Experiences and initiatives on pharmacokinetic modeling and simulation data analysis: Perspectives from the Brazilian Health Regulatory Agency (ANVISA)

• Published in: Regulatory toxicology and pharmacology 2024-12, Vol.154, p.105728, Article 105728
• Main Authors: Borges, Luiza Novaes, Fernandes, Eduardo Agostinho Freitas, Oliveira, Érico Miroro de, Pereira, Victor Gomes, Diniz, Andréa
• Format: Article
• Language: English
• Subjects: Biopharmaceutics; Biopharmaceutics - methods; Brazil; Clinically relevant dissolution specifications; Computer Simulation; Drug Development - legislation & jurisprudence; Drug Development - methods; Humans; MIDD; Modeling and simulation; Models, Biological; Patient-centric drug development; PBBM; Pharmaceutical Preparations; Pharmacokinetics; Pharmacometrics; Quality by design; Regulatory science
• ISSN: 0273-2300; 1096-0295; 1096-0295
• DOI: 10.1016/j.yrtph.2024.105728

The landscape of drug product development and regulatory sciences is evolving, driven by the increasing application of systems thinking and modeling and simulation (M&S) techniques, especially from a biopharmaceutics perspective. Patient-centric quality standards can be achieved within this context through the application of quality by design (QbD) principles and M&S, specifically by defining clinically relevant dissolution specifications (CRDS). To this end, it is essential to bridge in vitro results to drug product in vivo performance, emphasizing the need to explore the translational capacity of biopharmaceutics tools. Physiologically based M&S analyses offer a unique avenue for integrating the drug, drug product, and biological properties of a target organism to study their interactions on the pharmacokinetic response. Accordingly, Physiologically Based Biopharmaceutics Modeling (PBBM) has seen increasing use to support drug development and regulatory applications globally. In Brazil, a Model-Informed Drug Development (MIDD) policy and strategic project are not yet established, limiting applicability of M&S techniques. Drawing from the experience of the ANVISA-Academia PBBM Working Group (WG), this article assesses the opportunities and challenges for pharmacometrics (PMx) in Brazil and proposes strategies to advance the adoption of M&S analyses into regulatory decision-making. •Pharmacometrics significantly transform drug development and regulatory science.•Modeling and simulation analysis can be applied for biopharmaceutics purposes.•Brazilian Health Regulatory Agency landscape on modeling and simulation presented.•Strategic initiatives, collaborations and frameworks proposed for advancements.