CTD and eCTD - Common Technical Document
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The Common Technical Document (CTD) is a standardized format for regulatory submissions developed by three major regulatory authorities: the European Medicine Agency, the US FDA, and Japan's MHLW, aimed at streamlining the drug approval process. The electronic version, known as eCTD, will become mandatory for submissions to specific US FDA divisions starting in 2017, improving efficiency, organization, and resource management. The document outlines the structure and content requirements across various modules, detailing quality, non-clinical, and clinical data necessary for drug registration.
CTD and eCTD - Common Technical Document
- 1. CTD and eCTD Common technical document Presented By: Darewin Mendonsa 1st Mpharm Pharmaceutics Subject: Regulatory Affairs
- 2. CTD is a complete, predictable, consistent and well organised format for regulatory submissions CTD USFDA EMEA MHLW A joint effort of 3 major regulatory authorities; European Medicine Agency (EMEA, Europe, EU), US Food and Drug Administration (FDA) and Ministry of Health, Labour and Welfare (MHLW, Japan). Was agreed on November 2000, San Diego, USA Standard format for regulatory submissions like IND, AND, ANDA and BLA and DMFs Maintained by the ICH (International Conference on Harmonization)
- 3. Need for CTD All regulatory authorities had their own guidelines to submit regulatory dossiers to get marketing approval of the drug Thus approval process was slow and Time-consuming Thus the three ICH regions (US, Europe and Japan) collaborated and developed CTD format for regulatory submissions. It has been adopted by several other countries including Australia, Canada and Switzerland (2004). In 2009: CDSCO Adopted CTD format for Technical requirements for registration of biological products
- 5. eCTD the electronic form of CTD Developed by M2 EWG (Multidisciplinary 2 Expert Working Group) of ICH. An eCTD is the electronic form of CTD submissions Starting in 2017, eCTD will be required for submissions to CBER and CDER of USFDA. Submissions that are not in eCTD format will not be filed or received unless exempted from the requirement. ADVANTAGES More efficient and saves time Integrated document and life-cycle management Highly organized electronic table of contents Cross submission integration More efficient use of resources, less cost and stress to the organization New, replace, append & delete Self-validating Easy to distribute and review
- 6. The CTD Triangle 2.1 ToC of the CTD (Mod 2,3,4,5) 2.2 Introduction 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.5 Clinical Overview 2.7 Clinical Summary 2.6 Nonclinical Written and Tabulated Summaries Module 1 Module 3 Module 4 Module 5 2.1 2.2 2.3 2.4 2.5 2.6 2.7 1.0 Quality Data Nonclinical Study Reports Clinical Study Reports Module 2 Region Specific (not a part of CTD)
- 7. Method of Compilation 1. Files must be referenced in an XML Backbone (Extensible Markup Language) • It manages the large data for the entire submission and for each document within the submission. • This XML backbone allows the eCTD submission to be viewed via a web browser and can be loaded on a Web server.
- 8. Method of Compilation 2. The file formats that can be included in the eCTD are Portable Document Format (PDF) and XML • However other formats can be used for graphs and images. • Eg: .jpg , .png formats may be used for higher resolution.
- 9. Method of Compilation 3. Validate all Hyperlinks and Bookmarks using appropriate nomenclature and before you send in your submission •Incorrect Targets Unnerve Reviewers
- 11. The CTD Triangle 2.1 ToC of the CTD (Mod 2,3,4,5) 2.2 Introduction 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.5 Clinical Overview 2.7 Clinical Summary 2.6 Nonclinical Written and Tabulated Summaries Module 1 Module 3 Module 4 Module 5 2.1 2.2 2.3 2.4 2.5 2.6 2.7 1.0 Quality Data Nonclinical Study Reports Clinical Study Reports Module 2 Region Specific (not a part of CTD)
- 12. Modules of eCTD Module 1: It contains administrative and prescribing information and it is region specific and not the part of the CTD. Module 2: It consists of overall quality, non-clinical and clinical summary and clinical and non-clinical overview. Module 3: It provides the Data and Information on quality. Module 4: It provides the Data and Information on non-clinical study reports. Module 5: It provides the Data and Information on clinical study reports.
- 13. Module 1 • This module should contain documents specific to each region. Ex: Application forms regarding the prescribing information, proposed label. • This module is not part of the CTD. • The content & format of this module can be specified by the relevant regulatory authorities. FOR USFDA • Application form 356h • Proposed label • Patent certification / information • Debarment certificate (not to be debarred from contracts due to allegations of fraud, mismanagement, and similar improprieties) • Letter of Authorization (LoA)/ DMF letter • Labeling text FOR EMEA •Application form •Summary of product characteristics •Labelling text and mock-ups •Information about the experts •Environmental risk assessment •Description of the pharmacovigilance system •Risk management plan
- 14. Module 2 Contains 7 sections as mentioned below 2.1 CTD Table of content (Module 2-5) 2.2 CTD Introduction 2.3 Quality Overall Summary 2.4 Non-Clinical Overview 2.5 Clinical Overview 2.6 Non-Clinical Summary 2.7 Clinical Summary The individual organization of these summaries is described in three separate documents. a) M4 Q The CTD Quality. b) M4S The CTD Safety. c) M4 E The CTD Efficacy.
- 15. M4 Q, S and E M4 Q – Quality • The Quality section of the CTD provides a harmonized structure and format for presenting CMC (Chemistry, Manufacturing, Controls) • (Ex: Drug product manufacture, Drug substance synthesis), the content of CTD-Q is not totally harmonized M4 S – Safety • CTD for the Registration of pharmaceuticals for human use Safety • It describes the structure and format of the non-clinical data in module-2 of the CTD • It also provide the organisation of module- 4 i.e.; the non-clinical study reports M4 E – Efficacy • CTD for the Registration of pharmaceuticals for human use Efficacy • It describes the structure and format of the Clinical data in module-2 of the CTD, including summaries and detailed study reports.
- 16. Module 3: Quality Data Chemistry manufacturing and controls • Information on Quality should be presented in the structured format . • This is described in the guidance M4-Q. • Should contain Literature References 3.1 Table of content (Module 3) 3.2 Body of Data 3.2 S Drug Substance 3.2 S1 General Information (Name, Mfg.) 3.2 S2 Manufacture 3.2 S3 Characterization 3.2 S4 Control of Drug Substance (Specification, Analytical procedures, Validation of Analytical procedures, etc. ) 3.2 S5 Reference Standards 3.2 S6 Stability
- 17. Module 3: Quality Data Chemistry manufacturing and controls 3.2 P Drug Product 3.2 P1 Description and Composition of the Drug Product 3.2 P2 Pharmaceutical Development (name, dosage form) 3.2 P3 Manufacturer 3.2 P4 Control of Excipients 3.2 P5 Control of Drug Product (Specification, Analytical procedures, Validation of Analytical procedures, etc. ) 3.2 P6 Reference Standards 3.2 P7 Stability
- 18. Module 3: Quality Data Chemistry manufacturing and controls 3.2 A Appendices 3.2 A1 Facility & Equipment's 3.2 A2 Advertising agents safety evaluation 3.2 A3 Excipients 3.2 R Regional Information 3.3 Literature References
- 19. Module 4: Non-Clinical Study Reports 19 4.1 Table of content (Module 4) 4.2 Study Reports 4.2.1 Pharmacology 4.2.1. 1. Pharmacodynamics 4.2.1. 2. Safety Pharmacology 4.2.1. 3. Pharmacodynamics Drug Interaction 4.2.2 Pharmacokinetics 4.2.2. 1. ADME 4.2.2. 2. Pharmacokinetic Drug Interaction 4.2.2. 3. Other Pharmacokinetic Study
- 20. Module 4: Non-Clinical Study Reports 20 4.2.3 Toxicology 4.2.3. 1. Single/Repeat Dose Toxicity 4.2.3. 2. Genotoxicity 4.2.3. 3. In-Vivo/Vitro Toxicity 4.2.3. 4. Carcinogenicity 4.2.3. 5. Local Tolerance/Dependence 4.2.3. 6. Other Studies 4.3 Literature References
- 21. Module 5: Clinical Study Reports 5.1 Table of content (Module 5) 5.2 Tabular listing of Clinical Studies 5.3 Clinical study reports 5.3.1 Reports of Biopharmaceutical (BA-BE) Study 5.3.2 Reports of Pharmacokinetic (biomaterial) study 5.3.3 Reports of Pharmacokinetic (PK) studies 5.3.4 Reports of Pharmacodynamics (PD) studies 5.3.5 Reports of Efficacy and Safety studies 5.3.6 Reports of Post-Marketing experience 5.3.7 Case Report Forms & Individual patient listings 5.4 Literature References
- 22. Screenshot of Compiled eCTD
- 23. Advantages and Disadvantages ADVANTAGES DISADVANTAGES • Complete, well-organized submissions • CTD is only a format, its not a single dossier with a single content. • More predictable format • Legal requirements differ in the different regions • More consistent reviews • ICH guidelines have not yet harmonized in all requirements • Saves time and reduces cost • Pharmacopoeias are not harmonized • Easier exchange of information • Applicant may have regional preferences.
- 24. eCTD Management Softwares • eCTDXPress – Image Solutions –http://www.imagesolutions.com • MasterControl Submissions Gateway™ - Master Control, http://www.mastercontrol.com • Liquent’s EZsubs® software solution, http://www.liquent.com/ • Data Farm, http://www.datafarminc.com/ • Take solution : www.PharmaReady.com • Lorenz Life Sciences : www.lorenz.cc
- 25. 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. • Thus CTD has significantly improved the drug approval process which was earlier a tedious and time consuming task.
- 26. References 1. Guidance for Industry on Preparation of Common Technical Document for Import / Manufacture And Marketing Approval Of New Drugs For Human Use (New Drug Application – NDA)”. Available at http://cdsco.nic.in/CTD_Guidance%20-Final.pdf 2. “The Common Technical Document- Quality (CTDQ)”. http://www.ema.europa.eu/ 3. “Guideline M4: The Common Technical Document”. Available at http://www.ich.org/products/ctd.html 4. “ICH Harmonised Tripartite Guideline: Organisation Of The Common Technical Document For The Registration Of Pharmaceuticals For Human Use M4”. http://www.ich.org/fileadmin 5. www.ich.org 6. www.cdsco.nic.in 7. http://www.fda.gov/cder/regulatory/ersr/ectd.htm 8. http://esubmission.eudra.org/ 9. http://www.mhlw.go.jp/english/index.html 10. http://www.tga.gov.au/docs/html/eugctd.htm