Changes to PEP Regulations
The worldwide market for PEPs was $1.13 billion in 2008, and the U.S. market was expected to reach nearly $400 million in 2009, according to IMS Health. FDA’s NDA requirement resulted from the agency’s 2004 review of porcine-derived enzyme products, which concluded that no PEP products demonstrated “consistent bioactivity that results in predictable safety and effectiveness.”
One cause of these problems is the inherent instability in PEP products and their tendency to degrade over time, according to Eurand, one of three firms that has an FDA-sanctioned PEP. To compensate for this degradation, some manufacturers included an overfill of enzymes versus the label claim to ensure that each capsule delivered at least 90% of label-claimed lipase content throughout its shelf life. This practice can, however, cause variability and unpredictability in dosing, with patients receiving anywhere from 90–165% of the prescribed dose, according to the U.S. Pharmacopeia.
As a result of the FDA regulations several manufacturers have discontinued their unapproved pancreatic enzyme products, including Ethex, Major Pharmaceuticals, Solvay Pharmaceuticals (now part of Abbott Laboratories), and X-Gen Pharmaceuticals. To date, three porcine-derived products have received FDA approval: Solvay’s Creon was the first PEP sanctioned under the new process, Eurand’s Zenpep was approved in August 2009, and most recently, Johnson & Johnson’s (J&J) Pancreaze was given the go-ahead. J&J’s Ortho-McNeil will continue to market Pancrease MT for a short time to help patients transition over to its FDA-approved Pancreaze product; Pancrease MT and Pancreaze are identical products, however, the product packaging for Pancreaze complies with FDA requirements for reporting of enzyme contents.
FDA recommends that patients not currently taking an approved PEP “begin working with their healthcare professionals to switch to an FDA-approved PEP.” However, labeled enzyme contents may differ between FDA-approved products and unapproved ones: FDA-approved treatments reflect the actual enzyme content of the product, while labeled contents of unapproved therapies exclude overfill and may underestimate the actual enzyme content.
Michael Walters, evp, sales and marketing at Eurand, told GEN that the company developed Zenpep with “zero overfill so patients could be guaranteed the precise amount of lipase in every dose.” The company’s previous product, he noted, required overfill and “introduced the potential of getting too much lipase in one month and too little in another, creating challenges for patients and caregivers alike in managing the symptoms of EPI.”
Other differences, he added, include viral inactivation and better product characterization. With regard to transitioning patients from their unapproved PEP products to approved products, Walters said, “We believe that with the four dosage strengths of Zenpep—5,000, 10,000, 15,000, and 20,000—we offer precision dosing and flexibility as they transition from previous products.”