Introduction: In the ever-evolving landscape of pharmaceuticals, the pursuit of more efficient and streamlined processes in drug product registration has led to significant advancements. At the forefront of this transformation is the Electronic Common Technical Document (eCTD) v4.0, a revolutionary framework that promises to redefine the way drug products are registered. This article delves into the key features and implications of eCTD v4.0, shedding light on its potential to reshape the regulatory landscape and accelerate the approval process for new pharmaceuticals.

What is eCTD: A common format for submitting regulatory information (such as applications, supplements, and reports) to the relevant Health Authorities (HAs) is called an “eCTD” (electronic Common Technical Document). For both drug manufacturers and regulators, it is intended to make regulatory submissions simpler and more effective. There are still differences between nations and even ICH regions when it comes to eCTD submission. It offers a standardized method for putting the Common Technical Document (CTD) into use electronically. An eCTD is made up of distinct PDF documents that are organized hierarchically in accordance with the CTD structure. Creating eCTD-ready documents by using eCTD-compliant templates when writing them is crucial. Document reformatting takes up a significant portion of “publishing time” if this is not done. Additionally, it has an XML backbone that links necessary documents together and provides submission details. ECTD was introduced to lighten the workload of the HAs’ reviewers. Since all Regulatory authorities use it as a standard format, it also streamlines the submission process.

eCTD Modules: Five modules in two categories make up the eCTD. The first one is module 1, which includes:

Module 1: Administrative and prescribing data are not standardized and vary depending on the country as defined by each of the ICH regions (the USA, Europe, and Japan).

Modules 2 to 5 (Harmonised – Common to All Regions) are among the Common Modules.

Modules 2 – Common technical document summaries,

Module 3 – Deals with quality,

Module 4 – Nonclinical study reports, and

Module 5 – Clinical study reports

Module 1-Administrative information and prescribing information – The module 1 folder should be called m1. Every region’s specific administrative data is contained in this module. The creation of the eCTD backbone enables the transfer of the regional data contained in a regulatory dossier. The precise instructions will be provided by regional guidance on how to supply the administrative forms and comprehensive prescribing data. Regarding the structure and content of the regional requirements, each region offers specific guidance for each Module.

Module 2-Summaries – Quality, non-clinical, and clinical overall summaries are included in this module. Except for a few embedded images, the files in this module should be provided as text in the Portable Document Format (PDF) when required. The folder for module 2 should be called m2. The following names can be further shortened or omitted to reduce path length concerns. The folder structure is shown in Table 1 for Module 2.

Module 3-Quality – The intended drug or medicinal product’s quality aspects are included in this module. The folder for module 3 should be called M3. To reduce path length issues, the names of the folders in module 3 can be further condensed or omitted.

Module 4 – nonclinical study reports – Details of nonclinical studies are included in this module. The module 4 folder should be called m45. To reduce path length issues, the names of the folders in module 4 can be further condensed or omitted.

Module 5-Clinical study reports – Details of clinical studies are included in this module. The module 5 folder should be called m5. To reduce path length issues, the names of the folders in Module 5 can be further condensed or omitted.

eCTD around the world: The US, the European Commission, and Japan were the founding agencies of the ICH, which created eCTD. The standard has continued to develop over the years since its introduction. Several other nations, including Australia, Canada, Thailand, the GCC, Switzerland, and South Africa has now adopted the standard. In the future, the new eCTD 4.0 standard is finally getting close to being finished. The purpose of eCTD 4.0, which was based on the Health Level Seven (HL7) standard for Regulated Product Submissions (RPS), is to make it easier for applicants and regulators to process and review electronic submissions.

Evolution of eCTD: A Brief Overview: The Electronic Common Technical Document (eCTD) is a globally accepted electronic submission standard for regulatory submissions in the pharmaceutical industry. It originated from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and was designed to facilitate the electronic exchange of information between industry and regulatory authorities. As the pharmaceutical landscape evolved, so did the eCTD, leading us to the latest iteration—eCTD v4.0.

eCTD 4.0: RPS (Regulated Product Submission), a Health Level Seven (HL7) standard, is the foundation of eCTD 4.0. Instead of the content itself, which will continue to evolve with each iteration of the eCTD, this standard concentrates on simplifying the processing and review of regulated product information. RPS was created to be used in other industries in the future to obtain approval for regulated products such as medical devices, animal health, and other products.

eCTD 4.0’s main objectives are to:

• Two-way communication – Sponsors currently only have the option to submit an eCTD series to an entity. As a part of the eCTD series, eCTD v4.0 incorporates two-way communication, enabling agencies to communicate with sponsors in the form of letters like information requests. The US FDA has already stated that two-way communication will be incorporated in its regional implementation guide.
• Reuse of Document – Having access to files from an investigative application would make it much easier for regulatory operations practitioners to compile marketing applications. eCTD v4.0 now makes it easier to reuse document files. Each text now has a distinct ID assigned to it that can be used as long as it is stored in an Agency’s database.
• Controlled vocabularies – Which essentially permit straightforward, unambiguous communication between systems that send and receive XML messages, are one of the crucial elements of eCTD v4.0.
• Managed vocabularies – Regulated vocabulary will be regulated by a number of organizations, including the ICH, regional authorities like the FDA, and other third-party designated bodies.
• A new XML schema created to improve the messaging system’s durability, adaptability, and dependability over time.
• Collaboration with various Standards Development Organisations (SDOs) – Establishing the new norm with many SDOs rather than just the ICH was one of the other goals. eCTD v4.0 was consequently created. A project for the HL7 Regulated Product Submission (RPS) is also included. The complete release will be made available as an ISO standard. Establishing a much closer connection between eCTD dossiers and structured data directories (as described in the ISO IDMP) is the objective for business and regulators. This creates the possibility for numerous synergies, including effective regulatory review, finer granularity for quicker decision-making, and a practical dedication to patient safety.

Key Features of eCTD v4.0: A Glimpse into the Future

1. Structured Content and Enhanced Flexibility:

eCTD v4.0 introduces a more structured approach to content, allowing for greater clarity and consistency in submissions. The enhanced flexibility in data organization enables sponsors to present information in a more logical and coherent manner.

2. Improved Lifecycle Management:

One of the standout features of eCTD v4.0 is its emphasis on improved lifecycle management. This includes better versioning control, making it easier for sponsors to manage updates and changes throughout the product lifecycle.

3. Integration of Real-World Data:

With an increasing emphasis on real-world evidence, eCTD v4.0 embraces the integration of such data into submissions. This paves the way for a more comprehensive understanding of a drug’s performance in real-world scenarios, adding depth to regulatory evaluations.

4. Enhanced Support for Electronic Signatures:

Security is paramount in regulatory submissions. eCTD v4.0 bolsters this aspect by providing enhanced support for electronic signatures, ensuring the integrity and authenticity of submitted documents.

Implications for Drug Product Registration: A Paradigm Shift

1. Accelerated Approval Processes:

The streamlined structure and enhanced flexibility of eCTD v4.0 have the potential to accelerate the approval processes for drug products. Regulators can access information more efficiently, leading to quicker assessments and decisions.

2. Global Standardization:

As a globally recognized standard, eCTD v4.0 promotes greater consistency and standardization in drug product registrations worldwide. This not only benefits regulatory authorities but also facilitates global collaborations and market access for pharmaceutical companies.

3. Facilitating Real-World Evidence Integration:

The incorporation of real-world data is a game-changer, offering regulators a more holistic view of a drug’s performance. This can lead to more informed decisions, especially in post-marketing surveillance and assessments.

Challenges and Considerations: Preparing for the Transition

1. Training and Familiarization:

With any technological advancement, there’s a learning curve. Organizations need to invest in training programs to ensure that their teams are well-versed in the nuances of eCTD v4.0.

2. Technical Infrastructure:

The transition to eCTD v4.0 may necessitate updates to the technical infrastructure of organizations. Ensuring compatibility with the new standard is crucial for a seamless integration.

Advantages of eCTD 4.0:

In time, eCTD v4.0 will be mandated as the minimum requirement for electronic submissions. It will be easier to analyze electronic regulatory applications and coordinate with sponsors, regulators, and other third parties, like CROs or licensing partners.

• Simplify the evaluation of electronic regulatory files.
• Reusable material
• Better management of documents
• Updates to the metadata
• More efficient life cycle capabilities
• An increase in harmony

How ND Global can help: With ND Global’s expertise in regulatory compliance and pharmaceutical processes, organizations can confidently navigate the transition to eCTD v4.0, ensuring a smooth and successful integration of this groundbreaking framework.

1. Customized Training Programs
2. Technical Infrastructure Assessment and Upgrades
3. Documentation and Submission Support
4. Regulatory Compliance Expertise
5. Lifecycle Management Optimization
6. Real-World Data Integration Guidance
7. Electronic Signature Implementation
8. Regulatory Liaison Support
9. Global Standardization Alignment
10. Efficient Document Management
11. Comprehensive Compliance Review