UF researchers contributed to FDA decision to regulate pancreatic enzymes

A University of Florida professor of pharmacy and pediatrics calls this week’s decision by the Food and Drug Administration to regulate pancreatic enzyme replacements “a huge step in the protection of patients with cystic fibrosis.”

Leslie Hendeles, Pharm.D., a professor in the colleges of Pharmacy and Medicine and a clinical pharmacist in the Pediatric Pulmonary Clinic at Shands at UF medical center, has spent more than 10 years documenting the health risks faced by cystic fibrosis patients who take unregulated generic enzyme products. Pancreatic enzymes were available before the 1938 Federal Food, Drug and Cosmetic Act and thus were “grandfathered” in — escaping regulation, Hendeles said.

FDA reviews dating back to 1989 concurred that some enzyme products did not provide consistent doses or release of the enzymes, which could result in treatment failure in patients with pancreatic diseases, such as cystic fibrosis.

According to the Cystic Fibrosis Foundation, cystic fibrosis is a genetic disease that affects nearly 30,000 people in the United States. In addition to causing changes in the lungs that lead to chronic infection, the defective gene that causes cystic fibrosis also impairs digestion, rendering 90 percent of patients dependent on pancreatic enzyme replacement. Under the new ruling, unless a manufacturer voluntarily withdraws its product, it will continue to be available to patients for four years.

Hendeles, a consultant to the FDA’s pulmonary division, said there were 30 to 40 cases of treatment failure reported by doctors last year to the Cystic Fibrosis Foundation.

A long-time activist who has sought FDA regulation of enzyme replacements for years, Hendeles first reported treatment failures in three UF patients in 1990. Subsequently, he conducted research with Guenther Hochhaus, Ph.D., a professor of pharmaceutics at UF College of Pharmacy, to analyze all enzyme products on the market. Published in 1994, their research showed important differences among products and urged pharmacists not to substitute one for another. Although these products are available on the market, many have never been tested in humans, Hendeles said.

FDA officials said manufacturers of pancreatic enzyme replacements have been notified their products must be approved by the agency within the next four years in order to remain available to patients. This means product efficacy and safety must be proven in patients with CF.

“It will still be several years before the FDA weeds out the unreliable products,” said Hendeles. “Meanwhile, it will be absolutely necessary that pharmacists do not substitute generic products without discussion with the prescribing physician.”