Organ-on-a-Chip Designed to Overcome Major Flaws in Pharmaceutical ProcessesFebruary 06, 2020 by Luke James
Researchers in the U.S. and Israel have developed a multi-Organ-on-a-Chip (OoC) that is claimed to overcome many of the problems that hinder the development and approval of medicines.
It is no secret that one major reason for pharmaceuticals being so expensive is the cost and time needed to bring them to market. Due to current problems faced during the medication manufacturing pipeline, many will fail during the development process and this can drive up costs.
Bringing Pharmaceuticals to Market
Pharmaceuticals begin their journey in the lab, where scientists test thousands to tens of thousands of compounds to see if they have an impact on a given disease. Once promising ones are discovered, they are studied further to explore how they work and how our bodies process them, among other things.
These promising candidates are whittled down and then tested, usually on animals, to find potential side effects. Those that pass this round are then tested in non-human mammals before being taken to the clinical trial stage where they are tested on humans to assess safety, efficacy, and utility.
Only when a potential drug passes all of the above, and in some cases more, can it be brought to market.
Although this process is thorough and ensures that pharmaceuticals are safe and effective, it is a lengthy process that often stretches beyond a decade. It is also an expensive process, with the estimated cost of bringing a single drug to market sitting at around $2 billion. Failure rates are also eye-wateringly high at around 95%.
An example of an organ-on-a-chip device. Image used courtesy of Wyss Institute - Harvard University.
How New Methods (such as Organ-on-a-Chip) Could Help
Much of the failure in the pharmaceutical development process lies in two areas:
- When they react differently inside living organisms to how they reacted with lab-grown cells; and
- When the results seen during animal testing fail to translate to humans during clinical trials.
A potential solution to this is OoC technology. Its premise is simple: A collection of different devices that share one goal, to simulate human biological conditions by recreating the functions and natural environments of human organs in a miniaturized form. These chips are already capable of recreating some core physiological functions.
OoC devices rely on ‘microfluidics’ to function, a process that involves the movement of tiny volumes of liquid or air through chambers inside the 3-dimensional OoC. This simulates the natural environment of an organ in the human body. When these chips are coated with cells, the microfluidic process can be used to answer different questions and solve problems, allowing researchers to test how drugs function in a three-dimensional environment rather than the standard two-dimensional dish setting.
There have been several types of OoC technologies developed to date, including a lung-on-chip developed by the Wyss Institute at Harvard University, and others simulating the heart, skin, and even brain.
Lots of progress in OoC technology has been made in the UK, where the University of Cambridge went beyond using it to develop pharmaceuticals and created its own three-dimensional OoC for developing new types of treatment for disease. Their OoC incorporates a cell inside a 3D transistor made from a sponge-like material inspired by tissue structure. This gives scientists the ability to grow and study cells and tissues in three dimensions.
The components of a multi-human organ system developed by the Wyss Institute. Image used courtesy of Wyss Institute at Harvard University.
Using OoC to Speed Up Pharmaceutical Approvals
To solve the delays associated with getting pharmaceuticals to market, “we need to become much more effective at setting the stage for drugs that are truly promising and rule out others that for various reasons are likely to fail in people,” said Prof Donald Ingber, MD, PhD, founding director of Harvard University’s Wyss Institute for Biologically Inspired Engineering who has co-authored two new studies recently published in Nature Biomedical Engineering.
The research, co-led by scientists from Tel Aviv University’s (TAU) Department of Biomedical Engineering, has led to the development of a functioning comprehensive multi-OoC said to enable effective in-vitro-to-in-vivo translation of human drug testing and pharmacology.
The Potential Applications of OoC for Patient Care
Dr. Ben Maoz of TAU said, “We hope that this platform will enable us to bridge the gap on current limitations in drug development by providing a practical, reliable, relevant system for testing drugs for human use.”
In their first study, the researchers developed a robotic liquid transfer device, dubbed the “Interrogator”, which links individual OoCs in a way that mimics blood flow in the human body. This device was then attached to three linked organs alongside a newly developed computational model from their second study. The team then conducted tests using nicotine and cisplatin.
The researchers were able to accurately model the oral uptake of nicotine and intravenous uptake of cisplatin – a chemotherapy medication – and their first passage through organs with highly quantitative predictions of human pharmacokinetic and pharmacodynamic parameters.
Professor Ingber said, “The modularity of our approach and availability of multiple validated Organ Chips for a variety of tissues for other human Body-on-Chip approaches now allows us to develop strategies to make realistic predictions about the pharmacology of drugs much more broadly,” adding that future use could increase the success rates of Phase I clinical trials.