AAPS 2023 PHARMSCI 360

The BEST resource documentation defines seven categories of biomarkers and identifying predictive biomarker to improve drug development performance and/or clinical outcome while is highly desirable it can be very challenging. Modelling and simulation tools such as Physiologically Based Pharmacokinetic (PBPK) and Quantitative Systems Pharmacology (QSP) models can be used to identify and assess predictive biomarkers for small molecules and for new modalities. The physiological nature of these models helps to integrate various processes related to biomarkers including their synthesis in plasma and other organs and their elimination as well as their interactions with other processes affecting drug disposition, effect, or side-effect. They can also help to identify current gaps in our knowledge regards specific biomarker. Specifically, PBPK models can be used to assess the performance of biomarkers especially for understanding metabolism- and transporter-mediated interactions. In this presentation a PBPK based framework for modelling endogenous biomarkers and few case studies are presented for small molecules. For the new modalities the four topics of the session presentations are introduced.

5 years in the making, our ‘Gold Standard’ PBPK Technologies empower experts in biopharmaceutics, formulation, and CMC. Experience higher success rates, navigate regulatory challenges, and innovate fearlessly. Stop by our booth to see a live demo of our new product in action and learn how to elevate your drug formulations!

Hungry for knowledge? Satisfy your appetite for insights at our Phoenix Lunch & Learn! Join us for an enlightening presentation where we’ll dive into how Phoenix is transforming the world of PK data analysis.

5 years in the making, our ‘Gold Standard’ PBPK Technologies empower experts in biopharmaceutics, formulation, and CMC. Experience higher success rates, navigate regulatory challenges, and innovate fearlessly. Stop by our booth to see a live demo of our new product in action and learn how to elevate your drug formulations!

This presentation provides an in-depth overview of involved processes and how PBPK models are applied to predict oligonucleotide PK.

5 years in the making, our ‘Gold Standard’ PBPK Technologies empower experts in biopharmaceutics, formulation, and CMC. Experience higher success rates, navigate regulatory challenges, and innovate fearlessly. Stop by our booth to see a live demo of our new product in action and learn how to elevate your drug formulations!

Since the adoption of ICHQ3 under Step 3 in March 1995, the expectation for qualification studies to support specification limits has consisted of genotoxicity studies of 14 to 90 days duration, as well as an assessment of other specific toxicity endpoints as appropriate. Since that time, hundreds if not thousands of studies, with thousands if not tens of thousands of animals have been conducted. Such studies rarely demonstrate a change in the toxicologic profile of the active pharmaceutical ingredient (API) that would represent a clinical risk. Rising costs, limited availability of some animal species, the emphasis on the 3R’s (reduce, refine, replace) in animal testing, advances in in silico and in vitro technologies, improved understanding of mechanisms of biologic activity, and the need for timely qualification data indicate that it is time to consider alternative approaches to standard studies to qualify impurities/degradation products. This session will present possible alternatives, a case study, and possible next steps to influence regulators to consider alternatives to the standard ICHQ3 qualification studies to support impurity specification limits.

5 years in the making, our ‘Gold Standard’ PBPK Technologies empower experts in biopharmaceutics, formulation, and CMC. Experience higher success rates, navigate regulatory challenges, and innovate fearlessly. Stop by our booth to see a live demo of our new product in action and learn how to elevate your drug formulations!

Physiologically based pharmacokinetic (PBPK) modelling is recognised by the U.S. FDA as an alternative approach to clinical trials for the evaluation of pH-dependent drug-drug interactions (DDIs). To date, such DDIs have predominantly been assessed empirically by setting the stomach pH to match the worst-case scenario. We present here a mechanistic modelling approach encompassing a dynamic gastric acid secretion model, upon which PBPK-pharmacodynamic (PD) gastric pH effect models for proton pump inhibitors and H2-receptor antagonists were developed and verified. Performance verification cases show the ability of the models to successfully capture DDIs mediated by gastric pH. Mechanistic modelling should improve the qualitative and quantitative predictions of pH-dependent DDIs. It is a useful in silico tool to assess the efficacy of DDI mitigation strategies such as dose staggering or formulation changes.

5 years in the making, our ‘Gold Standard’ PBPK Technologies empower experts in biopharmaceutics, formulation, and CMC. Experience higher success rates, navigate regulatory challenges, and innovate fearlessly. Stop by our booth to see a live demo of our new product in action and learn how to elevate your drug formulations!