Pharmaceutical regulatory affairs have undergone immense evolution over the past few years, thanks to significant advancements in technology and processes. The introduction of Electronic Common Technical Document (e-CTD) formats and digital dossier management systems have transformed the submission and approval processes for new drugs around the world. 

The traditional regulatory systems rely on paper-based submissions, which require extensive costs, resources, and time to prepare documentation and get drug approvals. This is where employing e-CTD and digital dossier management systems come in, which not only supports faster submission processes but also improves the accuracy and reliability of the data presented to regulators.

In this article, we will give you a deeper insight into e-CTD and digital dossier management, their benefits, and how they can be implemented in traditional pharmaceutical regulatory affairs setups. 

So without further ado, let’s dive in.

Understanding e-CTD and Digital Dossier Management 

What is e-CTD?

Electronic Technical Document or e-CTD format is the digital version of the standard format used for submitting applications, amendments, supplements, and reports to the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). 

The USFDA has also published detailed guidance on compiling e-CTD submissions for pharmaceutical products.

Components of an e-CTD

The e-CTD is divided into several modules, each of which serves a distinct purpose. When preparing regulatory submissions, the regulatory affairs professionals follow the format of e-CTD in chronological order.  

The main components of an e-CTD are:

● Module 1- Administrative Information: Module 1 makes up the first component of an e-CTD format. It contains region-specific administrative information and varies by country or region, reflecting the specific requirements of each regulatory body. Module 1 includes documentation like cover letter, application forms, table of contents, labeling information, and compliance certifications.

● Module 2: Common Technical Document Summaries: The second module of an e-CTD consists of summaries of the information that are later provided in Modules 3, 4, and 5. These summaries include Quality Overall Summary, Non-Clinical Overview, and Clinical Summary.  

● Module 3 - Quality Information: As the name indicates, this module provides quality-related information on the drug substance and drug product. It compiles the quality information in two stages of the drug - as a drug substance that includes API and as a drug product that includes the drug in its final formulation. Stability data is also covered under this module. 

● Module 4 - Non-Clinical Study Reports: Module 4 makes up the fourth component of e-CTD, providing detailed information on pre-clinical data. It consists of sections like pharmacology studies and toxicology studies.

● Module 5 -Clinical Study Reports: This is the last component of an e-CTD and it provides insight into the clinical trial data of the drug. 

Benefits of Digital Dossier Management

While e-CTD serves as the perfect, paperless, and hassle-free alternative to traditional methods of compiling regulatory submissions, it still doesn’t simplify the cumbersome dossier management process. This is where digital dossier management comes in.

Digital dossier management systems are centralized repositories for all regulatory documents and data, allowing regulatory affairs professionals to store, access, and manage information from a single location, thus simplifying the retrieval process. It also reduces the risk of document loss and ensures that all stakeholders have access to the most current information at their fingertips. 

Other benefits of digital dossier management are:

● It allows access to submission documents in real-time, making updates and revisions easier.

● Unlike paper-based systems, where the risk of errors is high, digital systems help ensure document integrity by implementing version control and audit trails.

● Digital dossier management systems are designed to comply with international regulatory standards, which is a fundamental requirement for pharmaceutical companies operating in multiple regions.

● Digital systems have better security features compared to traditional paper-based methods. These include access controls, encryption, and secure cloud storage to protect sensitive information from unauthorized access and data breaches. 

Advantages of Using e-CTD in Regulatory Submissions 

Using (e-CTD) in regulatory submissions comes with several advantages, the biggest one being improved efficiency and speed.

The e-CTD format standardizes the structure and content of regulatory submissions, making it easier for pharmaceutical companies to prepare their documents. However, it’s the use of automated processing tools that makes the submission process more efficient and reduces the time traditionally spent on formatting and organizing submissions.

Furthermore, the structured nature of e-CTD submissions enables regulators to locate relevant information quickly, leading to faster review cycles.

Electronic submissions also simplify handling large volumes of submissions effectively, allowing regulatory agencies to process applications promptly.

The e-CTD system incorporates automated validation tools to check submissions for errors before they are sent to regulatory authorities, a process that otherwise requires more time and resources than traditional paper-based submissions.

Implementing e-CTD and Digital Dossier Management Systems 

If your company uses conventional CTD and manual dossier management systems, transitioning to electronic Common Technical Document (e-CTD) formats and digital dossier management systems might seem daunting. However, using the right strategy and proper planning can make this transition easier. We strongly recommend referring to the specific requirements of regulatory authorities in your region, such as the FDA’s "eCTD Specification" (for the US) and EMA’s "eCTD Implementation Guidelines” (for the EU).

Step 1: Understanding the eCTD Standard

Understanding the eCTD format starts with using a structured format based on XML and PDF formats to make document processing easier.

Step 2: Assessing Current Processes

Conducting a gap analysis to evaluate existing documentation and workflows, and identifying gaps between the current CTD system and the eCTD requirements can make this transition easier. Gap analysis can cover documentation structure, comparing current formats with eCTD requirements, and technology infrastructure, and assessing current IT systems and their capability to support eCTD.

Step 3: Planning the Transition

This step includes developing a detailed project plan and forming a project team. 

Step 4: Choosing the Right Technology

Selecting eCTD publishing software that meets regulatory requirements and integrates with existing systems is the key to choosing the right technology.

When selecting an e-CTD software solution, pharmaceutical companies should consider their specific needs and the features offered by various vendors. Leading e-CTD software solutions, such as MasterControl's eCTD software and Masuuglobal's NextGen eCTD,  have integrated tools for creating, managing, compiling, publishing, reviewing, validating, and archiving regulatory submissions in fully compliant eCTD formats. 

Another key component of vendor selection is to evaluate vendors based on their experience serving the pharmaceutical industry and the availability of ongoing support and training.

Step 5: Developing the eCTD System

Once the software is selected, the next step is to design the eCTD system architecture, organizing documents according to eCTD specifications (e.g., Module 1: Administrative Information, Module 2: Common Technical Document Summaries, Module 3: Quality Information, and so forth) and ensuring seamless data integration with other systems like document management systems (DMS) and electronic laboratory notebooks (ELN). 

Configure the chosen eCTD software to align with the designed system, focusing on template creation for different document types and workflow automation for document review, approval, and submission.

Step 6: Data Migration and Validation

By now, the eCTD system is implemented. The next step is to transfer existing CTD documents to the eCTD format. Data migration can done by mapping existing documents to the eCTD structure and using automated tools to convert documents to the eCTD format. 

At this stage, the eCTD system should also be validated covering functionality testing, to ensure that the system meets all regulatory requirements.

Step 7: Staff Training

This step includes conducting training programs for staff, covering eCTD basics to educate on the structure, benefits, and use of eCTD, and system training to provide hands-on experience with the new software and workflows.

Step 8: Submission and Continuous Improvement

Once an eCTD system is implemented, the last step is to prepare initial submissions to regulatory authorities using the newly implemented eCTD system, ensuring all documents are correctly formatted and meet submission guidelines. 

It’s important to collect feedback from regulatory authorities and internal users at this stage to address any issues encountered during the initial submissions and work on continuously improving the system and workflows based on feedback and lessons learned.

Conclusion

Pharmaceutical regulatory submissions have long remained a time-consuming and labor-intensive task. However, the ongoing technological advancements have simplified this process. Using e-CTD and digital dossier management not only speeds up regulatory submissions but also minimizes the risk of errors and makes the review process effortless for both organizations and regulatory reviewers.

It’s high time pharmaceutical companies start adopting these technologies to stay competitive and improve their approval rates.

About the Author

Saher Haider

Saher Binte Haider is a pharmacy graduate from Dow University of Health Sciences. She started her career as a Quality Management professional in the pharmaceutical industry where she developed a keen interest in good documentation practices, SOP creation, and content writing. She has 7+ years of experience in healthcare & life sciences content writing. Her key areas of expertise are healthcare, pharmaceuticals, health tech, and AI in healthcare.