Nanopharm and FLUIDDA’s SmartTrack™ is an integrated, model-informed evidence platform designed to demonstrate bioequivalence for orally inhaled drug products. By combining clinically relevant in vitro testing, patient-derived breath and lung data, with advanced in silico modeling, SmartTrack™ builds a data-driven comprehensive understanding of how an inhaled drug performs all the way from device actuation to regional delivery in the lungs. SmartTrack™ is an integrated alternative bioequivalence platform for the development of inhaled drug products that brings numerous benefits:
Shorter inhaled drug development times
Reduced reliance on comparative clinical endpoint (CCEP) studies for reduced clinical risk
Stronger regulatory submissions that align with evolving expectations of regulators
Faster time to market
SmartTrack™ incorporates real patient inhalation data captured in a clinical setting, which is initially either simulated in the lab during realistic in vitro testing or used to justify use of other relevant profiles. The real patient data is later used again to ensure that the in silico model accounts for the range of patient variability. The use of real patient data in the models ensures that they are grounded in clinically relevant conditions and are representative of real-world product use in a realistic patient population.
Developing realistic Aerodynamic Particle Size Distribution (APSD) methods is much more complex than traditional QC tests. Finding the optimal balance between the choice of breathing profile, throat selection and actuation parameters to deliver the target impactor-sized mass (ISM) and still achieving mass balance in one method for multiple test configurations is challenging and could take numerous iterations. Computational Fluid Dynamic (CFD) modeling of the in vitro set up can simulate which parameters are most sensitive in terms both of inputs and outputs, to minimize time to develop the method and increase chances of success downstream.
Using advanced in vitro techniques, SmartTrack™ characterizes inhaled drug products and the properties of its aerosolized form. This is accomplished through the conduct of highly specialized testing.
SmartTrack™, in partnership with FLUIDDA, applies computational fluid dynamics (CFD) that resolve airflow and aerosol transport within realistic geometries based on boundary conditions set through high-resolution CT scans of patient lungs generated from real patients. CFD is the optimal choice for conducting a highly granular analysis of intra-patient variability, exploring variables such as the coordination of actuation, or understanding the driving mechanics behind performance.
SmartTrack™ is also useful for a population level evaluation of patient-to-patient variability in lung geometries or inhalation capacities. Rapid Deposition Analysis (RDA) can be applied to simulate drug deposition in hundreds of patients, which would be representative of a clinical trial. At Nanopharm and FLUIDDA, RDA is derived from thousands of CFD simulations offering extremely rapid predictive power through simulations based on real patient data.
Regional deposition data and, where relevant, dissolution and other in vitro data, is then applied to Nanopharm and FLUIDDA’s proprietary Simhalation™ platform, which provides systemic and local exposure predictions via physiologically based pharmacokinetic (PBPK) simulations. Simhalation™’s PBPK model represents the entire human body and considers the impact of mass transport and tissues in relevant systems, refined for each drug under evaluation. The Simhalation™ platform allows for the flexible subdivision of both central and peripheral lung compartments so that the PBPK model can differentiate meaningful differences between local lung bioavailability, relative to other observed differences.
Nanopharm and FLUIDDA’s SmartTrack™ platform produces data-driven outputs that are compiled into a submission ready format that includes a range of data and modelling results. This alternative bioequivalence platform can generate:
SmartTrack™ uniquely combines this range of in vitro models and in silico simulations to provide a fully integrated framework that links patient use, drug product performance, lung deposition, absorption and exposure into a single, detailed understanding of inhaled drug delivery and that supportsing alternative bioequivalence studies with a reduced reliance on clinical endpoint studies.
