailand

Process Validation SingaporeStability Study Indonesia

Chair country : MalaysiaCo-Chair country : Thailand

The PPWG– Lead country & Assignment (1)

ThaiFDA

Administrative & Glossary Malaysia• ACTD : Overall ACTD & ACTD Organization Thailand

Quality Indonesia

Clinical /Efficacy ThailandNon-Clinical Philippines

• IWG :Indonesia (Co-Chair)Singapore (Chair)

• MRA-BA/BE: Indonesia / Malaysia (Co-Chairs)

• MRA-GMP : Singapore / Malaysia (Co-Chairs)

• Post-marketing Alert System (PMAS): Singapore / Malaysia

The PPWG– Lead country & Assignment (2)

ThaiFDA

Comparative studyon Registration Requirement & Regulation

Agreement(ASEAN Harmonized Product, MRAs)

Identification the “Key Area on Requirements”for Harmonization

the Works -“Lead Countries”/Members

the Meetings

Implementation Capacity Building/Strengthening

Endorsement (ACCSQ / SEOM / AEM /…)

Working Scheme of the PPWG

- Tech. discussion gr.- Dialogue w/ Association - IWG- MRA Task forces - HOD- PPWG

Current Activities(1) Implementing ASEAN Har.products

- for new application - for existing Drug license (by 2012)

(2) Establishing GMP-MRA JSC(3) BA/BE MRA(4) Updating Tech.gls.(5) New ares of integration: Biological ,

Biotech., Biosimilar product(6) Facilitating the AEC (7) Coop.with international forum: WHO,

ICH, etc.

ThaiFDA

1. Harmonized Key Areas2. ACTR & ACTD & Technical guidelines3. Full implementation timeline4. MRA-GMP Inspection5. Vaccine chapter

The PPWG– Recognition & Agreement

6. on going tasks ;- MRA – BA/BE Testing- Variation guideline- updating the Technical guidelines : Q, S, E- training activities- new area of harmonization

ThaiFDAMutual Recognition (1)

ACTR, ACTD, Technical guidelines• ACTR (ASEAN Common Technical Requirement)• ACTD (ASEAN Common Technical Dossier)• Technical “Quality, Safety, Efficacy” guidelines -

- adopted guidelines (from WHO, ICH, and International pharmacopoeia)- newly developed ASEAN Quality guidelines;

(1) Analytical Validation guideline(2) BA/BE Studies guideline(3) Process Validation guideline(4) Stability Study guideline

ThaiFDA

adopted 15 ICH-Safety gl.

S&E Technical guidelineGuideline - Safety

Guideline - Efficacy

adopted 11 ICH-Efficacy gl. (E1, E2A, E2C, E3, E4, E6-11)

accepted as Ref.gl. 4 ICH-Efficacy gl. (E2C(A), E2D, E2E, E12A)

ThaiFDA

ACTRA set of Written Materials

intended to guide applicants to prepare application dossiers

in a way that is consistent with the expectations of

all ASEAN Drug Regulatory Authorities

ACTDThe part of

marketing authorization application dossier that is common to

all ASEAN member countries

ThaiFDA

No. Parameter ComponentsRequirement *

NCE Bio. MaV MiV GP

Rt. S/P Ind.

Note: * = all studies should be complied to ICH Guidelines on Efficacy (current are E1-E12)NCE = New Chemical Entity

Bio. = Biotechnological productMaV = Major Variation (variation affecting 1 or MORE of following aspect: Rt., S/P, Ind., or other Non-MiV)

- Rt. = Route of Adminstrative- S/P = Strength & Posology- Ind. = Indication

MiV = Minor Variation (variation not affecting 1 or MORE of following aspect: Rt., S/P, Ind., API)GP = Generic Product

Format of ACTR

ThaiFDA

* = upon request

Format of ACTD

Part I

TOCAdmin.data / Product Info.

Part IIQuality

Overall Summary& Report

Part IIINon-Clinical

Overview,Summary,

& Study Report *

Part IVClinical

Overview,Summary,

& Study Report*

ThaiFDA

ACTR - Quality

Drug Substance - General info.- Manufacture - Characterisation- Control of Drug Substance- Ref. Std. or Materials- Container Closure System- Stability

Drug Product - Description and Composition- Pharmaceutical Development- Manufacture- Control of Excipients- Control of Finished Product- Ref. Std. or Material - Container Closure System- Stability - Product Interchangeability

Equivalence evidence

ThaiFDA

ACTR - Safety

Pharmacology - Primary P’dynamics- Secondary P’dynamics- Safety P’cology- P’dynamic Drug Interaction

Toxicology - Single Dose Toxicity- Repeat Dose Toxicity- Genotoxicity- Carcinogenicity- Reproductive & Development ToxicityPharmacokinetics

- Absorption- Distribution- Metabolism (inter-species comparison)- Excretion- P’cokinetic Drug Interaction

(Non-clinical)- Other P’cokinetic Studies

Local Tolerance

Other Toxicity Studies

List of Key Literature Ref.

ThaiFDA

ACTR - Clinical Data

BA & BE Studies- BA Studies- Comparative BA or BE Studies

Human P’cokinetic Studies

Studies Pertinent to P’cokinetics Using Human Biomaterials

Human P’codynamic Studies

Efficacy and Safety

Post Marketing Data (if available)

References

ThaiFDA

Part 1: TOC Admin.Data&Product Info.Section A: IntroductionSection B: Overall ACTD-ToCSection C: Doc. Required for Registration

Part 2 : Quality DocumentSection A: ToCSection B: Quality Overall SummarySection C: Body of Data

Part 3 : Non-clinical Document

Section A: ToCSection B: Non-clinical OverviewSection C: Non-clinical Written & Tabulated Summaries

1. ToC2. Pharmacology3. Pharmacokinetics4. Toxicology

Section D: Non-clinical Study Reports1. ToC2. Pharmacology3. Pharmacokinetics4. Toxicology

Part 4 : Clinical Document

Section A: ToCSection B: Clinical OverviewSection C: Clinical Summaries

1. Summary of Biopharm & Associated Analytical Methods

2. Summary of Clinical Pharmacology Studies3. Summary of Clinical Efficacy4. Summary of Clinical Toxicology5. Synopses of Individual Studies

Section D: Tabular Listing of All Clinical StudiesSection E: Clinical Study ReportsSection F: List of Key Literature References

Content of ACTD

ThaiFDA

• starting - 2005• goal - ASEAN Sectoral MRA on GMP Inspection

- signed by AEM- Apr.2009• working area ;

- Code of GMP Standards (PIC/S, or equivalence)- Quality System of GMP’s Inspection Unit (PIC/S quality requirement)- GMP Inspection System & Report

• the MRA ;- on Pharmaceuticals Product, not Bio./Radio/CT materials- recognition GMP Certificate & GMP Inspection Report for product registration- on principle “ASEAN+2”- establishment of Joint Sectoral Committee (JSC)

- assessment Competency of GMP Inspection Unit (Gov. org.)- listing the Recognized GMP Inspection Unit (of AMS)

Mutual Recognition (2)MRA– GMP Inspection

ThaiFDA

• starting - 2005• goal - ASEAN Sectoral MRA on BA/BE Studies Report• working area ;

- Comparator product (definition, decision tree, selection, list)- Accreditation of BA/BE Centres (criteria for audit/inspection, certification)- Standards on GCP & GLP- Framework for mutual acceptance of BA/BE Study Report

• the MRA ;- mutual acceptance of BA/BE Study Report

Mutual Recognition (3)MRA– BA/BE Study Report

on going !

ThaiFDA

• to facilitate AFTA & AEC• to eliminate Technical Barrier to Trade (TBT)• to align to International Standards• without compromising on Quality, Safety, Efficacy of

Pharmaceuticals

The PPWG– Recognition & Agreement

Product License

the Decisionof individual Member Country

ThaiFDA

Together !!!Thank You ...