A Symposium Session: In Vitro Microphysiological Systems: Advancing Regulatory Science through Innovation, was held on Wednesday, March 26, 2014 during the SOT 53rd Annual Meeting in Phoenix, Arizona. A summary of that session is provided below.
The In Vitro Microphysiological Systems: Advancing Regulatory Science through Innovation session was held this morning showcasing efforts to improve efficacy and safety testing in drug development by humanizing early preclinical systems. At issue is that neither 2D cell culture systems nor animal models are serving the pharmaceutical industry well enough to prevent late-stage clinical failures. The effort to improve cell-based systems can potentially overcome these deficiencies with the added benefit of reducing animal use.
The session was organized by Anthony Bahinski of the US Department of Defense, Defense Advanced Research Projects Agency (DARPA), and Suzanne Fitzpatrick of the US Food and Drug Administration (FDA). The speakers consisted only of individuals who had been funded through or were directly involved in the US DARPA/National Institutes of Health (NIH)/US FDA initiative from 2012. This initiative poured nearly $200M into creating a body on a chip with an aggressive 5-year goal to have a compact user platform with 10 different connected organ systems developed and commercialized in 5 years. This effort came about because US DARPA wants to create countermeasures for chemical and biological warfare, but US FDA cannot approve drugs that cannot be tested for efficacy in humans. Therefore, US DARPA needs to convince US FDA that such tests can be done in vitro. Whether or not such an effort has real application to other drug development efforts remains to be seen and will depend really on the availability of the technologies produced.
The accessibility of the resulting technologies had clearly crossed the minds of the audience as was reflected in the very first question of the session from Jon C. Cook of Pfizer, who specifically asked about the plans to commercialize. The answer was pretty vague: there have been “conversations” and Dr. Fitzpatrick replied that the responders supplied “commercialization plans” in their applications.
Dan Tagle opened the session with an overview of the program and was then followed by Tom Hartung from John’s Hopkins, Donald Ingber from the Wyss Institute, and John Wikswo from Vanderbilt University. The last speaker was Jacob Kram from the US FDA.
Dr. Hartung led with a discussion of the problems associated with current cell culture practices and the need to improve them. In this regard, cells are the very basis of these technologies and without good quality assessment, the deficiencies and variability of the entire systems will cause them to fail. He referenced the documents defining Good Cell Culture Practices that include validating your cell line identity and understanding the practices that influence quality and reproducibility.
The parade of highly sophisticated technologies from Wyss and Vanderbilt that followed has the potential to truly revolutionize medicine through the way we discover and validate lead drugs and evaluate diseases. Both groups have remarkable platforms that mimic in vivo physiologies including multi-tissue perfusion systems incorporating sheer and strain that mimic natural organ environments with good precision. It’s amazing what a strategic $200M investment can accomplish.
The final speaker, Dr. Kram from the US FDA, served up some cold water to douse the bravado, however. While sharing that he does believe ultimately that animals can be replaced in preclinical drug development, he reminded folks that safety is the prime issue for the US FDA, and until these technologies can prove to be equivalent or better than what is currently used, then he doesn’t see the implementation. When asked by an audience member who should be the entity to provide that proof, he said it’s up to the pharmaceutical industry. My question is: does the pharmaceutical industry know this?
Ultimately, I think US DARPA will get what it wants from these huge efforts, which are new ways to test antidotes to chemical warfare agents in human tissues in vitro. But it remains to be seen whether other industries are really incentivized enough to embrace any of the benefits. This is especially true if US FDA is waiting for the pharmaceutical and biotech industries to validate these technologies and yet are not making an effort to directly engage them in the process. Until then, the broader community of researchers and industries will most certainly enjoy the fancy light show that emits from these new technologies and continue to hope that one day they will get used for real commercial applications.