This Cooperative Agreement award from the U.S. Food and Drug Administration (FDA) under the FDA Research program (CFDA 93.103) provides $249,485 to Simulations Plus Inc. to develop and validate a workflow for conducting virtual bioequivalence (VBE) studies using physiologically-based pharmacokinetic (PBPK) modeling. The project aims to enhance understanding of how food and gastric pH affect the in vitro drug release and in vivo performance of amorphous solid dispersion (ASD) drug products. The...
This $1.5 million cooperative agreement from the Department of Health and Human Services' Food and Drug Administration (FDA) Research program (CFDA 93.103) supports the development and validation of a best practices framework for physiologically-based pharmacokinetic (PBPK) analysis to support model-informed biowaivers of fed bioequivalence studies for Biopharmaceutics Classification System Class II drugs. The University of Florida is the primary awardee. Under the award, the University of...
This Cooperative Agreement award from the Food and Drug Administration (FDA) under the FDA Research program (CFDA 93.103) provides $598,728 to the University of Texas at Austin to develop physiologically-based pharmacokinetic (PBPK) models and in vitro-in vivo correlations (IVIVC) for long-acting injectable drug products, specifically a PLGA-based buprenorphine implant. The key products and services to be delivered include: Developing a bio-predictive in-vitro release testing method to determine...
This $150,000 Project Grant award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) under the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286) will support the development of a personalized therapeutic drug monitoring (PTDM) system. The objective is to create a smart, home-use system that can provide frequent, noninvasive measurements of drug levels in a patient's saliva and deliver real-time data on circulating...
This Project Grant award from the National Institute of General Medical Sciences (NIGMS) under CFDA 93.859 Biomedical Research and Research Training program provides $1,207,500.00 in funding to the University of Connecticut over a 5-year period from August 1, 2024 to May 31, 2029. The project aims to advance mechanistic understanding and modeling of two key processes that influence oral drug absorption - the "particle drifting effect" and "de-supersaturation kinetics." The...
This $952,867 Project Grant awarded by the National Science Foundation (NSF) Division of Mathematical Sciences under the Mathematical and Physical Sciences (CFDA 47.049) program aims to develop a digital twin framework for virtual clinical trials. The University of Texas at Austin will lead this 3-year project to create computational models and virtual patient populations to enable high-throughput screening of novel therapeutic interventions, especially for cancer treatment. The key objectives...
This federal Project Grant award of $342,776 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), under the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286), aims to develop foundational data science methods and a pipeline for efficient and exceptional monoclonal antibody (mAb) formulation. The key objectives of this 4-year project are to: 1) prototype experimental and data handling methodologies, 2) perform a...
This Project Grant award from the National Institutes of Health (NIH) Research Infrastructure Programs (CFDA 93.351) provides $270,428 to TEO Therapeutics Incorporated, a small disadvantaged business, to develop a biomimetic platform for more efficient pharmaceutical drug development in oncology. The key products and services to be delivered include: Refining and testing a proof-of-concept hardware product line for a Shell-Free Quail Xenograft Assay, optimizing throughput and assessing...
This Cooperative Agreement award from the Food and Drug Administration (FDA) under CFDA 93.103 - Food and Drug Administration Research provides $298,422 in funding to Brigham & Women's Hospital Inc. for the period of September 1, 2024 to August 31, 2027. The project aims to develop a semi-automated surveillance system using tree-based scan statistics to evaluate the safety and effectiveness of generic drug-device combinations compared to brand-name reference products. The research will...
This Project Grant award from the National Institute of Child Health and Human Development (NICHD), under the Child Health and Human Development Extramural Research program (CFDA 93.865), will leverage artificial intelligence methods and electronic health records to conduct pharmacoepidemiologic studies on adverse pediatric outcomes associated with maternal substance use during pregnancy and pediatric drug exposures. The goal is to develop a stakeholder-informed real-time pediatric...
A STATE-OF-THE-ART VIRTUAL BIOEQUIVALENCE PLATFORM AND CASE STUDIES ON COMPLEX FORMULATIONS, SYSTEMIC AND LOCAL CONCENTRATION-BASED BIOEQUIVALENCE - 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.