Guidance for Industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions using

Name of Guidance: Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions using the eCTD Specifications

Status of Guidance: Final

Date of Guidance: October 2005

Name of Organizations Releasing the Guidance:

• United States Department of Health and Human Services, Food and Drug Administration (FDA)
• Center for Drug Evaluation and Research (CDER)
• Center for Biologics Evaluation and Research (CBER)

Target Audience: This guidance was designed for applicants preparing electronic regulatory submissions to the FDA using the CTD.

Guidance, Laws and Regulations Referenced:

• Code of Federal Regulations (CFR), chapter 21 – Regulation that outlines the content of regulatory submission documents. Subsections referenced include:
• 11.2(b)(2) – Gives guidance on what type of documents are acceptable in electronic format.
• 314.81(b)(3)(i) – Advertising and promotional labeling.
• 314.101 – Regulations for abbreviated new drug applications.
• 314.50(b) – Indexing of applications for FDA approval to market new drugs.
• 314.80(c)(2)(ii)(a) – Narrative summary of alert report.
• 314.550 – Promotional materials
• 600.80(c)(2)(ii)(a) and (c) – Periodic adverse experience report requirements and history of actions taken.
• 601.12(f)(4) – Advertising and promotional labeling, post marketing.
• 601.2 – Regulations for biologics licenses and procedures for filing the application.
• 601.45 – Biological products promotional materials.

• Guidance that describe formatting for specific subsections of the CTD:
• M2 eCTD: Electronic Common Technical Document Specification
• M4: Organization of the CTD
• M4Q: The CTD – Quality – Focuses on all quality sections of the CTD.
• M4S: The CTD – Safety – Focuses on all safety sections of the CTD.
• M4E: The CTD – Efficacy – Focuses on all efficacy sections of the CTD.
• International Conference of Harmonisation (ICH) E3 guidance – General guidance on all sections of the Clinical Study Report.

Definitions:

• Common Technical Document (CTD) – Also referred to as electronic CTD (eCTD). It is the standard format for submitting regulatory documents to Drug Regulatory Agencies in Europe, Japan, and the United States.
• International Conference on Harmonisation – Organization that addresses technical requirements for regulatory documents submitted in Europe, Japan, or the United States.
• eCTD backbone files – Indexing of files present in an electronic submission.
• Submission – Collection of documents containing information which may include forms, reports, and datasets.

Background:

This guidance is intended to improve communication between the FDA and sponsors submitting electronic documents for regulatory review. It implements ICH recommendations by encouraging the use of eCTD backbone files. Additionally, because of the agency’s limited accessibility to newer technology, a list of acceptable file formats are provided.

Summary:

This guidance applies to marketing applications, investigational applications, and related electronic submission documents. It gives specific direction on the use of the CTD, and lets the reader know where to find content guidance for each subsection of the CTD.

During an electronic submission, each document is provided as a separate file and arranged into one of the 5 CTD modules. Each document in turn becomes part the electronic indexing which facilitates review by the agency. Since each file has a specific given location, referencing to previously submitted material is simple.

The following are some of the issues specifically addressed by this guidance:

• Scanned documents – Text files are preferred because of their smaller size and because they are searchable.
• Naming of files and folders – The file names should be short and descriptive.
• Bookmarks and hyperlinks – They facilitate review and are essential.
• Organization of the main submission folder – For organizational purposes, subfolders should be included.
• Module 1 folder – Should include: a comprehensive table of contents, labeling documents, promotional materials, marketing annual reports, and informational amendments. A cover letter is optional.
• Module 2 and Module 3 folders – Each containing a table of contents and a PDF copy of all documents required by their appropriate guidance.
• Module 4 folder – Should include: a comprehensive table of contents, and complete non‑clinical study reports.
• Module 5 folder – Should include a comprehensive table of contents, a tabular list of all clinical study reports, complete copies of all clinical study reports, and periodic safety reports.
• Utility folder – This folder should contain information on the technology used to create the electronic submission.

Failure to comply with this guidance can result in the FDA refusing to accept the application.

Rationale:

This guidance was created to generate consistency across all regulatory submissions to the FDA and to simplify the review process.

Resulting Recommendations:

• The agency will eventually need to update its list of acceptable file formats.

Impact:

Moving to electronic submissions has had the following accomplishments:

• Decreased the amount of paperwork created by the sponsored.
• Decreased the amount of time needed for review by the agency.
• Decrease the turn around time of decisions by the agency.