The Standard for the Exchange of Nonclinical Data (SEND) is essential for organizations submitting nonclinical study data to the FDA. Although standardization and implementation guides are helpful, it can still be unclear when SEND applies. Implementing SEND can be complex, but its advantages go far beyond regulatory compliance. This blog explores when SEND is required, how to implement it effectively, and the broader benefits of alignment.
What is SEND?
SEND is an industry initiative established by the Clinical Data Interchange Standards Consortium (CDISC). However, its adoption by the FDA has seen it become the standard for formatting and organizing nonclinical safety assessment data for submission. SEND formatting is machine-readable and ensures consistent, structured data that aids regulatory review.
While implementing SEND standards can feel complicated, there are robust guides that help organizations achieve alignment:
- Implementation Guide – Outlines how study data should be organized across domains, records, and variables to meet SEND requirements1.
- Controlled Terminology – Provides standardized language to ensure consistent meaning and interpretation of data across submissions2.
- FDA Business Rules and CDISC Conformance Rules – Define the technical and regulatory requirements that SEND datasets must meet to be accepted by the FDA3,4.
SEND datasets are submitted as part of Module 4 of the electronic common technical documents with nonclinical study reports.
When Does SEND Apply?
Implementing SEND standards can require significant time and resources, so knowing when compliance is mandatory and when it may not be necessary is essential.
SEND is required for single-dose and repeat-dose toxicology studies, as well as for carcinogenicity studies and certain types of genetic toxicology, safety pharmacology, and developmental and reproductive toxicology studies.
Some study types not included within the scope of SEND at the time of writing include:
- Central nervous system
- Fertility
- Pup development
- Juvenile development
- Dermal
- Ocular
The ideal time to evaluate whether your study needs to comply with SEND is during the planning phase, before the study begins.
The FDA Technical Conformance Guide is the go-to document for determining if a study is within the scope of SEND5. However, organizations must remain cognizant of changes to FDA and SEND requirements as they are updated regularly, with SENDIG-Genetox being a prime example.
SENDIG-Genetox
SENDIG-GeneTox v1.0 is an implementation guide that describes how various genetic toxicology studies should be represented in SEND. For such studies starting on or after 15 March 2025, alignment with this guide is mandatory, bringing comet and micronucleus in vivo animal model assays within the scope of SEND.
Read more about SENDIG-GeneTox v1.0 and what it means for your workflows.
Challenges of SEND Compliance
Once an organization determines that its study falls within the scope of SEND, the next challenge is ensuring alignment. Most sponsors have dedicated teams for managing SEND, and many CROs include SEND as part of their service offering.
However, defining expectations early in your discussions with a CRO is essential. Be sure to clarify how the CRO sources its SEND guidance and establish a reliable process for verifying the compliance of the datasets you receive from them. If your chosen CRO lacks SEND capabilities, you should consider outsourcing SEND compliance to a specialized third-party provider, like Instem.
If data collection and reporting weren’t designed with SEND in mind from the start, retrofitting SEND later can be challenging, often leading to issues like missing data, difficulties integrating data from multiple sources, and the need to reformat and relabel large datasets. This emphasizes the need for early consideration of SEND requirements at the study outset.
SEND Changes on the Horizon
SEND is set for several changes and improvements in the coming years, these include:
SEND v4.0
SEND v4.0 introduces expanded coverage for pathology, immunogenicity, dermal and ocular studies, nervous system tests, and pharmacokinetics. It aims to improve data consistency and support more complex study types. Public review is expected in 2025, with publication in 2026.
Dataset-JSON
Dataset-JSON v1.1 is a CDISC standard for representing standardized data using the JSON (JavaScript Object Notation) file format. Eventually, it is intended to replace the outdated XPT as the standard format for SEND data submissions. Version 1.1 was published in 20246, and the FDA has issued a Federal Register Notice requesting feedback7.
CORE: CDISC Open Rules Engine
CORE is a validation engine that will allow researchers to freely check their datasets against CDISC conformance rules, FDA business rules, and custom rule sets8.
Other Uses of SEND
While many organizations may see SEND as a means to an end for regulatory compliance, it’s important not to overlook the benefits of SEND alignment in organizational efficiency and productivity. SEND standards mean improvements in the following areas:
- Data Mining and Storage – A standardized and centralized approach makes it easier to store and search through data.
- Collaboration – SEND enables internal and external teams to easily share, combine, and analyze data, even when collected at different times or across multiple sites.
- Monitoring – SEND allows data to be exchanged between a CRO and the sponsor to aid remote study monitoring.
- Virtual Control Groups – Having a wealth of control data in SEND is enabling research into the use of Virtual Control Groups, reducing the number of subjects needed in studies.
Conclusion
SEND alignment is essential for preclinical study submissions and provides a strategic advantage for improving data quality, collaboration, and long-term study value. As standards evolve, organizations must stay informed about updates from CDISC and the FDA. Adapting to these changes can be challenging, but early adoption and thoughtful implementation lead to more efficient submissions and improved research efficiency. Whether for compliance or better data management, aligning with SEND early sets you up for success.
Marc Ellison, Director of SEND Solutions at Instem, offers expert insights into SEND with practical tips and guidance to help you navigate SEND implementation with confidence.
Contact our team to learn more.
References
1. SEND | CDISC. March 30, 2021. Accessed May 13, 2025. https://www.cdisc.org/standards/foundational/send
2. Controlled Terminology | CDISC. Accessed May 13, 2025. https://www.cdisc.org/standards/terminology/controlled-terminology
3. SEND Conformance Rules v4.0 | CDISC. July 29, 2021. Accessed May 13, 2025. https://www.cdisc.org/standards/foundational/send/send-conformance-rules-v4-0
4. Commissioner O of the. Study Data Standards Resources. FDA. June 2, 2025. Accessed May 13, 2025. https://www.fda.gov/industry/fda-data-standards-advisory-board/study-data-standards-resources
5. Research C for DE and. Study Data Technical Conformance Guide – Technical Specifications Document. March 27, 2025. Accessed May 13, 2025. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/study-data-technical-conformance-guide-technical-specifications-document
6. Dataset-JSON | CDISC. December 5, 2024. Accessed May 14, 2025. https://www.cdisc.org/standards/data-exchange/dataset-json
7. Electronic Study Data Submission; Data Standards; Clinical Data Interchange Standards Consortium Dataset-JavaScript Object Notation; Request for Comments. Federal Register. April 9, 2025. Accessed May 21, 2025. https://www.federalregister.gov/documents/2025/04/09/2025-06051/electronic-study-data-submission-data-standards-clinical-data-interchange-standards-consortium
8. CORE | CDISC. Accessed May 14, 2025. https://www.cdisc.org/core
