Considerations from an International Regulatory and Pharmaceutical Industry (IQ MPS Affiliate) Workshop on the Standardization of Complex In Vitro Models in Drug Development.

In May 2022, there is an International Regulatory and Pharmaceutical Industry (Innovation and Quality [IQ] Microphysiological Systems [MPS] Affiliate) Workshop on the standardization of complex in vitro models (CIVMs) in drug development. This manuscript summarizes the discussions and conclusions of this joint workshop organized and executed by the IQ MPS Affiliate and the United States Food and Drug Administration (FDA). A key objective of the workshop is to facilitate discussions around opportunities and/or needs for standardization of MPS and chart potential pathways to increase model utilization in the context of regulatory decision making. Participation in the workshop included 200 attendees from the FDA, IQ MPS Affiliate, and 26 global regulatory organizations and affiliated parties representing Europe, Japan, and Canada. It is agreed that understanding global perspectives regarding the readiness of CIVM/MPS models for regulatory decision making and potential pathways to gaining acceptance is useful to align on globally. The obstacles are currently too great to develop standards for every context of use (COU). Instead, it is suggested that a more tractable approach may be to think of broadly applicable standards that can be applied regardless of COU and/or organ system. Considerations and next steps for this effort are described.

Organ-on-a-chip: current gaps and future directions.

As an emerging hot topic of the last decade, Organ on Chip (OoC) is a new technology that is attracting interest from both basic and translational scientists. The Biochemical Society, with its mission of supporting the advancement of science, with addressing grand challenges that have societal impact, has included OoC into their agenda to review the current state of the art, bottlenecks and future directions. This conference brought together representatives of the main stakeholders in the OoC field including academics, end-users, regulators and technology developers to discuss and identify requirements for this new technology to deliver on par with the expectations and the key challenges and gaps that still need to be addressed to achieve robust human-relevant tools, able to positively impact decision making in the pharmaceutical industry and reduce overreliance on poorly predictive animal models.

Organ-on-chip applications in drug discovery: an end user perspective.

Organ-on-chip (OoC) systems are in vitro microfluidic models that mimic the microstructures, functions and physiochemical environments of whole living organs more accurately than two-dimensional models. While still in their infancy, OoCs are expected to bring ground-breaking benefits to a myriad of applications, enabling more human-relevant candidate drug efficacy and toxicity studies, and providing greater insights into mechanisms of human disease. Here, we explore a selection of applications of OoC systems. The future directions and scope of implementing OoCs across the drug discovery process are also discussed.

Correlative Light-Ion Microscopy for biological applications.

Here we report a new technique, Correlative Light-Ion Microscopy (CLIM), to correlate SEM-like micrographs with fluorescence images. This technique presents significant advantages over conventional methods in enabling topographical and biochemical information to be correlated with nanoscale resolution without destroying the fluorescence signal. We demonstrate the utility of CLIM for a variety of investigations of cell substrate interactions validating its potential to become a routine procedure in biomedical research.