The CTD Triangle
The CTD document and dossier specifications serve as participating countries’ regulatory compliance guidelines for new drug applications. In the regions that recognize the CTD regulatory file format (specifically, the U.S., Europe, and Japan), CTD files are organized into dossiers that align with prescribed technical requirements for eventual submission to the appropriate regional regulatory authority as an application for the registration of pharmaceuticals intended for human use. As illustrated in the accompanying CTD triangle, all well-structured CTDs are divided into five distinct modules that contain the proper arrangement of CTD files
- Module 1: while technically not part of the categorical CTD sections, contains administration information particular to regionality. All submissions contain this CTD section that includes all the basic information pertaining to the application, country/agency, submission type, etc.
- Module 2: consists of summaries and overviews of the clinical and non-clinical sections of the CTD.
- Module 3: details the quality information pertaining to the manufacturer, control of drug substances, references to materials and standards, and similarly related CTD documents.
- Module 4: is reserved for safety information and includes toxicology, pharmacology, pharmacokinetics and similar reports.
- Module 5: contains efficacy data, study reports and clinical study data.
While Module 1 of the CTD is region specific, the other CTD sections (Modules 2, 3, 4 and 5) are common for all geographical regions. While the essential CTD regulatory information may be the same for registrations in countries that adhere to the CTD file-structure standard, the preparation, delivery and complexity of the information may vary greatly according to regional requirements.
eCTD v CTD Documents
Maintaining paper-based documentation according to the format requirements for common technical documents can be laborious and stressful. This reality led the ICH and united regulatory authorities to upgrade the original CTD document structure in February 2002 in the form of Version 2.0 of the eCTD. Regulatory agencies continue to lead the wider industry’s inclinations toward maximum electronic management of common technical documents. In fact, as of 2017, the FDA has mandated the electronic submission of all applications and the eCTD is now deemed the standard CTD file format.
Switching from paper to electronic systems for CTD document management helps eliminate many common CTD file management obstacles, such as:
- Manually compiling CTD documents that are generated from myriad sources and systems (i.e., PLM, ERP, etc.), which is an inefficient and painstaking process that ultimately leads to delayed submissions.
- Missed deadlines that frequently occur because managing timelines and tracking requirements for all countries in which registration is sought is prohibitively difficult (especially when using spreadsheets that don’t scale to the complexities required by CTD regulatory guidelines).
- The overwhelming task of keeping pace with the granularity of every registration due to the variables in exponentially increasing CTD regulatory requirements relative to the number of countries and number of products being registered.
- The use of disparate CTD file systems inevitably leads to communication breakdowns and an inability to provide timely response to issues relating to CTD regulatory guidelines.
- CTD file consistency declines when different teams are focused on customizing registrations to each market, causing CTD documents and data to be fragmented among myriad systems.
- When multiple products need to be registered in many countries, it is easy to become mired in minutiae and lose visibility into activities and deadlines that are critical to CTD regulatory compliance.
With the permissibility of submissions in NeeS (Non-eCTD Electronic Submission) formats ending in 2018, the eCTD will be the only accepted CTD file format for new drug submissions by the European Union’s European Medicines Agency (EMA) moving forward. The EU CTD format is the same as the standard CTD document formatting scheme for submissions in other geographies, with the possible exception of Module 1 (which contains region-specific administrative information for all common technical documents). To see the current EU CTD regulatory requirements for Module 1, visit the EU CTD Module 1 specifications page.
As with other regions and regulatory authorities, a strategy for ensuring the ultimate success of an EU CTD submission to EMA entails the following key components:
- Efficiency of product registration and CTD file management processes
- Adequate control of all CTD documents and timelines
- Effective tracking of the various CTD regulatory requirements pertaining to relevant geographies
- Maximum project transparency and effective monitoring of CTD file management bottlenecks (both within your organization and with associated regulatory agencies)
MasterControl’s Solution for CTD Files
To help companies alleviate common CTD file management concerns and streamline their submissions-related processes, MasterControl provides submissions management software solutions that are specifically engineered to facilitate adherence to the CTD regulatory standard. By including templates that have been expertly designed to help life sciences companies automate processes and meet CTD regulatory requirements, MasterControl Regulatory Excellence solutions allow companies to quickly launch projects that are harmonized with regulatory standards. MasterControl Regulatory Excellence is a holistic system for CTD submission management and product registration that will automate your processes and streamline your control of essential CTD documents and critical timelines.
MasterControl provides the basic structure for successful CTD file management and helps get your products to market sooner in the geographic locations you are targeting. It eliminates the painful process of manually compiling CTD documents from multiple sources and disparate systems, which increases efficiency and prevents delays in CTD regulatory submissions. MasterControl negates any need to manage timelines and tracking requirements using spreadsheets, an inefficient practice that can often result in missed deadlines and costly delays.
Exactness in the preparation of the various CTD sections that comprise a submission (not to mention the rigorous supervision of the many projects involved in generating and maintaining CTD documents and activities that is involved) can be incredibly challenging but is nonetheless necessary if a submission is to succeed. The Regulatory Excellence solution ensures that collaboration on the various CTD sections is effective and that filings are consistent.
To learn more about CTD files or MasterControl’s Regulatory Excellence solutions, contact a MasterControl representative.