Written by: Roshni Rainbow, PhD (Clerk), Nathan Holwell (Chair), and Laura McKiel (Editor)
A typical process of moving from bench to bedside includes developing a material and performing in vitro testing, followed by in vivo testing in animals, and finally human trials. In vitro analysis begins to test the biocompatibility of the material using cells outside the body. Animal models are used for in vivo testing to take a more detailed look at the biocompatibility within a living subject. Researchers usually explore the material’s role in tissue viability, inflammation, cellular infiltration, and fibrotic response. Finally, human trials explore the feasibility of the material for the intended application supported by clinical trials.
Figure 1: The typical process for drug development, testing, and approval. Source: http://oirm.ca/sites/default/files/oirm-infographic-nov2016-final.pdf
In the first breakout session, we explores the next steps of two different biomedical technologies in order to move them into a clinical application.
A major challenge of clinical trials is to appropriately scale-up the manufacturing process. A significant factor in scale-up is the propagation of cells and automating device production. As an example, microencapsulated pancreatic islets for diabetes treatment needs 500 islets for a 100 g mouse. To scale up to a 20 kg dog, 1,000,000 islets would be needed. Due to diffusion limitations, implanted capsules cannot be larger than ~200 µm in one direction. For a 100 g mouse, 1 microcapsule is required, but for a 20 kg dog one would need a 15 foot long string.
For clinical trials to begin, there are a few conditions that must be met. Firstly, the trial benefit must outweigh the risk. Secondly, the researchers must obtain free and informed consent from the patients involved in the trial. Finally, the protocol must be reviewed in advance by an independent review board. With this knowledge in mind, another example of a clinical trial was explored.
The Hepatassist Circuit Therapy by Circe Biomedical Inc. was a device to provide bioartificial liver support. When they performed their clinical trials, they had a total patient size of 116. However, 85 of these patients were part of the control portion of the study. This demonstrates the need to fully consider the number patients being studied with the actual device. The study population is especially important to consider when determining whether the material in questions has a true effect or not. And if the device does not show an effect, it is possible that it either doesn’t work or wasn’t tested in enough patients to show its true effect.
Next, we discussed the limited success of tissue engineering companies or firms. It was agreed that these companies or firms are good at discovery but lack in product development and regulatory medicine. Tissue engineered products are generally required to follow phase I/II/III regulatory pathways for pharmaceutical compounds. These submissions can cost anywhere from 300-500 million dollars. Tissue engineered products are usually discovered by smaller companies with limited funds. Due to this funds limitation, they cannot afford submission and must rely on investors. If trials are performed, they are usually done in a cheap manner. Unfortunately, these trials typically fail or only provide a narrow indication as to the material’s effect.
At the end of the session, we discussed a recent paper that commented on the greatest regulatory challenges in the translation of biomaterials to the clinic.
This article tackles the issue of clinical translation of biomaterials from a variety of viewpoints. Lawyers, regulatory officials, clinicians, and researchers comment on what they perceive to be the most difficult challenge of translating biomaterials from the bench to the clinic.
Among the arguments raised in this article by the various viewpoints, one question loomed at the end: Should scientists innovate or translate?