As a provider of service, CUSTOpharm offers Regulatory Support services and Pub-Assist, a regulatory support product in addition to other Services as CMC solutions. Many of our clients are transitioning from paper to electronic submissions and traditional format to CTD format. In line with our clients’ needs, we’re providing a list of the most frequently asked general questions regarding electronic submissions and the CTD.
In addition to the information below, please see our Links/Recent & Upcoming News and Events for additional references and information and Contact Us if you’d like additional information on any of the Products or Services we offer.
¨ What is CTD?
CTD is the acronym for Common Technical Document. It was created by the ICH in an attempt to harmonize the format of applications. Essentially, there are five major parts of the CTD called Modules. Module 1 is region specific; in general administrative documentation and labeling is included here. Module 2 is a summary section; a summary of Modules 3, 4 and 5 are included here. Module 3 contains CMC (Chemistry Manufacturing Controls), Module 4 contains nonclinical/preclinical information (‘animal studies’) and Module 5 contains clinical information (‘human studies’). Visit the ICH’s website for CTD for additional information. Each section is standardized to ease the location of information for reviewers and those creating the submissions.
¨ What is eCTD?
An eCTD is an electronic version of a CTD. The eCTD is comprised of various files and folders that together constitute a submission. Most of the documents in an eCTD containing submission text are provided in PDF (portable document format). Some other files may be in various formats to support data, programming and labeling (i.e., XML). Currently the FDA also requests that some sections be provided in Microsoft Word (.doc) format. In most cases, eCTD is the preferred method of submission for the FDA. Please see the FDA’s eCTD webpage for additional information.
¨ Who specifies the organization of content for CTD/eCTD?
For Modules 2-5 (excluding the Regional Section within Module 3), the ICH specifies the organization and content for CTD/eCTD. For Regional Sections (Module 1 and the Regional Section within Module 3), the specific Regulatory Authority (i.e., FDA) specifies the organization and content for CTD/eCTD. Regional Section Content may vary between Regions (i.e., US/Japan).
¨ How can someone create and submit an eCTD?
Organizations can choose to develop eCTDs in-house or outsource the creation and submission of eCTD to other organizations. CUSTOpharm offers Regulatory Support services to assist organizations in achieving both in-house development or outsourcing of eCTD compilation, authoring, publishing and submitting. Various tools and programs are available to assist in creating and validating eCTDs. Please see our Links/Recent & Upcoming Events and News website for tools we recommend.
¨ Does the US FDA require approval before submitting eCTDs?
The FDA wants to assure that new organizations submitting eCTDs conform to the standards. To do this, the FDA requests that applicants notify the FDA of their plans to submit electronically and complete a sample submission process. Please see the FDA’s website for additional information.
¨ What is a PDF?
PDF stands for portable document format; as a type of document format, it allows the user to see a graphical representation of file regardless of the system the user’s computer uses. Please see the FDA’s PDF specifications for additional information and settings/specifications for PDF files included in a submission.
¨ What is XML and what is it used for?
XML stands for eXtensible Markup Language—a computer programming language. Structured Product Labeling (SPL) is created using XML as is the table of contents (index.xml/us-regional.xml) for eCTD submissions.
¨ What is an MD-5 Checksum?
MD-5 stands for Message—Digest Algorithm 5; typically expressed as a 32-character hexadecimal number used for file security. The MD-5 checksums (in eCTDs) are provided in the eCTD backbone and used to check the integrity of the individual documents during validation. In theory, the MD-5 checksum generated for one document will be different if changes are made. Similarly, no two documents would have identical MD-5 checksums unless the documents themselves were identical. In other words, the MD-5 for a document before and after even a small change (to the same document) would be different. In eCTDs, if the calculated MD-5 during validation does not match the MD-5 listed in the eCTD backbone, the submission is not valid. Depending on how the eCTD submission is created, MD-5 Checksums may be automatically generated when documents change or they may have to be updated.
¨ What is the eCTD backbone?
The eCTD backbone is essentially a hyperlinked table of contents. The hyperlinks within this table of contents links the various files throughout the submission. Use of this table of contents eases access to different parts of the submission using a central focal point. The contents of the eCTD backbone are standardized by ICH and/or the FDA (for US submissions). There are generally 2 backbones: one for Module 1 (us-regional.xml) and one for Modules 2-5 (index.xml). The Module 1 backbone is region-specific and varies between other Regulatory Agencies accepting eCTD submissions. Please see the FDA’s Module 1 and Modules 2-5 backbone specifications.
¨ What is meant by validating the eCTD?
Validating the eCTD depends on how the validation is performed and/or what program is being used to validate the eCTD. Different validation programs may perform different levels of validation. There are several aspects of the eCTD that a validator can check.
¨ What is the ESG?
The Food and Drug Administration (FDA) Electronic Submissions Gateway (ESG) is an Agency-wide solution for accepting electronic regulatory submissions. The FDA ESG enables the secure submission of regulatory information for review. The electronic submission process encompasses the receipt, acknowledgment of receipt (to the sender), routing, and notification (to a receiving Center or Office) of the delivery of an electronic submission. The FDA ESG is the central transmission point for sending information electronically to the FDA. Within that context, the FDA ESG is a conduit along which submissions travel to reach their final destination. It does not open or review submissions; it automatically routes them to the proper FDA Center or Office. Prior to using the ESG to submit, organizations must receive approval to submit via the ESG. Visit the FDA’s ESG website for additional information. CUSTOpharm has received approval to submit via the ESG. If you would like additional information on this service, please Contact Us.
Click here to return to the Regulatory Support page or use the side navigation bar to visit another area.
If you have a question about eCTD or electronic submissions that you’d like to see answered here, please contact us and let us know. We will do our best to incorporate a response when the website is updated.