Dossier and Common Technical Document (CTD)

A dossier refers to a comprehensive collection of documents submitted to a regulatory authority to demonstrate that a product, such as a pharmaceutical drug, medical device, or cosmetic, meets the necessary requirements for approval. This may include data on safety, efficacy, quality, manufacturing processes, labeling, and compliance with applicable regulations.

1. DOSSIER PREPARATION AND SUBMISSION Presented By : Nidhi Tanwar M. Pharm Pharmaceutical Regulatory Affairs SGT College of Pharmacy SGT University Gurugram Guided By : Dr Bindiya Chauhan

2. A dossier refers to a comprehensive collection of documents submitted to a regulatory authority to demonstrate that a product, such as a pharmaceutical drug, medical device, or cosmetic, meets the necessary requirements for approval. This may include data on safety, efficacy, quality, manufacturing processes, labeling, and compliance with applicable regulations. The dossier serves as the basis for the regulatory review process, helping authorities evaluate whether to grant marketing authorization or other approvals. The most common format for a dossier is the electronic common technical document (eCTD), which is a digital format. In the U.S., an eCTD dossier is called a New Drug Application (NDA) , and in the European Union and other countries, it's called a marketing authorization application (MAA). INTRODUCTION 1

3. Paper Submissions 2 A dossier paper submission is the process of compiling and submitting a collection of data and records to regulatory authorities to get approval for the distribution and commercialization of a product. Here are some things to consider when preparing a dossier paper submission: 1. Format - some countries require a specific format or layout for the dossier, such as CTD or ASEAN dossier. Other countries may only require a list of documents without any presentation specifications. 2. Electronic submission - some countries prefer or require electronic submission. 3. Document organization - applicants can organize documents in folders that correspond to the CTD modules relevant to the application. .

4. 3 4. Document size - documents included in an OTC dossier should generally be no larger than 100 megabytes (MB). 5. Hard copy - if the content exceeds 20 sheets of paper, the information should be presented in binders with durable covers. The external dimensions of the binders should not exceed 270 mm in width, 320 mm in height, and 80 mm in thickness. 6. Access management - the dashboard owner can add team members to any of their dossiers. New users must be added with the same email address as their EU login.

5. 4 Dossier paper submissions in regulatory affairs typically includes: Product Information : Detailed descriptions of the product, including formulation and specifications. Preclinical Data : Results from laboratory and animal studies that assess safety and efficacy. Clinical Data: Data from human clinical trials, including study protocols, results, and analysis. Manufacturing Information: Details on the manufacturing process, quality control measures, and facility information. Labeling: Proposed labels, inserts, and packaging materials, including claims and usage instructions. Regulatory Compliance: Documentation demonstrating adherence to applicable regulations and standards.

6. Common Technical Document(CTD) The Common Technical Document (CTD) is a standardized format for submitting applications to register medicines with regulatory authorities. Overview It is organized into five modules: Module 1 Module 2 Module 3 Module 4 Module 5 Structure 5

7. 6 Overview The CTD was developed by the International Council for Harmonisation (ICH) to streamline the process of registering new medicines across different countries. Purpose The CTD's primary purpose is to simplify the process of preparing and evaluating dossiers for registering medicines. Enhance the consistency and efficiency of regulatory reviews. Facilitate better communication between regulatory authorities and applicants. Serve as an essential tool for both external agency reviewers and internal pharmaceutical reviewers. The CTD is a vital tool for regulatory submissions, by adhering to the CTD guidelines and understanding the specific requirements of the relevant regulatory authorities, pharmaceutical companies can significantly improve their chances of successful product registration.

8. 7 Modules of CTD

9. 8 The CTD is organized into five distinct modules, with Module 1 containing region-specific administrative information and the remaining modules being common across all regions: Module 1: Regional Administrative Information Includes application forms, proposed labels, and other regional-specific documents. Module 2: Summaries and Overviews Provides a comprehensive summary of the detailed reports in later modules, including: Quality Overall Summary Nonclinical Overview Clinical Overview CTD Structure and Format

10. 9 Module 3: Quality Details the pharmaceutical properties and manufacturing information, including: Drug substance and product specifications Manufacturing process controls Stability data Module 4: Nonclinical Study Reports Contains data on preclinical studies, covering: Pharmacology Pharmacokinetics Toxicology Module 5: Clinical Study Reports Presents data from clinical trials on the safety and efficacy of the pharmaceutical product, including: Study protocols and methodologies Results and interpretations

11. 10 Electronic Common Technical Document (eCTD) submissions represent the digital version of the CTD format, facilitating the submission process for regulatory approvals of pharmaceuticals and biologics. The concept of the eCTD was developed in the late 1990s as part of an effort to harmonize the regulatory submission process across different regions, including the United States, Europe, and Japan. Key Features of eCTD Submissions 1. Structured Format Maintains the same five-module structure as the traditional CTD but is formatted for electronic submission. Allows for easy navigation through hyperlinks and bookmarks. 2. Interactivity Includes features such as hyperlinks to documents and sections, making it easier for reviewers to access relevant information quickly. Electronic CTD Submissions

12. 11 3. Life Cycle Management Supports updates and amendments to submissions, allowing sponsors to submit new information or corrections while maintaining a clear history of changes. 4. Compliance with Regulatory Standards Designed to meet the specifications set by regulatory authorities like the FDA, EMA, and others, ensuring compatibility with their submission systems. 5. Data Integrity and Security Ensures the integrity and security of submitted data through secure file formats and electronic signatures, complying with regulatory requirements for data protection. Benefits of eCTD Submissions Efficiency: reduces the time and costs associated with preparing and submitting applications. Reduced Paper Use: minimizes the reliance on paper documents. Faster Review Processes: streamlined submissions can lead to quicker review times. Global Standardization: Facilitates international submissions

13. 12 The eCTD is required for certain types of submissions to the FDA, including: > NDAs - New Drug Applications > ANDAs - Abbreviated New Drug Applications > BLAs - Biologics License Applications > Commercial IND applications > Master files, such as DMFs Steps for Planning an eCTD Submission 1. Understand Regulatory Requirements. 2. Establish a Submission Timeline. 3. Develop a Submission Strategy Determine the scope of the submission (e.g., new drug application, biologics license application). Identify key stakeholders (e.g., regulatory affairs, clinical, quality, and IT teams) and define their roles in the process. Planning Electronic CTD Submissions

14. 13 4. Organize Documentation : gather all necessary documents for each module (Quality, Nonclinical, Clinical, etc.). 5. Prepare Module 1 (Regional Requirements) 6. Compile Common Technical Document Summaries (Module 2) 7. Create the Quality Module (Module 3) 8. Gather Nonclinical and Clinical Study Reports (Modules 4 and 5) 9. Review and Quality Assurance: conduct thorough internal reviews of all documents to ensure accuracy, consistency, and compliance. 10. Electronic Submission Preparation: Use eCTD publishing software to compile the documents into the eCTD format. Validate the eCTD package to check for errors and ensure adherence to specifications. 11. Submission and Tracking

15. Challenges in eCTD Submission Inconsistent Document Formatting Navigation Errors in Hyperlinking and Bookmarking Technical Validation Errors Common Challenges Regular Updates: stay updated with the latest regulatory guidelines. Quality Checks: implement multiple rounds of quality checks. Expert Review: consider engaging with regulatory experts. Tips for Ensuring Compliance 14

16. 15 To submit an Electronic Common Technical Document (eCTD) to the FDA, we must meet the following requirements: Application number: request an application number from the FDA. Gateway account: register for an Electronic Submissions Gateway (ESG) account. Submission size: if the submission is 10 gigabytes or less, we must use the FDA ESG. Document formatting: ensure all documents are in PDF format and follow the ICH guidelines (M8 Electronic Common Technical Document) . Document validation: use eCTD validation software to check for technical errors. Document content: include the following five modules in the submission: Region-specific information Summary documents Quality-related information Nonclinical study reports Clinical study reports Requirements for Submissions

17. 16 Difference between CTD and eCTD The Common Technical Document (CTD), provides a standardized format for submitting documentation to regulatory authorities. Manual document navigation by TOCs, page numbers and caption cross references. Submitted in binders in boxes. Guidelines given under ICH Multidisciplinary Guidelines(M4). CTD- Common Technical Document eCTD- Electronic Common Technical Document It is the electronic version of the CTD that allows applicants to submit regulatory information electronically to health authorities. Electronic document navigation by TOCs, bookmarks and hyperlinks. Submitted on CD or DVD or by email or portal. Guidelines given under ICH Multidisciplinary Guidelines(M8).

18. 16 https://en.wikipedia.org/wiki/Dossier https://www.ddregpharma.com/what-is-a-dossier-submission https://extranet.who.int/prequal/vector-control-products/dossier-preparation https://www.kolabtree.com/blog/what-is-regulatory-dossier-and-what-does-it-contain/ https://en.wikipedia.org/wiki/Common_Technical_Document https://www.ich.org/page/ctd https://www.researchgate.net/publication/333971164_Regulatory_requirements_for_preparation_of_Dossier_for_registration_of_Pharmaceutical_products_in_ACTD_CTD_format https://www.celegence.com/expert-tips-strategies-ectd-submissions https://www.fda.gov/files/drugs/published/eCTD-Submission-Requirements--What-You-Need-to-Know.PDF Reference

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