Proceed with Caution
Many technical hurdles remain to be overcome, notably cryopreservation and manufacturing, Dr. Langer observes. “Every tissue/organ has its own issues to solve.”
From Dr. Niklason’s perspective, “The two real stumbling blocks for the industry have been manufacturing (repeatability, reproducibility, and scaling) combined with cost of goods issues. But these are becoming a dragon that can be slain.” While the regulatory environment is not getting easier, she observes, “cell products are less of an unknown for the FDA than they were a decade ago, so there is more precedent for the FDA to regulate products and the number of complete surprises is fewer.”
“The evolving regulatory environment and affordability of healthcare, both in the U.S. and abroad, will continue to pose significant hurdles,” says Dr. Gemmiti.
“That said, speaking from personal experience, the FDA was very willing to work with us at Organogenesis on the recent approval of Gintuit™, our new living cellular sheet for the regeneration of oral soft tissue. The lessons learned through that successful process are already helping to educate the rest of the field. On the healthcare side, companies committing to evidence-based medicine and supporting that with health economics research will find themselves ahead of the pack in the future.”
When asked how the regulatory environment for tissue-engineered and stem cell products has evolved over the past four years, Dr. Gemmiti replied, “In certain instances, the amount of clinical evidence required to support the safety and efficacy of biologics and devices has increased.” However, he points to products such as Provenge, LaViv™ (Fibrocell Science), and Gintuit as “important examples to follow and set precedents, at least on the cell-based side.”
“Unquestionably, the FDA’s aggressive stance with respect to cell-based therapeutics is a dramatic hurdle,” says Dr. McAllister. For at least some applications—and he mentions the use of stem cell-based therapies to treat congestive heart failure and muscle loss associated with acute myocardial infarction as examples—“the risk/benefit analysis is dramatically skewed and, as an industry and a regulatory body, we should be revisiting our cumulative tolerance of risk.”
In 2005, for example, coronary heart disease caused 1 out of every 5 deaths in the U.S. The prevalence of heart failure in the U.S. was about 5.7 million, and mortality attributable to heart failure exceeded 292,000 per year. Mortality due to myocardial infarction (MI) was about 151,000 in 2005, and about 1 in 5 people 40 years of age or older who suffered a first MI would die within a year. “These patients have little hope of improvement with current therapies,” says Dr. McAllister.