ECTD BY NITESH

ALL ABOUT ECTD

1. . ASSIGNMENT ON: ELECTRONIC COMMON TECHNICAL DOCUMENT ( eCTD) SUBMITTED TO: DR. DIMPLE CHOPRA SUBMITTED BY: NITESH KUMAR M.PHARM (1 ST SEM.) 21301135 DEPARTMENT OF PHARMACEUTICAL SCIENCES AND DRUG RESEARCH PUNJABI UNIVERSITY, PATIALA 147002

2. The CTD is  a set of specifications for a dossier  for the registration of medicines . CTD is an internationally agreed “well structured common format” for the organization of the technical requirements that is to be submitted to the regulatory authority as an application for the registration of pharmaceuticals . Its electronic version is called eCTD.​ eCTD (electronic Common Technical Document) is a standard format of submitting Regulatory information (such as applications, supplements, and reports) to the concerned Health Authorities (HAs).​ This guideline provides recommendations to applicants on electronic submissions with the electronic Common Technical Document for the Registration of Medicines.   INTRODUCTION

3. In 2003 ectd was implemented in all ICH regions. The major version (v4.0) was added by ICH M8 EWG in 2015.

4. Advantages of eCTD v4.0 Single submission unit message Document Reuse Context of use life cycle eCTD submission tracking information

5. OBJECTIVE Establishing a worldwide standard for electronic submissions . eCTD  has been turned into the standard norm for industry-wide submissions around the world.​ It   give more accountability  and ease decision making .​ The purpose of introducing eCTD was to reduce the burden on the reviewers of the HAs . It also simplifies the process of submission as all the Regulatory authorities use it as a standard format .

6. FORMATE OF eCTD Module1 –  administration  information (specific region)​ Module 2 – summaries.  ​ Module3 – Quality.  ​ Module4 - non clinical study report  .​ Module5 - clinical study report.

7. S tructure format for eCTD Not part of eCTD These are part of eCTD

8. STRUCTURE FORMATE FOLDER e-Identifier Number: Every application is given a unique number by the Agency which becomes the top-level folder . eCTD Sequence Number: Every submission is given a sequential 4 digit number. The initial filing submitted in eCTD format is usually 0000. Module 1 National/Regional administrative data. Modules 2 to 5 follow ICH CTD granularity Util folder Working documents XML

9. eCTD UTIL FOLDER Style folder DTD folder Contains the Regional and ICH DTD/schema files for Module 1 and Modules 2-5 . Contains the Regional and ICH stylesheets for Module 1 and Modules 2 to 5. .

10. XML is backbone of eCTD XML FILES index-md5.txt file INDEX XML Forming table content submission unit, metadata submission unit xx-regional.xml File Backbone of m1 is the overall checksum for Submission .

11. META DATA Metadata is data about data. Structural metadata is used in eCTD to organize information by specific criteria; identification of data, grouping and dividing data, and the location of information.

12. Leaf titles Leaf titles including meaningful information in leaf titles makes submissions easier to navigate and facilitates the evaluator’s task. The leaf titles should be short, meaningful and indicative of the document’s content, so that someone who isn’t familiar with the application would know what the document is from the leaf title without having to open the document.

13. Module 1 This module contains administrative information that is unique for each region . Regional guidance will provide the specific instructions on how to provide the administrative forms and detailed prescribing information . It is not a part of eCTD. Because it is specific for particular region. Authorities have additional documentation requirements ( eg . batch analysis , method validation reports).

14. FOLDER 3.1.1 FDA Regional eCTD Backbone Files 3.1.7 Information Amendments 3.1.2 Cover Letter and Reviewers Guide 3.1.8 Risk Evaluation and Mitigation Strategy (REMS ) 3.1.3 Patient Experience Data 3.1.5 Labelling 3.1.6 Advertisements and Promotional Labeling Material

15. Module 2 The files in this module should be provided as PDF text with the exception of a few embedded images, when needed. The name of the folder for module 2 should be m2. SECTION OF ECTD​ DESCRIPTION​    FOLDER NAME ​ 2.2 ​ INTRODUCTION ​ 22 -intro ​ 2.3​ QUALITY OVERALL SUMMARY​ 23 -qos  ​ 2.4​ NON-CLINICAL OVERVIEW​ 24 -nonclin-over ​ 2.5​ CLINICAL OVERVIEW​ 25 - clin-over ​ 2.6​ CLINICAL SUMMARY​ 26- - clin -sum ​

16. MODULE 3 QUALITY CTD Module 3 is the section of the common technical document (CTD) regulatory submissions format that contains all the required quality information and data corresponding to the registration of a pharmaceutical product .      SECTION​               DISCRIPTION​      FOLDER NAME​  3.1​    Drug substance   [Drug Substance  Name] [Manufacturer]2 ​ substance-1-manufacturer-1 ​  3.2​ Manufacture (name, manufacturer)  ​ 32s2-manuf  ​  3.3​ Reference Standards or Materials (name, dosage form) ​ 32s5-ref-stand  ​  3.4​ Stability (name, dosage form)  ​ 32s7-stab  ​   3.5​ Description and Composition of the Drug Product (name, dosage form) ​ 32p1-desc-comp ​   3.6​ Validation of Analytical Procedures ​ 32p53-val-analyt-proc ​

17. Granularity An enhanced granularity is required in this module and to make easy to review/readable. The granularity should be built with Node Extensions( additional folder of granular) and Subfolders including numbering of the subfolders. Further information can be found in these folder.

18. MODULE 4 . Non - clinical study report      SECTION​          DISCRIPTION​     FOLDER NAME​ 4.1​ STUDY REPORT ​ 41-stud-rep ​ 4.2​ PHARMACOLOGY ​ 42pharmacol ​ 4.3​ PHARMACOKINETICS​ 43pk ​ 4.4​ PHARMACODYNAMIC​ 44-pd-drug ​ 4.5​ TOXICOLOGY ​ 45-tox  ​

19. MODULE 5 . clinical study report SECTION​ DESCRIPT​   FOLDER NAME​ 5.1 ​ CLINICAL STUDY REPORT  ​ 51-clin-stud-rep ​ 5.2​ REPORT OF BIOPHARMACEUTICS STUDIES ​ 52-rep-biopharm-stud ​ 5.3 ​ Reports of Human Pharmacokinetic (PK) Studies  ​ 53-rep-human-pk-stud  ​ 5.4​ Reports of Human Pharmacodynamic (PD) Studies  ​ 54-rep-human-pd-stud ​ 5.5 ​ Reports of Efficacy and Safety Studies ​ 55-rep-effic-safety-stud ​ 5.6​ Reports of  Post marketing  Experience ​ 56-postmark-exp ​

20. WORKING DOCUMENTS Additional documents required to be submitted alongside the eCTD content. Some examples of what may be required are document or versions of PDF content, and the eCTD validation report.

21. TECHNICAL REQUIREMENTS FOR SUBMISSIONS Submission media PDF files Hyperlinks and Bookmarks MD5 checksum Virus check

22. 1)Submission media : - The following media formats will be accepted for eCTD submissions CD-ROMs (conforming to ISO 9660 or ISO 13346) DVD-ROMS USB drives (2.0 or higher ) 2) PDF FILES:- Portable Document Format (PDF) is an electronic format and PDF v1.4 -1.7 Resolution 300 dpi (photographs up to 600 dpi) Acceptable file size is approx. 200MB. Pixels 1024*768 Times New Roman 12-point font text and 10 font for table . The International Color Consortium (ICC)6 color profile specification is used .

23. 3) HYPERLINKS AND BOOKMARKS:- hypertext links are blue color text and encouraged within the eCTD to facilitate swift navigation within the dossier. The eCTD should be structured and links provided in such a way as to ensure that the reviewer is constantly aware of the overall structure and narrative flow of the dossier. 4) MD5 CHECK SUM A checksum is unique identifier used to verify the integrity of file by comparing two set of data to make sure they are same .A checksum (MD5) should be included for each file in the eCTD, allowing the recipient to verify the integrity of physical files in the submission . It is generated by applicant to check integrity of file. 5)VIRUS CHECK The applicant is responsible for checking t he virus in submission unit.

24. Validation is process that ensure the eCTD dossier is technically correct after review the submission. VALIDATION Categories of Validation Rules Pass/Fail Criteria Best Practice Criteria

25. . APPLICANT SUBMITT eCTD application REGULATORY AUTHORITY REVIEW by RA Chance of rejection but better technical explanation given in eCTD fail/rejected Accepted Advise to app. Rectify the problem Process of validation

26. LIFE CYCLE MANAGEMENT (LCM) An eCTD application is an evolving entity that grow with each submission (sequence). Life cycle management at the submission layer (i.e. eCTD-sequence ) Life cycle management at the document layer (eCTD leaf ) Life cycle management of specific documents. Responses to Authority Recommendations. Tabulated Schedule of Amendment.

27. BASELINE SUBMISSIONS A baseline submission marks the change from a paper based submission, or an e-submission, to an eCTD submission The paper copies and the hard media should be submitted jointly. The eCTD on DVD/CD/USB should be submitted at specified address of RA. SUBMISSION

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