Summary of APSMI Country Report 2019

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Contents

Introduction…………………………………………………………………………… 2 I. Summary of OTC Regulation in Member Countries………………………. 3 II. Activities to Promote Self-Medication by Member Associations…………11 III. OTC Market in Asia-Pacific Region…………………………………………..23

Annex 1: Dossier Requirements for OTC Registration Annex 2: Rx-to-OTC Switch Products in Member Countries Annex 3: New and Amended Regulation from 2016 to 2019 in Member Countries

Introduction

Thanks to the contributions by its member associations and magnanimous provision of the market analysis by Nicholas Hall, Asia-Pacific Self-Medication Industry (APSMI) compiled the APSMI Country Report 2019 in October 2019. The Report was published on the occasion of the 12th Global Self-Care Federation Asia-Pacific Regional Conference & 4th APSMI General Assembly held in Beijing, October 2019, made available to the meeting participants and the APSMI members.

The Report outlines the OTC regulations and the activities to promote self- medication in APSMI member countries; i.e. China, Chinese Taipei, Indonesia, Japan, Korea, and Thailand. It also includes analyses of global and Asian OTC markets as well national markets in the region.

Though the access to the full Report remains to be the members’ privilege, APSMI has decided to publish its summary to the open public. The APSMI sincerely hopes that the information contained in the Summary Report will contribute to the OTC market growth, harmonization of OTC regulation, and promoting self-medication in the region.

APSMI Secretariat November 2019

I. Summary of OTC regulations in member countries

-Notes – The description of each country is simplified for the ease of comparison.

1. Category of drugs (OTC and Prescription and others?) China OTC and Rx. Herbal medicines are classified into OTC or Rx. OTCs are subcategorized with regard to allowable sales route. Some are general sales line items. Chinese OTC, RX and Traditional Chinese Drugs. OTCs are Taipei subcategorized into Pharmacy-only and general sales drugs. Indonesia OTC and Rx. Herbal medicines form another category different from OTC or Rx. OTCs are subcategorized with regard to allowable sales route. Some are general sales line items. Japan OTC and Rx. Herbal medicines are classified into OTC or Rx. OTCs are subcategorized with regard to allowable sales route. Korea OTC and Rx. Except for little exception, OTCs are sold only at pharmacies. Philippines OTC and Rx. Herbal medicines form another category. OTCs are sold only at pharmacies. Thailand Rx, Modern OTC, and Traditional OTC. OTCs are subcategorized into drug store-only and general sales drugs.

2. Abridged approval applications (for e.g. OTC with precedents, monograph- compatible OTCs, etc.) China Full application only. There is no difference in required data between Rx and OTC. Chinese Abbreviated applications for switch OTC and monographs- Taipei compatible OTCs Indonesia Abbreviated applications for drugs with precedents. Japan Abbreviated applications for switch OTC and monographs- compatible OTCs Korea Abbreviated applications for switch OTC and monographs- compatible OTCs Philippines Abbreviated applications for switch OTC and monographs- compatible OTCs Thailand No abbreviated application for OTC. OTC applications follow the guidelines for new drugs or generic drugs.

3. Review track /Review department specially for OTCs

China The authority has no specially designated review track or review department for OTC. Approval application for OTC is reviewed not differently from new drugs. Chinese The authority has no specially designated review track or review Taipei department for OTC. Approval application for OTC is reviewed not differently from new drugs. Indonesia The authority has specially designated review track and review department for OTC. Japan The authority has specially designated review track and review department for OTC. Korea The authority has no specially designated review track or review department for OTC. Approval application for OTC is reviewed not differently from new drugs. Philippines The authority has no specially designated review track or review department for OTC. Approval application for OTC is reviewed not differently from new drugs. Thailand The authority has no specially designated review track or review department for OTC. Approval application for OTC is reviewed not differently from new drugs.

4. Regulatory permission on Advertisement of OTC to the general public China Need of regulatory permission for advertisement in all media (TV, Radio, Internet, Printed materials). Chinese Need of regulatory permission for advertisement in all media Taipei (TV, Radio, Internet, Printed materials). Indonesia Need of regulatory permission for advertisement in all media (TV, Radio, Internet, Printed materials). Japan No regulatory permission is needed. But the Japanese OTC industry has self-imposed guideline on advertisement as well as a committee to survey member companies’ advertisements as to their adherence to the guidelines and to recommend rectification when there are any violations. Korea Need of regulatory permission for advertisement in all media (TV, Radio, Internet, Printed materials). Philippines Need of regulatory permission for advertisement in all media (TV, Radio, Internet, Printed materials).

Thailand Need of regulatory permission for advertisement in all media (TV, Radio, Internet, Printed materials).

5. Regulatory permission on revising labelling of OTCs China Necessary Chinese Necessary Taipei Indonesia Necessary Japan Necessary, but only for the essential part on the drug’s indication, dosage, and caution on use. Other parts to provide information of more promotional nature can be revised without permission. Korea Necessary Philippines Necessary Thailand Necessary

6. Standards and Guidelines applicable to OTC drugs (1) GMP China GMP applied to OTC is aligned to PIC/S GMP Chinese GMP applied to OTC is aligned to PIC/S GMP Taipei Indonesia GMP applied to OTC is aligned to PIC/S GMP Japan GMP applied to OTC is aligned to PIC/S GMP Korea GMP applied to OTC is aligned to PIC/S GMP Philippines GMP applied to OTC is aligned to PIC/S GMP Thailand GMP applied to OTC is aligned to PIC/S GMP

(2) Pharmacopoeia China The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees. Chinese The authority applies its domestic pharmacopoeia to OTC. Other Taipei countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees. Indonesia The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees.

Japan The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees. Korea The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees. Philippines The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees. Thailand The authority applies its domestic pharmacopoeia to OTC. Other countries’ pharmacopoeia e.g. USP, EP) are also used as reference to varying degrees.

(3) ICH guidelines applicability

i. Q1, 3, 6, 7 China Basic ICH Q Guidelines (Q1, Q3, Q6, and Q7) are generally applicable to both Rx and OTC. Chinese Basic ICH Q Guidelines (Q1, Q3, Q6, and Q7) are generally Taipei applicable to both Rx and OTC. Indonesia Basic ICH Q Guidelines (Q1, Q3, Q6, and Q7) are generally applicable to both Rx and OTC. Japan All ICH Q Guidelines are applicable to RX and direct OTC (new chemical entity approved first as OTC). Other OTC are exempted from application of ICH guidelines but subject to simpler domestic guidelines. Korea Basic ICH Q Guidelines (Q1, Q3, Q6, and Q7) are generally applicable to both Rx and OTC. Philippines Basic ICH Q Guidelines (Q1, Q3, Q6, and Q7) are generally applicable to both Rx and OTC. Thailand Relevant ASEAN guidelines apply. ICH Guidelines are used as reference. Q1 : Stability Q3: Impurities Q6 : Specifications Q7 : GMP for Active Pharmaceutical Ingredients

ii. S4 (Chronic Toxicity Testing)

China S4 Guideline is applicable to both Rx and OTC. Chinese S4 Guideline is applicable to OTC that is new drugs (direct Taipei OTC). Indonesia S4 Guideline is not applicable to OTC. Japan All ICH S Guidelines are applicable to RX and direct OTC (new chemical entity approved first as OTC). Other OTC are exempted from application of ICH guidelines but subject to simpler domestic guidelines. Korea S4 Guideline is applicable to OTC. Philippines S4 Guideline is applicable to OTC. Thailand S4 Guideline is applicable to OTC.

iii. E2B, E2D, E6 China E2B, E2D, E6 are all applicable to Rx and OTC. Regarding ADR reporting, OTC and Rx undergo the same regulation. Chinese E2B, E2D, E6 are all applicable to Rx and OTC. Regarding ADR Taipei reporting, OTC and Rx undergo the same regulation. Indonesia E2D and E6 are all applicable to OTC. Japan E2B, E2D, E6 are all applicable to Rx and OTC. Regarding ADR reporting, OTC and Rx undergo the same regulation. Korea E2B, E2D, E6 are all applicable to Rx and OTC. E2B is partly applicable. Philippines E2B, E2D, E6 are all applicable to Rx and OTC. Thailand E6 Applies to OTC. E2B and E2D are not implemented in Thailand (for Rx or OTC). E2B : Individual Case Safety Reports E2D : Standards for Expedited Reporting E6 : Good Clinical Practice iv. M1 and M4 China Pilot of M1 and China CTD (similar to M4) are implemented. Chinese M1 and M4 are applicable to OTC. Taipei Indonesia M1 and M4 are applicable to OTC. Japan M1 is applicable to both Rx and OTC. M4 is applicable to direct OTC. Other types of OTC are exempted from M4 application. Korea M1 is being applied to OTC in stages. M4 is not applicable to OTC. Philippines M1 is not applicable to OTC. M4 is applicable to OTC.

Thailand M1 and M4 are not applicable to OTC. M4 is applicable only to new drugs. M1 : MedDRA - Medical Dictionary for Regulatory Activities M4 : Common Technical Document

7. Rx-to-OTC Switch China The process starts when applicants make applications for manufacturing OTC version of a Rx. The authority has an OTC switch guideline, with which to judge switch-ability. Chinese The process starts when applicants make applications for Taipei manufacturing OTC version of a Rx. The authority publishes the checklist of required documents as well as review principles. The assessment is made by an advisory committee. Indonesia There is no switching scheme. Japan There is an official scheme to promote switching. An advisory committee to the Ministry of Health Labor and Welfare assesses Rx ingredients for switch-ability based on requests from the public. If judged appropriate, the ingredients are recommended for switching to the Minister. Based on the publicized recommendation, any applicants make approval applications for the recommended ingredients. Korea The process starts when applicants make applications for manufacturing OTC version of a Rx. The authority publishes an OTC switch guideline, with which to judge switch-ability. Philippines The authority publishes the conditions and requirements regarding switch. But there has been no Rx-to-OTC switch. Thailand The process starts when applicants make applications for manufacturing OTC version of a Rx. The authority defines clear criteria of switching as well as a guideline for Patient Information Leaflet user study. The assessment is made by an advisory committee taking the result of public hearing into consideration.

8. Drug Master File (DMF) China DMF for active pharmaceutical ingredients (API). is mandated for OTC

Chinese DMF and API GMP certificate are mandatory for OTC. Taipei Indonesia DMF is applicable for API in new product OTC. Japan DMF is not applicable for OTC. Korea DMF for API are mandated for some OTC Philippines DMF is not applicable for OTC. Thailand DMF is not mandated for OTC.

II. Activities to promote Self-Medication by member

Associations

1. China 1. Research and studies conducted by the member organization or in which the member organization has been involved in: On-going researches carried on for the following topics 1) Twin spans products (RX/OTC) management topic research 2) Non-prescription drug registration regulation research 2. Publications by organization or publications in which the organization was involved (please list the number of copies published, the target readers as specifically as possible) "China Non-Prescription Drugs Industry Development Blue Book 2018" will be published in 2019. The blue book is target to related regulatory agencies, industry and the media. Over 2,000 copies were provided to the industries and to the general public via a publishing agency. 3. Events for promotion of self-medication, hosted by the organization or in which the organization was involved 2017/2018/2019 International Self-Care Day promotion activities and events supported by CNMA. 4. Advertising activities utilizing media, in which the organization was involved 1) Through the mass media to promote “International Self-Care Day". 2) Through the mass media to launch the activity of OTC Brand promotion month in 2018 and 2019. 5. Utilization of organization website CNMA’s website included more information on OTC formulation and members activities. 6. Activities for government and regulatory authorities, lobbying activities Continue to be involved in many government research activities on OTC regulations. 7. Joint activities with other organizations NA

2. Chinese Taipei 1. Events for promotion of Self-Medication, hosted by association or in which the association is involved TPMMA hold several events to establish the plate form for OTC industry to share information and learning, including: 1) OTC Brand Marketing Forum: to share the marketing best practice from leading brands to the industry and highlight the importance of a brand image. 2) OTC Stakeholders Summit (Experience from Japan): speakers from Dentsu (pharmaceutical market overview), Santen (new entry to Taiwan market from brand point of view), Matsumotokiyoshi Drug Store (opportunity in Taiwan from channel point of view) and AC Nielson (OTC market overview) to share the view and opportunity in Taiwan. 2. Activities for Government and Health Authority, lobby activities 1) OTC Task Force (composed by regulators, academics, pharmacists and industry representatives) was working with TFDA to update and expand the OTC monograph from 10 categories to 16 categories. Expanding the dermatological category in to 7 sub-categories, including anti-fungal, anti-biotic & disinfectant, antipruritic & anti- inflammatory, anti-acne, diaper rash and dry skin. 2) Simplified DMF requirement for OTC registration: to exempt full dossier of DMF for OTC registration and only requires basic CMC documents. 3) Guidance for switch application (1st applicant): in order to encourage industry to apply for switch application, TFDA published a reference guidance (Rx-to-Pharmacy only) to outline basic requirements for switch application. In which, in addition to the overview of approval status in major countries, it requires the “Training materials to Pharmacists” for such application which is important to support the consultation to the pharmacists once the product is switched from Rx- to-OTC. An example of “pharmacist training” was established by TFDA and published in TFDA website. 4) TFDA announced Refuse to File (RTF) for new drug and accepted to exclude OTC New Drug from this requirement. In addition, industry submitted the proposal for “simplified requirements for OTC New Drug registration” and pending TFDA consideration.

5) Worked with Rx group to exempt the legalization requirements for: - API GMP (original copy) issued by 10 major countries - CoPPs issued by 10 major countries 3. Promotion of Self-medication with other associations _ International Network 1) Japan―Taiwan Workshop on the Regulation of OTC Medicine (OTC workshop) hold in December 2017 to exchange experience on OTC policy and regulatory requirements between Taiwan and Japan. 2) 6th Japan-Taiwan Joint Symposium (OTC section): to discuss the advertisement challenge in Taiwan (Oct 2018) 3) Support APSMI to host the 4th Self-CARER meeting in Taipei (March 2018) This meeting included a pilot training programme _ Self-CARER university (supported by TSMIA), closed part and open part. There were 32 regulators from 10 health authorities attended the meeting. Key topics were focus on “promotion of self-medication”, “switch” and “increase efficiency on registration/review process”.

3. Indonesia 1. The Smart Community Movement Program On Drugs Usage (GEMA CERMAT) A joint effort between the government and the community through a series of activities in order to create awareness, well understanding and community skills in using drugs appropriately and correctly. This movement aims to increase public understanding and awareness about the importance of using drugs properly, increasing independence and changing people's behavior in choosing and using drugs correctly, and ultimately will increase the rationality use of drugs. 2. Promotion of : “Let's Live Healthy, It Starts with Us” The national movement initiated by the President of the Republic of Indonesia announced in the context of strengthening health development which puts forward promotive-preventive efforts as first priority, without ruling out rehabilitative and curative efforts by involving all components of the nation in promoting paradigm of healthy with support from pharmaceutical industry. 3. Guidelines on the Use of OTC Guidelines on the Use of OTC is compiled to assist the public in conducting self medication. The purpose of this guideline is to guide people who wants to do self medication and Pharmacists as guideline to help communities in self medication. 4. Promotion of Self Medication at Communities and Pharmacies Education Care Of Medicine And Food Safety from National Agency of Drug and Food Control (NADFC), National movement to correctly GET, USE, SAVE, DISPOSE drugs. The first is GET, which means getting the medicine in the right place, so that its benefits, safety and quality are guaranteed. The right place means that there is legality, for example a pharmacy, hospital, licensed drug store, clinical pharmacy. Second, USE means to use drugs in accordance with the indications diagnosis of disease), according to the dosage, according to the rules of use, and according to the way of administration. Third, SAVE, i.e. store medicine as written on the package, except if it has to be stored in special condition. Generally the drug is stored in a cool place (15-25 ° C), not exposed to direct sunlight, not in a humid place, and keep out of reach of children.

Fourth is DISPOSE. Disposing of drugs must also be with the correct procedure. Drugs that are damaged or expired must be removed immediately, so that they can no longer be used. Disposal of over-the- counter drugs (green circle logo), limited over-the-counter drugs (blue circle logo) and prescription drugs (letter K with red circles) can be done by the communities themselves. In order not to be abused by other parties, the drug should be disposed of in a certain way so that it is completely out of shape. 5. Switch Rx to OTC Climate Switch will be done by Ministry of Health under the recommendation of National Agency of Drug and Food Control (NADFC) 6. Healthy Living Community Movement Program (GERMAS) GERMAS is a movement from Ministry of Health (MOH) that aims to promote a habit of healthy living and leave the habits and behavior that are less healthy. GERMAS action was also followed by promoting hygienic behavior and support for infrastructure programs on a community basis. This program focuses on several agendas such as: 1. building access to fulfill drinking water needs, 2. public health installations and 3. build of habitable settlements. These are the basic infrastructure that forms the foundation of the healthy living community movement. Changes in community life patterns that are becoming more modern are one of the bases of the GERMAS or the Healthy Living Community Movement launched by the Ministry of Health of the Republic of Indonesia. 7. Healthy Indonesia Program with a Family Approach Guideline Program from Ministry of Health (MOH) to ensure the state of well being of families. This program is developed by defining: a. Recognize developmental disorders on the health of each family member, b. Make decisions for correct action to achieve proper health, c. Provide care to sick family member, d. Maintaining an atmosphere at home, that is beneficially for the health of each family members, e. Good communication between families and health service facilities.

4. Japan 1. Self-Medication Tax deduction Consumers spending more than JPY 12,000 in a year on OTC drugs that were switched from Rx are eligible for tax deduction; the cost exceeding the limit is deducted from the consumer’s taxable income. Japan Self-Medication Industry (JSMI) has been promoting this system since its inception in 2016, by publishing booklets and posters, sponsoring newspaper articles and advertising. JSMI has been negotiating with the government to expand the scope of the eligible OTC drugs as well as to lower the minimum consumption. JSMI analyzes the statistics on the consumers receiving the deduction as well as the financial benefits they enjoy to suggest improvements to the mechanism to the authority.

2. Communication with Health Authority Japan Self-Medication Industry has been having periodical formal meetings with high-rank officials of Ministry of Health Labor and Welfare (MHLW). The topics discussed usually include those on promotion of self- medication. In 2018 there were held two such meetings. 3. Promotion of Self-medication at community pharmacies JSMI supported the Japan Pharmacist Association, in its training the pharmacists at the specially designated “Health Support Pharmacies” in 2016. 4. Promotion of Rx-to-OTC Switch In the new Rx-to-OTC switch mechanism established in 2016, JSMI has been playing an important role of provided MHLW with the information on the switch candidates. 5. “Self-medication” Handbook Since 2002, JSMI has been publishing the Handbook (2019 version: A5 size, 40 pages) issuing about 200,000 copies. The Self-Medication Handbook is an information booklet on OTC medicines and self- medication designed to be understandable for wide age groups, from 10- year-olds to the elderly. The handbook is distributed in pharmacies and at consumer events across Japan. 6. Press Conference JSMI organizes Press Conferences after major annual events, including New Year Celebration Party in January and JSMI General Assembly in May. The Conference covers JSMI policies including those

related to promoting Self-medication 7. Enlightenment on “Self-medication” (1) Self-Medication Day Symposium Twenty-fourth of July is the International Self-Care Day. JSMI with a help from the Ministry of Health, Labor and Welfare as well as JFSMI, organized a half-day symposium open to the public on the day in 2018 and 2019, inviting speakers from the regulatory authority, academia, Japan Pharmaceutical Association, and a chain pharmacy association. (2) Kids’ School how to use drugs right JSMI has been organizing enlightenment seminars in cooperation with educational institutes for parents and children to promote understanding of OTC drugs as well as the value of self- medication since 2011. In 2019, the seminars are held at 4 locations from the northern-most island of Hokkaido to the southern-most Kyushu for the total of 7 days. The seminars are held with supports from school of pharmacies of multiple universities. (3) Jamboree at Fukutoku Forest “Accurate knowledge on OTC drugs for proper use” JSMI has been organizing two-day outdoor event to encourage exact knowledge on and proper use of OTC drugs. The Jamboree takes place in the yard of “Fukutoku Shrine”, which worships a god of drug in the Japanese myth. The shrine in Tokyo has a yard of about 25m by 40m, which houses about 30 booths by OTC manufacturers, that disseminate information on their products. The event also features mock-pharmacies where one can experience compounding of drugs. The event in 2018 enjoyed more than 12,000 visitors. 8. Home Page JSMI maintains various information in Japanese and English on OTC drugs and self-medication on its Website. The information is categorized and indexed according to drug classes as well as symptoms. Japan Self- Medication Data Base Center (JSM-DBC) was established in 2000 to provide an on-line database covering all the OTC drugs sold in Japan. The Website carries frequently asked questions on OTC drugs and self- medication and their answers. The questions have been continuously replenished from those received by the member companies.

9. Helping Self-diagnosis Measurements

Since 2014, some of Japanese pharmacies started a service of measuring the HbA1c level. Consumers visiting pharmacies take a tiny volume of their blood by themselves and hand it to the pharmacist, who measures the blood level of the protein. When the measurement is high enough to justify medical intervention, the pharmacist recommends the consumer to see doctors. JFSMI has organized “Council for Self-diagnosis Measurements” to offer to help the self-diagnosis efforts. The Council has been offering lectures on the relevant regulations and helping the pharmacies calibrate the analytical devices. As of 2019 there are about 360 pharmacies throughout Japan, offering in total around 80 measurements per month. 10. Advertisement Guidelines and Seminars JFSMI periodically revises its voluntary guidelines that help understand and abide by the regulation issued by the regulatory authority. In 2019 the JFSMI guidelines were revised, whereupon the organization organized 2 seminars on OTC advertisements in Tokyo and Osaka in July. The seminars invited MHLW’s responsible officials and officers from JSMI Advertisement Committee as well as Japan Advertising Review Organization (JARO), overlooking Japan’s advertising in general.

5. Korea 1. Operating Drug Advertisement Pre-Review Committee In Korea, OTC drug is defined as a subject for preliminary review in public advertising, and The KPBMA has organized and operates a ‘Drug Advertisement Pre-Review Committee’ under the Pharmaceutical Affairs Act. In addition to the reviewing activities, KPBMA advises the industry to make sure that the advertisements and promotions of OTC items are not curtailed by the pre-review system, and encourages the industry to make full use of new media such as SNS. The KPBMA also regularly hold seminar for drug advertisement pre-review system and case studies, discussion sessions for stakeholders to improve the review system. 2. Conducting study to revitalize OTC drug market The KPBMA has commissioned relative academia to study on expanding the market of OTC drugs in Korea. The main contents are the expansion and improvement of Korean monograph items through the analysis of the domestic OTC drug status and comparative analysis with overseas cases. 3. Supporting the consumer enlightenment campaign by academic society Various domestic societies disseminate information to consumers about the treatment of diseases and the proper use of drugs, and domestic pharmaceutical companies provide financial funding for the societies. The KPBMA runs the Code Deliberation Committee, which considers and approves such funding to support the proper operation of the society. 4. Supporting stable operation of the full ingredient labeling system As of December 2017, the full ingredient labeling system has been implemented to provide the correct drug information to consumers. The KPBMA participates in a committee composed of governments, associations, companies, etc. to encourage stable settlement of the system and present industry opinions to the government.

6. Philippines 1. Events for promotion of self-medication, hosted by the organization or in which the organization was involved Member companies have participated in the Pilot Project on the Review of Over-the-Counter Applications of Philippine Food and Drug Administration. 2. Advertising activities utilizing media, in which the organization was involved Meeting with Ad Standards Council regarding updates on new advertising regulations and lobbying concerns of member companies. 3. Activities for government and regulatory authorities, lobbying activities 1) Review of the Philippine Code of Ethics 2) Review of OTC guidelines 3) Review of Pharmacy Law (in partnership with Philippine Healthcare Association of the Philippines) 4) Created initial list of Pharmacist Only Medicines (in partnership with Philippine Pharmacists Association) 5) Active participation in the Pilot Project on Review of Over-the-Counter Applications (ROTCA) with Philippine Food and Drug Administration 6) Submitted position papers on the increased of fees and evaluation of permit applications 4. Joint activities with other organizations 1) Review of Pharmacy Law (in partnership with Philippine Healthcare Association of the Philippines) 2) Created initial list of Pharmacist Only Medicines (in partnership with Philippine Pharmacists Association) 5. Current situations and issues regarding the permeation of self-medication October 2018: FDA issued Guidelines on the submission of application for the pilot project on ROTCA. Member companies of chosen associations had participated in the said project. After the pilot project on ROTCA, there is no significant update yet from FDA on the full implementation on tier 1 and tier 2 systems application in the aim to reduce the processing timeline.

7. Thailand 1. Self-CARER participation TSMIA participated in the 4th self-CARER meeting during 20 – 22 March 2018, in Taipei, as industry observer / expert to support regualtors’ discussion. TSMIA also work in collaboration with Thai FDA in designing and delivery of Self-CARER University (SCU), which is the module training on self-CARE medicines to regulatory authorities (total 38 participants from 10 countries). TSMIA is also the leader in the workshop “Simplified registration in action”, in the SCU program. 2. Partnership with Pharmacist Group TSMIA regularly supported the speaker and lecture for community pharmacist, and regulatory pharmacist groups, to build the network & partnership. The recent topics include: Medicine reclassification requirement and industry experience, OTC regulation updates etc. 3. Partnership with Thailand FDA TSMIA provided technical/regulatory support to Thai FDA in revision of the Medicine Reclassification guideline (2nd revision) (year 2017), and related documents including standard process, timeline and evaluation fee. TSMIA also initiate the proposal in OTC regulatory reform to Thai FDA, such as abbreviated dossier for OTC, advertising guideline, which is being progressed in FDA discussion stage. 4. Annual TSMIA technical conference TSMIA arranged the annual TSMIA technical conference “self-CARE: Keep Pace with self-care, OTC Drugs regulation and market trend” on 4th July 2019, in Bangkok. The conference provides the update on regulation, self-care policy and consumer health care market trend. There are about 100 persons attending the conference, with also the speaker from Thai FDA and industry. The aim is to promote self-CARE sector awareness within pharmaceutical industry.

III. OTC Market in Asia-Pacific Region

By courtesy of Nicholas Hall

Global OTC Overview 2018 provided by Nicholas Hall Europe in July 2019

All quoted data is for full year 2018 at manufacturers’ selling price from Nicholas Hall’s DB6 Global OTC Database. Does not include e-commerce and mail order sales unless otherwise stated

Global overview: OTC growth continues to slow There was little change in the retail CHC market during 2018, with sales growing by 4.0% vs the 4.1% recorded in 2017. Factors behind the disappointing result include a relatively poor year for CCA (+3.7%) and a lack of switch, most notably in the US. Growth slowed in both Europe (+2.6% vs +2.8%) and N America (+2.7% vs 3.2%), while there were only modest increases in Asia-Pacific (+4.6% vs +4.5%), LatAm (+9.5% vs +9.1%) and Rest of World (+7.2% vs +7.0%). GIs (12.2% share of global sales) was the only major category to break the 5.0% growth barrier in 2018, buoyed especially by antinauseants (+10.5%) and antidiarrhoeals (+9.2%) following double-digit growth in China, the largest market for these subcategories. We are seeing an increase in use of certain types of GIs globally as eating habits change, such as consuming food on-the-go amid hectic lifestyles and stressful work environments. No.1 major category by revenue, VMS (30.5% share) advanced by 4.3%, with below-average growth for leading subcategory multivitamins (+3.0%) partially offsetting the continued expansion of No.2 probiotics (+10.8%); six of the Top 10 global markets for this subcategory recorded double-digit increases (all 10 were positive), as product positioning widened beyond traditional use for GI disorders into other areas such as immunity and feminine intimate health. Our industry is heavily reliant on seasonal factors, and an unremarkable year for CCA (20.6% share) played a significant part in the poor global trend. Only cough remedies (+5.3%) and chest rubs & inhalants (+7.5%) performed above average, while a terrible year for allergy remedies in the US (-1.2%, 57% share of global allergy revenue) dragged down the overall result for that subcategory (+2.6%). Combined growth of allergy remedies excluding the US was 8.0%.

Derma (13.6% share) endured the lowest growth of all major categories (+2.7%), with below-average results in seven of the Top 10 global markets (including all of the Top 5). Haemorrhoid preparations and antiseptics & disinfectants performed best, advancing by just over 5%. Analgesics (+4.0%; 13.4% share) and Lifestyle OTCs (+4.0%; 9.8% share) both slowed marginally vs 2017; the former was impacted by a notable drop-off in growth of topical treatments, caused mainly by the US. Looking at the “all channels” version of the DB6 dataset – new for 2019 – which reports on topline figures of direct sales, internet & mail order plus key brands in selected leading markets, total OTC sales are worth US$174bn, of which store-based sales account for 78%, with direct sales generating 14%. Internet & mail order currently accounts for 9% of the “all channel” universe, with sales dominated heavily by VMS supplements in China and the US. However, this channel has seen a CAGR of 20% since 2014 and will continue to increase dramatically over the next decade.

Global: Sales and growth by major OTC category 2018

US$mn Growth US$mn 2017 Market share 2018 2018/2017 GLOBAL TOTAL OTC SALES 130278.634 135436.415 4% 100.0 Vitamins, Minerals & 39585.107 41280.157 4.3% 30.5 Supplements Cough, Cold & Allergy 26881.036 27881.484 3.7% 20.6 Dermatologicals 17912.807 18389.111 2.7% 13.6 Analgesics 17419.722 18114.299 4% 13.4 Gastrointestinals 15736.155 16521.133 5% 12.2 Lifestyle OTCs 12743.807 13250.232 4% 9.8

Source: Nicholas Hall’s DB6 Global OTC Database (MSP)

Key trends by region 2018

• Asia-Pacific’s OTC market grew by 4.6%, with a strong cold & flu season in leading market China (+5.8%) partially offset by a weak performance

from key TCMs. Japan remained sluggish (+0.8%), while India (+9.3%) was the main growth driver among the core regional markets once again • N America increased by 2.7%, closely mirroring the result of the key US market (+2.6%), which was hindered by a weak allergy season (allergy remedies -1.2%) and a lack of switch • Europe advanced by 2.6%; W Europe continued to disappoint with a 1.6% increase, not helped by France remaining negative (-0.3%); CEE slowed to +5.2% following a lacklustre performance in key market and long-term growth driver, Russia (+1.7%) • The best growth once again came in LatAm (+9.5%), although price inflation played a significant role in a number of markets, not least regional No.1 Brazil (+10.1%) • Rest of World maintained its above-average performance (+7.2%)

Global: OTC sales & growth by region 2018

US$mn US$mn Growth Market Share % 2017 2018 2018/2017 GLOBAL TOTAL OTC SALES 130278.634 135436.415 4% 100 North America 35383.099 36334.142 2.7% 26.8 E & SE Asia 31233.943 32879.302 5.3% 24.3 Western Europe 24782.444 25176.814 1.6% 18.6 C & E Europe 10172.566 10701.212 5.2% 7.9 Rest of World 8305.457 8899.672 7.2% 6.6 Japan 7901.918 7967.131 0.8% 5.9 Latin America 6488.125 7102.22 9.5% 5.2 Indian Subcontinent 3306.029 3606.351 9.1% 2.7 Australasia 2705.054 2769.571 2.4% 2

Source: Nicholas Hall’s DB6 Global OTC Database (MSP)

Marketers: M&A to shake-up the rankings GSK retained the No.1 spot in the CHC leader board in 2018 and the company’s share is set to increase significantly once it assumes majority ownership of the j-v company incorporating Pfizer’s CH business. The all- equity agreement, announced in December 2018 and expected to complete in

H2 2019, will see the new GSK Consumer Healthcare potentially generate around 7% of global OTC sales, although brand divestments may reduce this. GSK CH will be the No.1 marketer in all four major global DB6 regions (Asia, Europe, Americas and RoW), including all subregions with the exception of Japan and LatAm, and the No.1 player in four of the global Top 10 markets, including No.1 US (it will rank 2nd in global No.2 market, China). RB, which grew by 2.2% in 2018 (2.4% share), will take Pfizer’s place in the Top 5, followed by P&G, which now encompasses the CH business of German-based Merck following completion of that deal in December 2018 for around €3.4bn (US$3.8bn) cash, but excludes Teva sales from the dissolved PGT j-v (effective 1st July 2018). P&G was the only Top 10 player to post above-market growth in 2018, boosted by flagship cough & cold brand Vicks (+6.3%), which recorded especially strong results in its No.2 market India (+13.9%), No.3 Brazil (+16.5%) and No.5 Mexico (+12.6%). J&J leapfrogged Sanofi and Bayer into 2nd place, aided by continued growth from Tylenol (+6.3%) and the acquisition of natural products specialist Zarbee’s (announced in August 2018 for an undisclosed sum). Despite a sales increase of 3.1%, Sanofi lost share owing to the spin- off of its Zentiva European generics business (split out of our 2018 annual sales total for the company) to Advent International for €1.9bn (US$2.1bn), which completed in October 2018. Bayer was held back by poor performances in the US (-3.3%) and China (-9.3%); its operations in the latter market were hit by the reverse switch of Kang Wang antifungal and scalp treatments in September 2017, although the scalp product has now been reformulated and re-launched OTC and Bayer mentioned the brand as a contributing factor in strong A-P regional growth in Q3 2018.

Asia-Pacific overview 2018 provided by Nicholas Hall Europe in July 2019

All quoted data is for full year 2018 at manufacturers’ selling price from Nicholas Hall’s DB6 Global OTC Database. Does not include e-commerce and mail order sales

Asia-Pacific is the world’s largest region for OTC sales and growth was modestly above the global average in 2018 (+4.6% vs +4.0%). Its performance is heavily dependent on China (+5.8%), where over 50% of regional sales are generated, while India was once again the most dynamic of the key markets (+9.3%). However, as in previous years sluggish growth in No.2 market Japan (+0.8%) and underwhelming results in Australia and S Korea (both below 3%) dampened the overall increase. While China continued to perform above average, growth was down vs 2017 (+6.2%), impacted mainly by a significant decline (-7.6%) in the US$1.5bn tonics & cure alls subcategory. Donkey hide gelatin brands, including the country’s No.1 OTC Dong-e E-Jiao (Dong-e E-Jiao / China Resources Pharmaceutical), have seen prices rise owing to a lack of raw materials (making them less affordable), while negative press reports over safety resulted in sales of No.3 tonic Hong Mao Medicated Wine (Neimenggu Hong Mao) falling by around 43%. Meanwhile, the reverse switch of compound ketoconazole in September 2017 also seriously impacted general antifungals (-13.5%) and scalp treatments (-12.9%), with overall derma revenue increasing by only 2.0%. Positive growth factors included a strong cold & flu season buoying No.2 major category CCA (+7.7%); marketer investment in TCM brands; development of paediatric / maternal healthcare products following the introduction of a two-child policy; and general recovery from the transition to China’s new two-invoice system. The declining trend among tonics & cure alls saw total VMS growth fall to 4.7% (vs +7.6% in 2017), while growth also slowed in No.2 and No.3 subcategories calcium (+5.9% vs +7.4%) and multivitamins (+2.4% vs +5.4%). Probiotics continued to star however (+19.4%) thanks to product launches

(especially brands aimed at paediatric development). A flu outbreak early in the year boosted CCA, with systemic cold & flu growth rising to 8.8% (vs +2.4% in 2017), while cough remedies advanced by a similar margin. Sore throat remedies & medicated confectionery also enjoyed a turnaround in fortunes (+5.7% vs -0.2% in 2017), owing mainly to category leader Golden Throat (Guangxi Golden Throat) rebounding following completion of distribution restructuring in 2018. GIs recorded a healthy increase once again (+7.9%) and was China’s best-performing major category in 2018, driven by antidiarrhoeals (+18.4%), where marketers are investing in A+P and increased distribution to take advantage of higher demand resulting from rising incidence of irregular and unhealthy eating patterns. Liver & bile remedies also had a strong year (+17.4%) thanks to academic marketing and consumer education for key brands, while the switch to full OTC status of several key brands in early 2018 boosted antinauseants (+15.7%). Analgesics growth was in line with the previous few years (+7.1%), with both topicals and systemics largely matching this rate. Derma disappointed, although things are looking more positive for scalp treatments as Bayer reformulated and relaunched OTC Kang Wang in July 2018, and there were some strong results in other subcategories, including haemorrhoid preparations (+6.9%), antiseptics & disinfectants (+7.7%) and wound healers (+9.1%), while the more modest hair loss treatments enjoyed the best result (+19.1%) thanks to a rebound for category leader Bawang (Bawang) and A+P that aims to attract the younger generation.

Japan’s OTC market has been sluggish for many years, held back by issues such as health insurance coverage encouraging consumers to visit a doctor instead of buying OTCs. Largest category VMS, which generates almost 40% of total sales, declined slightly (-0.5%) as the leading tonic drinks subcategory (-1.6%) continued to face competition from other sectors (such as energy drinks). The crucial vitamin B segment also fell (-9.5%), following a decline at a similar rate for dominant brand, Alinamin (Takeda). Analgesics (+3.6%) performed best, benefiting from premium line extensions and the ageing population using pain-relieving OTCs to alleviate

29 aches & pains, with systemics especially dynamic (+6.0%). Future sales could benefit from the MHLW recommending the Rx-to-OTC switch of systemic naproxen in August 2018. CCA (+3.1%) also did well, especially allergy remedies (+9.6%). The subcategory was buoyed by a high incidence of seasonal allergies in 2018 and could be further boosted following the registration as Instruction-required Drugs in November 2018 of Rohto’s Alguard Clear Nose Seasonal Allergy and GSK’s Flunase Nasal Spray. The former launched in December 2018 and is the first flunisolide-based OTC allergy remedy in Japan. While derma growth of 1.4% appears low, this was actually the best result for the major category in several years, aided by a strong level of NPD. GIs (-1.6%) and lifestyle OTCs (+0.5%) could not emulate this level of improvement.

India remained the main regional growth driver, with major categories contributing towards the positive result. No.1 by sales revenue, VMS (+9.3%) was aided by growth of over 12% for leading subcategory iron, while chyawanprash (+8.0%) recovered from a flat result in 2017; Dabur’s dominant entry reaped the benefits of strategic pricing implemented to mitigate the threat from a lower-cost mid-tier product from Patanjali, as well as enhanced efforts to encourage wider use throughout the year (such as to reduce the effects of pollution). GIs (+10.8%) recovered from lower consumer spending power resulting from demonetisation in Q4 2016, particularly in largest subcategory antacids (+12.5%). Demand for antacids has been boosted by the growing incidence of dyspepsia, particularly in urban areas, which is linked to modern hectic lifestyles and diet. Growth in laxatives continued to improve (+12.1%), boosted by marketers’ efforts to reduce the taboo associated with constipation. CCA sales were up by 10.4% in 2018; air pollution has boosted demand in product categories such as sore throat remedies & medicated confectionery (+12.2%) owing to the increased incidence of respiratory ailments in recent years. No.1 subcategory cough remedies grew by 9.7%, driven by the strong performance of No.1 entry Phensedyl (Abbott). Several cough remedies have been affected by the decision to ban over 300 fixed dose combination

30 medicines in early 2016. The Delhi High Court quashed the order in December of that year but it was reinstated in September 2018, although some affected CCA brands such as Phensedyl and Piriton Expectorant (GSK) were granted exemption by the Supreme Court as they were being manufactured prior to 1988 (the government’s cut-off date beyond which FDCs were not being assessed). Meanwhile, in February 2019 the government rescinded a ban on the sale of FDCs formulated with paracetamol, caffeine, phenylephrine + chlorphenamine, with immediate effect. The formulation is used in systemic cold & flu remedies (+9.0%) such as Alex Cold (Glenmark), Zedex Cold (Wockhardt) and Hatric 3 (Aristo). An 8.1% increase for analgesics was driven by a 10.2% upturn for the larger topicals category, where faster-acting formats such as sprays and gels are becoming more popular owing to rising numbers of fitness-conscious consumers in urban areas looking for fast and convenient pain relief. There is also a burgeoning topical menstrual pain relief niche, with Redcliffe Hygiene launching Pee Safe Feminine Cramp Relief Roll On in November 2018 and Sanfe Period Pain Relief Roll on (Sanfe) launched in March 2019. The systemics category has struggled in recent years, however factors such as worsening dengue fever outbreaks helped sales to grow by 5.2% in 2018. Derma and lifestyle OTCs were the only major categories to record slower growth vs 2017, although both remained relatively buoyant (+8.4% and +6.2% respectively).

Although Australia’s growth remained well below average in 2018, the 2.4% advance was its best result for several years, as largest major category VMS recovered from a slight decline in 2017 with an increase of over 5%. A resurgence in daigou sales to China was an important factor. Probiotics was the best-performing subcategory (+18.8%), while vitamin C (+14.1%) and iron (+13.8%) also impressed. However, a sluggish result from CCA (+0.8%) and a decline for analgesics (-3.7%), which has struggled since the reverse-switch of codeine- based brands in February 2018, offset the overall result.

S Korea performed slightly better than Australia. All major categories recorded growth of around 2-3% with the exception of lifestyle OTCs, which declined by almost 1%.

In Indonesia, growth improved slightly to 2.0% in 2018 vs 1.4% in 2017 but this is still below the regional average as Indonesia is recovering from recent economic challenges that have reduced consumer spending power. As such, all major categories grew by low single digits.

Asia-Pacific: OTC sales & growth by country 2018

US$mn US$mn Growth Market

2017 2018 18/17 Share % OTC Sales - Asia 45146.944 47222.355 4.6% 100 China 23777.243 25157.883 5.8% 53.3 Japan 7901.918 7967.131 0.8% 16.9 India 2985.453 3263.838 9.3% 6.9 Australia 2375.791 2432.596 2.4% 5.2 South Korea 2152.456 2210.471 2.7% 4.7 Indonesia 1487.94 1518.316 2.0% 3.2 Philippines 801.934 845.153 5.4% 1.8 Thailand 785.83 821.061 4.5% 1.7 Taiwan 674.532 701.526 4.0% 1.5 Hong Kong 541.973 569.152 5.0% 1.2 Vietnam 432.088 449.502 4.0% 1 Malaysia 350.038 366.597 4.7% 0.8 Pakistan 320.576 342.513 6.8% 0.7 New Zealand 329.263 336.975 2.3% 0.7 Singapore 229.909 239.639 4.2% 0.5

Source: Nicholas Hall’s DB6 Global OTC Database (MSP)

Asia-Pacific: OTC sales & growth by major category 2018

US$mn US$mn Growth Market

2017 2018 18/17 Share % OTC Sales - Asia 45146.944 47222.355 4.6% 100 Vitamins, Minerals & 15532.85 16122.4 3.8% 34.1 Supplements Cough, Cold & Allergy 8564.576 9085.398 6.1% 19.2 Gastrointestinals 5822.552 6189.441 6.3% 13.1 Analgesics 5476.71 5769.722 5.4% 12.2 Dermatologicals 5551.948 5695.094 2.6% 12.1 Lifestyle OTCs 4198.307 4360.299 3.9% 9.2

Source: Nicholas Hall’s DB6 Global OTC Database (MSP)

Annex 1: Dossier Requirements for OTC Registration

1 Country: Indonesia Country: Indonesia

X: Required, Y:Required depending on the drug, Blank: Not required. New Mono- New New New Chemical graph- Data Switch administra dosage combi- test/description Entity compatible, Category OTC tion route form nation (Direct generic OTC OTC OTC OTC) OTC Origin and XXXXX Background Use in foreign General/ XXXXX Background countries Comparison with XXXXXX other drugs

Chemical Structure Manu-facture and Physico-chemical X XX and Speci- properties fication Manufacture XXXXX Specification XXXXXX long-term X Y1 Y1 Y1 Y1 Y1 Stability stress X XXX accelerated XXXXXX efficacy X XXX Pharma- safety X XXX cology others X XXX Absorption XXXXX Distribution X Metabolism X ADME Excretion X Bioequivalence X Others X single-dose XYY Y repeated dose XYY Y genotoxicity X

Toxicity carcinogenicity X reproductive toxicity X local irritation XYY Y others XYY Clinical clinical X X1 X1 X1 X2 Labelling Package insert XXXXX

X1: more than 5 trial sites, more than 150 cases X2: more than 3 trial sites, more than 60 cases Y1: For drugs whose stability for 3 years cannot be estimated with the stress test, long-term stability test is required.

2 Country: Japan Country: Japan

X: Required, Y:Required depending on the drug, Blank: Not required. New New Mono- New Chemical administ New graph- Switch combi- Data Category test/description Entity ration dosage compatible, OTC nation (Direct route form OTC generic OTC OTC) OTC OTC Origin and XXXXX Background of drug Use in foreign General/Backgr XXXXX ound countries Comparison with XXXXXX other drugs Chemical Structure Manufacture and Physico- X and chemical properties Specification Manufacture X Specification XXXXXX long-term X Y1 Y1 Y1 Y1 Y1 Stability stress X accelerated X Y1 Y1 Y1 Y1 Y1 efficacy X Pharmacology safety X others X Absorption XYYYY Distribution X

ADME Metabolism X Excretion X Bioequivalence X Others X single-dose XYY Y repeated dose XYY Y genotoxicity X Toxicity carcinogenicity X reproductive toxicity X local irritation XYY Y others XYY Clinical clinical X X1 X1 X1 X2 Labelling Package insert XXXXX

3 Country: Korea Country: Korea

X: Required, Y:Required depending on the drug, Blank: Not required. New New Mono- New New Chemical administr graph- Switch dosage combi- Data Category test/description Entity ation compatible, OTC form nation (Direct route generic OTC OTC OTC) OTC OTC Origin and X XXXX Background of drug General/Backgr Use in foreign X XXXX ound countries Comparison with X XXXX other drugs Chemical Structure and Physico-chemical X YYY Manufacture properties and Specification Manufacture X XXX X

Specification X XXX

long-term X XXX Stability stress X accelerated X XXX efficacy Y Y Pharmacology safety Y others Absorption Y Y Distribution Y Y Metabolism Y Y ADME Excretion Y Y Bioequivalence Y Others single-dose Y Y Y

repeated dose Y Y Y

genotoxicity Y

Toxicity carcinogenicity Y reproductive toxicity Y Y local irritation Y others Y Y Y Clinical clinical Y XYX Labelling Package insert

4 Country: Philippines Country: Philippines 1

X: Required, Y:Required depending on the drug, Blank: Not required. New Chemical Entity (Direct Data Category test/description Switch OTC New administration route OTC OTC)

X X Origin and X classification of product from country Justification for the changes Background of drug of origin proposed

X General/Backgr X List of countries where product is ound Use in foreign approval letters from reference X marketed and corresponding countries regulatory authorities or the classification of the product, approval country of origin letters

Comparison with other drugs

X Chemical Structure unit dose formulation, tech specs X and Physico-chemical Manufacture raw materials, COA raw description, formulation properties and materials, analytical procedures Specification

Manufacture X Specification X long-term X Stability stress accelerated X efficacy X Pharmacology safety X others X Absorption X Distribution X Metabolism X

ADME Excretion X X Bioequivalence where applicable X Others dissolution profile single-dose X repeated dose X genotoxicity X Toxicity carcinogenicity X reproductive toxicity X local irritation X others X X X Part IV as per ACTD Clinical X Part IV as per ACTD Clinical Clinical clinical expert reports and/or clinical Part IV as per ACTD expert reports and/or clinical trial trial reports reports X X X Labelling Package insert including all other impacted including all other impacted labels including all other impacted labels labels (e.g. carton) (e.g. carton) (e.g. carton)

Other ADR report showing low occurrence of approved SmPC/PIL from country Requirements CPP drug interaction (clinically of origin or approved reference (PH specific) insignificant) regulatory agency

5 Country: Philippines Country: Philippines 2

X: Required, Y:Required depending on the drug, Blank: Not required.

New combi-nation Mono-graph-compatible, generic Data Category test/description New dosage form OTC OTC OTC Origin and Background of X X drug Justification as line extension

General/Background Use in foreign countries X

Comparison with other drugs

X X unit dose X Chemical Structure and unit dose formulation, tech specs raw formulation, tech unit dose formulation, tech specs Physico-chemical materials, COA raw materials, specs raw materials, raw materials, COA raw materials, Manufacture and properties Specification analytical procedures COA raw materials, analytical procedures analytical procedures

Manufacture X X X Specification X X X long-term X X X Stability stress accelerated X X X efficacy X Pharmacology safety X others X Absorption X Distribution X Metabolism X

ADME Excretion X X X X Bioequivalence where applicable where applicable where applicable X X X Others dissolution profile dissolution profile dissolution profile single-dose X repeated dose X genotoxicity X Toxicity carcinogenicity X reproductive toxicity X local irritation X others X

X Part IV as per ACTD Clinical clinical Clinical expert reports and/or clinical trial reports

X X X including all other Labelling Package insert including all other impacted labels including all other impacted labels impacted labels (e.g. (e.g. carton) (e.g. carton) carton)

Other Requirements CPP CPP CPP (PH specific)

6 Country: Taiwan

Country: Taiwan

X: Required, Y:Required depending on the drug, Blank: Not required.

New Mono- New New administr New graph- Data Chemical Switch combi- test/description ation dosage compatible, Category Entity OTC nation route form OTC generic (Direct OTC) OTC OTC OTC Origin and X XXXX Background of drug Use in foreign General/Back X XXXX ground countries Comparison with X XXXX X other drugs Chemical Structure and Physico-chemical X Manufacture properties and Specification Manufacture X XXXX X

Specification X XXXX X

long-term X XXXX X Stability stress Y YYYY Y accelerated X XXXX X

efficacy X XX X Pharmacology safety X XXYX others Y YY Y Absorption X X X Distribution X X X Metabolism X X X ADME Excretion X X X Bioequivalence Y Y2 Others Y1 Y1 Y1 single-dose X XYX repeated dose X YYY genotoxicity X Toxicity carcinogenicity X reproductive toxicity X Y Y local irritation X Y Y others X Y Y Clinical clinical X YX Y2 X Labelling Package insert X XXXX X

Y1: BA is required. Y2: Either BE or BA with Clinical is required.

7 Annex 2: Rx-to-OTC Switch Products in Member Countries

8 Country: China

Note: China had no OTC active ingredient monography, HA approved switch based on product case by case.

Ingredients & Dosages Transferred From Rx-to-OTC Status Authorized No. Product Name Ingredient Name Dosage Form Drug Efficacy Maximum Dose / Day Note Year 0.8gcalculate as 1 Ibuprofen Arginine granule Ibuprofen Arginine Oral antipyretic/analgesia ibuprofen VitaminA 5000IU, VitaminD400IU, VitaminE 10mg, VitaminB1 5mg, VitaminA , VitaminD, VitaminE , VitaminB2 5mg, VitaminB6 VitaminB1, VitaminB2, 0.5mg, VitaminB12 1ug, VitaminB6, VitaminB12, iron, iron 10 mg, copper 1mg, Zinc Prevention and treatment copper, Zinc, magnesium, 0.5mg, magnesium 1mg, Vitamins and Mincrals of various diseases 2 nicotinamide, calcium Oral nicotinamide 15mg, calcium Dispersible Tablets caused by the lack of pantothenate, calcium pantothenate 5mg, calcium vitamins and minerals. hydrophosphate, L-Lysine, hydrophosphate 558mg, L- lipotropin , inositol, VitaminC, Lysine 25mg, lipotropin iodine, manganese, potassium 50mg, inositol 50mg, VitaminC 50mg, iodine 100ug, manganese 1mg, potassium 10mg

hydroxypropyl methylcellulose 12 drop per time,3 3 hydroxypropyl methylcellulose Eye drop eliminate Eye discomfort 8ml24mg eye drop times per day 4 Bacillus subtilis capsule Bacillus subtilis Oral diarrhea relief 2.25g 5ml:2.5mgcalculate as 12 drop per time, 4 5 Ketotifen Fumarate eye drop ketotifen fumarate Eye drop allergic conjunctivitis ketotifen times per day patch15mg/16h nicotine Patch/ 6 nicotine Patch smoking deterent transdermal patch nicotine transdermal patch 21mg/24h Levocabastine Hydrochloride 400ugcalculate as 7 Levocabastine Hydrochloride Nasal antiallergic Nasal Spray Levocabastine per nostril

8 caffeine cold/influenza 90mg 9 kalium sulfoguajacolicum; Oral cold/influenza 180mg Compound Paracetamol and 10 mephedrine Oral cold/influenza 28.8mg Sulfogaiacol Oral Solution 11 chlorpheniramine maleate Oral cold/influenza 7.2mg 12 acetaminophen Oral cold/influenza 720mg cold/influenza/anaphylacti 13 pseudoephedrine sulfate Oral 240mg c rhinitis Loratadine Paracetamol and cold/influenza/anaphylacti 14 Pseudoephedrine Sulphate acetaminophen Oral 2g c rhinitis 2011 Sustained -release Tablet cold/influenza/anaphylacti 15 loratadine Oral 10mg c rhinitis 16 dl-camphor Patch analgesic 28.4mg 17 Compound Methyl Salicylate Vitamin E Patch analgesic 48mg 18 and Menthol Patch l-menthol Patch analgesic 132mg 19 methyl salicylate Patch analgesic 144mg

20 Guaifenesin chlorpheniramine maleate Oral antibechic 4.5mg Dextromethorphan 21 mephedrine; Oral antibechic 45mg Hydrobromide 22 Methylephedrine Hydrochloride guaifenesin Oral antibechic 225mg and Chlorphenamine Maleate 23 Syrup dextromethorphan hydrobromide Oral antibechic 67.5mg

24 Loratadine and pseudoephedrine sulfate Oral cold/influenza 240mg Pseudoephedrine Sulfate 25 Sustained Release Tablets; loratadine Oral cold/influenza 10mg

Relieve thevisual fatigue 26 chlorpheniramine maleate Eye drop 1ml:0.1mg symptoms

Relieve thevisual fatigue 27 Compound Neostigmine vitamin B6 Eye drop 1ml:1mg symptoms 12 drop per time, Methylsulfate and Taurine Eye 4-6 times per day Drops; Relieve thevisual fatigue 28 taurine Eye drop 1ml:1mg symptoms

Relieve thevisual fatigue 29 prostigmine methyl sulfate Eye drop 1ml:0.01mg symptoms

30 calcium hydrophosphate Oral supplement Calcium 1g Lysine Hydrochloride and Calcium Hydrogen Phosphate promote the normal 31 Granules lysine hydrochloride Oral growth and development 1g of children

assist to improve the toxic liver injury in patients with Polyene Phosphatidyl choline 32 Polyene Phosphatidyl choline Oral fatty liver and hepatitis / 1368mg capsule anorexia, right upper abdominal pressure.

33 orlistat tablet orlistat Oral obesity / overweight 360mg

9 Country: China

Note: China had no OTC active ingredient monography, HA approved switch based on product case by case.

Ingredients & Dosages Transferred From Rx-to-OTC Status Authorized No. Product Name Ingredient Name Dosage Form Drug Efficacy Maximum Dose / Day Note Year 34 hydrochloric acid granule hydrochloric acid Oral analgesic 1.44g 35 Smectite Suspension Smectite Oral Antidiarrheal 9g 36 chlorpheniramine maleate Oral cold/influenza 12mg 37 Compound Dextromethorphan dextromethorphan hydrobromide Oral cold/influenza 90mg 38 Hydrobromide dry suspensions pseudoephedrine hydrochloride Oral cold/influenza 180mg 39 acetaminophen Oral cold/influenza 1950mg

40 dimeticone Oral antiflatulent 160mg calcium carbonate dimeticone chewable tablet 41 calcium carbonate Oral antiacid 3360mg

42 lactulose oral solution lactulose Oral laxative 20g 43 glucosamine sulfate tablet glucosamine sulfate Oral analgesia 1.5g

Relief of pain caused by 44 extractum belladonnae Oral 30mg smooth muscle spasm 2012 Vitamin U belladonna aluminum gastric mucosal 45 Vitamin U II Oral 150mg dispersible tablets protection

antiacid/gastric mucosal 46 aluminium hydroxide Oral 420mg protection

loratadine granule/Loratadine anaphylactic 47 loratadine Oral 10mg Orally Disintegrating Tablets rhinitis/idiopathic urticaria

0.8gcalculate as 48 Ibuprofen Arginine Tablets Ibuprofen Arginine Oral antipyretic/analgesia ibuprofen Ketotifen Fumarate Nasal 0.9mgcalculate as 49 ketotifen fumarate Nasal anaphylactic rhinitis Sprays ketotifen

Domperidone Orally 50 Domperidone Oral prokinetic agents 30mg Disintegrating Tablets;

51 compound phenylephrine hydrochloride Oral cold/influenza 20mg 52 Paracetamol,Bromhexine caffeine Oral cold/influenza 120mg 53 Hydrochloride and brompheniramine maleate Oral cold/influenza 20mg 54 2013 Brompheniramine Maleate bromhexine hydrochloride Oral cold/influenza 32mg 55 Capsules acetaminophen Oral cold/influenza 1120mg 56 Vitamin B6 external eczema/dermatosis 1g: 1.5mg fluocinonide Vitamin B6 paste 23 times per day 57 fluocinonide external eczema/dermatosis 1g: 0.01mg

antiacid/gastric mucosal 58 hydrotalcite granule hydrotalcite Oral 2g protection

59 acetylcysteine tablet acetylcysteine Oral expectorant 0.6g amorolfine hydrochloride Fungal nail/Toenail 60 amorolfine hydrochloride external 5% 12 times per week liniment infection

2014 clotrimazole vaginal 61 clotrimazole vaginal Candida vaginal disease 0.5g effervescent tablets

62 magnesium hydroxide Oral antiacid 330mg famotidine Fytic Acid chewable 63 calcium carbonate Oral antiacid 1.6g tablet 64 famotidine Oral antiacid 20mg 65 ibuprofen spansule ibuprofen Oral antipyretic/analgesia 0.8g 66 levonorgestrel tablet levonorgestrel Oral contraception 1.5mg 67 ibuprofen dispersible tablet ibuprofen Oral antipyretic/analgesia 0.8g 2015 male pattern 60ml:3g. no more 68 minoxidil liniment minoxidil external 100mg alopecia/alopecia areata than 2ml per day

Pepsin activity per 1 ml of not 20ml one time2-3 69 pepsin oral solution pepsin Oral digestive less than 14 units times per day

70 Drospirenone ethinyloestradiol Drospirenone Oral contraception 3mg 71 tablet ethinyloestradiol Oral contraception 0.03mg 2016 10g:0.1g1-2 times 72 piroxicam paste piroxicam external analgesia 0.04g per day, 1-2g per time

73 orlistat capsule orlistat Oral obesity / overweight 180mg

10 Country: Japan

Ingredients & Dosages Transferred From Rx-to-OTC Status

No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year 1 soysterol oral hypercholesterolemia 600mg 1983 2 sodium picosulfate oral laxative 7.5mg 3 exalamide external tinea pedis/ringworm 50mg (*2-3 times per day) 4 dimemorfan oral antitussive/expectorant 60mg 1985 5 indomethacin external external analgesic 1% 6 ibuprofen(450mg/day) oral analgesic 450mg 7 1986 polyenephosphatidylcholine oral hypercholesterolemia 1500mg 8 Sodium polyethylenesulfonate external analgesic 1% 9 butylscopolammonium bromide oral gastrointestinal antispasmodic 30mg 10 bromhexine hydrochloride oral cold remedy 12mg 11 1987 cetraxate hydrochloride oral gastrointestinal 600mg 12 timepidium bromide hydrate oral gastrointestinal antispasmodic 45mg 13 ciclopiroxolamine external tinea pedis/ringworm 1% 14 miconazole nitrate external tinea pedis/ringworm 1% 15 isothipendyl hydrochloride oral (dermatological) toothache/pyorrhea 2mg 16 gefarnate oral gastrointestinal 150mg 1988 17 econazole nitrate external tinea pedis/ringworm 1% 18 carbocysteine oral antitussive/expectorant 750mg 19 hepronicate oral bloodstream disorder 100mg 1989 20 loperamide hydrochloride oral antidiarrheal 1mg 21 ubidecarenone oral cardiac 30mg 22 hydrocortisone butyrate external eczema/dermatitis 0.05% 23 1990 mequitazine oral antiallergic 6mg 24 bisoxatin acetate oral laxative 60mg 25 ibuprofenpiconol external acne 3% 26 tolciclate external tinea pedis/ringworm 1% 27 ufenamate external eczema/dermatitis 5% 1991 28 eprazinone hydrochloride oral antitussive/expectorant 90mg as anhydride 29 tioconazole external tinea pedis/ringworm 1% 30 mecobalamin oral vitaminB12 1500µg 31 prednisolone valerate acetate external eczema/dermatitis 0.15% 1992 32 calcium Laspartate oral calcium 1200mg 33 ibuprofen* oral cold remedy 450mg 34 sulconazole nitrate external tinea pedis/ringworm 10% 35 bifonazole external tinea pedis/ringworm 1% 1993 36 mequitazine** oral cold remedy 4mg 37 oxiconazole nitrate external tinea pedis/ringworm 1% 38 piroxicam external external analgesic 5mg/1g 1994 39 ketoprofen external external analgesic 0.3% 40 oxethazaine oral gastrointestinal 5mg 41 trimebutine maleate oral gastrointestinal 300mg 1995 42 felbinac (0.5%) external external analgesic 0.5% 43 pirenzepine hydrochloride hydrate oral gastrointestinal 47.1mg 44 sodium cromoglicate eye drop antiallergic 100mg/100ml 45 cimetidine oral gastrointestinal 300mg 1997 46 famotidine oral gastrointestinal 20mg 47 ranitidine hydrochloride oral gastrointestinal 63mg 48 1998 sofalcone oral gastrointestinal 300mg 49 2000 teprenone oral gastrointestinal 112.5mg 50 2001 nicotine oral (chewing gum) stop smoking 8-24mg 51 amorolfine hydrochloride external tinea pedis/ringworm 0.5% 52 butenafine hydrochloride external tinea pedis/ringworm 1g/100ml 53 2002 neticonazole hydrochloride external tinea pedis/ringworm 1% 54 terbinafine hydrochloride external tinea pedis/ringworm 1% 55 pranoprofen eye drop analgesic 50mg/100ml 56 roxatidine acetate hydrochloride oral gastrointestinal 75mg 57 2005 nizatidine oral gastrointestinal 150mg 58 ketotifen fumarate nasal antiallergic 50mg/100ml 59 lanoconazole external tinea pedis/ringworm 1% 60 tiquizium bromide oral gastrointestinal antispasmodic 15mg 61 2006 azelastine hydrochloride oral antiallergic 2mg 62 ketotifen fumarate *1 oral antiallergic 50mg/100ml 63 triamcinolone acetonide external stomatitis 0.1%

11 Country: Japan

Ingredients & Dosages Transferred From Rx-to-OTC Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year 64 aciclovir external oral herpes 5% 65 ketotifen fumarate eye drop antiallergic 50mg/100ml 2007 66 ambroxol hydrochloride oral expectorant 45mg 67 felbinac (3.5%)*3 external external analgesic 3.5% 68 flavoxate external overactive bladder/residual urine 600mg 69 isoconazole nitrate vaginal vaginal candidiasis 100mg 70 2008 nicotine*1 patch stop smoking 78mg 71 emedastine Fumarate oral antiallergic *2 2mg 72 miconazole nitrate vaginal vaginal candidiasis 100mg 73 miconazole nitrate external vaginal candidiasis 1% 74 isoconazole nitrate external vaginal candidiasis 1% 2009 75 diclofenac sodium external external analgesic 1% 76 vidarabine external oral herpes 3% 77 loxoprofen sodium hydrate oral analgesic 120mg 78 epinastine hydrochloride oral antiallergic 10mg 79 2010 troxipide oral gastrointestinal 300mg 80 oxiconazole nitrate*1 vaginal vaginal candidiasis 100mg 81 beclomethasone dipropionate nasal antiallergic 0.1% 82 clotrimazole*1 vaginal vaginal candidiasis 100mg 83 oxymetazoline hydrochloride nasal rhinitis 50mg/100ml 84 2011 acitazanolast hydrate eye drop antiallergic 100mg/100ml 85 pemirolast potassium oral antiallergic 10mg 86 mequitazine oral antiallergic 4mg 87 fexofenadine hydrochloride oral antiallergic 120mg 88 neticonazole hydrochloride external vaginal candidiasis 1% 89 2012 ethyl icosapentaenoate*1 oral 1800mg 90 cetirizine hydrochloride oral antiallergic 10mg 91 ibuprofen(600mg/day) oral analgesic 600mg 92 trimebutine maleate*1 oral irritable bowel syndrome 10mg 93 pemirolast potassium*1 eye drop antiallergic 100mg/100ml 2013 94 tranilast eye drop antiallergic 0.5% 95 ebastine oral antiallergic 5mg 96 2014 alminoprofen oral analgesic 400mg 97 sodium fluoride external dental prophylaxis 50mg/100ml 98 loxoprofen sodium hydrate*1 external analgesic 120mg 2015 99 beclomethasone dipropionate (0.1%) nasal antiallergic 0.1% 100 epinastine hydrochloride(20mg) oral antiallergic 20mg 101 Bepotastine Besilate oral antiallergic 20mg 2017 102 Loratadine oral antiallergic 10 103 2018 Flunisolide nasal antiallergic 25.5mg/100ml 104 2019 Fluticasone propionate nasal antiallergic 50mg/100ml

*1 ingredients additionally authorized for new effects and/or new dosage forms. *2 dermatological effect (against swelling on the skin and itching caused from nettle rash, eczema and skin-eruption) in addition to the effect against rhinitis. *3 ingredients additionally authorized for new dose (amount)

12 Country : Korea

Ingredients & Dosages Transferred From Rx-to-OTC Status

No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year 1 2013 oxolamine citrate oral antitussive/expectorant 1200mg 2 2013 neltenexine monohydrate oral antitussive/expectorant 112.2mg 3 2013 nizatidine oral gastrointestinal 150mg glycyrrhiza/chlorpheniramine maleate/guaifenesin/dl- 200mg as 4 2013 methylephedrine oral antitussive/expectorant 40ml guaifenesin hydrochloride/diprophylline/armeniacae semen/liriopis tuber/polygalae radix 5 2013 lanoconazole external antifungal 10mg/ml 6 2013 ranitidine hydrochloride oral gastrointestinal 150mg as 7 2013 levocabastine hydrochloride nasal antiallergic 0.05g/100ml levocabastine 8 2013 loratadine[0.1g] oral antiallergic 10mg 9 2013 loratadine[10mg] oral antiallergic 10mg 10 2013 loperamide hydrochloride oral antidiarrheal 16mg glycyrrhiza/armeniacae semen/dl- methylephedrine 11 2013 hydrochloride/polygalae oral antitussive/expectorant 40ml radix/chlorpheniramine maleate/guaifenesin/liriopis tuber 12 2013 anhydrous liquid lanolin eye drop ophthalmic remedy 3% 30mg/g 13 2013 benzydamine hydrochloride gargle anti-inflammatory 67.5mg as aluminium 14 2013 boehmite oral gastrointestinal 3.636g oxide 15 2013 bisacodyl oral laxative 15mg tocopherol as 16 2013 oral cardiovascular 30mg acetate[4.53iu]/ubidecarenone[10mg] ubidecarenone 17 2013 ubidecarenone[5mg] oral cardiovascular 30mg 18 2013 ubidecarenone[10mg] oral cardiovascular 30mg 19 2013 ethylene oxide[8.6g/cm2] - sterilization of surgical instruments - 20 2013 ethylene oxide[89wt.%] - sterilization of surgical instruments - 21 2013 ethylene oxide[10wt.%] - sterilization of surgical instruments - 22 2013 cetrimide eye drop ophthalmic remedy 0.01% 0.1mg/g dizet-100/scopolia/calcium carbonate/aluminium 23 2013 oral digenstive 7.5g hydroxide/magnesium carbonate/sodium bicarbonate 24 2013 amorolfine hydrochloride[2.788mg] external antifungal 0.2788% 2.788mg/g 25 2013 amorolfine hydrochloride[5.574g] external antifungal 5.574g/100ml 26 2013 acrivastine oral antiallergic 8mg 27 2013 erdosteine oral antitussive/expectorant 900mg 28 2013 sodium N-acetylaspartyl glutamate eye drop antiallergic 49mg/ml 29 2013 neticonazole hydrochloride external antifungal 10mg/ml 30 2013 fexofenadine hydrochloride oral antiallergic 120mg 31 2013 sodium chloride[20mg] eye drop ophthalmic remedy 2% 20mg/g 32 2013 sodium chloride[50mg] eye drop ophthalmic remedy 50mg/ml 33 2013 isopropanol/propanol external antiseptic/germicide - 34 2013 sodium cromoglycate[20mg] eye drop antiallergic 20mg/ml 35 2013 sodium cromoglycate[40mg] eye drop antiallergic 40mg/ml 36 2013 clotrimazole/hydrocortisone external antifungal 1% 10mg/g berberine chloride/albumin as albumin 37 2013 oral antidiarrheal 1200mg tannate/acrinol tannate scopolia/sodium as sodium 38 2013 bicarbonate/magnesium oxide/ l- oral gastrointestinal 1200mg bicarbonate menthol/gentian/calcium carbonate 39 2013 calcium carbonate oral gastrointestinal 5g 40 2013 troxerutin eye drop ophthalmic remedy 50mg/ml 41 2013 phenylephrine hydrochloride nasal nasal decongestant 5mg/ml 42 2013 polyethylene glycol oral laxative 17g

The Reclassification has been made in 2013 and there will be additional reclassification in every 5 years or in case of necessity.

13 14 Country :Taiwan

Ingredients & Dosages Transferred From Rx-to-OTC Status Ddosage No. Aauthorized Ingredient Name Drug Efficacy Maximum Dose/Day Note Year Form 1 2009 BIFONAZOLE Cream Anti-fungal agent - AMOROLFINE 2 2009 Cream Anti-fungal agent - HYDROCHLORIDE HORSE-CHESTNUT RELEASE Herbal supplement for 3 2010 100mg (triterpene glycosides) EXTRACT TABLET circulatory health 4 2011 LORATADINE TABLETS Anti-histamine agent 10mg 5 2011 LORATADINE SYRUP Anti-histamine agent 10ml (10mg) Gingival Anti-inflammatory 6 2012 Enoxolone/Rongalite - Paste agent for gum care CERNITIN Anti-inflammatory & 7 2013 Tablets 360mg/18mg T60/CERNITIN-GBX Decongestant VAGINAL 8 2013 CLOTRIMAZOLE Anti-fungal agent 500mg TABLETS VAGINAL 9 2013 CLOTRIMAZOLE Anti-fungal agent 500mg TABLETS Synthetic TRIAMCINOLONE 10 2016 ORABASE corticosteroid for - ACETONIDE topical use Proton pump inhibitor 11 Pantoprazole Tablets 20mg (PPI) Chlorpheniramine Chlorpheniramine 2mg Maleate, Meclizine HCl, Meclizine 25mg 12 Tablets Motion sickness Caffeine Anhydrous, Caffine 20mg Pyridoxine HCl Pyridoxine HCl 2mg Prevention of Calcium Calcium amino acid Calcium amino acid chelate 2000mg 13 Tablets and Vitamin D chelate, Vitamin D Vitamin D 400IU deficiency Relief of fever, pain 14 Ibuprofen 400mg/tab Tablets 1200mg and inflammation

Nasal steroid to 15 Fluticasone propionate Nasal Spray 200mcg relieve allergic rhinitis 2017-2018 Prevention of Calcium, Mineral amino acid, Mineral amino acid 4000mg 16 Tablets Magnesium and cholecalciferol cholecalciferol 600IU Vitamin D deficiency Exsiccated milk thistle 17 Tablets Liver protectant 450mg extract + silymarin 18 Lactulose Liquid Relief of constipation 30g/ml 19 Fexofenadine Tablets Anti-histamine agent 120mg

Analgesic and anti- 20 Benzydamine HCl Oral spray inflammatory agent for Strength: 1.5mg/ml the throat and mouth OTC Topical 21 Diethyltoluamide (DEET) Repellent Strength: 120mg/ml switched to solution Quasi Drug B

15 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status

No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year Per tablet (4, 10 tablets): Aluminium Hydroxide 200-600 mg. Adult: 4 tablets 1 1999 Oral tablet Gastrointestinal GSL Magnesium Hydroxide 200-400 Children 2 tablets mg.

Per 5 ml (240, 450 ml): Aluminium Hydroxide 165-650 mg. Adult: 20 ml 2 1999 Oral solution Gastrointestinal GSL Magnesium Hydroxide 103-500 Children 10 ml mg.

Per tablet (4, 10 tablets): Adult: 6 tablets 3 1999 Sodium Bicarbonate 300 mg. Oral tablet Gastrointestinal GSL Children 3 tablets Peppermint Oil 0.003 ml

Per 15 ml (180, 240, 450 ml): Capsicum Tincture 0.060-0.500 ml. Adult: 30 ml 4 1999 Compound Cardamom Tincture Oral solution Gastrointestinal GSL Children 15 ml 0.035-1.800 ml. Strong Ginger Tincture 0.024- 0.240 ml.

Per 15 ml (180, 240, 450 ml): Sodium Bicarbonate 0.15-0.60 g. Compound Rhubarb Tincture 0.50- 2.00 ml. and/ or other tinctures sunch as: Compound Cardamom Tincture 0.01- 1.00 ml. Compound Gentian Tincture 0.18-1.10 ml. Compound Tinospora Tincture 0.50 ml. Adult: 30 ml 5 1999 Oral solution Gastrointestinal GSL Weak Ginger Tincture 0.48-2.01 ml. Children 15 ml Strong Ginger Tincture 0.10-0.30 ml. Nux Vomica Tincture 0.09-0.10 ml. Ipecacuanha Tincture 0.18-0.30 ml. and/ or other Volatile Substances sunch as: Peppermint Spirit 0.15-0.30 ml. Peppermint Oil 0.03-0.20 ml. Menthol 0.05-0.30 ml. Concentrated Dill Water 0.10 ml. Camphor 19.00 mg.

Per 5 ml (60 ml): Adult: 15 ml 6 1999 Oral solution Gastrointestinal GSL Sodium Bicarbonate 50 mg. Children 10 ml

7 1999 Asafetida 20 % w/v (15, 30, 60 ml) Topical Gastrointestinal Apply 3 times GSL

One sachet (for 250 ml) : Sodium Chloride 0.875 g. Sodium Bicarbonate 0.625 g. Potassium Chloride 0.375 g. Glucose Anhydrous 5.000 g. 8 1999 Oral powder Anti-diarrheal (ORS) As required GSL or Sodium Chloride 0.875 g. Trisodium Citrate Dihydrate 0.725 g. Potassium Chloride 0.375 g. Glucose Anhydrous 5.000 g.

9 1999 Glycerin 91 % w/w per1.5 gram Suppository Anti-constipation As required GSL 10 1999 Glycerin 91 % w/w per 2.55 gram Suppository Anti-constipation As required GSL Per 15 ml (60, 120 ml): Adult: 45 ml 11 1999 Oral solution Anti-constipation GSL Magnesium Hydroxide 1.2 g Children: 30 ml

Per tablet (4, 10 tablets): Adult: 4 tablets 12 1999 Sennosides eq. to Sennoside B 7.5 Oral tablet Anti-constipation GSL Children 2 tablets mg

16 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year Adult: 40 ml 13 1999 Sodium Chloride 15 % w/v (10, 20 ml) Suppository Anti-constipation GSL Children 20 ml 14 1999 Mebendazole 100 mg Oral tablet Anti-parasite 1-2 tablets GSL Adult: 2 tablets Children 1 tablets Per tablet (4, 10 tablets): GSL 15 1999 Oral tablet Pain/ fever reliever every 4-6 hr. (4 times max) Paracetamol 500 mg Dosing is changed as of the 7th issue, 2017 Adult: 2 tablets Children 1 tablets Per tablet (4, 10 tablets): 16 1999 Oral tablet Pain/ fever reliever every 4-6 hr. (5 times max) GSL Paracetamol 325 mg Dosing is changed as of the 7th issue, 2017 30 ml pack: 2.4 ml Per 5 ml (30, 60 ml): 60 ml pack: 10 ml 17 1999 Oral solution Pain/ fever reliever GSL Paracetamol 120 mg every 4-6 hr. (5 times max)

Borneol 0.21-1.00 %w/w Camphor 1.00-2.80 %w/w Caoutchouc 30.00 %w/w Ethylene Glycol Salicylate 2.00-6.00 %w/w Eucalyptus Oil 0.50 %w/w Menthol 0.30-6.49 %w/w Methyl Salicylate 0.14-6.00 %w/w 18 1999 Peppermint Oil 0.50-2.00 %w/w Plaster Pain/ fever reliever 2 pads GSL Thymol 0.14-0.50 %w/w Capsaicin Extract 0.65 %w/w Polybutene 12.00 %w/w Capsicum Powder 11.00 %w/w Capsicum Oleoresin 3.00-11.00 %w/w and/ or Zinc Oxide 14.00-22.00 %w/w Per tablet (4, 10 tablet): Adult: 12 tablets 19 1999 Oral tablet Anti-histamine GSL Chlorpheniramine Maleate 2 mg Children 6 tablets Per 5 ml (60, 120 ml): 20 1999 Ammonium Carbonate 0.02 g. Oral solution Anti-cough 10 ml 3-4 times GSL Glycyrrhiza Fluidextract 0.25 ml. Per 5 ml (60 ml): Glycyrrhiza Fluidextract 0.6 ml. Adult: 10 ml Antimony Potassium Tartrate 1.2- 21 1999 Oral solution Anti-cough Children: 5 ml GSL 2.0 mg. 3-4 times Camphorated Opium Tincture 0.6 ml. Ammonium Carbonate 3.40 %w/v 22 1999 Inhalant Dizziness, decongestant As required GSL Strong Ammonia Solution 3.60-6.75 %v/v (15 ml)

17 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year Menthol 0.07-77.90 %w/v Camphor 0.45-42.00 %w/v Methyl Salicylate 3.00-15.00 %w/v Anise Oil 0.68 %v/v Burgamot Oil 0.50-0.68 %v/v Cajuput Oil 0.50-11.00 %v/v Cassia Oil 0.50 %w/v Clove Oil 1.25 %v/v Dwarf-Pine Needle Oil 1.00 %w/v Eucalyptus Oil 1.50-23.00 %v/v Lavender Oil 4.69-8.00 %v/v Peppermint Oil 2.20-10.38 %v/v Sage Oil 6.00 %w/v Sassafras Oil 5.00 %w/v 23 1999 Inhalant Dizziness, decongestant As required GSL Turpentine Oil 0.71-8.00 %w/v Capsicum Tincture 4.00-8.00 %v/v Myrrh Tincture 1.00 %w/v Ratanghia Tincture 0.40 %v/v Terpinol 3.33 %v/v Thymol 0.10 %w/v Camphor Spirit 3.00 %v/v Borneo Camphor 9.00 %w/v Bornyl Acetate 0.42 %w/v Linalyl Acetate 0.47 %w/v Phenyl Salicylate 0.60 %w/v Standard Chamomile Extract 10.00 %w/v (Not more than 14 ml) Menthol 1.35-3.00 %w/w Camphor 3.00-9.00 %w/w Cajuput Oil 3.00 %w/w 24 1999 Topical Dizziness, decongestant As required GSL Eucualyptus Oil 0.08-5.00 %w/w Terpentine Oil 4.68-5.00 %w/w (Not more than 50 gram) Per tablet (2 tablets): 25 1999 Oral tablet Dizziness 1 tablet GSL Dimenhydrinate 50 mg. 26 1999 Sulfacetamide Sodium 10 %w/v (10 ml) Eye drop Eye infection 2 drops 3-4 times GSL Sodium Chloride pack not more than 240 ml (Isotonic, pH6-8 with 27 1999 Benzalkonium chloride 0.002-0.020 Eye solution Eye irrigation 3 times GSL %w/v or Chlorhexidine (Gluconate/ Acetate) 0.01 %w/v as preservative)

15 ml contain: Potassium lodide 2.50 g. Iodine 1.25 g. 28 1999 Ethyl Alcohol (90 percent) 4.00 ml. Topical Astringent As required GSL Purified Water 2.50 ml. Peppermint Oil 0.40 ml. Glycerin to 100.00 ml.

29 1999 Gentian Violet 1 %w/v (15, 30 ml) Topical Astringent As required GSL

8 ml contain: 30 1999 Chlorobutanol 25 g. Topical Toochache As required GSL Clove Oil to 100 ml.

18 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year

Abietis Pine Oil 0.30 %v/w Anise Oil 0.25 %w/w Borneol 1.66-2.00 %w/w Cinnamon Oil 0.35 %w/w Creosote 0.20 %v/w Eucalyptus Oil 0.15-0.16 %w/w Lemon Oil 0.30-0.52 %v/w Menthol 0.06-5.00 %w/w Peppermint Oil 0.19-3.33 %w/w Sylvestris Pine Oil 0.30 %v/w Licorice Extract 7.31-16.67 %w/w Tincture Capsicum 0.02 %w/w Amomum 1.00-4.00 %w/w 31 1999 Lozenge Throat irritation 5 tablets GSL Aniseed 2.00 %w/w Catechu 8.33-38.00 %w/w Cinnamon 2.00-10.00 %w/w Clove 0.67-4.00 %w/w Costus 0.67 %w/w Fennel 1.67-2.00 %w/w Ginger 2.00-8.00 %w/w Licorice 26.67-71.38 %w/w Saffron 2.00 %w/w Saussurea 1.00-3.00 %w/w Silver Leaf 0.93 %w/w and/ or Honey 1.50-2.40 %w/w (100 tablets or not more than 30 gram)

Iodine 2.0-2.5 %w/v 32 1999 Potassium Iodide 2.4-2.5 %w/v Topical Wound dressing As required GSL (15, 30 ml)

33 1999 Thimerosal 0.1 % w/v (15, 30 ml) Topical Wound dressing As required GSL

Povidone-lodine 10 % w/v 34 1999 Eqivalent to lodine 1 % w/v Topical Wound dressing As required GSL (not more than 120 ml)

Isopropyl Alcohol Solution 70 % v/v 35 1999 Topical Wound dressing As required GSL (not more than 450 ml)

Ethyl Alcohol Solution 70 % v/v (not 36 1999 Topical Wound dressing As required GSL more than 450 ml)

Sodium Chloride 0.9 % w/v (not 37 1999 Topical Wound irrigation As required GSL more than 1000 ml)

Silver Sulfadiazine 1 % w/w (5, 15, 38 1999 25 gram)Switch back to Rx (6th Topical Burns As required GSL issue, 2017)

Methyl Salicylate 1.14-50.00 %w/w Camphor 1.76-25.00 %w/w Menthol 3.00-20.00 %w/w Cinnamon Oil 1.00-2.40 %w/w Clove Oil 0.50-5.00 %v/w 39 1999 Eucalyptus Oil 1.50-13.70 %v/w Topical Sting/ pain As required GSL Peppermint Oil 0.70-16.00 %w/w Terpentine Oil 2.00-3.80 %v/w Capsicum Tincture 0.80-8.00 %v/v Colophony 2.51 %v/w (not more than 30 gram)

Benzyl Benzoate 25 % w/v (30, 60 40 1999 Topical Scabies/ Louse As required GSL ml)

Sublimed Sulphur 10 %w/w (5, 15 41 1999 Topical Scabies As required GSL gram)

19 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year

Benzoic Acid 2.5-6.5 % w/w 42 1999 Salicylic Acid 3.0-5.0 % w/w Topical Ringworm As required GSL (5, 15 g)

43 1999 Coal Tar 1 % w/w (5, 15 gram) Topical Skin reaction As required GSL Calamine 8-15 % w/v 44 1999 Zinc Oxide 3-12 % w/v Topical Skin rash As required GSL (not more than 180 ml) Sodium Thiosulfate 100 % w/w (15 45 1999 Topical Ringworm As required GSL g for 60 ml solution) Per tablet (4, 10 tablets): Thiamine Hydrochloride or Thiamine Mononitrate 5 mg. Adult: 2 tablets 46 1999 Oral tablet Supplement GSL Pyridoxine Hydrochloride 2 mg. Children: 1 tablet Riboflavine 2 mg. Nicotinamide 20 mg. Per tablet (4, 10 tablets): Adult: 2 tablets 47 1999 Oral tablet Supplement GSL Ascorbic Acid 100 mg. Children: 1 tablet Per tablet (4, 10 tablets): Adult: 2 tablets 48 1999 Ferrous Sulfate Equivalent to Iron Oral tablet Supplement GSL 3 times 60 mg. Per tablet (4, 10 tablets): Vitamin A 2,500 I.U. Vitamin D 300 I.U. Adult: 1 tablet 49 1999 Vitamin C 15.00 mg. Oral tablet Supplement GSL Vitamin B1 Monoitrate 1.00 mg. Vitamin B2 0.50 mg. Nicotinamide 7.50 mg. Per tablet (4, 10 tablets): Cod Liver Oil equivalent to Adult: 1 tablet 50 1999 Oral tablet Supplement GSL Vitamin A not more than 4,000 IU. Vitamin D not more than 300 IU. Per 5 ml (120, 240, 400 ml): Cod Liver Oil equivalent to 51 1999 Oral solution Supplement 5 ml GSL Vitamin A not more than 4,000 IU. Vitamin D not more than 300 IU. Amyl metacresol not more than 0.6 mg. 2,4 Dichloro Benzyl Alcohol not 52 2006 more than 1.2 mg. Lozenge Throat irritation every 2-3 hours GSL or with Ascorbic acid not more than 100 mg. (8 tablets) Per tablet (4, 10 tablets): Aluminium Hydroxide 200-600 mg Adult: 4 tablets 53 2012 Oral tablet Gastrointestinal GSL Magnesium Hydroxide 200-400 mg Children: 2 tablets Simethicone 40-125 mg Per 5 ml (240, 450 ml): Aluminium Hydroxide 165-650 mg Adult: 20 ml 54 2012 Oral solution Gastrointestinal GSL Magnesium Hydroxide 103-500 mg Children: 10 ml Simethicone 20-40 mg

20 Country: Thailand

Ingredients & Dosages Transferred From Dangerous/Non-dangerous drug (DD/NDD) into GSL (grocery medicine) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year Per sachet (4.3 g): Citric Acid Anhydrous not more than 1.850 g. 55 2012 Sodium Bicarbonate not more than Oral powder Gastrointestinal 1 sachet every 2-3 hours GSL 1.960 g. Sodium Carbonate not more than 0.430 g. Per tablet (10 tablets): 56 2012 Oral tablet Anti-diarrheal 16 tablets GSL Activated charcoal 250-350 mg Chloroxylenol 4.8 % w/v 57 2012 Isopropyl Alcohol Solution 12 % v/v Topical Wound disinfectant As required GSL (450 ml) One sachet (for 250 ml) : Sodium Chloride 0.650 g. 58 2012 Trisodium Citrate Dihydrate 0.725 g. Oral powder Anti-diarrheal (ORS) As required GSL Potassium Chloride 0.375 g. Glucose Anhydrous 3.375 g. Per tablet/ capsule (10 59 2012 tablets/capsules): Oral tablet/ Capsule Gastrointestinal 12 tablets GSL Simethicone 40 mg Per tablet/ capsule (10 60 2012 tablets/capsules): Oral tablet/ Capsule Gastrointestinal 6 tablets GSL Simethicone 80 mg Depending on weight: < 34 kg: Consult physician or phamacist before using 34-50 kg: 1 tablet every 4 hours Per tablet (4, 10 tablets): 61 2017 Oral tablet Pain/ fever reliever as needed GSL Paracetamol 500 mg 50-67 kg: 1.5 tablet every 4 hours as needed (5 times max) > 67 kg: 2 tablet every 4 hours as needed (4 times max) Depending on weight: 22-33 kg: 1 tablet every 4 hours as needed Per tablet (4, 10 tablets): 62 2017 Oral tablet Pain/ fever reliever 33-44 kg: 1.5 tablet every 4 GSL Paracetamol 325 mg hours as needed > 44 kg: 2 tablet every 4 hours as needed For infant (Age <2 months): Consult physician before using

For infant/child (Age 2 months and above): 4-6 kg: 2.5 ml every 4 hours as needed (5 times max) Per 5 ml (30, 60 ml): 63 2017 Oral solution Pain/ fever reliever 6-8 kg: 3.75 ml every 4 hours as GSL Paracetamol 120 mg needed (5 times max) 8-12 kg: 5 ml every 4 hours as needed (5 times max) 12-16 kg: 7.5 ml every 4 hours as needed (5 times max) 16-24 kg: 10 ml every 4 hours as needed (5 times max) Per tablet (not more than 20 tablets): Sodium Alginate 250 - 500 mg acid reflux relief, with 12 years and above: 2-4 tablets, 64 2018 Oral tablet GSL Sodium Bicarbonate 95 - 300 mg antacid benefit 4 times/day Calcium Carbonate 70 - 360 mg Per 10 ml (not more than 150 ml): Sodium Alginate 250 - 500 mg acid reflux relief, with 12 years and above: 10-20 ml, 4 65 2018 Oral Suspension GSL Sodium Bicarbonate 95 - 300 mg antacid benefit times/day Calcium Carbonate 70 - 360 mg

21 Country: Thailand

Ingredients & Dosages Transferred From Rx /Dangerous Drug (DD)-to-NDD (pharmacy medicines, advertisable) Status No. Aauthorized Ingredient Name Ddosage Form Drug Efficacy Maximum Dose/Day Note Year As required (12 times max) 1-19 cigarrettes using: 2 mg Per gum 1 2018 Chewing gum smoking cessation chewing gum NDD Nicotine 2 mg and 4 mg > 20 cigarrettes using: 4 mg chewing gum As required (1 patch/24 h) 1-20 cigarrettes using: 14 mg Per patch 2 2018 Transdermal patch smoking cessation patch, 7 mg patch NDD Nicotine 7 mg, 14 mg and 21 mg > 20 cigarrettes using: 21 mg patch, 14 mg patch, 7 mg patch Per tablet (10 tablets/strip, not 3 2019 more than 2 strip/box) Oral tablets/capsules allergic conditions 12 years and above: 1 tablet/day NDD Loratadine 10 mg

22 Annex 3: New and Amended Regulation from 2016 to 2019 in Member Countries

23 Country China

Year Month Regulation Name N/A Note Report on the work of the govermnet in "Two sessions" of 2014: Emphersized market function 3 from 'basic‘ into 'crucial'. N

"Bad record" policy : The company in "Bad 3 record" will been restricted in sales and bidding. N

Low-price drug policy & list: The highest retail 2014 price will be abolished which daily treatment cost under 3 yuan (chemical medicine) and 5 yuan 5 (Chinese patent medicine), the actual trade price N will be determined by market, it 's good for some OTC.

Interim regulation on enterprise information bulletin : Disclosing administrative punishment 10 information will damage enterprises' reputation. N

Public hospital drug bidding purchasing work guidance : Implement classification of 3 procurement, common low price drug will N purchase via internet by hospitals directly.

Advertisement law : Medical precursor chemicals will be forbidden from public advertisement, 4 Medical advertisements can't be recommended N and proved by anybody.

Reform of drug prices : Apart from narcotic drugs and the first psychotropic substances, the prices of 5 other drugs have been abolished since June 1, N 2015 2015

Reforming Drugs & Medical Devices Review & Approval System : Pilot License-holder mechanism of Drugs Launch. Simplified and 9 improved examination and approval procedures N over drugs(including clinical trial test) and medical devices.

13th five-years planning suggestion : Encourage the social capital engagement in medical field, 11 private hospitals will become the sales growth N point in future.

24 Consistency evaluation of generic drugs : Require generic drugs conduct consistency evaluation, 3 products which pass the evaluation have potential N threat to high quality originals.

Double invoice system : Only allow two invoice through the drug circulation, one is from 4 manufacturer to distributor, another is from N distributor to hospital.

Reimbursement payment standard guidance(exposure draft) : For those drugs with 2016 their payment standard formulated according to 4 A different companies, the sale prices in pharmacies should not exceed the standard.

Precursor chemicals administration regulation(exposure draft) : PSE compound 7 preparations enter into the special monitoring list. A

GSP : Delete the relevant provisions of the electronic supervision, increase the establishment 7 N of drug traceability system.

25 国院于印“十三五”国家食品安全和“十三五”国家品安全的通知：保障品安全，提高品量安全水平。 The State Council’s Notification regarding 2 Issuance of National Food Safety Planning and N National Drug Safety Planning for the ‘13th Five- Year Plan’ Period ：Assurance of drug safety and improvement of the drug quality and safety.

《国家食品品督管理局于整部分品行政批事批程序的决定》（国家食品品督管理局令第31号） (2017-04-05). 一加品注册管理，切提高批效率，将下列由国家食品品督管理局作出的品行政批决定，整由国家食品品督管理局品中心床批，品充批，口品再注册批决定，其他品注册申由CFDA作出决定。 CFDA Published Adjustment of Decision-making Procedures for Administrative Approval Items(2017-04-05) 4 In order to further strengthen drug registration N 2017 management and effectively improve the efficiency of review and approval. The State Council of Food and Drug Administration decided to adjust the following administrative approvals for pharmaceuticals made by the State Food and Drug Administration to be approved by the State Food and Drug Administration's Drug Evaluation Center for clinical trial approval, drug supplement approval, and import. The drug renewal approval decision, other drug registration applications are decided by the CFDA.

2017 1. 。2. 。 The State Council’s Notification regarding key 5 point of work in 2017 on deepening reform of the N medical and health care systems1 promote the building and development of medical consortia 2 reform and improve the mechanism for ensuring the supply of drugs in short supply. and so on.

26 局于推品上市可持有人制度点工作有事的通知 (2017-08-21) ，加快推持有人制度点工作，一探索持有人的利和法律任、委托生中的量管理体系和生售全条的任体系、跨区域品管机管接、分以及任落地等事宜行了具体要求通知。 CFDA notice on promoting Pilot Program of Drug Registrant System(2017-08-21). In order to 8 accelerate the pilot work of the holder system, the N company further explores the rights and obligations and legal responsibilities of the holders, the quality management system in the production and the responsibility system for the production and sales chain. The cross-regional drug regulatory agencies' supervision and connection, division of responsibilities, and responsibility landings were notified of specific responsibilities.

中共中央公国院公印《于深化批制度改革鼓励品医器械新的意》：一、改革床管理,二、加快上市批,三、促品新和制展,四、加品医器械全生命周期管理,五、提升技支能力,六、加施 2017 General Office of the Communist Party of China and General Office of the State Council Printing and Distributing “the Opinion on Deepening the 10 Reform of the Review and Approval System and N Encouraging the Innovation of Drugs and Medical Devices”：1. Reform the management of clinical trials. 2. Accelerate evaluation and approval. 3. Promoting drug innovation and Generic drug development; 4. Strengthen full life cycle administration on drug and medical device; 5. Promoting technology supporting capability;6. strengthen organization implementation

(2017-11-21) 加品生的督管理制定本法，食品品督管理部依法品生条件和生程行、可、督。 Drug Manufacturing and Administrative regulation 11 (2017-11-21). In order to strengthen the supervision N and management of pharmaceutical production, the management activities of the food and drug supervision and administration department to review, permit, supervise and inspect the production conditions and production processes of drugs.

27 (2017-11-21) 加品可工作的督管理制定本法，国家食品品督管理局主管全国品可的督管理工作，明了品批企理《品可》、、更的程序及要求。 Drug business license Administrition(2017-11-21) . 11 In order to strengthen the supervision and management of drug business license work. The State Food and Drug Administration is in charge of the supervision and administration of the national drug business license, and clarifies the procedures and requirements for the drug wholesale enterprises to handle the issuance, renewal and change of the Drug Business License.

(2017-11-21) . 加品督管理，范互网品信息服活，保互网品信息的真、准，根据《中人民共和国品管理法》《互网信息服管理法》, 制定互网品信息服格管，明了按照属地管原的申要求。 Drug internet information service administartion(2017-11-21). In order to strengthen 2017 11 drug supervision and management, standardize Internet drug information service activities, and ensure the authenticity and accuracy of Internet drug information, according to the "People's Republic of China Drug Administration Law" and "Internet Information Service administration", the establishment of Internet drug information service qualification supervision, clearly in accordance with Declaration requirements for territorial supervision principles.

局于鼓励品新行先批的意 (2017-12-28): 加品注册管理，加快具有床价的新和床急需制的研上市，解决品注册申的矛盾，提出先批的范，程序及工作要求。 In order to strengthen drug registration 12 management, speed up the research and N development of clinically valuable new drugs and clinically urgently needed generic drugs, and resolve the contradiction of backlog of drug registration applications, the scope, procedures and work requirements for priority review and approval are proposed. (2017-12-28)

28 国家品督管理局布接受品境外床数据的技指原：用于指品在中人民共和国境内申注册，接受申人采用境外床数据作床价料的工作。 Technical Guidelines for Acceptance of Overseas 7 N Drug Clinical Trial Data：These guidelines apply to the acceptance of adopting overseas clinical trial data as clinical evaluation data in drug registration applications within the territory of the People’s Republic of China. 2018:2012 2018 520685 、。 National list of essential medicines (2018 edition) : is based on the 2012 version of 10 the directory to adjust, 1) to increase the number A of varieties, increased from 520 to 685, 2) to optimize the structure 3)to further standardize the types, specifications, 4) continue both on Chinese and western medicine, increased the function range of the attending, cover more TCM clinical symptoms. 5) strengthens the clinical necessity

11 Notice of the general office of the state council on the issuance of pilot programs for centralized procurement and use of drugs organized by the 1 state11 cities were selected to select the pilot N varieties from generic drugs corresponding to generic drugs that have passed the consistency evaluation of quality and efficacy. The state organized the centralized procurement and use pilot of drugs, so as to achieve a significant reduction in drug prices and reduce the burden of drug costs on patients

国家局于一完善品批和管工作有事宜的公告（2019年第56号） NMPA's Announcement on Further Improvement 7 of Bundling Evaluation and Approval for N Pharmaceutical, Pharmaceutical Packaging Materials and Pharmaceutical Excipients, and also the Related Regulatory Work (No.56, 2019)

29 国家局于宣《中人民共和国疫苗管理法》的通知 (2019-07-30) 。《中人民共和国疫苗管理法》于2019年6月29日由第十三届全国人民代表大会常委会第十一次会通，自2019 年12月1日起施行。 CFDA notice regarding Vaccine Administration 7 N Law of People's Republic of China (2019-07-30). The "Vaccine Administration Law of the People's Republic of China" was reviewed and approved by the 11th meeting of the Standing Committee of the 13th National People's Congress on June 29, 2019, and will take effect on December 1, 2019. 中人民共和国品管理法：自1984年布以来的第二次系性、性的重大修改，将品域改革成果和行之有效的做法上升法律，公健康提供更有力的法治保障。 the drug administration law of People's Republic of 8 China will be implemented on 1st Dec 2019. This A is the second major systemic and structural reform since its promulgation in 1984, which has translated the achievements and effective practices of drug reform into law and provided stronger legal protection for public health.

国家局于印品量抽管理法的通知：自2006年，13年之后，加品督管理，范品量抽工作，修了本法。用于在中人民共和国境内依批准生、、使用品展的量抽工作。 NMPA notification on Measures for the administration of spot check and inspection of 8 drug quality: since 2006, after 13 years, This law A has been revised to strengthen drug supervision and control and to regulate the random inspection and testing of drug quality. It is applicable to the quality sampling inspection of drugs produced, sold and used in accordance with the approval within the territory of the People's Republic of China

30 List of New Regulation and Amended Regulation from 2017 to 2019 Country Indonesia Country INDONESIA

NADFC NOTE REGULATION NAME No. YEAR Procedure for Certification of Good Distribution New 25 2017 Practices 24 2017 Criteria and Procedure for Drug Registration Amendment 8 2017 Drug Advertising Guidelines Amendment Control of Drug and Food Imports into Indonesian Amendment 4 2017 Territory Amendment Guidelines for Good Manufacturing Practises 34 2018 (GMP)

Implementation of 2D Barcodes in Drug and Food 33 2018 Control Integration of Electronic Licensing Service of New 26 2018 Drug and Food Sector

Control the Management of Drugs, Drug Raw Amendment Materials, Narcotics, Psychotropics, and 4 2018 Pharmaceutical Precursors in Pharmaceutical Services Facilities Amendment to the Regulation of the NADFC Amendment 15 2019 Number 24/ 2017 Regarding Criteria and Procedure for Drug Registration Amendments to Drugs Withdrawal and Amendment Elimination Drugs that Do Not Meet Safety, 14 2019 Efficacy, Quality and Label Standards and / or Requirements Amendment Guidelines for the Management of Certain Drugs 10 2019 that are Often Abused

Technical Guidelines for Good Distribution Amendment 9 2019 Practises (GDP) New Evaluation of Fulfillment of Requirements for 7 2019 Good Manufacturing Practises for Imported Drug Manufacturing Facilities

31 List of New Regulation and Amended Regulation from 2016 to 2019

Country Country Japan Japan N:New A:Amend Year Month Regulation Name N/A Note Notice No. Yakuseishinsahatasu With the review of ethical medicines 0325-10 on 25 March, 2016 containing Lysozyme hydrochloride, 3 A the registration for the OTC cold remedies or antitussives and expectorants were terminated. New consultation body "Review board It was aimed to build up the reflecting 2016 for the reclassification of ethical scheme to accept timely on the medicines to OTC medicines" was reclassification trends in abroad and established. request for the assessment from the 4 N various stakeholders including consumers and academia, and to be contributed in the decision for the reclassification in the MHLW. Notice: Yakuseihatsu 0626-3 Based on the incidents where the three "On the Function of General Manager major responsible officers in marketing for manufacturing and Marketing, authorization holders did not fulfill their 6 Executive Quality Manager, and A expected responsibilities, the MHLW Executive Safety Manager" instructed drug firms to ensure their proper functioning.

Notice: Yakuseianhatsu 0704-2 Based on the safety evaluation, MHLW "Revising the use instruction of drugs indtructed the manufacturers of drugs containing codeine phospate or containing the said ingredients (Rx or dihydrocodeine phosphate" OTC) to do the following; (a) an immediate revision of the 2017 labelling so that the drug should not be used for children under age 12. 7 N (b) within 18 months, a change of the ingredients to eliminate codeines should be made or the products should indicate that it is not for children (c) in 18 months the products should be conttra-indicated for children under age 12.

Notice: Yakuseihatsu 0929-4 The standard for advertising drugs 9 "Revision of Drug Advertisement A underwent a major revision. Standard"

The standars underwent a major Japanese Pharmaceutical Excipients 3 N revision. The standards contain 2018 specifications of 489 excioients. 2018 The standars underwent a major Extra-pharmacopoeia Herbal 12 N revision. The standards contain Medicine Standards 2018 specifications of 83 herbal medicines.

32 List of New Regulation and Amended Regulation from 2016 to 2019 Country Korea Country Korea

If a new OTC product is satisfy following conditions, comparative clinical data or bioequivalence data is not required; 1) only the dosage form is modified from oral solid Regulation on pharmaceuticals approval, form to orally integrating tablet (or film) 2016 Oct A notification and review 2) all ingredients and specs are proper to OTC monograph 3) it is proved that the ingredients are not absorbed orally

"Lysozyme HCl" was deleted from OTC monograph 2017 Dec OTC monograph A

caluse added Regulation on pharmaceuticals approval, Former regulation was listing required data on both 2018 Nov A notification and review ETC & OTC products without distinction, with this revise, regulation on OTC products are separated

33 List of New Regulation and Amended Regulation from 2016 to 2019

CountryCountry Philippines Philippines N:New A:Amend Year Month Regulation Name N/A Note FC2014-008 Application Process and Requirement for Post-Approval 2 N Changes of Pharmaceutical Products

FA 2014-016 Review of Guidelines for 3 OTC Drugs N

FC2014-011 Application Process and Requirement for Post-Approval 4 A Changes of Pharmaceutical Products

FC2014-026 Guidelines on the 2014 Implementation of New Rules and 11 Regulations on the Licensing of Drug N Distributors

FC2014-028 Guidelines on the Implementation of New Rules and 11 Regulations on the Retail Outlets for N Non-Prescription Drugs

FC2014-034 Rules and Regulations 10 on the Licensing of Estalishments N

AO 2015-0053 Implementing Guidelines on the Promotion and 2015 12 Marketing of Pharmaceutical N Products

AO2016-008 Revised Rules and Regulations Governing Generic 3 A Labelling Requirements

FC2016-004 e-License To Operate 2016 5 Application N

FC2016-017 Addition Post Approval 10 Changes for Pharma Products N

FC 2018-014 Validity of Registration of Pilot Products under Review of 2018 10 N OTC Applications

34 List of New Regulation and Amended Regulation from 2016 to 2019

CountryCountry Taiwan Taiwan

N:New A:Amend Year Month Regulation Name N/A Note Revision on format and submission timing of periodic Jan safety update report required in Regulations for Drug A Safety Monitoring for new medicines and other cases

Jan Guideline of judgement on combination drugs N Announcement of the implemention items and schedule Feb for Western Drug PIC/S GMP Guide Part III: GDP N 2016 Guideline of labeling format and QR code on product Mar packaging material for non-prescription drug N

Mar Revision of Pharmaceutical Stability Testing Benchmark A Revision of Regulations for Registration of Medicinal Apr Products (mainly for API GMP and source, repacking A site registering and etc.) Announcement of Refuse to File (RTF) implementation Jan N for Generic Drug Registration submission review Announcement of the Clinical Benefit and Risk Re- Aug assessment for codeine containing product used in N children The update is mainly for articles in Chapter 1 Pharmaceutical Sep Revision of Western Drug PIC/S GMP Guide Part I A Quality System, Chapter 2 Personnel, Chapter 6 Quality 2017 Control and Chapter 7 Outsourced Activities Announcement of implementation of Switch submission Nov N requirement checklist Revision of Regulations for Registration of Medicinal The update is mainly for articles related to package e-file Dec A Products uploading requirements, API document requirements, and etc. Announcement of the establishement of Good Dec N Distribution Practice guideline for Western Drug For Non-prescription drugs which are not new chemical entities or under new drug surveillance and whose API source Announcement of the applicable drug and substituted complies with GMP, the submission of an outline of May document type for DMF requirement exemption in the N synthesis route / manufacturing process, testing Regulations for Registration of Medicinal Products specifications, methods and results of active ingredients can substitute the full DMF requirement Announcement of implementation mechanism and Sep N 2018 timeline of Good Distribution Practice for Western Drug The update is mainly for the new introduction of Topical Antiseptic and Antimicrobial drug products, Topical Antifungal drug products, Topical Antipruritic and anti-inflammatory drug Revision of Guidelines on the Review of Over-The- Oct A products, Topical Acne drug products, Diaper rash and Counter (OTC) Drug (OTC Monograph) antimiliaria drug products, and Dry skin and exfoliation drug products and minor update of the remaining existing monographes The update is mainly for articles related to e-submission Revision of Regulations for Registration of Medicinal Feb A management, Advanced 10 country CPP legalization Products exemption, expiration dating format, and etc. The update is mainly for articles in Chapter 3 Premises and May Revision of Western Drug PIC/S GMP Guide Part I A Equipment, Chapter 5 Production, and Chapter 8 Complaints and Product Recall Announcement of implementation of Patent linkage for Jul N Western Drug Refuse to File (RTF) checklist for Generic Drug The update is mainly for the addition of patent link declaration 2019 Jul A Registration submission review sections Revision of Regulations Governing the Trace and Track Medicine containing ephedrine or pseudoephedrine Jul A System for Medicinal Products (excluding controlled drug) is new item in scope The update is mainly for the new introduction of Nasal drug Revision of Guidelines on the Review of Over-The- Aug A products and Topical hemorrhoidal drug products and minor Counter (OTC) Drug (OTC Monograph) update of the remaining existing monographes Announcement of Refuse to File (RTF) implementation Aug for New Drug and Biological Drug Registration N submission review

35 List of New Regulation and Amended Regulation from 2016 to 2019

CountryCountry Thailand Thailand

N:New A:Amend Year Month Regulation Name N/A Note Reclassification Guideline for Dossier Applicable for reclassification for: 1) Preparation and Evaluation Criteria on Dangerous medicines, 2) Specially reclassification of Human Modern controlled medicines 3) non- 26-Feb Medicines N dangerous/non-specially controlled (Food and Drug Administration medicines and 4) Household Remedy Announcement) medicines 2016 Guideline, criteria and conditions for Mandatory for Selling drug license, justification of Good Pharmacy Wholesale selling drug license, Selling Practice (Food and Drug drug license for non-dangerous and 27-May Administration) N non-specially controlled medicines in pre-package, Selling drug license for veterinary drug in pre-package

Revised Drug Act BE 2510 (version 6) License renewal (every 7 years) – , under the old version of Drug Act, all medicine licenses granted by Thailand License renewal (every 7 years) FDA is life-long validity (unless not manufacturing/ importing continuously for 2 years). With this, all licenses will need to renew & submit technical A documents for review (e.g. quality section, esp stability, specification etc.). License renewal dossier & process guideline is being drafted by Thailand FDA and expected to publish by end 2019 at earliest time. The first batch of licenses to be renewed will be in next 5 years (Yr 2024). 2019 Revised Drug Act BE 2510 (version 6) FDA introduce this process formally in the Drug Act (Rev 6), allowing the License re-evaluation review of quality, safety, efficacy of products & suitability as medicines. Upon the license re-evaluation, the outcome could be the withdrawal of license, label modification, dosage A adjustment etc. depending on the risk level. License re-evaluation dossier & process guideline is being drafted by Thailand FDA and expected to publish by end 2019 at earliest time. The license re-evaluation could take place anytime and initiated by FDA or any stakeholder.