The pharmaceutical industry is constantly looking for ways to streamline drug development while maintaining rigorous safety and regulatory standards. One of the most significant advancements in this effort is the International Council for Harmonisation (ICH) S1B(R1) Addendum, which introduces a Weight of Evidence (WoE) approach for assessing carcinogenic potential. This framework allows sponsors to bypass costly, time-consuming two-year carcinogenicity studies if sufficient alternative data are available1.
However, gathering and organizing this supporting data remains a significant challenge for sponsors. Many organizations may not realize that they may already have a structured, regulator-friendly dataset that can be leveraged for WoE submissions: Standard for Exchange of Nonclinical Data (SEND) datasets2. By reusing existing SEND data, sponsors can accelerate data-gathering processes, reduce costs, and make more informed decisions – maximizing the value of prior studies while minimizing redundant subject testing.
In this article, we explore how SEND data can be used in data gathering for WoE submissions and the key time and cost benefits for sponsors looking to streamline their submissions.
The ICH S1B (R1) Addendum and the Role of SEND Data
Traditionally, assessing carcinogenicity has required two-year in-subject studies, which are expensive – costing almost $4 million per study3 – and take three to five years when planning, execution, and analysis are all taken into account, thereby having the potential to lengthen drug development timelines.
The ICH S1B(R1) Addendum provides an alternative pathway: a WoE approach that integrates multiple nonclinical data sources to determine a drug’s carcinogenic potential1. This means that data collected from any previously conducted study can be of value in determining carcinogenic potential. If the WoE assessment suggests that a compound is unlikely or likely to be carcinogenic, a two-year study may be avoided, reducing costs and potentially speeding up development.
The Challenge?
Gathering and presenting relevant data from fragmented sources across multiple studies is complex and time-consuming, representing a significant hurdle to the WoE approach for many sponsors. This is where SEND data makes a difference.
SEND provides a structured, standardized format for nonclinical study data, allowing sponsors to quickly retrieve, analyze, and integrate findings into regulatory submissions4. By reusing SEND data, organizations can dramatically reduce the time and resource burdens of WoE assessments while ensuring compliance with regulatory requirements. While SEND is not required to be used in the WoE, organizations can utilize existing SEND datasets to easily search and identify studies and findings that will contribute to the WoE dossier.
Key Benefits of Reusing SEND Data for WoE Submissions
1. Significant Cost Savings
ICH S1B(R1) identifies six key factors that should be included in the WoE to assess the carcinogenic potential of a drug1. SEND data can be leveraged for four of these factors, providing huge advantages for users.
Each two-year carcinogenicity study costs between $2-4 million, with the ICH quoting $3.75 million per study in their 2012 business plan3. By taking the WoE approach, sponsors can avoid redundant studies, reducing costs while maximizing the value of prior nonclinical research.
Since SEND is already required by the FDA for nonclinical submissions, most organizations already have these datasets available. Instead of spending additional resources on data collection and formatting, sponsors can reuse SEND data to efficiently identify data to be included in WoE assessments, saving even more resources and, consequently, costs.
2. Faster Submission Timelines
Planning and conducting a two-year subject study followed by processing and analyzing data can take up to five years, which has the potential to significantly impact turnaround times. By using WoE assessments informed by SEND, sponsors can complete submissions faster, reducing regulatory delays and bringing life-changing therapies to market, potentially years sooner.
Because SEND data is already structured in a machine-readable format for regulatory use, it enables automated data retrieval and cross-study comparisons5, which can then be included in the WoE in a human-readable format.
3. Improved Regulatory Compliance
SEND datasets are structured with controlled terminology, ensuring clarity, consistency, and transparency in regulatory submissions. SEND datasets undergo strict quality control, minimizing the risk of errors and compliance issues5.
Consequently, regulatory reviewers benefit from structured, easily interpretable datasets, increasing the likelihood of a smoother review process and faster approvals.
4. Reduction in Subject Use
Traditional carcinogenicity studies require hundreds of subjects per study. The WoE approach supports the 3Rs principles (Replacement, Reduction, and Refinement6) by reducing unnecessary subject testing when sufficient data is already available.
By leveraging SEND data, sponsors can use previously collected nonclinical study results to support data gathering for WoE assessments, avoiding unnecessary duplication of studies while still meeting regulatory requirements.
Seamless Integration of SEND Data into WoE Assessments
Effectively leveraging SEND data for WoE requires expertise in data extraction, structuring, and regulatory alignment. Many sponsors face challenges in navigating SEND datasets or lack the tools to efficiently utilize them.
This is where using a third-party provider, like Instem, can be hugely advantageous:
- SEND conversion and data structuring services ensure nonclinical study data is formatted in a submission-ready, machine-readable structure.
- The Advance™ carcinogenicity risk assessment service applies WoE techniques to evaluate carcinogenic potential using both SEND and non-SEND data.
- Instem’s Centrus platform enables automated data retrieval and visualization for rapid cross-study comparisons to maximize the value of SEND datasets.
With advanced tools and regulatory expertise, Instem helps sponsors maximize SEND data, reducing the regulatory burden, cutting costs, and accelerating submission timelines.
Conclusion
The ICH S1B Addendum offers pharmaceutical companies an opportunity to:
- avoid unnecessary $2-4M carcinogenicity studies,
- potentially reduce submission timelines,
- ensure regulatory compliance with structured datasets, and
- minimize subject testing in alignment with the 3Rs.
By reusing SEND data, sponsors can efficiently gather and present WoE evidence, ensuring faster, more cost-effective regulatory submissions.
Want to learn more? Download the full whitepaper for specific insights into exactly how SEND data can be leveraged for WoE submissions.
References
1. ICH Guideline. TESTING FOR CARCINOGENICITY OF PHARMACEUTICALS S1B(R1). Published online August 4, 2022. https://database.ich.org/sites/default/files/S1B-R1_FinalGuideline_2022_0719.pdf
2. SEND | CDISC. March 30, 2021. Accessed February 11, 2025. https://www.cdisc.org/standards/foundational/send
3. ICH. Business Plan: S1: Rodent Carcinogenicity Studies for Human Pharmaceuticals. Published online November 14, 2012. Accessed February 24, 2025. https://database.ich.org/sites/default/files/S1%28R1%29%20Business%20Plan.pdf#:~:text=Conducting%20unnecessary%202%2Dyear%20rat%20testing:%20(1)%20uses,of%20each%20unnecessary%202%2Dyear%20rat%20carcinogenicity%20study
4. Briggs K. Making sense of SEND; the Standard for Exchange of Nonclinical Data. Regul Toxicol Pharmacol. 2017;91:77-85. doi:10.1016/j.yrtph.2017.10.012
5. Choudhary S, Walker A, Funk K, Keenan C, Khan I, Maratea K. The Standard for the Exchange of Nonclinical Data (SEND): Challenges and Promises. Toxicol Pathol. 2018;46(8):1006-1012. doi:10.1177/0192623318805743
6. The 3Rs | NC3Rs. Accessed May 1, 2024. https://www.nc3rs.org.uk/who-we-are/3rs
