ACTD ASEAN COMMON TECHNICAL DOSSIER

1 One vision one identity one communityASEANCOMMONTECHNICALDOSSIERACTD ACTDASEAN: A Community of COMMON TECHNICAL DOSSIER (ACTD)The ASEAN SecretariatJakartaThe Association of Southeast Asian Nations ( ASEAN ) was established on 8 August 1967. The Member States are Brunei Darussalam, Cambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Singapore, Thailand and Viet Nam. The ASEAN Secretariat is based in Jakarta, inquiries, contact:The ASEAN SecretariatCommunity Relations Division (CRD)70A Jalan SisingamangarajaJakarta 12110 IndonesiaPhone : (62 21) 724-3372, 726-2991 Fax : (62 21) 739-8234, 724-3504E-mail : Catalogue-in-Publication DataASEAN COMMON TECHNICAL DOSSIER (ACTD)Jakarta, ASEAN Secretariat, December 2016 ASEAN Guideline2. Standard TECHNICAL Regulations3. Pharmaceuticals Registration ISBN 978-602-6392-27-5 ASEAN : A Community of OpportunitiesThe text of this publication may be freely quoted or reprinted, provided proper acknowledgement is given and a copy containing the reprinted material is sent to the Community Relations Division (CRD) of the ASEAN Secretariat, information on ASEAN appears online at the ASEAN Website: Association of Southeast Asian Nations ( ASEAN ) rights iiiTAbLE Of CONTENTSPart 1 Organisation of the DOSSIER .

2 1 Part 2 Quality of Document .. 7 Part 3 Nonclinical Document.. 35 Part 4 Clinical Document..113iv ACTDTHE ASEAN COMMON TECHNICAL DOSSIER (ACTD) fOR THE REGISTRATION Of PHARMACEUTICALS fOR HUMAN USEORGANIZATION Of THE DOSSIERACTD 3 THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) fOR THE REGISTRATION Of PHARMACEUTICALS fOR HUMAN USEORGANIZATION Of THE DOSSIERPREAMbLEThis ASEAN COMMON TECHNICAL DOSSIER (ACTD) is a guideline of the agreed upon COMMON format for the preparation of a well-structured COMMON TECHNICAL DOSSIER (CTD) applications that will be submitted to ASEAN regulatory authorities for the registration of pharmaceuticals for human use. This guideline describes a CTD format that will significantly reduce the time and resources needed to compile applications for registration and in the future, will ease the preparation of electronic documental submissions.

3 Regulatory reviews and communication with the applicant will be facilitated by a standard document of COMMON guideline merely demonstrates an appropriate write-up format for acquired data. However, applicants can modify, if needed, to provide the best possible presentation of the TECHNICAL information, in order to facilitate the understanding and evaluation of the results upon pharmaceutical the ACTD, the display of information should be unambiguous and transparent, in order to facilitate the review of the basic data and to help a reviewer become quickly oriented to the application contents. Text and tables should be prepared using margins that allow the document to be printed on either A4 or x 11 paper. The left-hand margin should be sufficiently large that information is not obscured by the method of binding. Font and size, (Times New Roman, 12-point font), for text and tables should be of a style and size that are large enough to be easily legible, even after photocopying.

4 Every page should be numbered, with the first page of each part designated as page 1. For a paper, COMMON TECHNICAL Acronyms and abbreviations should be defined the first time they are used 4 ACTDin each part. References should be cited in accordance with the 1979 Vancouver Declaration on Uniform requirements for Manuscripts Submitted to Biomedical COMMON TECHNICAL Document is organized into four parts as follows:Part I. Table of Contents, Administrative Data and Product InformationPart I contains initially the overall Table of Contents of the whole ACTD to provide basically the informations that could be looked through respectively. Secondly, the next content is the Administrative Data where required specific documentation in details is put together such as application forms, label, package insert etc. The last section of this part is Product Information where necessary information includes prescribed information, mode of action, side effects general introduction to the pharmaceutical, including its pharmacologic class and mode of action should be II.

5 Quality DocumentPart II should provide the Overall Summary followed by the Study Reports. The quality control document should be described in details as much as III. Nonclinical1 DocumentPart III should provide the Nonclinical Overview, followed by the Nonclinical Written Summaries and the Nonclinical Tabulated Summaries. The document of this part is not required for Generic Products, Minor Variation Products and some Major Variation Products. For ASEAN member countries, the Study Reports of this part may not be required for NCE, Biotechnological Products and 1 The word Nonclinical replaces Pre-clinical ACTD 5other Major Variation Products if the Original Products are already registered and approved for market authorization in Reference Countries.

6 Therefore, the authority who requires specific Study Reports should ask for the necessary IV. Clinical DocumentPart IV should provide the Clinical Overview and the Clinical Summary. The document of this part is not required for Generic Products, Minor Variation Products and some Major Variation Products. For ASEAN member countries, the Study Reports of this part may not be required for NCE, Biotechnological Products and other Major Variation Products if the Original Products are already registered and approved for market authorization in Reference Countries. Therefore, the authority who requires specific Study Reports should ask for the necessary overall organisation of the COMMON TECHNICAL DOSSIER is presented on the following in Parts:Part I: Table of Content Administrative Information and Prescribing InformationSection A: IntroductionSection B: Overall ASEAN COMMON TECHNICAL DOSSIER Table of ContentsSection C: Documents required for registration (for example, application forms, labelling, Product Data Sheet, prescribing information)Part II: Quality DocumentSection A: Table of ContentsSection B: Quality Overall SummarySection C: Body of Data6 ACTDPart III: Nonclinical DocumentSection A: Table of ContentsSection B: Nonclinical OverviewSection C: Nonclinical Written and Tabulated Summaries 1.

7 Table of Contents 2. Pharmacology 3. Pharmacokinetics 4. ToxicologySection D: Nonclinical Study Reports 1. Table of Contents 2. Pharmacology 3. Pharmacokinetics 4. ToxicologyPart IV: Clinical DocumentSection A: Table of ContentsSection B: Clinical OverviewSection C: Clinical Summary1. Summary of Biopharmaceutics and Associated Analytical Methods2. Summary of Clinical Pharmacology Studies3. Summary of Clinical Efficacy4. Summary of Clinical Safety5. Synopses of Individual Studies Section D: Tabular Listing of All Clinical StudiesSection E: Clinical Study ReportsSection F: List of Key Literature ReferencesTHE ASEAN COMMON TECHNICAL DOSSIER (ACTD) fOR THE REGISTRATION Of PHARMACEUTICALS fOR HUMAN USEQUALITYACTD 9 THE ASEAN COMMON TECHNICAL DOSSIER (ACTD) fOR THE REGISTRATION Of PHARMACEUTICALS fOR HUMAN USEQUALITYTAbLE Of CONTENTSS cope of The Guideline.

8 10 Section A: Table of Contents.. 10 Section B: Quality Overall Summary.. 10 Section C: Body of Data .. 161. Drug Substance .. 162. Drug Product .. 25 Section D: Key Literature References .. 3410 ACTDS cope of The GuidelineThis document is intended to provide guidance on the format of a registration application for drug products regarding ASEAN CTR. This format is appropriate for NCE (New Chemical Entity), Biotech (Biotechnological Products), MaV (Major Variations), MiV (Minor Variations) and G (Generics). To determine the applicability of this format for a particular type of product, applicant should consult with the appropriate National Regulatory Authorities. The Body of Data in this guideline merely indicates where the information should be located. Neither the type nor extent of specific supporting data has been addressed in this guideline and both may depend upon national guidance and or accepted leading international references (pharmacopoeias).

9 For NCE and Biotech requirements please refer to the relevant ICH A: Table of ContentsA table of contents for the filed application should be b: Quality Overall Summary (QOS) SUBSTANCES1 General Nomenclature Information from the S1 * Structure Structural formula, including relative and absolute stereochemistry, the molecular formula, and the relative molecular mass. Schematic amino acid sequence indicating glycosylation sites or other post- translational modifications and relative molecular mass as appropriate. General Properties Physico chemical characteristics and other relevant properties including biological activity for biotech. * ACTD Manufacturer(s)Name and address of the manufacturer (s). Description of Manufacturing Process and Process Controls The description of the drug substance manufacturing process and process control that represents the applicant's commitment for the manufacture of the drug substances.

10 Information on the manufacturing process, which typically starts with a vial(s) of the cell bank, and includes cell culture, harvest(s), purification and modification reaction, filling, storage and shipping conditions. Control of Materials Starting materials, solvents, reagents, catalysts, and any other materials used in the manufacture of the drugs substance indicating where each material is used in the process. Tests and acceptance criteria of these materials. Control of source and starting materials of biological origin. Source, history and generation of the cell substrate. Cell banking system, characterisation and testing. Viral safety evaluation. Controls of Critical Steps and Intermediates Critical steps: Tests and acceptance criteria, with justification including experimental data, performed at critical steps of the manufacturing process to ensure that the process is controlled.