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An Open Systems Pharmacology Workshop

Monday, June 5^th, Budapest, Hungary
PAGE 2017 Satellite Workshop

In this one-day workshop, we will teach and demonstrate how to build fully integrated systems pharmacology models using the Open Systems Pharmacology Suite with PK-Sim^® and MoBi^®. Attendees will learn how to easily deal with challenging modeling tasks in pharmacokinetics and pharmacodynamics, exemplified by several real-life use cases. Each of these use cases will be introduced with a background lecture on the questions to be answered and the biology to be represented, reflecting its special characteristics and the consequences for modeling. Each individual use case will additionally be accompanied by a short update lecture giving an overview of most recent scientific developments and comments on current hot topics in the field. Whenever feasible and relevant, community feedback and input sessions will be interspersed.

Agenda:

During an introductory lecture, we will briefly introduce the Open Systems Pharmacology community. We will then focus on a general introduction into concepts, features and most beneficial application of mechanistic and physiologically-based modeling.  An open discussion about ideas how we all can benefit best from an open community approach should conclude the first part of this workshop – we encourage all participants to share their thoughts and ideas. This part will be followed by a first hands-on lesson. During this session, attendees will learn how to develop PBPK models for small molecules and for biologics, elucidating the peculiarities that need to be reflected in both cases.

In the following parts of the workshop, the focus will be directed on pharmacokinetic drug-drug interactions and the assessment of pharmacokinetic properties in different populations. An overview will show the variety of different applications and current challenges for modeling. By example of scaling to different age-groups (children/elderly) it will be shown, how integration of physiological knowledge leads to an expectation for different populations. In the second part, the changes in diseased populations (hepatic/renal impairment) will be discussed and related PBPK modeling of populations will be shown by example. An overview will show use of different ethnical virtual populations in PK-Sim^® and MoBi^®.

In the fifth session, it will be shown how to customize and address sensitivity and uncertainty in PBPK models. The session will first discuss the different mathematical concepts and then – using examples – show how to use it in PK-Sim^® and MoBi^®. A detailed introduction to parameter identification will be part of this session.

We will wrap up the day with a summary and give room for more discussion and Q&A. Special relevance will be given to discussions around ideas, setup and opportunities to participate in the Open Systems Pharmacology community.

List of Sessions:

Session 1: Introduction
- Introduction of the community
- Purpose, current status and opportunities for application of PBPK/PD models along the drug development process

Session 2: Small molecules and biologics
- Distribution models
- Modeling of a small molecule
- Modeling of biologics

Session 3: Drug-drug Interaction
- Coupling perpetrator and victim PBPK models and simulate changes in PK

Session 4: Specific populations and age-related scaling
Use of mechanistic models to assess pharmacokinetics in different populations including:
- The younger and the elderly – how to address age-related changes in PBPK models
- Specific populations – renal/hepatic impairment

Session 5: Advanced PBPK/PD modeling - Customizing models, parameter identification and sensitivity analysis
Application examples:
- Identification and optimization of parameters – How to find the best representation of data with the most biologically plausible parameters
- Sensitivity, variability and uncertainty – Quantify the quality of the model to answer questions
- Outlook: How to use Markov Chain Monte Carlo (MCMC) methods for characterization of pharmacokinetics.

Session 6: Open discussion, Q&A, exchange of ideas

Workshop instructors:

Thomas Wendl, Bayer AG

Ibrahim Ince, Bayer AG

Markus Krauss, Bayer AG

Christian Diedrich, Bayer AG

Dzianis Menshykau, Bayer AG

 (and other community members, tbd)

Training materials and slides used will be provided. A laptop and an installed version of the Open Systems Pharmacology Suite are required for participation in the hands-on session.

Software installation packages can be downloaded from the Open Systems Pharmacology GitHub portal (www.open-systems-pharmacology.org/suite). System requirements for installation are as follows:

Operating System: Windows 7^®, Windows 8^®, Windows 10^®

Processor: at least Pentium III, 1 GHz (the faster the better!)

Main Memory: at least 4GB RAM

Free Disk Space: at least 2 GB of disk space

Administrator privileges are a prerequisite for installation.