Preclinical Development
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Jake McDonald, PhD
VP, Applied Sciences
Lovelace Biomedical
Albuquerque, New Mexico
Jim McKim, PhD, DABT
Executive Director
LifeNet Health
Kalamazoo, Michigan
Lorna Ewart, PhD
Chief Scientific Officer
Emulate
Boston, Massachusetts
The quest for alternatives to animal safety testing has fueled the development, characterization,
and validation of many new technologies. There have been advances in cell and tissue models as
well as the various platforms that utilize these models. Regulatory groups around the world have
started to accept the data from these new models and, in some instances, have allowed full
replacement of the existing animal tests. Although the use of these single organ models has been
successful, the ability to model the more complex systemic multiple organ exposure scenario has
not been realized. The success of an in vitro integrated organ model depends upon the presence
of a simulated blood system, isolated organ compartments, the presence of key biological
barriers, and metabolism. The fluid volumes must be large enough to allow for multiple
samples over time, and the tissue mass must be sufficient to allow for the detection of
biomarkers. The presentation today will present the development and characterization of a novel
platform that addresses these important areas. A human dynamic multiple organ plate
(HuDMOP) designed on a meso-scale will be discussed. The platform can accommodate up to
six organ chambers each isolated and hence cultured under optimal conditions. The organs are
connected via a simulated blood system which keeps the simulated blood separate from the organ
culture media. Movement of the test drug or chemical is via passive diffusion across a semi-
permeable membrane. The system can be used with most 3D tissue types, as well as 2D cultures
already developed and validated. Data will be presented that demonstrate the three primary
routes of drug or chemical exposure: oral, dermal, and inhalation. By using well known drugs or
chemicals such as diclofenac, acetaminophen, cannabidiols, and cycloheximide it is possible to
make comparisons to in vivo data. Pharmacokinetic data obtained with three organ circuits (e.g.
Intestine-liver-kidney) will be shown. The HuDMOP platform demonstrates the ability of an in
vitro integrated organ system to study systemic exposure by single or multiple doses as well as
the development of physiologically based pharmacokinetic models. Ultimately, models like
HuDMOP and organ-on-a Chip will enable the use of in vitro data to predict drug or chemical
behavior in humans.