Developing and implementing VIrtual Control groups To reducE animal use in toxicology Research

Project Information

VICT3R

Grant agreement ID: 101172693

DOI

10.3030/101172693

EC signature date 26 July 2024

Start date 1 September 2024

End date 29 February 2028

Funded under

• Health

Total cost

€ 26 995 885,75

EU contribution

€ 13 524 750,00

Coordinated by

UNIVERSIDAD POMPEU FABRA
Spain

Periodic Reporting for period 1 - VICT3R (Developing and implementing VIrtual Control groups To reducE animal use in toxicology Research)

Reporting period: 2024-09-01 to 2025-08-31

Summary of the context and overall objectives of the project

VICT3R (Developing and implementing VIrtual Control groups To reducE animal use in toxicology Research) is a public-private partnership bringing together 37 organisations from 12 countries, including 23 industry leaders, eight SMEs, and six academic institutions.

Launched in September 2024 for 42 months, VICT3R is funded by the Innovative Health Initiative Joint Undertaking (IHI JU). The project develops, validates, and supports regulatory acceptance of Virtual Control Groups (VCGs), a data-driven approach to reducing animal use in toxicology research.

Building on work from the IMI2 eTRANSAFE project, VICT3R advances VCGs as a New Approach Methodology (NAM), improving their applicability, reliability, and integration into regulatory testing.

Traditional toxicology studies evaluate new drugs and chemicals using three treatment groups and one control group. Control animals receive no active substance and are essential for comparison but significantly increase total animal use. Sentinel animals, used to monitor study conditions, add further numbers.

VICT3R demonstrates VCGs as an alternative to traditional control groups. By leveraging large volumes of historical control data from industry partners, combined with advanced statistics and AI, the project aims to replace part or all control animals in a study, reducing animal use by up to 25% per study while maintaining scientific and regulatory standards. VCGs may also reduce the need for sentinel animals, further optimizing study design.

Beyond reduction, VCGs can improve study quality by:
• Increasing statistical power and reliability
• Providing control data where none traditionally exist
• Defining normal ranges for in-life measurements
• Detecting rare spontaneous histopathology findings

VCGs may also reduce costs by:
• Lowering animal purchase and maintenance expenses
• Eliminating costs linked to concurrent control groups
• Reducing energy and water use in animal facilities

Through this work, VICT3R generates scientific evidence to support regulatory adoption of VCGs, aligned with the 3Rs (Replacement, Reduction, Refinement) and contributing to more ethical, efficient, and cost-effective toxicology research.

More information: https://www.vict3r.eu/

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During its first year, VICT3R has made great progress in developing the technical and scientific infrastructure for VCGs.

A key achievement was the launch of the VICT3R database and data collection and curation workflows ensuring data quality. After year one, the database already contains over 100,000 control animal records in a standardised format (CDISC SEND) and incorporates data query, analysis and visualisation capabilities. A Computer System Validation (CSV) framework has also been established, that ensures all VICT3R developments and data adhere to regulatory standards.

Extensive exploratory data analyses have also been conducted to assess data gaps, variability across studies and to identify key covariates influencing toxicity outcomes. These activities have been key for laying the groundwork for VCG generation in the next phases of the project applying advanced statistical and AI approaches.

On the regulatory side, VICT3R has submitted a request for qualification to the European Medicines Agency (EMA) for the use of VCGs in dose-range finding studies. This represents one of the first formal regulatory evaluations of the VCG concept. While expecting feedback from this first qualification process, the project is preparing a similar submission to the U.S. Food and Drug Administration (FDA). Discussions have also been initiated with the Organisation for Economic Co-operation and Development (OECD) toward the creation of an OECD Guidance Document on the use of VCGs.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

VICT3R is advancing the scientific and regulatory use of Virtual Control Groups (VCGs), a new approach that replaces certain control animals in safety studies with data-based alternatives built from previous experiments. This helps reduce animal use while maintaining scientific reliability.

• Large, standardised control data resource: VICT3R has created one of the largest curated datasets of control animal data from repeated-dose toxicity studies, harmonised using international standards (SEND). This structured dataset enables reliable reuse of historical data for regulatory research. The database is accessible to project partners under data-sharing agreements and managed by UPF as honest broker.

• AI-supported generation of virtual controls: The project is developing advanced statistical and Artificial Intelligence (AI) methods to create virtual control animals and address missing data. These tools improve the robustness and flexibility of safety assessments while reducing the need for new control animals.

• Progress toward regulatory acceptance: VICT3R is engaged in an ongoing qualification process with the European Medicines Agency (EMA), marking an important step toward potential regulatory recognition of VCGs and supporting broader acceptance of innovative non-animal methods.

• Public tools and open science: The project promotes transparency through open-access publications and publicly available digital tools. One example is the ALURES NTS Experimental Methods Browser, an interactive online tool that allows users to explore how animal experiments are designed and conducted across Europe. It organises publicly available information into clear categories and visual displays, helping researchers, regulators, and the public identify trends, compare methods, and better understand experimental practices.
o Publications: https://www.vict3r.eu/publications/
o Public IT tools: https://www.vict3r.eu/public-it-tools/

VICT3R Process, Outcome & Impact

The VCG Concept

Data Flows and Operations

VCGs on a Global Scale

VCG Concept_Areas of Application