Documente Academic
Documente Profesional
Documente Cultură
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Drug Regulation
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in Thailand
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VIVAN PROMPRADITH, M.Sc.
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Pre-marketing control
Bureau of Drug Control
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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
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Pre-marketing Division
Development Division
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Post-marketing Division
Pharmaceutical (Chemical) Product Biological Product Veterinary Drug
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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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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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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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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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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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Manufacturers – PIC/S
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Pharmaceutical (Chemical) Product
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Sub-division
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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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• New Delivery System (ND)
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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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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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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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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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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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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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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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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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timelines)
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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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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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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 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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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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- 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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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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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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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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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
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• Full assessment report of benchmark/reference agency
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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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• The pharmaceutical product including its
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indications, dosage regimens, directions for use
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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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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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for misuse/abuse
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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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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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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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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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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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http://www.fda.moph.go.th/psiond/index.htm
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