Principles of preparing CTD and eCTD for drug registration in EMA and FDA

Introduction

The preparation and submission of technical documentation for drug registration to international regulatory agencies, including the EMA (European Medicines Agency) and the FDA (US Food and Drug Administration), requires adherence to standardized and harmonized structures. The CTD (Common Technical Document) format and its electronic version, eCTD, are the two main formats for submitting this information. This article focuses on the requirements for preparing CTDs and eCTDs, and examines their structuring, benefits, and key differences in the drug registration process at the FDA and EMA.

1. Introduction to CTD and eCTD

• CTD: A harmonized structure for presenting scientific and technical documentation for drugs for registration in global markets. This format was created by ICH to harmonize the drug registration process between different institutions.
• eCTD: A digital version of the CTD that provides a uniform structure for online submission of information in the form of electronic files with an XML backbone.

2. The five-part CTD structure

CTD consists of five main modules:

• Module 1: Regional Information
  • Includes application forms, country-specific information (displayed in eCTD only in XML format)
• Module 2: Summaries
  • Non-clinical, clinical and quality summaries (Quality Overall Summary)
• Module 3: Quality Information
  • Including API specifications, formulation, manufacturing process, raw material control and finished product
• Module 4: Nonclinical Studies
  • Pharmacological, pharmacokinetic and toxicological data in animals
• Module 5: Clinical Studies
  • Human study data, clinical trials, safety, efficacy

3. Key differences between CTD and eCTD

4. FDA specific requirements for eCTD

• Since May 2017, eCTD submission has been mandatory for NDA/ANDA/IND.
• The FDA uses a dedicated Gateway to receive information.
• XML information must comply with the US Regional Level 3 standard.
• Sequences should be numbered and each update should be sent independently.

5. EMA specific requirements for eCTD

• EMA has also made it mandatory to submit eCTD for MAA (Marketing Authorisation Application).
• Using the CESP platform for electronic submission at European level
• Compliance with EU Regional XML Specification
• Compliance with RPS (Regulated Product Submission) in future versions

6. Preparation and required technical tools

• eCTD preparation software: Lorenz docuBridge, Extedo eCTDmanager, MasterControl
• File structuring: naming conventions, PDF format with bookmarks and search capabilities
• Quality Check: Using the eCTD Validator tool to check compliance

7. Benefits of using eCTD

• Facilitate the tracking, review, and exchange of information between companies and institutions.
• Reduce paper consumption and processing time
• Increasing accuracy and reducing the possibility of errors in sending information
• Ability to track versions and modifications using Sequences

8. Common challenges in preparing eCTD

• Need for specialized training for the documentation team
• Change Management (Lifecycle Management)
• Initial costs of software and technical infrastructure
• Time-consuming to prepare standardized content

Conclusion

In the modern world of drug registration, the use of CTD formats, and especially eCTD, has become a legal and technical requirement. Pharmaceutical companies must be familiar with the structure of these formats, technical tools, and specific requirements of each regulatory body (FDA and EMA) and implement them correctly. Adherence to these principles not only speeds up the registration process, but also increases the likelihood of faster and more successful approval.