Standard for Exchange of Nonclinical Data (SEND), developed by CDISC, plays a critical role in how regulatory authorities conduct FDA SEND reviews for nonclinical toxicology studies. Pharmaceutical and biotech companies are required to follow SEND requirements defined by the FDA to ensure that nonclinical study data is submitted in a structured, consistent, and reviewable format.
As regulatory agencies increasingly rely on SEND datasets for efficient data analysis, understanding how regulators validate, assess, and interpret these datasets is essential for ensuring compliance, reducing submission delays, and achieving faster approvals.
In this blog, we explain how regulatory authorities review CDISC SEND datasets, key validation checks performed during FDA review, common compliance issues, and best practices to improve toxicology data submission quality.You can read more about our SEND conversion services.
What Is SEND and Why It Matters to Regulators
SEND is a CDISC standard designed to organize and submit nonclinical toxicology data in a consistent, machine-readable format. Regulatory authorities such as the FDA, PMDA, and other global agencies mandate SEND datasets for specific nonclinical studies to ensure compliance with regulatory expectations and streamline the FDA SEND review process.
By using standardized SEND data, regulators are able to:
Improve data consistency and transparency across toxicology studies
Enable faster and more accurate regulatory review
Support automated analysis and risk assessment through validated datasets
Reduce manual data handling errors during submission evaluation
For regulatory authorities, properly validated SEND datasets allow efficient assessment of drug safety, toxicology findings, and overall study integrity, helping ensure reliable decision-making during regulatory review.
How Regulatory Authorities Review SEND Datasets
1. Technical Validation and Compliance Checks
The first step in an FDA SEND review is technical validation. Regulatory authorities use automated validation tools such as Pinnacle 21 to verify that SEND datasets comply with CDISC SEND implementation guides and regulatory requirements.
During this validation process, reviewers assess whether the datasets include:
Correct SEND dataset structure
All required SEND domains and variables
Proper use of controlled terminology
Absence of critical errors or unresolved warnings
SEND datasets that fail technical validation may result in refuse-to-file (RTF) actions, regulatory queries, or submission delays, impacting overall compliance and review timelines.
2. Dataset Completeness and Study Coverage
During the FDA SEND review, regulatory reviewers assess whether the SEND datasets accurately and completely represent the nonclinical studies described in the study reports. Ensuring alignment between SEND data and documentation is essential for regulatory compliance and effective toxicology evaluation.
Reviewers verify that:
- All required CDISC SEND domains are included
- Study design, dosing information, and toxicology findings are accurately captured in the datasets
- Proper linkage exists between SEND datasets and corresponding study reports
Incomplete, inconsistent, or poorly linked SEND datasets raise concerns about data integrity and may delay regulatory review, impacting overall compliance and submission timelines.
3. Consistency Between SEND Datasets and Study Reports
One of the most critical steps in an FDA SEND review is cross-checking SEND datasets against the corresponding nonclinical study reports. Regulatory authorities rely on this comparison to confirm data accuracy, consistency, and overall compliance with CDISC SEND standards.
During this review, regulators examine:
- Alignment between SEND datasets and submitted PDF study reports
- Consistency in study design, dose groups, and reported results
- Accurate matching of adverse findings and key toxicology endpoints
Any mismatch between the SEND data and study reports may trigger regulatory questions, requests for clarification, or additional validation efforts, potentially delaying the review process.
4. Data Quality and Logical Accuracy
Beyond dataset format, regulatory authorities assess the overall data quality of SEND datasets during the FDA SEND review process. High-quality data is essential for accurate toxicology evaluation, regulatory compliance, and reliable decision-making.
Regulators check for:
- Logical consistency across CDISC SEND domains
- Accurate population of toxicology findings
- Correct and consistent use of controlled terminology
- Proper handling and documentation of missing or derived values
Errors in SEND data logic or terminology can negatively impact regulatory risk assessment, trigger review questions, and slow down drug development timelines.
5. Use of SEND for Safety Signal Detection
SEND datasets enable regulatory authorities to perform independent analyses beyond what is presented in nonclinical study summaries during the FDA SEND review process. By using structured CDISC SEND data, regulators can explore safety findings in greater detail and strengthen regulatory decision-making.
Regulatory reviewers may:
- Run exploratory data analyses across SEND domains
- Identify dose–response trends relevant to toxicology evaluation
- Compare findings across multiple nonclinical studies
- Detect unexpected or emerging toxicological signals
This capability makes SEND a powerful tool for ensuring drug safety, supporting accurate risk assessment, and maintaining regulatory compliance.
6. Review of Metadata and Define.xml
Metadata plays a crucial role in the FDA SEND review process. Regulatory authorities rely on Define.xml files to clearly understand the structure of SEND datasets, variable definitions, and the use of controlled terminology in accordance with CDISC SEND standards.
During metadata review, regulators check for:
- Clear and accurate metadata descriptions in Define.xml
- Correct mapping of variables across SEND domains
- Consistent and standardized terminology definitions
Poor or incomplete metadata can make SEND datasets difficult to interpret, even when the underlying toxicology data is correct, potentially leading to review delays and compliance concerns
Common Issues Identified by Regulatory Authorities
During FDA SEND reviews, regulatory authorities frequently encounter issues within SEND datasets that can impact regulatory compliance and delay submission timelines. Many of these issues arise due to insufficient validation or inconsistent application of CDISC SEND standards.
Common challenges identified by regulators include:
- Validation errors or unresolved warnings flagged during SEND validation
- Missing required SEND domains or critical variables
- Incorrect or inconsistent use of controlled terminology
- Mismatches between SEND datasets and nonclinical study reports
- Inconsistent units or dose representations across toxicology data
These issues often result in regulatory queries, extended review cycles, or requests for dataset correction and resubmission, highlighting the importance of high-quality SEND preparation.
Best Practices to Ensure Smooth SEND Review
To meet regulatory expectations and ensure a smooth FDA SEND review, sponsors must follow best practices when preparing SEND datasets. Proactive planning and adherence to CDISC SEND standards play a critical role in maintaining regulatory compliance and minimizing review delays.
Sponsors should:
- Perform SEND validation early and frequently throughout dataset development
- Ensure consistent alignment between SEND data and nonclinical study reports
- Follow the latest SEND Implementation Guides issued by CDISC
- Use standardized controlled terminology across all SEND domains
- Conduct internal quality checks to confirm data accuracy and compliance
- Collaborate with experienced SEND conversion experts for complex toxicology submissions
Proactive preparation of high-quality SEND datasets significantly reduces review cycles, minimizes regulatory risk, and supports efficient toxicology data evaluation.
Why Understanding the Regulatory Review Process Matters
Understanding how regulatory authorities conduct FDA SEND reviews enables organizations to optimize the preparation of SEND datasets and strengthen overall regulatory compliance. As CDISC SEND continues to evolve, this knowledge is critical for successful nonclinical submissions.
By aligning with regulatory expectations, organizations can:
- Improve the overall quality of SEND submissions
- Avoid costly review delays and resubmissions
- Reduce regulatory questions related to validation and data consistency
- Accelerate drug approvals by streamlining toxicology data review
- Strengthen long-term compliance strategies across nonclinical programs
SEND is no longer just a technical requirement it has become a core component of modern regulatory science, supporting efficient toxicology evaluation, drug safety, and regulatory decision-making.Learn more about common SEND submission challenges in our detailed article on SEND Submission Pitfalls During FDA Review.
Final Thoughts
Regulatory authorities rely heavily on SEND datasets to evaluate nonclinical safety and toxicology data efficiently and accurately during the FDA SEND review process. From rigorous validation checks and data quality assessments to advanced safety analyses, every aspect of a SEND submission is carefully examined to ensure regulatory compliance.
By understanding how regulatory agencies review CDISC SEND datasets and following best practices, pharmaceutical and biotech companies can submit high-quality, compliant SEND data that minimizes review delays, supports faster drug approvals, and ultimately contributes to the development of safer medicines.
FAQ’S
1. What does SEND stand for in regulatory submissions?
SEND stands for Standard for Exchange of Nonclinical Data, a CDISC standard used for submitting structured toxicology data to regulatory authorities like the FDA.
2. Who reviews SEND datasets?
FDA, PMDA, and other global regulatory authorities review SEND datasets to assess nonclinical study integrity, compliance, and drug safety.
3. Why is data validation important in SEND submissions?
Validation ensures SEND datasets meet technical and regulatory requirements, reducing errors and supporting compliance during the FDA SEND review.
4. What are common issues found in SEND submissions?
Frequent problems include missing domains, inconsistent variables, errors in controlled terminology, or mismatches with study reports, which may lead to review delays.
5. How do SEND datasets help toxicology evaluation?
Structured SEND data allows regulators to analyze dose–response trends, detect unexpected adverse effects, and perform comprehensive toxicology risk assessment.
6. What tools are used for SEND validation?
Automated tools like Pinnacle 21 are used to check dataset structure, controlled terminology, and adherence to CDISC SEND implementation guides.
7. How can sponsors ensure SEND compliance?
By following SEND implementation guides, performing internal validation, aligning data with study reports, and working with experienced SEND conversion experts.
8. How does SEND improve regulatory efficiency?
SEND enables faster FDA review, reduces queries, improves data quality, and helps companies maintain compliance while supporting safer drug development.