In drug development, the Food and Drug Administration (FDA) issued final guidance on reproductive and developmental toxicity. DART studies are critical for many potential new drugs.
Standardizing this study data is a priority for the FDA. Standardization helps the agency process and analyze submissions more effectively. The FDA’s DART Fit for Use pilot provided a first test of the new standards.
Learn more about the expansion of SEND to include DART studies and what the Fit for Use pilot revealed.
The FDA is gradually implementing data standardization for study submissions. The Standard for Exchange of Nonclinical Data (SEND) is the standard for collecting and formatting nonclinical data. The Clinical Data Interchange Standards Consortium (CDISC) developed and maintains SEND.
The scope of SEND is expanding. SEND-DART extends SEND into reproductive toxicology.
Development and reproductive toxicity (DART) studies evaluate the potential effects of pharmaceuticals on the complete human reproductive cycle. Studies look at reproductive phases, including:
• Pregnancy and fetal development
Studies can include the effects of a proposed drug on the pediatric population.
DART studies usually run in parallel to clinical trials. They often start in Phase 1 and end before the conclusion of Phase 3 trials.
DART studies include the entire reproductive cycle, but SENDIG-DART v1.1 does not. The standard currently only covers embryo-fetal developmental toxicity studies. It will eventually include a wider range of DART studies.
Support for SENDIG-DART v1.1 began on March 15, 2021. It will become a requirement for certain study submissions on March 15, 2023. The first studies to fall under SEND-DART are:
• New drug applications (NDAs)
• Abbreviated new drug applications (ANDAs)
• Some biologics license applications (BLAs)
Some investigational new drug applications (INDs) will need to comply with SEND-DART by March 15, 2024.
In preparation for SENDIG-DART coming into effect, the FDA announced a Fit for Use pilot in 2021. The pilot allowed the FDA Center for Drug Evaluation and Research (CDER) to test the processing and analysis of data in SEND-DART format.
The agency wanted to ensure that the standard was ready for implementation. The FDA also used the pilot to discover improvements to the process. The FDA would share the insights gained from the pilot with the public.
Individual firms that wanted to participate in the FDA’s DART Fit for Use pilot submitted requests for consideration. CDER prioritized applicants whose packages contained embryo-fetal development toxicity studies with data that complied with SENDIG-DART v1.1.
Each applicant submitted a nonclinical study package that included:
• SEND-DART v1.1 datasets
• Final related study report with tables for individual animal data and summaries
• Nonclinical Study Data Reviewers Guide
• Define.xml file
• Sample standardization study protocol
Participants could choose whether to share anonymized data with the CDISC pilot team. They could also redact sensitive information.
CDER chose six participants for the SEND-DART pilot. FDA reviewers examined each participant’s study package and provided feedback.
Participants then had several months to prepare and compile their anonymized and/or redacted submissions. They submitted these revised packages to the pilot assessment team.
An FDA Fit for Use pilot has two main goals. First, it seeks to ensure that a process meets the needs of the FDA for effectively reviewing new drug and product applications. If the pilot reveals issues with the process, the FDA can make appropriate adjustments.
The second main goal of an FDA Fit for Use pilot is that the public can benefit from the participants’ experiences. It helps other stakeholders in the drug development process comply with FDA rules.
The CDISC published the insights gained from the participants in the SEND-DART pilot on their wiki. The information includes:
• FDA comments on each submission package.
• Responses to the participant questionnaire with feedback and takeaways
• Summarized learnings
The results highlight the complexity of complying with SENDIG-DART. They offer suggestions for how other organizations can implement it more successfully.
One example of an issue that emerged from the FDA DART pilot concerns reporting the timing of study results. Repro phase timing variables are an addition to existing SENDIG v3.1 domains. Representing the timing of results is significantly different for a DART study compared to general toxicology.
In a general toxicology study, the study day and the dose day are usually the same. However, a DART study has three independent variables:
• Dose day
• Study day
• Gestation day
The gestation day takes precedence for reporting and analysis.
This distinction is explained by SENDIG-DART.Several study packages in the pilot didn’t follow the guidelines, though. This situation highlights the complexity of fully complying with SEND-DART rules.
SENDIG-DART combines all of SENDIG’s requirements with the additional demands of DART data collection and reporting. A very high level of detail is required.
Organizations may need additional staff. Staff will need in-depth training.
For many organizations, SEND intelligence services offer an effective solution. SEND intelligence services can produce SENDIG-DART datasets without needing to invest in new personnel, training, or infrastructure. The platform can accurately package nonclinical study data into compliant datasets for FDA submission.
Xybion offers a complete SEND service. It delivers the complete SEND dataset, define.xml file, and study reviewer data guide.
Xybion’s proprietary Savante software will incorporate study data from different sources. This includes manual collection or third-party systems.
The platform can output to DART v1.1 as well as SENDIG v3.0 or 3.1. The final SEND datasets are in .xpt for regulatory submission.
Xybion can convert and verify datasets faster and more accurately than other vendors. Savante allows for the automation of many workflow processes. This provides high-quality and cost-effective results ahead of expected deadlines.
Compliance with FDA DART will soon be a requirement for many FDA submissions. The FDA’s DART Fit for Use pilot provided important insights into the compliance process.
Following the guidelines can be complicated. Xybion’s SEND intelligence services can help streamline your data submission. Our SEND solutions give you a rich toolset, SEND subject matter experts, and machine learning technology.
Our structured line of services and solutions can meet your needs across the SEND spectrum. Talk to our SEND Experts today to best prepare for the FDA DART compliance.