Simulations Plus, Inc. · NASDAQ:SLP
Simulations Plus — Technical Presentation (2017)
14 slides from Simulations Plus's technical presentation, 2017
Slide 1: Applying PBPK modeling & simulation to assist with pharmaceutical research and regulatory submissions
Applying physiologically-based pharmacokinetic (PBPK) modeling & simulation to assist with pharmaceutical research and regulatory submissions Denise Morris , PhD. Assistant Director, Clinical Pharmacology Denise.Morris@cognigencorp.com 1
Slide 2: Outline
Outline • GastroPlus™ PBPK models – the big picture • PBPK M&S applications at the FDA • Future directions 2
Slide 3: Mechanistic Absorption Modeling (MAM) / PBPK
Mechanistic Absorption Modeling (MAM) 3 Physiologically based Pharmacokinetics (PBPK)
Slide 4: The Big Picture – Drug Inputs
The Big Picture – Drug Inputs Structure in vitro IV/Oral PK in vitro Structure in silico experiments data metabolism in silico Formulation: dose, dosage form, Physical properties - particle size, PKPlus- Vd, CL, K12, Peff, Sw, pKa, logP, release profile K21, K13, K31 fup, Rbp PBPKPlus - CLint
Slide 5: Recent PBPK Modeling Trends: Regulatory Information
Recent PBPK Modeling Trends: Regulatory Information 5 Cole et al., 2016 JPAG Meeting Parrott et al., 2015 AAPS Annual Meeting
Slide 6: PBPK Modeling: Encouragement from Regulatory Agencies
PBPK Modeling: Encouragement from Regulatory Agencies • Both FDA and MHRA/EMA hosted PBPK workshops in 2014 – Additional workshops in 2016 • Discussed areas where PBPK modeling is helpful: – Dose selection & First-in-Human (FIH) predictions – Drug-drug interactions (DDIs) – Pediatric & special popul
Slide 7: FDA Office of Generic Drugs: Publications
FDA Office of Generic Drugs: Publications Using M&S to predict virtual BE and assess Incorporating M&S to assist with dissolution specifications Quality by Design (QbD) (Babiskin et al., 2015) (Zhang et al., 2011) Role of M&S in drug development and Generating mechanistic IVIVCs regulatory evaluatio
Slide 8: Collaboration Agreement with FDA (2014-19)
Collaboration Agreement with FDA (2014-19) • 5-year collaborative project with the FDA Office of Testing and Research on the utility of GastroPlus Mechanistic Absorption Modeling (MAM) and IVIVCs to predict complex absorption characteristics – Goal is to facilitate drug product development by decrea
Slide 9: Advancing the Science – Together
Advancing the Science – Together • Open communication between regulatory agencies, pharmaceutical companies, universities, and software providers will help identify new M&S applications: – Food effect modeling – Disease state populations – Oral/non-oral delivery of drug products – virtual BE • FDA i
Slide 10: Questions for Discussion
QUESTIONS FOR DISCUSSION
Slide 11: Action BG2, Day 2, Q6
Action BG2, Day 2, Q6 • What parameter fitting (and what deviation from experimental data) is acceptable? E.g. if in vivo solubility is optimized, what deviation from experimental solubility is acceptable? Same about permeability? How to know whether the optimized parameters are haphazardly adjusted
Slide 12: Action BG2, Day 2, Q7
Action BG2, Day 2, Q7 • For biowaiver/IVIVC applications, should the criteria outlined in the IVIVC guidance be used for model qualification?
Slide 13: Action BG2, Day 2, Q8
Action BG2, Day 2, Q8 • In analogy to IVIVC principles, should model build up be done on an individual or average basis? Given that individual physiology information is almost never not available (although one could generate individual virtual populations), is average acceptable?
Slide 14: Action BG2, Day 2, Q9
Action BG2, Day 2, Q9 • Dissolution is a key input in models especially for QbD/biowaiver type of applications – what are acceptable ways to link in vitro and in vivo dissolution for the model setup (mechanistic approach vs. empirical IVIVC?)