Best Practices in Modeling and Simulation Why do we need? Industry example

1. Best Practices inModeling and SimulationWhy do we need? Industry example Wonkyung Byon Pfizer Global Clinical Pharmacology

2. Best Practices in M&S Great idea! …….well, why do we need any guidance on Pop PK modeling??? Hi Won, we need to develop an internal pop PK guidance…. and you are the chair!

3. Best Practices in M&S Pharmacometrics/MBDD

4. Best Practices in M&S Pharmacometric analyses • Six-fold increase in the number of New Drug Applications that include pharmacometric analyses over a recent 9-year span (from 2000 through 2008) [Lee, J.Y. et al. Clin. Pharmacokinet. 2011] • Enhanced knowledge management and decision-making through model-based drug development [FDA Critical Path 2004]

5. Best Practices in M&S

6. Best Practices in M&S Objectives? Assumptions? Communications?

7. Best Practices in M&S Best Practices/Guidance… Why? Pharmacometrics = Evolving and interdisciplinary science Pharma industry = GLP,GCP,GMP

8. Best Practices in M&S Good “Modeling” Practice Benefit Risk “One size fits all.” Soon to be outdated • Increased consistency • High quality output • Greater efficiency • Training

9. Best Practices in M&S FDA/EMA Guidance For Industry • Population Pharmacokinetics • Guideline on reporting the results of Pop PK analyses • Exposure-Response Relationships • End-of-Phase 2A Meetings • Pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products

10. Best Practices in M&S Recent Publications • Fundamentals of population pharmacokinetic modelling: modelling and software/validation methods [Clin Pharmacokinet. 2012;51(8):515-25/51(9):573-90] • Basic Concepts in Population Modeling, Simulation, and Model-Based Drug Development—Part 1/ Part 2: Introduction to Pharmacokinetic Modeling Methods [CPT: PSP. (2012) 1, e6 / 2: e38] • White Paper: Landscape on Technical and Conceptual Requirements and Competence Framework in Drug/Disease Modeling and Simulation [CPT: PSP. (2013) 2: e40]

12. (iii) An update to the current regulatory guidance on dose ranging/finding (see also BOS2 paper) will be debated. (iv) M&S methodology and reporting standards and good practice documents are required (see also BOS4 paper). This will be an industry-led initiative in the first instance, though regulators wish to be involved early in the discussion with the ultimate objective to develop guidance documents.

14. Best Practices in M&S Acknowledgement Phylinda Chan Carol Cronenberger Haiqing Dai Jennifer Dong Steve Riley Ana Ruiz Mike K. Smith Kevin Sweeney Mike Tortorici Sandra Allerheiligen Kevin Dykstra Megan Gibbs Rik De Greef Pravin Jadhav Mats Karlsson Lan Ni Daniele Ouellet Vikram Sinha

15. Best Practices in M&S Best Practices Process-related Analysis plan/report/unblinding plan templates Technical PK/PD modeling Model-qualification Strategic Go/No-Go decision-making

16. Coming Soon!

17. Clin Pharm GuidancePopulation Pharmacokinetic Analyses AtoZof PopulationPK Analysis

18. ASSUMPTIONS Covariate selection Diagnostics Kowalski G K H R N I A E K G H R N I A E S S Prior knowledge

19. Assumptions/sensitivity analyses • Analysis plan and report • Leverage prior-knowledge • Clinical relevance • Communication

20. Challenges?

21. Opportunities! Internal “Wikipedia” page • Hub for collaboration • To facilitate discussions • To capture differing viewpoints • To assist in collaborative writing

22. “Why do you publish?” • It provides opportunities to learn and improve • “Living document”

23. Best Practices in M&S Good Modeling Practice Benefit Risk “One size fits all.” Soon to be outdated • Increased consistency • High quality output • Greater efficiency • Training

24. THANK YOU