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Drug Regulation

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in Thailand

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by
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VIVAN PROMPRADITH, M.Sc.
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PATHARAVAN CHIMVONG, M.Sc.

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Pre-marketing control
Bureau of Drug Control
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Thai Food and Drug Administration (Thai FDA)

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August 3, 2017
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Outline

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• Organization of Bureau of Drug Control

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• Laws and Regulations concerning Drug Registration
• Drug Registration and Approval

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 Definition of New Drugs and Generic Drugs

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 ASEAN Harmonization and Requirements
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for New Drugs Registration
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 New Drugs Review Process
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- Standard review
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- Priority review
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- Abridged review
- Conditional Approval and Unconditional Approval of New Drugs
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The Organization Chart of Bureau of Drug Control

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Bureau of Drug Control

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Administrative Sub-division

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System
AN Standards and Regulations Division
Pre-marketing Division
Development Division
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Post-marketing Division
Pharmaceutical (Chemical) Product Biological Product Veterinary Drug
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Sub-division Sub-division Sub-division

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Advertising Control IND Sub-division

Sub-division Herbal and
Traditional Drug Sub-division
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Roles and Responsibilities

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The main role of the Thai FDA is to protect

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consumers health, especially, to ensure safety,

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quality and efficacy of health products within its

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remit. These include foods, drugs, psychotropic
substances, narcotics, medical devices, volatile
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substances, cosmetics and hazardous substances
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available in the country. This has to be implemented

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in accordance with national legislation and

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international agreements.
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Regulation of Drugs

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Current Laws and Regulations :

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•Drug Act B.E. 2510 (1967)
•Drug Act (2nd Revision) B.E. 2518 (1975)

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•Drug Act (3rd Revision) B.E. 2522 (1979)
•Drug Act (4th Revision) B.E. 2527 (1984)
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•Drug Act (5th Revision) B.E. 2530 (1987)
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•Ministerial Regulation on Drug Registration

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B.E. 2555 (2012)

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Pre-Marketing : Licensing

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The drug Act requires that persons who wish

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to sell, produce or import drugs into Thailand have

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to obtain a license from the Thai FDA

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• License to manufacture
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• License to sell
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• License to import
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Pre-Marketing : Registration

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• Registration process is to ensure efficacy,

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safety and quality of drugs freely sold in the

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Kingdom

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• Only the authorized licensees can apply for
drug registration
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• Upon receipt of Drug Registration Certificate,
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the drug can be lawfully marketed

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• The granted certificate is valid to the validity of

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its authorized licensee

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Pre-Marketing : Advertising Control

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• Drug Advertisements and other promotional

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materials need to embody truth and accuracy

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•
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Advertisements of any kinds must be approved
by Thai FDA before being disseminated
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Post-Marketing

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• Marketed products regularly sampled for

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testing at the drug analysis Laboratory of

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the Department of Medical Sciences

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• Inspection of manufacturing sites and
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pharmacy stores
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• GMP Clearance of Overseas Pharmaceutical

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Manufacturers – PIC/S
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Pharmaceutical (Chemical) Product

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Sub-division

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New Drugs Generic Drugs

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Definition “New Drugs”

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• New Chemical Entities (NCE)

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• New Indication (NI)

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• New Combination (NCO)

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AN
• New Delivery System (ND)
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• New Route of Administration (NR)

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• New Dosage Form (NDOS)

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• New Strength (NS)

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Definition “Generic Drugs”

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• Same active ingredient(s)

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• Same dosage form

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• Same strength

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• Same route of administration
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• Same conditions of use
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Compared to reference drugs (New Drugs

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in Thailand which registered after 1991)

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Drug Registration Process

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Step 1

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The permission to

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import/manufacture

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2 main steps drug samples

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Step 2
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Application for product registration approval

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The permission to import/manufacture

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drug samples

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Documents:

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1. Application form (Por Yor 8/Nor Yor 8/Yor Bor 8)*

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- Manufacturer/Importer Name and Address

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- License to manufacture/import Number

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- Product Name and Description

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- Drug Formula (active ingredient(s) only)
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- Packaging
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- Quantity of drug sample to manufacture/import
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2. Labels
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3. Leaflets
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*Por Yor 8 = Manufacturer drug product

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Nor Yor 8 = Importer drug product

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Yor Bor 8 = Manufacturer Thai Traditional drug

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Flowchart of Drug Review Process

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Applicant* Step 1

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Submit Application at OSSC Step 2

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[Completeness Review] Dossier Screening Review Step 3

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[Technical Review] AN Review by Experts/ Step 4
Subcommittee
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Make Decision by FDA Step 5

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Approved Rejected Drug Committee

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*Applicant: Persons licensed to produce/import drugs

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From step 1 to step 2

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Since July 2015 - Licensing Facilitation Act B.E. 2558 (2015)

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Applicants

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Prepare Dossier

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(ASEAN HARMONIZATION)
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Submit Application at OSSC

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Step 2

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Since July 2015 - Licensing Facilitation Act, B.E. 2558 (2015)

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Dossier Screening Review

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[ Review for completeness within 1-2 days]

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✔

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Accept Correction

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[Within 15 days]
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✖ ✔
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Reject Accept
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From step 4 to step 5

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Review by Experts

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Queries issued to applicant

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[Within 30 days]

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Query response submission
to Thai FDA

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AN2nd Round Review by Experts /
Subcommittee
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Make decision by FDA

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Approved Rejected Drug Committee

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Application for product approval

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registration

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To ensure quality, efficacy

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Product Registration and safety of the products

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• New Drugs

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• Generic Drugs

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• ASEAN harmonization on pharmaceutical registration

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 ACTD, ACTR

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• Fast track or priority review for life-threatening medicines
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and medicines in urgent need for public health problems
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• Abridged evaluation of new drugs using reference drug

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regulatory authority assessment (~30% reduction of

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timelines)
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• Safety Monitoring Program for New Drugs

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ASEAN Harmonization

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On Pharmaceutical Registration

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- ASEAN Common Technical Requirement (ACTR)

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- ASEAN Common Technical Dossier (ACTD)

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Thailand has fully implemented ASEAN harmonized products

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in pharmaceutical registration since 2009

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AN
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ASEAN HARMONIZATION

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ON PHARMACEUTICAL REGISTRATION

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FDA Notification 2008: Implementation of ASEAN Harmonized

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Product on Pharmaceutical Registration

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Date started: 1Jan 2009

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• Manual/Guidance on New Drug Registration (ASEAN Harmonization)

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• Requirements and Documents to be submitted for New Drug Registration
(ASEAN Harmonization)

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• Manual/Guidance on Generic Drugs Registration (ASEAN Harmonization)

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4 Technical Guidelines
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(1) Analytical Validation Guideline
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(2) BA/BE Studies Guideline

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(3) Process Validation Guideline

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(4) Stability Study

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New Drugs Registration

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(ASEAN Harmonization)

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ASEAN Common Technical Dossier (ACTD)

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Documents to be submitted 4 Parts

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Part 1: Administrative Data and Product Information
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Part 2: Quality Document

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Part 3: Nonclinical Document

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Part 4: Clinical Document

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Part 1: Administrative Data and Product Information

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3 Sections:

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Section A: Introduction
Section B: Overall Table of Contents

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Section C: Documents required for registration

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- Application form(Yor1)

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- Certifications: License to manufacture/import, GMP Certificate,

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Certificate of Pharmaceutical Product (CPP)/Certificate of Free Sales (CFS)

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- Labeling
- Product Information:
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Package Insert (PI)
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Summary of Product Characteristics (SPC): required for NCE
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Patient Information Leaflet (PIL)

- Por Yor 8/Nor Yor 8
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- Photograph of drug product

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- Comparative data between new drug and existing drugs

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Part 2: Quality Document

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ACTD 4 Sections:

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Section A: Table of Contents

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Section B: Quality Overall Summary: Drug Substance, Drug Product

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Section C: Body of Data: Drug Substance, Drug Product

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Section D: Key Literature References

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ACTR:

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Drug Substance Drug Product

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- General Information
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- Manufacture - Pharmaceutical development
- Characterization - Manufacture
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- Control of Drug Substance - Control of excipients
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- Reference Standards - Control of Finished Product

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- Container Closure System - Reference Standards

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- Stability - Container Closure System

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- Stability
- Interchangeability
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Part 3 : Nonclinical Document

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ACTR

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1. Pharmacology 3. Toxicology

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-Primary Pharmacodynamics - Single dose toxicity

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-Secondary Pharmacodynamics - Repeat dose toxicity

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-Safety Pharmacology - Genotoxicity
-Pharmacodynamics Drug - Carcinogenicity

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Interactions - Reproductive and developmental

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toxicity

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2. Pharmacokinetics - Local tolerance
-Absorption AN - Other toxicity studies, if available
-Distribution
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-Metabolism
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-Excretion
-Pharmacokinetics Drug
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Interactions
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-Other Pharmacokinetics Studies

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Part 4 : Clinical Document
ACTR

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1. Bioavailability (BA) and Bioequivalence (BE) Studies
2. Studies Pertinent to Pharmacoknetics using Human Biomaterials:

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- Plasma Protein Binding Studies
- Hepatic Metabolism and Drug Interaction Studies

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- Studies using Other Human Biomaterials

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3. Human Pharmacokinetic (PK) Studies:

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- Heathy Subject PK and Initial Tolerability Studies
- Patient PK and Initial Tolerability Studies

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- Intrinsic Factor PK Studies

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- Extrinsic Factor PK Studies
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- Population PK Studies
4. Human Pharmacodynamic (PD) Studies
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- Healthy Subject PD and PK/PD studies
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- Patients PD and PK/PD studies

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5. Efficacy and Safety

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- Controlled Clinical Studies Pertinent to the Claimed Indication

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- Uncontrolled Clinical Studies

6. Post Marketing Data (if available)
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7. References
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General considerations in New Drugs Review

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• Trial design and conduct

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• Reliability of studies and submitted documents

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• GLP and GCP compliance

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• Efficacy; relevance endpoints

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• Safety; seriousness of adverse reactions,
drop-outs
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• Significant difference in ethnic factors?
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• Risk-benefit assessment
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• Benefit outweighs risk

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• Identified risks can be controlled

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• Ensure product quality and their reproducibility

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New Drugs VS Generic Drugs

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Review Process

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New Drugs Generic Drug

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Requirements Requirements

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1. Chemistry 1. Chemistry

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2. Manufacturing 2. Manufacturing

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3. Quality Controls 3. Quality Controls

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4. Labeling 4. Labeling
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5. Nonclinical Studies
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(animal) 5. Bioequivalence
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6. Clinical Studies
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Thai FDA Notification

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Abridged Evaluation of New Drugs

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• Thai FDA Notification on New Drugs using

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Reference Drug Regulatory Authority Assessment

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was issued in July 2015

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• It has come into effect since October 1, 2015
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• 3 channels for new drugs registration
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• Standard review
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• Priority review
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• Abridged review
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Abridged Evaluation of New Drugs

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• Reducing the number of experts to evaluate

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new drugs dossiers

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• Using the assessment report of benchmark /

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reference agencies as part of the evaluation
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SE
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Priority Review

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• A fast track or priority review channel for

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life-threatening medicines and medicines
in urgent need for public health problems

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 HIV/AIDS drugs, anticancer, anti-TB,
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anti-malarial drugs
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• Pharmaceutical products of which R&D is
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in Thailand
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Conditions

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Drugs which have been approved by one of the

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following benchmark / reference agencies and

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being sold in the country

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• US FDA

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• EMA, EU (Centralized System)
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• MHRA, UK
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• Swiss Medic
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• TGA, Australia
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• Health Canada
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• PMDA, Japan
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Conditions

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• The application must be submitted within two years from

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the approval date of benchmark/reference agency

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• The same pharmaceutical products and the proposed

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indications, dosage regimens, patient groups and/or

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directions for use must be the same as those approved
by the reference agency
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• Full assessment report of benchmark/reference agency
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and all list of questions and answers during the

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assessment process together with post-approval

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variations and related documents in English must be

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submitted
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Conditions

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• The product’s manufacturing and quality must

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be the same as that currently approved by the

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reference agency and must comply with

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Thai FDA regulation and requirements

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AN
• The pharmaceutical product including its
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indications, dosage regimens, directions for use
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and patient populations has not been rejected or

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withdrawn, approved through appeal process or

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pending deferral by a drug regulatory agency

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New Drugs Evaluation

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(Standard VS Abridged evaluation)

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• 6 Experts for 1 New Drug Application (Standard)

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• 2 Experts for quality part (Manu 1, QC 1)

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• 2 Experts for nonclinical part

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• 2 Experts for clinical part

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• 4 Experts for 1 New Drug Application (Abridged)
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• 2 Experts for quality part (Manu 1, QC 1)
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• 1 Experts for nonclinical part

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• 1 Experts for clinical part

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• Subcommittee on New Drugs Evaluation

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Evaluation process

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• Generally, review by experts and internal

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reviewers

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• Propose to New Drug Subcommittee for

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consideration if

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• Expert opinions are not unanimous
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• Not approved
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• Drugs that may cause social or other
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problems or may have high potential

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for misuse/abuse
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• Pending for phase III clinical trials

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Timelines for Drug Registration

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Abridged
Working day
Type of Drugs

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Evaluation
(Working Days)
(Working Days)

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NCEs and other New drugs
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Priority Review NCEs and

220 150
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other New drugs
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Generic drugs 155 -

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Safety Monitoring Program (SMP)

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• To confirm the drug safety in Thai patients

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• To generate earlier safety signals and gather more

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safety information of New drugs before granting

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and unconditional approval
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• To more rigorously control the usage of New drugs
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• To more rigorously control the usage of New drugs
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• To encourage physicians, pharmacist and other

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health professionals to have more concerns on the

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safety of New drugs and their usage

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Safety Monitoring Program (SMP)

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Original Products (New Drugs)

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Step I Experts/Subcommittee
Approval

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Conditional approval

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SMP & Limited distribution (2 yrs)
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Unconditional approval
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Step II
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Spontaneous ADR Reporting System

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Conditional Approval

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• Safety Monitoring Program (SMP) will be conducted

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for approximately 2 years

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• Drug packages must bear labeling to show

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conditional approval status:

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 Triangle shows monitoring status
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 Specially control drug – ยาควบคุมพิเศษ

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 Registration No. (NC) – 1C 5/52 (NC)

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 Limited distribution only through medical

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institutes or hospitals – ใช้ เฉพาะสถานพยาบาล/ใช้ เฉพาะโรงพยาบาล

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Unconditional Approval

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Labeling:

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• Not to show triangle mark

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• Can be distributed through normal market

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channels and categorized as
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 Specially control drug – ยาควบคุมพิเศษ
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 Dangerous drug – ยาอันตราย

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• Registration No.(N) – 1C 5/52 (N)

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http://www.fda.moph.go.th/psiond/index.htm

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ory
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