Pharmaceuticals & Healthcare Asia Pacific ASEAN Pharmaceutical Harmonization ASEAN Economic Community Baker & McKenzie's ASEAN Pharmaceutical Harmonization Guide Editors' Note Dear Valuable Clients, ASEAN has the potential to become a key driver of the global economic structure. With a total population of about 600 million people, a combined GDP of US$ 2.1 trillion, an abundance of natural resources and a well-educated workforce, regional economic integration into a single market and production base will boost ASEAN's competitive edge. As we move closer to the establishment of the ASEAN Economic Community ("AEC") in 2015, the freer flow of capital, goods, services, investment and people may substantially change the way we do business and interact with our neighboring countries. To achieve the ASEAN's objectives, barriers such as the different laws, rules, regulations and standards governing goods and services need to be eliminated. As a result, a long-term, concerted effort to harmonize different laws and standards was put in place with 13 sectors identified as areas of importance. Healthcare, including pharmaceuticals and other relevant products, is one of these identified sectors, where efforts to achieve harmonization are to be concentrated. Baker & McKenzie, a law firm entrenched in the ASEAN, has rolled out several AEC Pharma initiatives, including seminars, publications and other communications, in response to this industry trend. The AEC Seminar – Spotlight on the Pharmaceutical Industry brought together key regulatory authorities, investment specialists and pharmaceuticals & healthcare clients to talk about current updates, insights, opportunities and threats surrounding the AEC efforts. The first leg of many took place in Bangkok in 2012, to be followed by similar seminars in Manila, Singapore and Kuala Lumpur in 2013. i This ASEAN Pharmaceutical Harmonization Guidebook addresses five key AEC harmonization issues and aims to provide information on how to navigate your business through the ASEAN pharmaceutical harmonization process. Included in the guidebook are majority of the ASEAN member countries, namely, Cambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam. We would like to extend our gratitude to all the contributors, especially correspondent law firms, namely Sciaroni & Associates and South East Asia Law Office, whom we have partnered with for the Cambodia and Lao PDR chapters, respectively. ASEAN has proven that it can endure economic challenges. This fact, along with regional integration efforts, has not gone unnoticed by international corporations and investors. An integrated ASEAN market, particularly in the pharmaceuticals & healthcare industry, with harmonized standards, registration and evaluation, mutual recognition of qualifications and cross-border cooperation, will propel companies to become more prominent players in the global landscape. We hope that our seminars and publications serve as a useful resource and we look forward to engaging you more on the AEC as we spot opportunities and help your company gain the first-mover advantage. Yours truly, Peerapan Tungsuwan Partner Head, Asia Pacific Pharmaceutical & Healthcare Industry Group ii Contributors Baker & McKenzie INDONESIA Daru Lukiantono +62 21 515 4853 Daru.Lukiantono @bakernet.com Cahyani Endahayu +62 21 515 4893 Ext.4893 Cahyani.Endahayu @bakernet.com MALAYSIA Kherk Ying Chew +60 3 2298 7933 KherkYing.Chew @wongpartners.com Sonia Ong +60 3 2298 7931 Sonia.Ong @wongpartners.com MYANMAR Saw Yu Win +66 2 636 2000 X6001 SawYu.Win @bakermckenzie.com PHILIPPINES Christina Macasaet-Acaban +63 2 819 4947 Christina.Macasaet-Acaban @bakermckenzie.com Charles Veloso +63 2 819 4954 Charles.Veloso @bakermckenzie.com SINGAPORE Andy Leck +65 6434 2525 Andy.Leck @bakermckenzie.com Ren Jun Lim +65 6434 2721 Ren.Jun.Lim @bakermckenzie.com iii THAILAND Peerapan Tungsuwan +66 2 636 2000 X4333 Peerapan.Tungsuwan @bakermckenzie.com Prim Uditananda +66 2636 2000 X4330 Prim.Uditananda @bakermckenzie.com VIETNAM Yee Chung Seck +84 8 3520 2633 YeeChung.Seck @bakermckenzie.com Correspondent Law Firms CAMBODIA Bretton Sciaroni Sciaroni & Associates +855 (23) 21 0225 Brett@sa-cambodia.com LAO PDR Kitchrat Kontain South East Asia Law Office +856 980 2221 firstname.lastname@example.org iv Minh Ha Vu +84 8 3520 2664 MinhHa.Vu @bakermckenzie.com Table of Contents Editors' Note ......................................................................................... i Contributors ........................................................................................ iii ASEAN Pharmaceutical Harmonization ............................................. 1 AEC Pharmaceutical Questionnaire .................................................... 3 Cambodia ...................................................................................... 5 Indonesia ....................................................................................... 8 Lao PDR ..................................................................................... 12 Malaysia ...................................................................................... 14 Myanmar ..................................................................................... 17 Philippines .................................................................................. 20 Singapore .................................................................................... 24 Thailand ...................................................................................... 27 Vietnam ....................................................................................... 30 ASEAN Pharmaceutical Harmonization In 2015, the ten countries which form ASEAN ("Association of Southeast Asian Nations") will implement the ASEAN Economic Community ("AEC") with the goal of creating a common economic community in Southeast Asia, characterized by a single market and production base. The establishment of this community has the potential to substantially change the way we do business and interact with our neighboring countries. In order to achieve the ASEAN's objectives, there is a need to eliminate the barrier of having different laws, regulations and standards governing goods and services. Thirteen sectors have been identified as areas of importance, where efforts to achieve harmonization should be concentrated. The Healthcare industry, including pharmaceuticals and other relevant products, has been particularly identified as one of these 13 sectors. The ASEAN Pharmaceutical Product Working Group ("PPWG"), the regulatory body responsible for overseeing the ASEAN harmonization efforts, has formally stated the following objective: "To develop harmonization schemes of pharmaceutical regulations of the ASEAN member countries to complement and facilitate the objective of AFTA, particularly, the elimination of technical barriers to trade posed by these regulations, without compromising drug quality, safety and efficacy." Through harmonization efforts, the PPWG envisions an ASEAN pharmaceutical product, for which the same regulatory requirements would apply for all ASEAN member countries. Its development would encourage increased supplies by multinational companies to the ASEAN region and presumably, increased supplies between members. Baker & McKenzie ASEAN Pharmaceutical Harmonization 1 If an ASEAN pharmaceutical product is achieved, ASEAN manufacturers could have renewed unity and coherence as well as the benefits of cost savings and greater economies of scale. These should enable them not only to supply the needs of ASEAN markets more quickly and effectively, but also to compete more vigorously in the wider market of ASEAN +3 (i.e. ASEAN and its key partners, Japan, South Korea and China). Harmonization is the key to the success of the AEC. With the establishment of the AEC, the ASEAN Free Trade Agreement ("AFTA") and the creation of the ASEAN pharmaceutical product, there lies opportunities and challenges, especially for the pharmaceutical and healthcare industry. The ASEAN Pharmaceutical Harmonization Guidebook aims to provide you an overview of the key harmonization issues in the pharmaceutical industry for the various ASEAN jurisdictions, namely Cambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam. 2 ASEAN Pharmaceutical Harmonization Baker & McKenzie AEC Pharmaceutical Questionnaire To address the key harmonization issues in the pharmaceutical industry, each of the ASEAN member countries responded to these five questions: 1) What is the definition of a "new drug"? New drugs are defined differently in the various ASEAN countries. For instance, Thailand and Cambodia have 7 "new drug" categories, while other countries have 2 or 3 categories only. It is important to identify and understand how new drugs are defined for product registration and/or application purposes. 2) What are the current requirements and timelines for pharmaceutical product registrations? The ASEAN has initiated pharmaceutical harmonization efforts, including the development of the ACTR and ACTD format for product registration documents. However, not all countries are at the same pace in terms of implementation. While some countries have fully implemented the ACTR/ACTD format, other countries have not gone so far as strictly requiring the ACTR/ACTD for submissions. 3) Have the ASEAN Common Technical Requirements ("ACTR") and ASEAN Common Technical Dossiers ("ACTD") been implemented? If not, when can it be expected? Baker & McKenzie ASEAN Pharmaceutical Harmonization 3 4) What are the requirements for pharmaceutical facilities? In terms of the registration of pharmaceutical facilities, compliance with the Pharmaceutical Inspection Cooperation Scheme ("PIC/S") standards is the end goal of the ASEAN harmonization. Although some countries have already enforced this, not all countries have fully adopted the PIC/S compliance requirement. 5) Will there be a revision of application files, which were not in accordance to the ACTD format? Since not all ASEAN countries have fully implemented the ACTR/ACTD format for documents, for some countries, revisions for previous product registrations may be required. The desired outcome of the ASEAN pharmaceutical harmonization efforts is to have a review and/or revision of application files every five years to ensure product quality and validity. This differs from the current status for the various countries as some product licenses do not expire. To navigate your business through the ASEAN pharmaceutical harmonization process, the responses to these five AEC questions aid in identifying where the various ASEAN countries are in terms of implementation as well as managing the needed preparations for product registration submissions. 4 ASEAN Pharmaceutical Harmonization Baker & McKenzie Cambodia 1. What is the definition of a "new drug"? Cambodia follows practices similar to other ASEAN countries, such as Thailand. According to the Department of Drugs and Food, a new drug refers to drugs having at least one of the following qualities: 1) new chemical entity 2) new indication 3) new delivery system that affects bioavailability/bioequivalence ("BA/BE") 4) new route of administration 5) new dosage form 6) new strength 7) new combination of: i. new chemical entities and new derivatives ii. two registered chemical entities or more but not the same as combination drugs already registered iii. combination drugs already registered but of different strength Baker & McKenzie ASEAN Pharmaceutical Harmonization 5 2. What are the current requirements and timelines for pharmaceutical product registrations? Pharmaceutical product application files (innovative drugs and generic drugs) must be submitted following ACTR and ACTD. The timeline for registration of an innovative drug is approximately three months and the timeline for registration of a generic drug is approximately six months, starting from the day the FDA issues an actual acknowledgement number. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? On 1 March 2010, the ACTR/ACTD was implemented in Cambodia. Cambodia does not have an actual trial period but began voluntary submission in 2008. 4. What are the requirements for pharmaceutical facilities? Local pharmaceutical manufacturing facilities must comply with Good Manufacturing Processes ("GMP") standards (refer to PIC/S), and must undergo training by the Ministry of Health. However, according to the Department of Drugs and Food, facilities established overseas need to submit full documentation, including the Plant Master File, Plant Layout, latest GMP Assessment Report and latest GMP Certificate as well as other documents for consideration for certifying overseas manufacturing facilities. 6 ASEAN Pharmaceutical Harmonization Baker & McKenzie 5. Will there be a revision of application files, which were not in accordance to the ACTD format? According to the Department of Drugs and Food, starting March 2010, pharmaceutical product licenses of currently registered products must be revised according to the ACTR/ACTD (Part I and II) format. A bioequivalence document must be submitted along with the Quality documents for those Generic drugs in the List of Molecules required for Bioequivalence Study and Quality documents. The Non-clinical document (Part III) and Clinical document (Part IV) must also be submitted for the registration of New Chemical Entities ("NCE") and Biotech products. Applications in the revised format may retain the existing registration numbers. The result is that an application file will need to be revised every five years as in other ASEAN countries. Baker & McKenzie ASEAN Pharmaceutical Harmonization 7 Indonesia 1. What is the definition of a "new drug"? A "new drug" is a drug with a new active chemical entity, new additive chemical, new dosage form/new route of administration, new strength, or new combination that has not been approved in Indonesia. 2. What are the current requirements and timelines for pharmaceutical product registrations? Before registering drugs, the registrant should go through a preregistration process. A pre-registration process is conducted in order to filter drug registrations, decide on the registration category, evaluation line, evaluation cost, and decide on the documents needed for drug registration. The registration takes most time in the evaluation process, depending on which evaluation line the drugs should go through. There are 4 evaluation line categories, which are: 1) Forty (40) days line for: a) Registration of minor variations that need approval; b) Registration of drugs specialized for export 2) One hundred (100) days line for: a) Registration of new drugs and biology products indicated for serious illness therapy that: i. threatens human life (life saving), and/or ii. is easily contagious to other people, and/or 8 ASEAN Pharmaceutical Harmonization Baker & McKenzie iii. does not have or there is a lack of choice for safe and effective therapy; b) Registration of new drugs and biology products, which are, based on justification, indicated for serious and rare illnesses (orphan drugs); c) Registration of new drugs and biology products for public health programs; d) Registration of new drugs and biology products, which have been through a development of new drug process that is developed by a pharmacy industry or research institution in Indonesia with all phases of the clinical tests conducted in Indonesia; e) New registration of essential generic copy drugs which are completed with supporting documents for program needs or supporting data as a generic drug; f) New registration of copy drugs with electronic information standards ("Stinel"), or g) Registration of major variations of new indications/new posology for drugs, intended for as mentioned in 2a, 2b, 2c and 2d; h) Registration of major variations which are not included in 2g. 3) One hundred and fifty (150) days line for: a) New registration of new drugs, biology products, and registration of major variations of new indications/new posology that has been approved in countries applying the harmonized evaluation system and in countries with well known evaluation systems. Baker & McKenzie ASEAN Pharmaceutical Harmonization 9 b) New registration of new drugs, biology products, and registration of major variations of new indications/new posology that has been approved in at least three countries with well known evaluation systems. c) New registration of copy drugs without Stinel. 4) Three hundred (300) days line are for new registration of new drugs, biology products, similar biology products, or registration of major variations of new indications/new posology that are not included in the evaluation line stated in item 2 and 3. After submitting the registration form containing information from the pre-registration process and enclosing the relevant documents, the Head of the National Agency of Drug and Food Control ("BPOM") will decide whether to accept or decline the drug registration. In practice, it may take 12 to 18 months for BPOM to issue a pre-market approval, starting from the day BPOM issues an acknowledgement letter stating that the application letter and the supporting documents have been completely submitted. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? ACTD has been implemented since 12 October 2011 through the enactment of 2011 BPOM regulation on Criteria and Procedure of Drugs Registration, which results in all drug registrations to follow ACTD format as of that date. Whereas ACTR has been implemented since December 2011 by the Indonesian government through conducting national workshops and providing capacity building. 10 ASEAN Pharmaceutical Harmonization Baker & McKenzie 4. What are the requirements for pharmaceutical facilities? All pharmaceutical facilities must acquire a Pharmaceutical Industry License. Starting 9 April 2012, all pharmaceutical facilities must also comply with the updated requirement of GMP (refer to CPOB) proven by the GMP Certificate, which is valid for 5 years. 5. Will there be a revision of application files, which were not in accordance to the ACTD format? Application files which were submitted for registration before 12 October 2011 will still be processed based on the old format and those which are submitted after such date will be processed based on the ACTD format. Baker & McKenzie ASEAN Pharmaceutical Harmonization 11 Lao PDR 1. What is the definition of a "new drug"? "New drugs" refer to drugs with the following qualifications: 1) Modern drugs or any traditional medicine, resulting in positive effect 2) Not completely defined and mentioned in international medical documents 3) Not registered in its country of origin 4) Registered for less than five years 5) Differs in formula, method of use, form, and packing from drugs that have been registered 2. What are the current requirements and timelines for pharmaceutical product registrations? Registration of a pharmaceutical product requires submitting an application form and supporting documents following ACTR and ACTD to the Department of Food and Drug ("FDD"). Registration of a pharmaceutical product normally takes approximately six months upon the FDD confirming that the application and all supporting documents have been duly received by the FDD. 12 ASEAN Pharmaceutical Harmonization Baker & McKenzie 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? The trial period for voluntary submission started in 2009. From August 2011 onwards, the FDD has gradually imposed that pharmaceutical application files must follow ACTR/ACTD. 4. What are the requirements for pharmaceutical facilities? Local pharmaceutical manufacturing facilities must comply with GMP standards. For the overseas facilities that do not comply with the GMP standards, they are required to submit the manufacturing and product information to the FDD. 5. Will there be a revision of application files, which were not in accordance to the ACTD format? It is not clear whether the application files approved prior to August 2011 must be revised. However, it is obvious that all applications filed from August 2011 onwards will follow ACTR format, in which such applications are subject to be revised from time to time in accordance with the ACTR format. Baker & McKenzie ASEAN Pharmaceutical Harmonization 13 Malaysia 1. What is the definition of a "new drug"? The Drug Registration Guidance Document ("DRGD") issued by the National Pharmaceutical Control Bureau ("NPCB") of the Malaysian Ministry of Health defines "New Drug Product" or "NDP" as one which has not been registered in accordance with the Control of Drugs and Cosmetics Regulations 1984 ("Regulations"). An NDP may fall under any one of the following categories: 1) New chemical entity (an active moiety that has not been registered in any pharmaceutical product) or radiopharmaceutical substance (a radionucleotide ligand or the coupling mechanism to link the molecule and the radionucleotide that has not been registered in any pharmaceutical product). 2) New combination product - a new pharmaceutical product containing two or more drugs that are physically, chemically or otherwise combined or mixed and produced as a single pharmaceutical product, in a combination that has not been registered in any other pharmaceutical product. 3) Supplemental product - a new pharmaceutical product containing a drug that has been previously registered as a pharmaceutical product but differing in properties with regard to safety and/or efficacy from the product that has been previously registered. 14 ASEAN Pharmaceutical Harmonization Baker & McKenzie 2. What are the current requirements and timelines for pharmaceutical product registrations? Applications for registration of pharmaceuticals must be submitted online to the Drug Control Authority ("DCA") via the QUEST 3 system. Registration takes between 210 - 245 working days from the date of final and complete submission of the application to the NPCB. The registration is valid for five (5) years or such other period as specified in the registration certificate. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? Yes, the DRGD incorporates the ACTR and ACTD. 4. What are the requirements for pharmaceutical facilities? Compliance with the DCA's GMP guidelines is a prerequisite for the application of a manufacturing license, as well as product registration. 'Manufacturing' is defined under the Regulations to include (i) the making or assembling of the product, (ii) the enclosing or packaging of a product in any container in a form suitable for administration or application, and the labeling of the container, and (iii) the carrying out of any process in the course of any of the foregoing activities. The DRGD states that a manufacturing site should comply with current GMP standards. Local manufacturing sites are subjected to pre-licensing inspections and for manufacturing sites outside Malaysia, certification by the competent authority is sufficient. However, the DCA reserves the right to conduct an inspection on any manufacturing site. Baker & McKenzie ASEAN Pharmaceutical Harmonization 15 5. Will there be a revision of application files, which were not in accordance to the ACTD format? There is no confirmation from the DCA whether applications submitted prior to the implementation of ACTD and ACTR that are not in ACTD format must be revised to comply. 16 ASEAN Pharmaceutical Harmonization Baker & McKenzie Myanmar 1. What is the definition of a "new drug"? Drug is defined under the National Drug Law as a substance for use, whether internal or external, in the diagnosis, prevention and treatment of disease, birth control or for any beneficial effect in human beings and animals. "New drug" is not defined specifically in the National Drug Law. The Myanmar Food and Drug Administration ("FDA") requires updating changes to registered drugs to be made only with the approval of the FDA. For example, changes to registered drugs such as relevant data or findings from studies used as basis for the justification of change, significant effect of changes to the specification of drugs, changes to strength and dosage form. 2. What are the current requirements and timelines for pharmaceutical product registrations? Drug registration applications must be filed to the FDA in a form (Form 1 Registration) prescribed by the FDA following ACTD for the registration of pharmaceuticals for human use. Enquiring and getting approval of the FDA may take around six months after submission of the completed Form 1 Registration and documentation for common, established drugs, and approximately nine months for less common drugs and non-new chemical entities, and approximately 12 months for new chemical entities. Baker & McKenzie ASEAN Pharmaceutical Harmonization 17 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? According to the current practice in applying for registration of drugs, the FDA mandates that the standard ACTD has to be used in connection with complete information of drugs accompanying Form 1 Registration, when submitting them to the FDA. Therefore, ACTD has been referred to by the FDA to be strictly complied with. 4. What are the requirements for pharmaceutical facilities? GMP applies to the products which are categorized as medicine, medical equipment, cosmetics or sanitation products in Myanmar. Pursuant to the National Drug Law, the Myanmar Food and Drug Board of Authority can, among others, determine good practices for assurance of quality in respect of manufacturing, clinical tests and laboratory analyses of the pharmaceutical raw material or registered drug and all matters relating to drugs. The National Drug Law requires a person who has been granted the right to manufacture, import, export, store, distribute or sell pharmaceutical raw material or registered drug to abide strictly by the order, directive and conditions issued by the Myanmar Food and Drug Board of Authority in respect of quality assurance of the drug. Moreover, according to "A Guideline on Drug Registration Application (revised in February 2009)" prescribed by the FDA (the "Guideline"), GMP certificate of manufacturing plant is also required to be submitted to FDA, together with other relevant documents such as: a) a product certificate issued by the regulatory authority of its own country indicating that the product is authorized to be sold in country of origin, b) properly endorsed photocopy of valid manufacturing license, etc. Please also refer to 18 ASEAN Pharmaceutical Harmonization Baker & McKenzie answer in item 2, regarding good practices in manufacturing and drug quality control. 5. Will there be a revision of application files, which were not in accordance to the ACTD format? The Guideline mandates that the ACTD format has to be strictly observed when applying for registration of drugs. The FDA does not accept applications for registration of drugs which are not in conformity with ACTD format. Baker & McKenzie ASEAN Pharmaceutical Harmonization 19 Philippines 1. What is the definition of a "new drug"? A "new drug" refers to: 1) any drug which is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety of drugs, as safe for use under the conditions prescribed, recommended, or suggested in the labeling thereof. 2) any drug, the composition of which is such that said drug, as a result of investigations to determine its safety for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under new conditions. The term "new drug" shall include drugs: a) containing a newly discovered active ingredient; b) containing a new fixed combination of drugs, either by molecular or physical combination of drugs; c) intended for new indications; d) an additional new mode of administration; or e) in an additional dosage or strength of the dosage form, which meets the conditions as defined under the new drug. 2. What are the current requirements and timelines for pharmaceutical product registrations? Applications for registration of pharmaceutical products must be submitted to the Food and Drug Administration ("FDA") in accordance with the ACTD format. In addition, the following documents must generally be submitted: 20 ASEAN Pharmaceutical Harmonization Baker & McKenzie 1) Notarized Letter of Application; 2) Form No. 8, as prescribed by the FDA; 3) Distributorship Agreement over the product to be distributed / imported; 4) Copy of valid License to Operate; 5) Unit Dose and Batch Formulation; 6) Technical specifications of all raw materials; 7) Certificate of Analysis of all active raw materials from the manufacturer of the active raw material and from the manufacturer of the finished product; 8) Technical specifications of the finished product; 9) Certificate of Analysis of the finished product; 10) Master manufacturing procedure, production equipment, sampling and in-process controls, and master packaging procedure; 11) Assay and other test procedures, including assay with data analysis; 12) Stability studies; 13) Representative sample in market or commercial presentation; 14) Labeling materials, with actual color text; 15) Bioavailability / bioequivalence studies, where applicable; 16) Dissolution profile for certain drugs; Baker & McKenzie ASEAN Pharmaceutical Harmonization 21 17) For new drug applications, a copy of FDA's approval on preclinical, clinical and protocol for Monitored Release, the rationale of Fixed Dose Combination Product (if applicable), and Post-Marketing Surveillance ("PMS") or Letter of Extension of Monitored Release Status (if applicable); 18) For imported products, original Certificate of Pharmaceutical Product ("CPP"), issued at least one year from the date the application for registration was filed, or, if CPP is not available, Certificate of Free Sale from the country of origin, duly authenticated by the Philippine consulate of the place of execution, and a government certificate attesting to the registration status of the manufacturer, duly authenticated by the Philippine consulate of the place of execution; 19) For products contained in plastic container: general information on the container, studies done on the plastic to substantiate claim that the product is safe to use, test procedure and limits, and empty plastic container and closure with corresponding proof of payment for laboratory analysis; 20) Payment of registration fee. The approval timeline for product registration is eight to 12 months, depending on the volume of work of the FDA, and the applicant's submission of complete documentation or immediate compliance with any additional requirements. Applications for new drugs may take a longer period. New drug applications for general use shall be issued either two or five years based on the application of the company while renewal registrations are valid for 5 years. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? The FDA issued a circular in 2007, which stated that the ACTD/ACTR will be fully implemented by January 2009. 22 ASEAN Pharmaceutical Harmonization Baker & McKenzie However, based on informal conferences with the FDA, it confirmed that in practice, the FDA still accepts applications that are not compliant with the ACTD/ACTR. It has been communicated with Philippines regulators/health authorities that ACTD/ACTR must be fully implemented by 2015. 4. What are the requirements for pharmaceutical facilities? Pharmaceutical facilities being referred to are drug establishments engaged in the manufacturing, importation, exportation, sale, offer for sale, distribution, donation, transfer, use, testing, promotion, advertising, or sponsorship of health products, including the facilities and installation needed for its activities. Drug establishments are inspected using the PIC/S GMP Guides as standard for Good Manufacturing Practice. On June 2012, full implementation of the PIC/S GMP Guides created under the ASEAN Mutual Recognition Agreement ("MRA") was adopted. For compliance, a one year transition period starting from the effectivity of the adoption was given. In addition, a drug establishment must obtain a License to Operate from the FDA. The requirements for obtaining a License to Operate will depend on the activity the drug establishment is engaged in (as manufacturer/repacker, trader, or importer). 5. Will there be a revision of application files, which were not in accordance to the ACTD format? According to a responsible officer of the FDA, under the current policy of the FDA, no revisions are required for applications not made in accordance with ACTD format. Baker & McKenzie ASEAN Pharmaceutical Harmonization 23 Singapore 1. What is the definition of a "new drug"? There are 3 different types of new drug applications ("NDA"): 1) NDA-1: For the first strength of a product containing a new chemical or biological entity ("new" means it has not been registered before in Singapore); 2) NDA-2: (i) For the first strength of a new drug product: • containing a new combination of registered chemical or biological entities; • containing registered chemical or biological entity/ies in a new dosage form; • containing registered chemical or biological entity/ies for use by a new route of administration; or • containing registered chemical or biological entity/ies for new indication/s, dosage recommendation/s and/or patient population/s. (ii) For new drug products that do not fall under the requirements for NDA-1, NDA-3 or generic drug application ("GDA"). 3) NDA-3: For subsequent strength/s of a new drug product that has been registered or has been submitted as an NDA-1 or NDA-2. The product name, pharmaceutical dosage form, indication, dosing regimen and patient population shall be the same as that for the NDA-1 or NDA-2. 24 ASEAN Pharmaceutical Harmonization Baker & McKenzie 2. What are the current requirements and timelines for pharmaceutical product registrations? Pharmaceutical product application files must be submitted following either the International Conference on Harmonization ("ICH") CTD or the ACTD format. Timelines vary from 60 to 270 working days, depending on whether the submission is a verification, abridged or full dossier submission. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? Yes, they have been implemented since December 2005. 4. What are the requirements for pharmaceutical facilities? Documentary evidence must be provided to certify that the manufacturer complies with current applicable GMP standards. Applicants must submit a GMP certificate issued by a drug regulatory agency for all drug product manufacturing sites including, but not limited to, bulk product manufacturers, primary packagers and secondary packagers. All new overseas drug product manufacturing sites not previously registered with the regulators before 1 April 2004 and who intend to register their Western medicinal products in Singapore will be subjected to a GMP Conformity Assessment. Baker & McKenzie ASEAN Pharmaceutical Harmonization 25 5. Will there be a revision of application files, which were not in accordance to the ACTD format? Only if variation applications need to be submitted or if there are changes to a product's efficacy, quality and/or safety. 26 ASEAN Pharmaceutical Harmonization Baker & McKenzie Thailand 1. What is the definition of a "new drug"? "New drugs" refer to drugs with the following qualifications: 1) new chemical entity 2) new indication 3) new delivery system that affects bioavailability/bioequivalence ("BA/BE") 4) new route of administration 5) new dosage form 6) new strength 7) new combination of: i. new chemical entities and new derivatives ii. two registered chemical entities or more but not the same as combination drugs already registered iii. combination drugs already registered but with different strength 2. What are the current requirements and timelines for pharmaceutical product registrations? Pharmaceutical product application files for innovative drugs and generic drugs must be submitted following ACTR and ACTD. The registration timelines for innovative drugs and generic drugs are roughly around 1.5 - 2 years and 8 - 10 months, respectively, Baker & McKenzie ASEAN Pharmaceutical Harmonization 27 starting from the day the FDA issues an actual acknowledgement number. 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? The trial period for voluntary submission started in 2003. On the first day of January 2009 onwards, pharmaceutical application files must follow ACTR/ACTD. 4. What are the requirements for pharmaceutical facilities? Local pharmaceutical manufacturing facilities must comply with GMP standards (refer to Pharmaceutical PIC/S). Therefore, overseas facilities must comply to these GMP standards as well. From 1 October 2012 onwards, new overseas facilities who have not yet had any pharmaceutical products registered with the FDA prior to the date, must submit Plant Master File, Plant Layout, latest GMP Assessment Report and latest GMP Certificate as detailed in the FDA Notification on specification of application form, format of the Certificate and other documents for consideration of certifying overseas manufacturing facilities dated 17 October 2012. 5. Will there be a revision of application files, which were not in accordance to the ACTD format? Currently, pharmaceutical product licenses do not expire. The FDA will soon announce that around 20,000 application files approved before 31 December 2008 are to be revised according to ACTR/ACTD (parts: Administrative and Quality) as an update and obsolete products will be eliminated. These revisions may be in the form of the variations to keep the existing registration 28 ASEAN Pharmaceutical Harmonization Baker & McKenzie numbers. The outcome is that an application file will need to be revised every five years as in other countries. Baker & McKenzie ASEAN Pharmaceutical Harmonization 29 Vietnam 1. What is the definition of a "new drug"? "New drug" means a drug which is registered for the first time in Vietnam, including: 1) drugs containing a new chemical entity; or 2) drugs with a new combination of substances which were already circulated in Vietnam 2. What are the current requirements and timelines for pharmaceutical product registrations? Application dossiers for drug registration for both innovative drugs and generic drugs must be submitted following ACTR/ACTD. By law, the approval timeline for a newly registered drug or reregistered drug is six months from the date of submission of a duly completed application dossier. However, in practice, this approval process may take 8 to 12 months, depending on the Ministry of Health's ("MOH") workload. Approval timeline for both major variation and minor variation is two months (by law). In practice it may take 3 to 6 months, depending on the MOH's workload. The Product registration number is valid for five years since the date of issuance and can be renewed. 30 ASEAN Pharmaceutical Harmonization Baker & McKenzie 3. Have the ACTR and ACTD been implemented? If not, when can it be expected? Starting 24 May 2010, all application dossiers for drug registration must follow ACTD. 4. What are the requirements for pharmaceutical facilities? World Health Organization ("WHO") GMP is a mandatory requirement for all local pharmaceutical manufacturers of (i) chemical drugs since 1 July 2008 and of (ii) vaccine and medical biologicals since 1 January 2011. GMP certificate is valid for 3 years and can be renewed. 5. Will there be a revision of application files, which were not in accordance to the ACTD format? For product registration application dossiers submitted before the ACTD requirement (i.e., before 24 May 2010), once the product registration numbers are expired, the company must submit the application dossier under ACTD format for renewal. This includes the data of method validation and manufacturing process validation. Baker & McKenzie ASEAN Pharmaceutical Harmonization 31 www.bakermckenzie.com Baker & McKenzie has been global since our inception. Being global is part of our DNA. 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