ASEAN Association of South East Asian Nations Brunei

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

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

Major Exports : Guar gum Menthol Chyawanprash Herbal extracts etc. Drug Registration in ASEAN : Dr. G. V. R. Joseph

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

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

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

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

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 overthe-counter medicines and by licensed practitioners. Lao PDR has its own has drug registration format and also follows ASEAN CTD. Drug Registration in ASEAN : Dr. G. V. R. Joseph

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

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 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-thecounter medicines and herbal medicine as a separate category. Herbal medicines are sold in pharmacies as over-the-counter medicines and without restriction Drug Registration in ASEAN : Dr. G. V. R. Joseph

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

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

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

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

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 A: Table of Contents Section B: Nonclinical Overview Section C: Nonclinical Written and Tabulated Summaries 1. Table of Contents 2. Pharmacology 3. Pharmacokinetics 4. Toxicology Drug Registration in ASEAN : Dr. G. V. R. Joseph

CTD format cont… Section D: Nonclinical Study Reports 1. Table of Contents 2. Pharmacology 3. Pharmacokinetics 4. Toxicology Part IV : Clinical Document Section A: Table of Contents 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 Drug Registration in ASEAN : Dr. G. V. R. Joseph

ASEAN Countries having their own Registration formats Drug Registration in ASEAN : Dr. G. V. R. Joseph

Indonesia: ASEAN Countries having their own Registration formats : 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 contra- indication (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 Drug Registration in ASEAN : Dr. G. V. R. Joseph

ASEAN Countries having their own Registration formats : Lao People’s Democratic Republic: Name and address of the local manufacturer, importer The International Non-Proprietary Name (INN) of the active ingredients) Brand name (if any) Composition of the product (formulation) Unit price in US$ Dosage strength Dosage form Storage Condition Shelf-life Primary packaging Size of packaging Dispensing category (prescription or over-the counter drug) Product Description Pharmacological category (according to Lao EDL) Contra-indications Side/Adverse effects Certificate of Analysis of the Finished Product Assay method and other test procedure for the finished product Manufacturing Method and Process of Production, Samples in Market or Commercial Presentation Labeling Materials Including Label, Package Leaflet, etc. Certificate of Drug Registration Issued by the Regulatory Authority of the manufacturing country List of countries in which the product is registered Drug Registration in ASEAN : Dr. G. V. R. Joseph

Malaysia: ASEAN Countries having their own Registration formats : PRODUCT VALIDATION: Product Name: Dosage Form: Active Ingredients: Substance Name: Active Ingredients, strength of substance, origin either plant, animal, others Excipient: Substance Name: strength of substance, origin either plant, animal , others. Any porcine materials: yes or no Manufacturer: product classification SECTION –A: PRODUCT PARTICULARS: Name of Product description Dosage form Active Substance Excipient substance Product 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 formula Attachment of Batch manufacturing formula documentation if any: Manufacturing process: Attachment of Manufacturing process documentation if any: In process Quality control Drug Registration in ASEAN : Dr. G. V. R. Joseph

Malaysian Drug Registration format Cont. . 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 price Recommended Retail Price. SECTION- D: Mock up for Immediate Container Mock up for outer container Proposed package insert patient information leaflet) SECTION – E: Product owner Manufacturer other Manufacturer involved if any Store address (if any) SECTION- F: Letter of Authorization from product owner Is the active substances) patented in Malaysia : yes or no Certificate 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: Drug Registration in ASEAN : Dr. G. V. R. Joseph

ASEAN Countries having their own Registration formats : Philippines: APPLICATION FOR REGISTRATION OF PHARMACEUTICAL PRODUCT To be filled up by the applicant A. COMPANY APPLICANT Company Name: Complete Address: Contact Numbers: Type of establishment Complete Name: Complete Address: B. TYPE OF APPLICATION INITIAL REGISTRATION RENEWAL REGISTRATION MONITORED RELEASE EXTENSION C. 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-Counter Restricted/Regulated Essential Drug List (EDL) 8. Claimed Shelf Life 9. Storage Condition 10. Primary Packaging (Market/Commercial Presentation): 11. Suggested Retail Price: 12. Reference Monograph: Official: Non-Official Drug Registration in ASEAN : Dr. G. V. R. Joseph

Singapore: ASEAN Countries having their own Registration formats : Company Particulars Company shall be based and registered in Singapore Applicant particulars Application Details Type of Application Type of Product Type of Dossier Reference Product intended for export * Product Information * Packaging, Shelf Life & Storage Condition Forensic Classification Registration Status in Other Countries Drug Registration in ASEAN : Dr. G. V. R. Joseph

ASEAN Countries having their own Registration formats : 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 Drug Registration in ASEAN : Dr. G. V. R. Joseph

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 Address Phone Fax e-mail: + + + 9 Name of Manufacturer + + + Premises Address Postal Address Phone Fax e-mail + + + Drug Registration in ASEAN : Dr. G. V. R. Joseph

Countries having separate Herbal Medicine Registration format Cont. . 10 Name of Local Agent + 11 Business Address Phone Fax e-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 + + + Drug Registration in ASEAN : Dr. G. V. R. Joseph

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

Comparative Chart with respect to details of Plant Monographs in standard books S. No. Headings WHO AHP ESCOP 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 √ √ √ Organoleptic properties √ EMEA community monograph & Quality tests BH C BH P √ √ √ √ √ SL M √ IP API UP HP ICMR √ √ √ √ √ √ √ √ √ √ Botanical Identification ii PD R √ √ Macroscopic Identification √ √ √ iii Microscopic characteristics √ √ √ iv Powdered plant material √ √ √ √ √ Drug Registration in ASEAN : Dr. G. V. R. Joseph √

Comparative Chart with respect to details of plant Monographs in standard books Cont. . S. No. 08 Headings WHO AHP ESCOP PDR EMEA community monograph & Quality tests BH C BHP SLM IP 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 API UP IHP √ √ √ √ √ √ Foreign Organic Matter √ √ √ vii Loss on Drying √ √ viii. Pesticide residues √ √ Heavy Metals √ √ ix HP √ √ √ Drug Registration in ASEAN : Dr. G. V. R. Joseph √ ICM R

Comparative Chart with respect to details of plant Monographs in standard books Cont. . S. No. Headings WHO AHP ESCOP PD R EMEA community monograph & Quality tests 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 √ BH C BH P SL M IP API √ √ √ UP HP ICMR √ √ √ √ √ √ √ √ Drug Registration in ASEAN : Dr. G. V. R. Joseph √

Comparative Chart with respect to details of Plant Monographs in standard books Cont. . S. No. Headings WHO AHP ESCOP PD R EMEA community monograph & Quality tests BH C √ √ 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 SL M IP API UP HP ICMR √ √ √ √ √ BH P √ √ √ Drug Registration in ASEAN : Dr. G. V. R. Joseph

Abbreviations: WHO AHP ESCOP PDR ICMR EMEA BHC BHP SLM IP UP API HP IHP – – - Comparative Chart with respect to details of plant Monographs in standard books Cont. . World Health Organization American Herbal Pharmacopoeia and Therapeutic Compendium German Commission E Monograph Physician Desk Reference for Herbals Indian Council of Medical Research European Medicines Evaluation Agency British Herbal Compendium British Herbal Pharmacopoeia Sri Lanka Monograph Indian Pharmacopoeia Unani Pharmacopoeia Ayurvedic Pharmacopoeia Homeopathic Pharmacopoeia Indian Herbal Pharmacopoeia Drug Registration in ASEAN : Dr. G. V. R. Joseph

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