Armand Keating, MD, Epstein Chair in Cell Therapy and Transplan-tation, Univer-sity of Toronto.
BioPharm: What do you see as the biggest challenges related to commercialization of stem-cell therapy?
Keating: We can break the issue down into three components. The first issue is funding for preclinical studies that are required to
obtain an IND in the US or a Clinical Trial Application (CTA) in Canada. Those studies can be moderately expensive, but the
challenge is to find funding, becasue they are not really hypothesis driven. Most evaluation of research projects is based
on the quality of hypothesis-driven work. Preclinical studies, however, go a step beyond that. The hypothesis has been established,
and there are very good data that may well have been published in outstanding journals. FDA and similar agencies require validation
and preclinical data demonstrating both safety and efficacy. Neither of those sorts of applications are going to receive a
particularly good score in the ususal study sections, because they'll be competing with more conventional hypothesis-driven
research. Here, we're really attempting to validate something—demonstrate its safety and efficacy. Funding preclinical validation
studies is an area where I think there's a real challenge.
The second challenge is in moving to the next step, which is scaling-up and performing the cell manufacturing with all the
tests that are required, short of actually administering it to a patient. Manufacturing to GMP standards is expensive, and
the expectation is that you would do two or three dry runs, which has to be funded somehow. Doing the scale-up studies is
absolutely vital, because it isn't necessarily a linear process going from laboratory-scale manufacturing to clinical-scale.
Once a manufacturing process has been developed, the final aspect of moving from the laboratory to the clinic is how to actually
fund the cell manufacturing for patients in a clinical trial. Many of these trials are investigator-driven and are not supported
by industry. Unlike drug-development studies, which are often supported by industry, industry funding is significantly less
common for cell therapies, and therefore more of a challenge to obtain.
It's really the funding, from the initial observation through to the completion of early phase clinical trials, that presents
the biggest challenge. Later-phase clinical trials are so expensive that it's unlikely that they can be accomplished at academic
health-sciences centers with manufactured cells, particularly prospective, randomized, placebo-controlled trials. It's just
enormously expensive to do that.
I think the scientific issues around stem-cell development can be addressed in the usual ways and can compete with hypothesis-driven
proposals. Also, I think that now there's pretty reasonable experience both at academic centers and also in industry to deal
with many of the regulatory issues—they're not as onerous as the regulatory issues confronting those wanting to do gene therapy,
for example—but they're still formidable. But for cell-based therapies to successfully move from the laboratory to the clinic,
there needs to be some way of dealing with the expense of development.
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phrma.org/track-pdf.php?q=/sites/default/files/2488/biologics2013.pdf, accessed March, 15, 2013.
2. K.Takahashi and S. Yamanaka Cell, 126 (4), 663-676 (2006)