drug registration in asean countries

ASEAN : Association of South East Asian Nations

Brunei Cambodia

Indonesia Lao People’s Democratic Republic

Malaysia Myanmar

Philippines Singapore

Thailand Vietnam

Drug Registration in ASEAN : Dr.G.V.R.Joseph

Drug registration :

Permission granted by the relevant state authority to use and distribute a certain drugs;

Main aim of registration is to ensure that the users get only safe, effective drugs of high quality.


AYUSH Product Exports to ASEAN Countries

Year Value in mn.US$

2004 8.23

2005 10.58

2006 21.58

2007 25.18

2008 38.13


Guar gum

Menthol

Chyawanprash

Herbal extracts etc.

Major Exports :


Format for Drug Registration :

ACTD - Common Technical Dossier

Common application format that will be submitted to ASEAN regulatory authorities for the registration of pharmaceutical products for human use.

Even though some of the Individual ASEAN Countries have their own drug registration formats, all ASEAN countries accept the ACTD.

Countries like Brunei Darussalam, Cambodia, Myanmar, Thailand, does not have any separate drug registration format but follow ACTD.


Brunei

Brunei Darussalam :

There is separate cell for Pharmaceutical services and the Department of

Pharmaceutical service is mainly responsible for executing the control of

drugs. There are more than 3500 Pharmaceutical products are registered.

For the registration of Pharmaceutical products one has to submit the

detailed monograph of the said product giving the details of the product

pertaining to its

Pharmacology,Pharmacokinetics,Toxicology,Biopharmaceutics,

Clinical Pharmacology, Clinical efficacy, Safety etc. as required for CTD and

any other supporting documents like Clinical trial, comparative studies.


Cambodia :

National policy on TM/CAM was issued in 1996 and regulations were issued in

1998. Regulation of herbal medicines in Cambodia was introduced in 1998.

Herbal medicines are regulated as over-the-counter medicines and for self-

medication only.

Cambodia follows the common ASEAN CTD for registration of Pharmaceutical

Product for Human use. There are more than 48 registered herbal medicines;

however, none of them are included on National essential drug list. Herbal

medicines in Cambodia are sold in pharmacies as over-the-counter

medicines, in special outlets, by licensed practitioners and without restriction.


Indonesia :

“National Policy on Development of Traditional Medicine” was issued in

2000. Laws and regulations on TM/CAM were first issued in 1993. Through a

separate law for herbal medicines, regulation was established in 1993, and

updated in 1994 and 1995. Herbal medicines are regulated as over-the-

counter medicines, as a separate regulatory category and as traditional

medicines. There are approx. 8632 registered herbal medicines in Indonesia.

No herbal medicines are included on a National essential drug list. Herbal

medicines are sold in pharmacies as over-the-counter medicines, in special

outlets, by licensed practitioners and without restriction. Indonesia has its

own drug registration format and also follows ASEAN CTD.


Lao People’s Democratic Republic :

National policy on TM/CAM was included in the National Drug Policy

issued in 1998. Regulations on herbal medicine in the Lao People’s

Democratic Republic were issued in 2002; Herbal medicines are

regulated as over-the-counter medicines. In the Lao People’s

Democratic Republic herbal medicines are sold in pharmacies as over-

the-counter medicines and by licensed practitioners. Lao PDR has its

own has drug registration format and also follows ASEAN CTD.


Malaysia :

National policy on TM/CAM, which was launched in the year 2001. The

registration and licensing of TM/CAM is legislated through the Control of

Drugs and Cosmetics Regulations 1984. Regulation for traditional

medicines, including herbal medicines and dietary supplements formed

part of the Control of Drugs and Cosmetics Regulations in 1984.

Traditional medicines are allowed to be sold as over-the-counter

medicines. As of December 2003, approximately 1200 traditional

medicines, including herbal products are registered and regulated by

DCA. However, none of these products are included on the National

essential drug list. In Malaysia, herbal medicines are sold in pharmacies

as over-the-counter drugs without any restrictions. For registering

Pharmaceutical product on-line drug registration facility is available.


Myanmar :

National policy on TM/CAM was issued in 1993.Myanmar follows the

common ASEAN CTD for the registration of Pharmaceutical Products

for human use. There are approx 3,678 registered traditional medicines

in Myanmar. In Myanmar, the Traditional Medicines Drug law was

enacted in 1996 to ensure the quality, safety and efficacy of traditional

medicines. The regulatory statues used for herbal medicine are over-

the-counter medicines and herbal medicine as a separate category.

Herbal medicines are sold in pharmacies as over-the-counter

medicines and without restriction


Philippines :

National policy on TM/CAM was issued in 1997. The regulations on

herbal medicines were issued in 1984; these regulations are separate

form those for conventional pharmaceuticals. Herbal medicines are

regulated as over-the-counter medicines. The Philippines has separate

registration system for herbal medicines; however, the number of

registered herbal medicines is not available. In the Philippines, herbal

medicines are sold in pharmacies as over-the-counter medicines and

in special outlets. Philippines has its own drug registration formats

and also follows ASEAN CTD.


Singapore :

National policy on TM/CAM was issued in 1995. There are

National regulations on herbal medicines in Singapore. Herbal

medicine is regulated as over-the-counter medicines. Singapore

has its own drug registration format and follows common

ASEAN CTD. There are no restrictions on the sale of herbal

medicines, as long as they comply with the National regulations.


Vietnam :

National policy on TM/CAM is currently being developed. Laws

and regulations on TM/CAM were issued in 1989.Herbal

medicines are regulated as prescription and over-the-counter

medicines. Vietnam has its own drug registration format and

also follows ASEAN CTD. There are approx. 1573 registered

herbal medicines in Vietnam; 267 herbal medicines are

included on the National essential medicines list of 1996. In

Vietnam, herbal medicines are sold in pharmacies as

prescription and over-the-counter medicines, in special outlets

and by licensed practitioners.


Thailand :The National policy and programme on traditional medicine was issued in 1993,

when the Institute of Thai Traditional Medicine was officially established under

the Department of Medical Services. National laws and regulations on

traditional medicines were issued in 1967 under the Drug Act B.E. 2510, which

is divided into two parts covering modern and traditional medicines. Registered

traditional medicines can be divided into prescription medicines or over-the-

counter medicines. Medical, health and structure/function claims may be made

about herbal medicines. Thailand has its own drug registration format and also

follows ASEAN CTD. There are more than 2000 herbal medicines registered in

Thailand; a total of more about 20 herbal preparations are included in the

National list of essential drugs, A.D. 1999. Herbal medicines are sold in

pharmacies as over-the-counter drugs, or licensed practitioners may make their

own herbal preparations and sell them to patients. For registered household

herbal medicines, there are no restrictions on sales.


CTD Format:Part I : Table of Content Administrative Information and Prescribing Information

Section A: Introduction

Section B: Overall ASEAN Common Technical Dossier Table of Contents

Section C: Documents required for registration (for example, application forms,

labeling, Product Data Sheet, prescribing information)

Part II : Quality Document

Section A: Table of Contents

Section B: Quality Overall Summary

Section C: Body of Data

Part III : Nonclinical Document


Section B: Nonclinical Overview

Section C: Nonclinical Written and Tabulated Summaries

1. Table of Contents

2. Pharmacology

3. Pharmacokinetics

4. Toxicology


Section D: Nonclinical Study Reports

1. Table of Contents

2. Pharmacology

3. Pharmacokinetics

4. Toxicology

Part IV : Clinical Document


Section B: Clinical Overview

Section C: Clinical Summary

1. Summary of Biopharmaceutics and Associated Analytical Methods

2. Summary of Clinical Pharmacology Studies

3. Summary of Clinical Efficacy

4. Summary of Clinical Safety

5. Synopses of Individual Studies

Section D: Tabular Listing of All Clinical Studies

Section E: Clinical Study Reports

Section F: List of Key Literature References

CTD format cont…


ASEAN Countries

having their own

Registration formats


Indonesia:

Traditional Medicines Name

Package size

Registration Number, name and industry address (at least

name of city and country)

Composition (species name of raw ingredient)

Effects/Usefulness

Usage

Warning and contraindication (if exist)

Production Code Number

Expired Date

level of production/ Standard Operational Procedure; Utility or

machine Source of available raw ingredients

Quality Evaluation of Raw Ingredients

Methods and Test Result of Stability/Durability

ASEAN Countries having their own Registration formats :


Lao People’s Democratic Republic: Name and address of the local manufacturer,importerThe International Non-Proprietary Name (INN) of the active ingredients)Brand name (if any)Composition of the product (formulation)Unit price in US$Dosage strengthDosage formStorage ConditionShelf-lifePrimary packagingSize of packagingDispensing category (prescription or over-the counter drug)Product DescriptionPharmacological category (according to Lao EDL)Contra-indicationsSide/Adverse effectsCertificate of Analysis of the Finished ProductAssay method and other test procedure for the finished productManufacturing Method and Process of Production,Samples in Market or Commercial PresentationLabeling Materials Including Label, Package Leaflet, etc.Certificate of Drug Registration Issued by the Regulatory Authority of the manufacturing countryList of countries in which the product is registered



Malaysia:

PRODUCT VALIDATION:Product Name:Dosage Form:Active Ingredients:Substance Name: Active Ingredients, strength of substance, origin either plant, animal, othersExcipient:Substance Name: strength of substance, origin either plant, animal , others.Any porcine materials: yes or noManufacturer: product classificationSECTION –A:PRODUCT PARTICULARS:

Name of ProductProduct descriptionDosage formActive SubstanceExcipient substanceProduct indication/usage:Dose/use instruction:contraindication:Warning/precautions:Drug Interactions:Side Effects:Signs and symptoms of overdose:Storage Condition:Shelf life:Therapeutic code.

SECTION – B:Batch Manufacturing formulaAttachment of Batch manufacturing formula documentation if any:Manufacturing process:Attachment of Manufacturing process documentation if any:In process Quality control



Attachment of finished product specification documentation:(details of specification and quality control test for finished product which include a list of tests and specifications and state the limits or criteria of acceptance for each test or specification).Attachment of Stability Data Documentation (for two batches)SECTION – C:Pack size : weight, volume, quantity,Immediate container type:Container type description:Barcode/serial no.Recommended Distributors priceRecommended Retail Price.SECTION- D:Mock up for Immediate ContainerMock up for outer containerProposed package insert patient information leaflet)SECTION – E:Product ownerManufacturerother Manufacturer involved if anyStore address (if any)SECTION- F:Letter of Authorization from product ownerIs the active substances) patented in Malaysia : yes or noCertificate of Pharmaceutical product (CPP):Certificate of Free Sale(CFS):Certificate of Good Manufacturing Practice (GMP):summary of product characteristics product data sheet if any):Patient information leaflet (PIL) if any:Attachment of Protocol of Analysis if any:Attachment of Certificate of analysis for two batches:Attachment of Specifications and Certificate of analysis of active ingredient if any:other supporting Document if any:

Malaysian Drug Registration format Cont..


Philippines:ASEAN Countries having their own Registration formats :


APPLICATION FOR REGISTRATION OF PHARMACEUTICAL PRODUCTTo be filled up by the applicantA.COMPANY APPLICANTCompany Name:Complete Address:Contact Numbers:Type of establishmentComplete Name:Complete Address:B.TYPE OF APPLICATIONINITIAL REGISTRATIONRENEWAL REGISTRATIONMONITORED RELEASE EXTENSIONC.COMPLETE INFORMATION REGARDING THE PRODUCT

1. Generic Name (s):2. Brand Name, if any:3. Dosage Strength:4. Dosage Form:5. Route of Administration:6. Pharmacologic Category:7. Classification: Rx (Prescription Drug)

OTC (Over-the-CounterRestricted/RegulatedEssential Drug List (EDL)

8. Claimed Shelf Life9. Storage Condition10. Primary Packaging (Market/Commercial Presentation):11. Suggested Retail Price:12. Reference Monograph:

Official:Non-Official

Company Particulars

Company shall be based and registered in Singapore

Applicant particulars

Application Details

Type of Application

Type of Product

* *

Reference Product

Product intended for export

Type of Dossier

Product Information

Singapore:

Packaging, Shelf Life & Storage Condition

Forensic Classification

Registration Status in Other Countries



Vietnam:

Summary of product characteristics.Free Sale Certificate. GMP Certificate.Manufacturing process (fully detailed).Quality specifications and analytical methods (fully detailed).Certificate of analysis released by the manufacturer.Report of stability studies.Labeling samples.Product samples.Study report on toxicology.Study report on experimental pharmacology.Study report on pharmaco-kinetics and bioavailability.Study report on clinical pharmacology.Effects, indications, contra-indications, dosage, toxicity,side-effects and the safety of that products



Countries having separate Herbal Medicine Registration format

S.No NAME OF THE COUNTRY PHILIPPINES MALAYSIA ACTD

1 Name of Herbal or Homeopathic Medicine

+ + +

2 Dosage Form + + +

3 Strength + + +

4 Color + + +

5 Commercial Presentations + + +

6 Country of Origin + +

7 Name of Applicant + + +

8 Business AddressPhone Fax e-mail:

+ + +

9 Name of Manufacturer + + +

Premises Address Postal AddressPhone Faxe-mail

+ + +


10 Name of Local Agent +

11 Business AddressPhone Faxe-mail

+

12 Product details + + +

13 List all active ingredients + + +

14 List all non active ingredients + + +

15 Origin or source of the raw materials + + +

16 Summary of the manufacturing procedure.

+ + +

17 Shelf-life of the medicine. + + +

18 Certificate of analysis + + +

19 Toxicological, pharmacological and clinical information, as well as therapeutic effects of the herbal preparation

+ + +

Countries having separate Herbal Medicine Registration format Cont..


20 Indication + + +

21 Dosage and administration + + +

22 Contraindications + + +

23 Adverse reactions/Side effect + + +

24 Precautions + + +

25 Use in pregnancy and lactation +

26 Treatment of over dosage + + +

27 Interactions with other drugs or food + + +

28 Storage conditions + + +

29 Application fee paid

30 Declaration by applicant +

Countries having separate Herbal Medicine Registration format Cont..


Comparative Chart with respect to details of Plant Monographs in standard books


S. No.

Headings WHO AHP ESCOP PDR

EMEA community monograph

& Quality tests

BHC

BHP

SLM

IP API UP HP IHP ICMR

01 Definition √ √ √ √ √ √ √ √ √ √ √ √

02 Nomenclature √ √ √ √ √ √ √ √ √

a. Botanical Nomenclature

√ √ √ √ √ √ √ √ √

b. Botanical Family √ √ √ √ √ √ √ √ √

03 Synonyms √ √ √ √ √ √ √ √ √ √

04 Selected vernacular names/ Common Name

√ √ √ √ √ √ √

05 Description √ √ √ √ √ √ √ √

06 History √ √ √

07 Plant Material of interest

√ √

i. General Appearance √ √ √ √

Botanical Identification

√ √ √

ii Organoleptic properties

√ √ √ √

Macroscopic Identification

√ √ √ √ √ √ √ √ √

iii Microscopic characteristics

√ √ √ √ √ √ √ √ √ √ √

iv Powdered plant material

√ √ √ √ √ √

Comparative Chart with respect to details of plant Monographs in standard books Cont..


S. No. Headings WHO AHP ESCOP PDR EMEA community

monograph & Quality tests

BHC

BHP SLM IP API UP HP IHP ICMR

08 Commercial Sources & Handling

√

i Collection √ √

ii Cultivation √ √

iii Drying √

iv Handling √ √

v Storage √ √ √

vi Adulterants √ √

vii Preparations √ √

09 Geographical distribution

√ √ √ √ √ √

10 General identity tests √ √ √ √ √

11 Purity tests √ √ √ √

i. Microbiology √ √ √ √

ii. Total Ash √ √ √ √ √ √

iii Acid-insoluble ash √ √ √ √ √ √ √

iv. Water-soluble extractive

√ √ √ √ √ √

v. Alcohol-soluble extractive

√ √ √ √ √ √

vi Foreign Organic Matter √ √ √ √ √ √

vii Loss on Drying √ √ √

viii. Pesticide residues √ √

ix Heavy Metals √ √ √ √



S. No.



& Quality tests

BHC

BHP

SLM


x Radioactive residues √ √

xi Other purity tests √

12 Chemical assays √ √ √ √ √ √ √ √

13 Major Chemical constituents/ Constituents

√ √ √ √ √ √ √ √ √ √

14 Dosage forms √ √ √ √ √ √ √ √ √ √ √

15 Adulterants and Substitutes

√ √

16 Therapeutics √ √ √ √ √ √ √ √

a. Pharmacokinetics √ √ √

b. Pharmacodynamics √ √ √

c. Preclinical Safety Data

√

17 Medicinal uses √ √ √ √ √ √

i. Uses supported by clinical data

√ √ √ √

ii. Uses described in pharmacopoeias and in traditional systems of medicine

√ √ √ √

iii Uses described in folk medicine, not supported by experimental or clinical data

√

Comparative Chart with respect to details of Plant Monographs in standard books Cont..


S. No.



& Quality tests

BHC

BHP

SLM


18 Pharmacology √ √ √ √ √ √ √ √

a. Experimental pharmacology

√ √

b. Clinical pharmacology

√ √ √ √

19 Contraindications √ √ √ √ √

20 Warnings √ √

21 Pregnancy and lactation

√ √ √

22 Effects on ability to drive and use machines

√ √

23 Overdose √ √ √

24. Precautions √ √ √ √ √ √ √

a. Carcinogenesis, mutagenesis, impairment of fertility

√ √

b. Other precautions √

c. Adverse reactions √ √ √ √ √

d. Interactions √ √

e. Posology √ √

f. Toxicology √ √

25 Regulatory Status √ √

26 References √ √ √ √ √ √



Abbreviations:

WHO - World Health Organization

AHP - American Herbal Pharmacopoeia and Therapeutic Compendium

ESCOP - German Commission E Monograph

PDR - Physician Desk Reference for Herbals

ICMR - Indian Council of Medical Research

EMEA - European Medicines Evaluation Agency

BHC – British Herbal Compendium

BHP – British Herbal Pharmacopoeia

SLM – Sri Lanka Monograph

IP – Indian Pharmacopoeia

UP - Unani Pharmacopoeia

API - Ayurvedic Pharmacopoeia

HP - Homeopathic Pharmacopoeia

IHP - Indian Herbal Pharmacopoeia

Thank You
