, Associate Director, Product Management, Digital Projects at Charles River.

Laura Lotfi

Pharma Fundamentals Episode One: Using Virtual Control Groups to Reduce Animal Testing in Drug Development

Pharma Fundamentals Episode One: Virtual Control Groups in Drug Development

, Associate Director, Product Management, Digital Projects at Charles River

Mouse. | Image Credit: ©BillionPhotos.com -stock.adobe.com

 (EMA) issued a draft qualification opinion

 for a preclinical research methodology to reduce the use of animals in specific dose-range finding studies.

 The new approach method (NAM) would replace standard animal control groups with virtual groups, and once qualified, would allow EMA to accept evidence generated from virtual control groups in medicine approval applications.

 to limit the use of animals in drug development. In April 2025, the agency published its Roadmap to Reducing Animal Testing in to modernize drug development through human-relevant science.

 The core of the initiative is the advancement of NAMs, which include advanced in vitro systems (such as organ-on-a-chip), computational modeling, and artificial intelligence (AI). 

, the FDA draft guidance to reduce or eliminate 6-month primate studies for monoclonal antibodies. The agency also qualified its first AI-based drug development tool, AIM-NASH, and updated guidance to support a transition away from horseshoe crab-derived testing, a move that could spare over one million animals annually.

 To provide regulatory certainty, the FDA launched a searchable database documenting exactly where alternative methods are currently acceptable. Furthermore, the agency has prioritized international alignment, collaborating with global regulators to ensure these new strategies are accepted worldwide.

Virtual control groups are a NAM that can be used to support initiatives to reduce the use of animals in drug development and regulation. According to EMA, characterized control data identify appropriate virtual comparator animals to create virtual control groups that are then used to conduct testing that would be traditional performed on animals.

Laura Lotfi, associate director, Product Management, Digital Projects at Charles River, says that in addition to replacing, reducing, and refining the use of animals, virtual control groups may reduce study timelines and bring more “statistical power”. However, there are limitations to their use, including the reliability of the data.

“The data are highly dependent on the quality, the completeness of the underlying infrastructure that may contain sometimes biases or gaps that can affect the reliability of those results.

They may also be less suitable for certain scenarios,” Lotfi explains. “For example, there are some studies that involve new biological mechanism or rare endpoints, maybe some species that are not very well understood, where the limited historical data are not, quietly there yet, so there is a lack of sufficient historical data that are available. In those cases, traditional approaches may still be necessary.”

In the video above, Lotfi provides an explanation of how virtual control groups are used in drug development, their limitations, and the cost associated with their implementation.

Draft qualification opinion for Virtual Control Groups (VCG) to replace Concurrent Control Groups (CCG) in rat non-GLP Dose-Range Finding (DRF) studies. EMA. March 31, 2026. Accessed April 1, 2026. 

https://www.ema.europa.eu/en/documents/other/draft-qualification-opinion-virtual-control-groups-vcg-replace-concurrent-control-groups-ccg-rat-non-glp-dose-range-finding-drf-studies_en.pdf

EMA consults on virtual control groups to help reduce animal use in medicines development. EMA. Press release. March 31, 2026. Accessed April 1, 2026. 

https://www.ema.europa.eu/en/news/ema-consults-virtual-control-groups-help-reduce-animal-use-medicines-development

FDA’s Roadmap to Reducing Animal Testing in Preclinical Safety Studies. 

https://www.fda.gov/media/186092/download?attachment

FDA Achieves Year 1 Goals in Reducing Animal Testing in Drug Development. Press release. April 20, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-achieves-year-1-goals-reducing-animal-testing-drug-development

Laura Lotfi, Associate Director, Product Management, Digital Projects at Charles River

Laura Lotfi, associate director, Product Management, Digital Projects at Charles River. Laura is a toxicologist that specializes in digital transformation within drug discovery and safety. She focuses on integrating advanced data platforms and innovative methodologies, such as virtual control groups.

Siegfried Schmitt, PhD, Vice President, Technical, Parexel

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of PharmTech’s Editorial Advisory Board.

Draft Qualification opinion for Virtual Control Groups 5 (VCG) to replace Concurrent Control Groups (CCG) in rat 6 non-GLP Dose-Range Finding (DRF) studies. 

New Approach Methodologies (NAMs). FDA.gov. Accessed April 27, 2026. 

https://www.fda.gov/science-research/science-and-research-special-topics/new-approach-methodologies-nams

CDER/Office of New Drugs Streamlined Nonclinical Studies and Acceptable New Approach Methodologies (NAMs). FDA.gov, Accessed April 27, 2026. 

https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/cderoffice-new-drugs-streamlined-nonclinical-studies-and-acceptable-new-approach-methodologies-nams

General Considerations for the Use of New Approach Methodologies in Drug Development Guidance for Industry, Draft Guidance

https://www.fda.gov/media/191589/download

Monoclonal Antibodies: Streamlined Nonclinical Safety Studies Guidance for Industry, Draft Guidance

https://www.fda.gov/media/189920/download

Guidance for Industry, Pyrogen and Endotoxins Testing: Questions and Answers (Edition 2)

S5(R3) Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals, Guidance for Industry

https://www.fda.gov/media/148475/download

Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations, Guidance for Industry

https://www.fda.gov/media/124829/download

S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies: Focus on Microsampling Questions and Answers, Guidance for Industry

https://www.fda.gov/media/100027/download

M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, Guidance for Industry

https://www.fda.gov/media/85885/download?attachment

FDA. Reducing Animal Testing in Nonclinical Studies Year One Progress and the Path Forward, April 2026. FDA.gov. Accessed April 27, 2026. 

https://www.fda.gov/media/191986/download?attachment

FDA’s Roadmap to Reducing Animal Testing in Preclinical Safety Studies


Innovative Science and Technology Approaches for New Drugs (ISTAND) Program


https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/innovative-science-and-technology-approaches-new-drugs-istand-program

Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER)


https://www.niehs.nih.gov/research/supported/translational/victer

Lotfi L, O'Neill TW, Wilcox A, Bulera S. Virtual control groups in nonclinical research: A Re-analysis of 20 studies using virtual control group data. 

https://doi.org/10.1016/j.yrtph.2026.106077

https://www.sciencedirect.com/science/article/pii/S0273230026000504?dgcid=author

Unlock Hidden Insights: Virtual Control Groups as a Data-Driven Novel Method. Webinar. 

https://www.criver.com/resources/webinar-pi-sa-unlock-hidden-insights-virtual-control-groups-data-driven-novel-method

 Z. What Lilly’s $2.75B bet on AI-discovered drug candidates means for drug development. 

https://www.pharmtech.com/view/what-lilly-s-2-75b-bet-on-ai-discovered-drug-candidates-means-for-drug-development

Thomas F. DCAT Week 2025: Quality and compliance for animal-derived products. 

https://www.pharmtech.com/view/dcat-week-2025-quality-and-compliance-for-animal-derived-products

Haigney S. USP permits use of non-animal-derived reagents for endotoxin testing. 

https://www.pharmtech.com/view/usp-permits-use-of-non-animal-derived-reagents-for-endotoxin-testing

Thomas F, Haigney S. Non-animal-derived reagents for endotoxin testing. 

https://www.pharmtech.com/view/non-animal-derived-reagents-for-endotoxin-testing

Haigney S. The impact of USP Chapter <86> on endotoxin testing. 

https://www.pharmtech.com/view/the-impact-of-usp-chapter-86-on-endotoxin-testing

Focusing on the Fundamentals of Formulation


https://www.pharmtech.com/view/focusing-on-the-fundamentals-of-formulation

https://www.pharmtech.com/view/ich-q6b-for-analytics

Design Quality in Pharmaceutical Design: A Primer for Facility Executives


https://www.pharmtech.com/view/design-quality-in-pharmaceutical-design-a-primer-for-facility-executives

 Pharma Fundamentals video series. Episodes in this educational series aim to provide knowledge in the basics needed for pharmaceutical development and manufacturing, such as chemistry and pharmacology, breaking things down to the basics to help those working in the industry to better perform their jobs. Be sure to check the episode webpage for more topic information and resources. We hope you enjoy the series.

Videos

Alternative methods to the use of animals in pharmaceutical testing are becoming more used and accepted. Laura Lotfi of Charles River breaks down the basics of virtual control groups in drug development.

Laura Lotfi

Articles