Simulations Plus, Inc. (“Simulations Plus” or the “Company”), a global leader in model-informed and AI-accelerated drug development that advances biopharma innovation, responded to the U.S. Food and Drug Administration’s draft guidance on streamlined nonclinical safety studies for monospecific monoclonal antibodies. The guidance encourages reduced reliance on animal studies and elevates mechanistic understanding, pharmacokinetics, and integrated weight-of-evidence (WoE) assessments for nonclinical decision-making.
“The FDA’s draft guidance signals a clear regulatory mandate towards mechanistic, model-informed science, and Simulations Plus is uniquely positioned to help clients respond with confidence,” said Shawn O’Connor, Chief Executive Officer of Simulations Plus. “Our scientific engines, workflows, and cross-disciplinary capabilities have supported these integrated approaches for years.”
Mechanistic WoE Approaches Already Embedded in Simulations Plus’ Practice
Simulations Plus enables clients to integrate physiologically based pharmacokinetics (PBPK), quantitative systems toxicology/pharmacology (QST/QSP), clinical pharmacokinetics (PK), and mechanistic insights to support WoE assessments aligned with FDA-recommended approaches. This includes PBPK modeling in GastroPlus® to project human exposure and guide dose selection, mechanistic toxicity assessment in BIOLOGXsym™, and population modeling in MonolixSuite® to connect preclinical and clinical understanding.
Case studies published in the International Journal of Molecular Sciences , Pharmaceutics , and elsewhere show how combining PBPK and QST can strengthen the scientific rationale for streamlined nonclinical strategies for monospecific antibodies, including determining when extended non-human primate toxicology studies may not be warranted.
Ecosystem-Level Alignment with the New Regulatory Paradigm
The Simulations Plus ecosystem aligns with the FDA’s focus on mechanistic, model-informed evidence. Its validated scientific engines—including GastroPlus, MonolixSuite, ADMET Predictor®, and QSP platforms—provide the transparency, traceability and cross-domain mechanistic reasoning regulators expect. Supporting this scientific core is an AI-orchestrated framework that enables reproducible multi-engine workflows and guided decision support through AI copilots, all grounded in validated methods.
Continued investment in biologics modeling, including planned enhancements to GastroPlus and BIOLOGXsym, will expand support for monoclonal antibodies, antibody-drug conjugates, and immune-related pathways highlighted in recent FDA guidances.
“The draft guidance gives the industry a clear direction, and as model-informed safety and toxicology become essential disciplines, a new growth frontier opens for Simulations Plus in areas of our customer organization which have historically been underpenetrated,” said O’Connor. “Our mission is to help innovators navigate this transition with clarity, rigor, and confidence.”
