CTD structure

Basic information for beginners...

1. COMMON TECHNICAL DOCUMENT (CTD ) By, CHANDRA MOHAN

2. What is CTD? Evolution of CTD Why CTD? CTD structure Guidance for the industry Advantages of CTD Benefits Limitations Conclusion

3. What is CTD ? Prior to the advent of the CTD, regulatory reviewers received an application from one company and spent a year or more engaged in its review. When the review was completed, reviewers received the next application—most likely in a different format—and had to learn the structure of the new application. 1996- Industry proposed CTD but ICH regulators were hesitant Regulators asked industry to do a feasibility study. That study, conducted in May 1996, evaluated the time it took to convert an FDA new drug application into an European Medicines Agency (EMA) submission, and the reverse. Regulators quickly saw the potential value of harmonizing submission formats.

4. Application format, The registration documents that needs to be filed is in a format called CTD 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 for human use in all three ICH regions (U.S.A., Europe and Japan). The modular framework of CTD is described in the ICH guidelines (ICH Topic M4). What is CTD ?

5. ORIGIN OF CTD…

6. CTD IS A JOINT EFFORT OF 3 REGULATORY AGENCIES: 1.European Medicines Agency (EMEA, Europe), 2 . Food and Drug Administration (FDA, USA) and 3 . Ministry of Health, Labour and Welfare (MHLW , Japan ). CTD is maintained by ICH through EWG . In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA. It has been adopted by several other countries including Australia, Canada and Switzerland (2004).

7. Evolution of CTD In ICH Region 1995 : Concept of CTD proposed by Industry. November 2000: ICH CTD guideline finalized. September 2002: Guideline re-edited with Numbering & Section Header changes. Prior to July 2003: Voluntary Submission Phase in 3 ICH Region. July 1, 2003: Mandatory Requirement in Three ICH Regions. In India 2009 : CDSCO Adopt CTD format for Technical requirements for registration of biological products. October 28, 2010: CDSCO give guideline for feedback purpose for Industry on Preparation of CTD for Import/Manufacture and Marketing Approval of New Drug for Human Use (i.e. NDA) & ask for comments and suggestion within 60 days.

8. This guidance is developed by CDSCO based on, The ICH Harmonised Tripartite Guideline on “Organisation of the Common Technical Document for the Registration of Pharmaceuticals for Human Use”. M4, Step 4 version dated January 13, 2004, and Drugs & Cosmetics Act 1940 and Rules made thereunder. In India…

9. Why CTD? To provide a harmonized common format/template for the submission of technical requirement to the regulatory authorities (FDA) that is acceptable in all 3 ICH regions Reduce the time and resources used to compile applications It will ease the preparation of electronic submissions. To facilitate simultaneous submission in three regions. To facilitate exchange of regulatory information. Faster availability of new medicines

10. CTD STRUCTURE The CTD is organized into FIVE modules: Module 1: Administrative Information. Module 2: CTD Summaries Module 3: Quality Module 4: Nonclinical Study Reports Module 5: Clinical Study Reports

11. CTD STRUCTURE Module 1: Administrative Information Table of contents of the submission including Module 1 Documents specific to each region (for example, application forms, prescribing information)

12. MODULE- 2 CTD Summaries Module 2 should contain 7 sections in the following order : CTD Table of Contents CTD Introduction Quality Overall Summary Nonclinical Overview Clinical Overview Nonclinical Summary Clinical Summary The organisation of these summaries is described in guidelines for M4Q, M4S, and M4E.

13. MODULE-3 QUALITY Consists of detail information on Drug Substance [API] & Drug Product [FP] Consists of detail information on Drug Substance [API] & Drug Product [FP] Drug Substance part broadly covers: General Information Manufacture Characterisation Control of drug substance Reference standard Container closure system Stability Drug Product part broadly covers: Description and Composition Pharmaceutical Development Manufacture Control of excipients Control of drug product Reference standard Container closure system Stability

14. MODULE- 4 NON CLINICAL STUDY REPORTS Contains non clinical data Study Reports on Pharmacology Pharmacokinetics Pharmacokinetic drug interactions (nonclinical) Other pharmacokinetic studies Toxicology ( Genotoxicity , Carcinogenicity, Teratogenecity , Genotoxicity /Mutagenicity etc.) Other studies

15. MODULE-5 CLINICAL STUDY REPORTS Contains clinical data Study reports on: Reports of studies pertinent to pharmacokinetics using human Biomaterials Reports of human pharmacokinetic (PK) studies Reports of human pharmacodynamic (PD) studies Reports of efficacy and safety studies Reports of postmarketing experience Case report forms and individual patient listings

16. Guidance for the industry

17. Advantages of CTD To make the reviewing of each application more easy and also to avoid omission of critical data or analyses. Omissions of such data can result in unnecessary delays in approvals. To save time and resources To facilitate regulatory review and communications Appropriate format for the data Easy to understand and evaluation of data Applicable to all types of products (NCE, radiopharmaceuticals, vaccines, herbals, etc.)

18. Silent Benefits of The CTD More “reviewable” applications Complete , well-organized submissions More predictable format More consistent reviews Easier analysis across applications Easier exchange of information Facilitates electronic submissions

19. Limitations… CTD is only a format, its not a single dossier with a single content. Legal requirements differ in the different regions ICH guidelines have not yet harmonized in all requirements Pharmacopoeias are not harmonized Applicant may have regional preferences . The eCTD has proved critical to improving application submission efficiencies as well as reviewer efficiency. Besides delivering submission material to the reviewer in an expedited manner, the eCTD format has made it easier to develop standardized reviewer e-templates and review tools for each of the review disciplines.

20. Conclusion Whilst the realization of the CTD took many years, there is now a common format for the submission of Marketing Authorizations Applications across the three ICH regions - Europe, Japan and the USA. This should facilitate pharmaceutical companies to make simultaneous filings in the ICH regions as it will eliminate the extensive work previously required to convert, for example, a US dossier to an EU dossier and vice versa.

21. THANK YOU! Questions ?