Project Summary/ Abstract
In the field of biopharmaceutics, virtual bioequivalence (VBE) trial simulations have the potential to
increase the speed of drug development, lower its cost and reduce exposure of human volunteers
and patients to unneeded therapies. VBE is based on the proven ability of mechanistic
physiologically-based pharmacokinetic (PBPK) models to simulate realistic virtual cohorts of patients
which can replace full clinical trials. However, well-defined and verified workflows and examples of
VBE applications are not yet fully established. Having well-defined workflows in a seamless, user-
friendly, and widely accessible modeling platform tested with multiple case studies will ensure a
wider adoption VBE by industry and regulatory bodies. This project proposes to develop an
integrated VBE platform yielding optimal decisions for a matter directly related to the health and
safety of patients, and their optimal and cost-effective treatment. The capacity to integrate various
streams of data (in vitro information on drug and formulations, physiological knowledge of what
conditions the ability of a drug to reach its site of action, variability physiology and metabolism
across patients) is not just a software production exercise but requires deep knowledge of each area
and expertise in the field. This needs to be complemented by rigorous statistical analyses, as applied
to real clinical data, of the VBE simulations. Our overall objectives are to
• Develop a software platform allowing for flexible, fit-for-purpose, VBE workflows taking
advantage of existing tools and adding user-defined modules.
• Provide guidance on VBE workflow design (how to solve particular questions, pitfalls to avoid,
help with the design of supporting experiments and trials) for regulatory agencies/industries.
• Make maximum use of the capabilities of existing in vitro data analysis and modeling tools to
extract key parameters values relevant to formulation differences for selected routes of
administration (e.g., oral, intra-muscular injection).
• Conduct six in-depth VBE case studies, very close to real life cases, where individualized BE
clinical data are available to the team through literature reports or internal investigations;
Experimental in vitro data is already available or will be generated as required.
• Create automated default reporting templates that clearly document the workflow and its
results and are easily understood by non-users for assessment purpose (with flexibility to
modify default templates when needed).
Our specific aims are divided in workflow design, software implementation and case studies. We
anticipate that the proposed research will result in a wider patient centric application of population
PBPK models in generic drug development and regulatory reviews, but also for innovators’ drugs,
enhancing drug efficacy, availability and safety for all the world’s population.