Introduction and Qualification of CIVM and MPS
Over the past decade, CIVM have become increasingly more diverse in design, capabilities, and sophistication, reaching a point where industry can now begin to apply these tools across drug discovery and development. While the rigor of qualification required to apply these models are largely dependent upon the specific context of use, there are fundamental technical and methodological considerations to be taken into account when designing CIVM experiments. This module will provide an overview of CIVM and how they are being used in drug discovery and development, and offer insights into how CIVM data may eventually be used in concert with in-silico modeling. This module will also outline key technical considerations, such as cell sources, statistical design, confounding device variables, and construction methodologies. The module will close with an overview of high-level qualifications considerations, such as recapitulation of known drug response and comparability to gold standards.
Introduction to CIVM and MPS
This session will provide an overview of the objectives and content of the IQ MPS Affiliate Training course followed by an overview of MPS platforms and how the pharmaceutical industry is currently using these and other Complex In Vitro Models.
Technical Considerations for Experimental Design (Part I)
This session will cover the key components that should be considered when developing a MPS model, such as the context of use, and physical and biological inputs (including cells, matrices and media). Furthermore, the concept of good experimental design for MPS will be presented using a case study example.
Technical Considerations for Experimental Design (Part II)
Basic 2D monolayer cultures can fail to predict in vivo pharmaceutical candidate properties such as efficacy, ADME, or toxicity as they lack the necessary physical and biochemical cues found in vivo. MPS aim to fill this gap by exploiting advances in material sciences, microfabrication processes, and engineering to recreate the in vivo environment. In this session, technical design considerations of MPS are discussed with respect to:
- Material considerations
- Fluid dynamics in systems with flow
- Mechanical stimuli were applicable
- Device qualification and operation
- Body-on-a-chip configuration
- Immune cell incorporation
Leveraging MPS Data for in-Silico Modeling
With new approach methodologies (NAM) evolving in tandem and at a rapid pace, there is an opportunity to integrate them in ways previously thought impossible. This session aims to initiate discussion on how the diverse and complex datasets derived from CIVM and MPS models may be analyzed using quantitative systems biology (QSP), machine learning, and in silico modeling approaches. Examples will be provided through case studies, and a realistic view of the current gaps as well as future outlooks and opportunities will be discussed.
CIVM/MPS Qualification Considerations and Challenges
This session will provide an overview of qualification efforts for the use of CIVMs in various contexts of use and will include both a high-level overview of the current qualification landscape as well as examples of internal fit-for-purpose qualification efforts within Pharma companies for different contexts of use and discuss how these complex models present unique challenges to using traditional assay validation framework.
Module I Summary
In this session, we summarize the key takeaways from Sessions 1-5 and further elaborate on some of the questions received by attendees throughout Module I. We will also provide an overview of a Reference Guide we have prepared and introduce the content for next year’s sessions, which will focus on specific organs and relevant COUs.