CTD and eCTD.pptx

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1. CTD and eCTD Prepared by : Gaurav R. Panchal Guided by : Ms. Hardi Joshi M.Pharm QA (sem 1) Assisstant Professor, GSP-GTU 1

2. CTD (Common Technical Document) The Common Technical Document is a set of specification for application dossier for the registration of medicines . It is an internationally agreed “well structured common format” for the organization of the technical requirement authority as an application for the registration of pharmaceuticals for human use in all three ICH regions (USA, Europe, Japan). It was agreed in Nov. 2000 in San Diego. USA. In July 2003, CTD became mandatory format for new drug application in the EU and Japan, and strongly recommended the format of choice of NDAs submitted to the FDA.US. It is maintained by ICH (International Council on Harmonization). 2

3. CTD Need for CTD : Substantial documentation and data are required in submission for import /manufacture and marketing approval of drugs for human use, resulting in large, complex applications. Till date, applicants have used many different approaches in organizing the information and difference in organization of data in each application has made reviewing more difficult and can lead to omission of critical data or analyses. Such omissions can result in unnesccesary delays in approvals. Thus, a common format of submission will help in overcoming these hurdles. 3

4. CTD Need for CTD : Prior to the implementation of the Common Technical Document (CTD) in 2002, each of the three major regulatory regions (European Union (EU), USA, and Japan) had its own set of guidelines and format for the submission of a regulatory dossier to obtain marketing approval for a new drug or a variation to the licensing of an existing drug. In Japan, the GAIYO was required, which organised and presented a summary of the technical information; in Europe, Expert Reports and Tabulated Summaries were required and Written Summaries were recommended; and in the USA, the Food and Drug Administration (FDA) had guidance documents regarding the format and content of the New Drug Application (NDA). 4

5. CTD Need for CTD (Contd.) : To avoid the need to generate and compile different registration dossiers, this guideline describes a format for the Common Technical Document that will be acceptable in all three regions.. In 2000, representatives from the European Medicines Agency (EMA), the USA FDA, and the Ministry of Health, Labour, and Welfare in Japan developed a set of guidelines defining the structure and content of the dossier for an application for the registration of a new medicine that could be used across all three regions. Now it is adopted by Switzerland(SwissMedic), Canada(Health Canada), Australia(TGA), etc. 5

6. CTD Scope : This guideline primarily addresses the organisation of the information to be presented in registration applications for new pharmaceuticals (including biotechnology-derived products). This guideline is not intended to indicate what studies are required. It merely indicates an appropriate format for the data that have been acquired. Applicants should not modify the overall organisation of the Common Technical Document as outlined in the guideline. However, in the Nonclinical and Clinical Summaries, applicants can modify individual formats if needed to provide the best possible presentation of the technical information, in order to facilitate the understanding and evaluation of the results 6

7. CTD Objectives : Avoid duplicate animal and human testing. More economical use of human, animal and material resources. Elimination of unnecessary delays in global development Fast availability of new medicines Maintain safeguards on quality, safety, efficacy and regulatory obligations to protect public health. Reduce time and resources used to compile applications 7

8. CTD Organisation : Module 1 : Administrative information and prescribing information Module 2 : Overviews and Summaries of Modules Module 3 : Quality (pharmaceutical documentation) Module 4 : Non-clinical reports (pharmacology/ toxicology) Module 5 : Clinical study reports (clinical trials). 8

9. CTD CTD Triangle : 9

10. CTD Module : 1 Administrative and prescribing information It contains documents specific to each region. Eg. Application form regarding the prescribing information, proposed label. This module is not part of CTD. The content and format of this module can be specified by the relevant authorities. 10

11. CTD Module : 1 (contd.) Cover Letter Comprehensive Table of Content Application Form Product information SPC’s, Labelling and Packaging Mock-up Specimen Consultation of target special group Information about the Experts Specific Requirements for different types of application 11

12. CTD Environmental Risk Assessment Information relating to Orphan Market Exclusivity Information relating to Pharmacovigilance Information relating to clinical trials Information relating to pediatrics Response to Queries Additional data 12

13. CTD Module : 2 Quality Overall Summaries (QOS) It contains seven sections that should be maintained in following order : Table of contents Introduction Quality Overall Summary Non-clinical Overwiew Clinical Overview Non – clinical Written and tabulated Summaries Clinical Summary 13

14. CTD Module 2 (contd.) : The quality overall summary (QOS) is a summary of the chemical and pharmaceutical data in the dossier (including data for biological/biotechnological products) . The structure of the QOS broadly follows the structure of the data included in Module 3. The QOS should not include information that has not already been included in Module 3 or in other parts of the CTD. The aim of the QOS is to discuss the critical parameters of the product, but it should also address issues that arose during development and provide justification for instances where guidelines were not followed etc. 14

15. CTD Module 2 (contd.) : The main purpose of the Non-Clinical Written and Tabulated Summaries is to provide a comprehensive factual summary of the non-clinical information on pharmacology, pharmacokinetics, and toxicology. The interpretation of the data, the clinical relevance of the findings, any association between non-clinical findings and quality aspects of the IMP, and any implications of non-clinical findings for the safety of the IMP in humans should be addressed in the Non-Clinical Overview. 15

16. CTD Module 2 (contd.) : Clinical Overview is a key document in the CTD dossier. The Clinical Overview is divided into six sections: product development rationale, biopharmaceutics, clinical pharmacology, efficacy, safety, and risk/benefit conclusions. The Clinical Summary is divided into sections covering biopharmaceutics and associated analytical methods, clinical pharmacology, efficacy, and safety. 16

17. CTD Module 3 : It presents the chemistry, manufacturing, and controls reports for the product included in the registration dossier. The section of the application covering chemical and pharmaceutical data for biological/biotechnological products. Information on quality should be presented in structure and format. The Quality section of CTD provides a harmonized structure and format for presenting (CMC) information in registration dossier. 17

18. CTD Module 3 (contd.) : The main headings in this section are as follows: Table of Content Body of Data Drug Substances Drug Product 3. Literature References 18

19. CTD Module 4 : It presents the non-clinical reports included in the dossier. The structure and content of Module 4 is specified in the ICH M4S guidelines. The main headings in this section are as follows: Table of contents of Module 4 Study reports Pharmacology Pharmacokinetics Toxicology 19

20. CTD Module 5 : Clinical Study reports Module 5 presents the clinical reports included in the dossier. The structure and content of Module 5 is specified in the ICH M4E guidelines. main headings in this section (that must not be altered) are as follows: Table of contents of Module 5 Tabular listing of all clinical studies Clinical study reports Reports of biopharmaceutic studies Reports of studies pertinent to pharmacokinetics using human biomaterials 20

21. CTD Module 5 (contd.) : Reports of human pharmacokinetic (PK) studies Reports of human pharmacodynamic (PD) studies Reports of efficacy and safety studies Reports of post-marketing experience Case report forms and individual patient listings Literature references 21

22. eCTD (Electronic Common Technical Document After decades of using paper, the goal is the electronic transfer of drug application and their review across submission formats, procedures, and reasons came in electronic technical document. Defination : “eCTD is an interface and international specification for the pharmaceutical industry to agency transfer of regulatory information.” The focus of the specification is to provide the ability to transfer the registration application electronically from industry to regulatory authority. 22

23. eCTD Reasons : Manages the large data for entire sybmission and for each document within the submission. XML backbone allows the eCTD submission to be viewed via a web browser and canbe loaded on a web server. The file formats that can be included in the eCTD are Portable document Format (pdf) and XML. 23

24. eCTD eCTD submission are accepted for : Investigational New Drug (INDs) New Drug Application (NDAs) Abbreviated New Drug Applications (ANDAs) Biologics License Application (BLAs) All the application following the submission of the above stated applcations. All the Master Files which are part of any above mentioned applications 24

25. eCTD Advantages : Allows agencies to upload sequences automatically with the help of XML backbone. Reviewers can refer the information easily with of hyperlinks No need to scan, copy or store paper documents. Changes and updates made to the dossiers can be easier identified. Easy product lifecycle tracking. Simultaneous accessibility of documents is possible. 25

26. Thank you 26