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A Guide on FDA Study Data Submission Requirements

The Challenges in Complying with SEND

The evolving guidance of the FDA on nonclinical dataset submissions requires organizations to adapt procedures to ensure full regulatory compliance. The Food and Drug Administration rejects as many as one in three study data submissions due to technical factors. Nonclinical studies often fail because of a missing trial summary dataset. The Standard for Exchange of Nonclinical Data (SEND) sets out the data format and terminology that the FDA requires for submitting preclinical study data. The SEND study data submission process can be complicated because even small errors can lead to rejection.

Do you need to know more about how to submit study data for nonclinical studies to the FDA? Learn about SEND study data submission here. You’ll find out what data submission requires and how to reduce the risk of rejection.

Current Versions of SEND for the Food and Drug Administration Submission

The SEND Implementation Guide (SENDIG) defines SEND. The FDA collaborated with the Clinical Data Interchange Standards Consortium (CDISC) and other stakeholders to develop SEND. SENDIG is currently on versions 3.0 and 3.1. The SENDIG is available on the CDISC website.

Study data must be in a format that the FDA supports at the time the study starts. Version 3.0 applies to studies that started on or after:

· December 17, 2016 for NDA/ANDA and some BLA studies
· December 17, 2017 for some IND studies

Studies should comply with v3.1 if they started on or after:

· March 15, 2019 for NDA/ANDA and some BLA studies
· March 15, 2020 for some IND studies

The FDA will give notice at least a year ahead of time for a new version of a standard. The notice period will be at least two years for an entirely new standard. The notice period will be at least two years for an entirely new standard. Version 3.1.1 will come into effect on March 15, 2023.

Which Studies Require a SEND Study Data Transmission?

SEND applies to data from preclinical animal studies. SENDIG v3.0 covers three types of studies:

· Single-dose general toxicology
· Repeat-dose general toxicology
· Carcinogenicity

SENDIG v3.1 adds cardiovascular and respiratory data from some safety pharmacology studies. Future versions of SENDIG will include reproductive toxicology data. This type of data is currently exempt.

The Food and Drug Administration recognizes that these study types can include a wide range of study designs and purposes. If the nonclinical study data is necessary to support the FDA regulatory decision, the study requires SEND. The Study Data Technical Conformance Guide gives more information about the requirements for specific types of studies.

SEND applies to submissions to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). However, SEND datasets will not be a requirement for CBER submissions until after March 15, 2023.

Creating a Study Data Standardization Plan

The best time to implement SEND is before the study starts. Reviewers must be able to trace the results in the study report back to the original data. According to the Food and Drug Administration, the Study Data Standardization Plan should be involved in the submission process no later than the end of phase 2.

Complying with the FDA data submission standards is a complex process. Sponsors need to create a plan for submitting standardized study data to the FDA. They should make this Study Data Standardization Plan (SDSP) early in the development process.

The SDSP is very important. It helps sponsors and reviewers resolve any potential issues with study standards early in the process. Preparing the SDSP should be done by SEND experts with in-depth knowledge of clinical or non-clinical data since it requires expertise, attention to detail, and cross-study consistency and dependency.

Study Data Reviewer Guides

Study Data Reviewer Guides (SDRGs) are related to the SDSP. The guides describe any additional information the reviewer may need to use the submitted data effectively. Reviewer Guides can help explain the relationships between the data and the study report.

The Food and Drug Administration recommends SDRGs, but they are not a requirement.

Exchange Format for Electronic Submissions

The FDA requires electronic data submission in a format that both humans and machines can read. For this reason, study data packages must use the following formats:

· Extensible Mark-Up Language (XML)
· Portable Document Format (PDF)
· SAS Transport Format (XPORT) version 5

XPORT is the file format for submitting electronic datasets. Each transport file should contain one dataset. The FDA will not process files in the wrong format. The Study Data Technical Conformance Guide provides guidance for using the approved types of files.

Tabulation Datasets for SEND Study Data Submission

SEND describes the organization, structure, and format of tabulation datasets for submission to the FDA. SEND is based on the Study Data Tabulation Model (SDTM) standard for human clinical trials.

The SENDIG provides domain models, assumptions, and examples for preparing tabulation datasets. Each SEND dataset needs a description with complete metadata in the define.xml file. Each dataset may also need an explanation in the Reviewer Guides.

Structure of the Datasets

SEND has a predefined format for data submission. The Study Data Technical Conformance Guide describes the definition and content of domain fields. It also shows the file folder structure for the study datasets.

Controlled Terminology

Following controlled terminology standards makes the analysis of study data easier. All controlled terms that appear in SEND datasets should match the spelling, case, and punctuation that the terminology maintenance organization uses.

Sponsors should use the most current version of the relevant dictionary available when the study starts. If a newer version becomes available after the study has started, sponsors may use the new version.

Data Definition File

The data definition file describes the metadata of the datasets. This file is extremely important. It defines the metadata structures that describe:

· Datasets
· Variables
· Possible values of variables when applicable
· Controlled terminologies and codes

The code list and origin for each variable should be easy to access. Each type of electronic dataset submission needs its own data definition file. These files should each be a working define.xml.

SEND Study Data in the eCTD

SEND study data is part of the full electronic Common Technical Document (eCDT) submission. Submissions to CDER and CBER must be in eCTD format. The following is the eCTD which has five modules: · Module 1 is not technically part of the CTD. It includes region-specific administrative information. · Module 2 includes overviews and summaries. It gives an overview of manufacturing information as well as the nonclinical and clinical study reports. · Module 3 describes detailed manufacturing information. · SEND study data makes up Module 4. This part of the CTD covers nonclinical study reports. · Module 5 includes clinical study reports. Having SEND study data correctly documented and formatted is one important step in properly completing the eCTD.

Managing the SEND Study Data Submission Process

The SEND study data submission process is complex. Data must be complete and accurate. It must meet the detailed FDA standards for formatting and organization.

Studies that fail to meet the FDA study data requirements for submission will face rejection. Without the right assistance and solutions, your submission may face costly delays. According to the Food and Drug Administration, the submission of SEND nonclinical datasets is expected to continue to increase in the future. The increasing demand for SEND submissions proves the importance for reviewers to receive standardized data, that will help them save time and increase efficiency in the review process.

As the requirement for electronic submissions using version 3.1.1 of CDISC SENDIG for NDAs, ANDAs, certain BLAs, and certain INDs begins on March 15, 2023, Xybion can help you put a plan in place to help with your timely dataset submission. Xybion can help streamline and simplify your SEND submissions through SEND Intelligence Services.

Avoid common errors that lead to FDA rejection, avoid technical rejection, and have your datasets reviewed, prepared, and delivered to you, ready to be sent to the FDA.

Talk to a SEND Expert today to experience the benefits of our SEND Intelligence Services.


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