If you are in drug development, there is one question regulators will almost certainly ask: How does your compound interact with other drugs?
Drug-Drug Interaction (DDI) assessment is the dominant application of PBPK modeling in regulatory submissions, accounting for 74.2% of all PBPK-supported FDA submissions between 2019 and 2023 (Guo et al., 2024).
Three out of every four PBPK regulatory submissions are related to DDI liability.
Are you covered?
What are DDI liabilities, and how can PBPK modeling help?
When patients take multiple drugs simultaneously, one compound can alter the pharmacokinetics of another by inhibiting or inducing metabolizing enzymes (e.g., CYP3A4) or transporters (e.g., P-gp), leading to elevated systemic exposures, reduced efficacy, and serious safety signals. PBPK-based DDI simulations integrate in vitro data with human physiology to predict these interactions mechanistically, often replacing the need for dedicated clinical studies entirely.
The cost of getting DDI wrong
Unaddressed DDI liabilities translate directly into program setbacks: avoidable clinical DDI studies, delayed IND/CTA submissions, poor dose selection, suboptimal candidate selection, and inefficient trial design, all costly and preventable.
What ESQlabs brings to the table
We specialize in PBPK DDI simulations that de-risk development programs and accelerate regulatory success:
- Prospective DDI liability assessment before IND submission
- Simulation-based justification to minimize additional clinical studies
- Dose adaptation strategies for polypharmacy scenarios
- DDI exploration in special populations (pediatric, hepatic impaired)
- Mechanistic modeling to inform trial design and regulatory discussions
Why partner with us?
Open-Source Software: We work exclusively with the OSP Suite (PK-Sim® and MoBi®). All models are delivered with full, licence-free access, full source code visibility, and no black boxes. Our team actively contributes to OSP Suite development, and our platform maintains a growing library of fully validated compounds updated automatically with each new PK-Sim release.
Expert Insight: "Start your mechanistic DDI assessment as early as possible, ideally as soon as your first in vitro metabolism, transporter, and inhibition data become available. Even with early datasets, you can estimate potential liabilities in the context of projected human exposure. That said, DDI assessments remain valuable at every stage, including post-marketing. PK-Sim's open-source compound library, automated qualification workflows, and fully controlled GitHub versioning make it not just a tool, but a living, community-driven ecosystem for high-quality mechanistic modeling." — Ingrid Michon, Principal Scientist, ESQlabs
A Living Ecosystem: A DDI model built at IND stage can be refined and reused through Phase 2, NDA/MAA, and beyond, growing in value at every stage.
Proven Regulatory Expertise: Our scientists are fluent in the FDA, EMA, and ICH regulatory frameworks. We have provided PBPK training to FDA scientists and actively contribute to open-source modeling standards.
Ready to address your DDI questions? Contact us at info@esqlabs.com or visit our service page
References
- Guo Y et al. (2024). Trends in PBPK modeling submissions to the FDA: A review of applications and regulatory impact. Regulatory Toxicology and Pharmacology.
- ICH M12 Guideline on Drug Interaction Studies. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. May 2024.
