White Papers about Medications for Cystic Fibrosis
ILLEGAL GENERIC PANCREATIC ENZYMES
Leslie
Hendeles, Pharm.D.
Professor,
Pharmacy and Pediatrics
University
of Florida*
Several generic drug companies (e.g. Eurand, Mutual, KV) have begun manufacturing and distributing microencapsulated pancreatic enzyme products. Wholesalers are stocking these products and at least one chain has designated the Mutual product as the preferred brand for their pharmacists to dispense. Consequently, pharmacists have begun substituting these products for Creon, Pancrease MT and Ultrase. According to FDA’s Office of Generic Drugs, none of these companies have received FDA approval to sell these products. FDA’s final rule, published on April 25, 1995, declared that exocrine pancreatic insufficiency drug products, whether marketed on an OTC or prescription basis, are new drugs for which approved applications are required for marketing.(1) Such applications require efficacy or bioequivalence studies and it is unknown whether these products have been tested in humans.
Because pancreatic enzymes were available before the passage of the 1938 Federal Food, Drug and Cosmetic Act, they were exempt from FDA regulation.(2) Even the newer microencapsulated formulations were marketed without FDA approval.(2) They contain a different amount of enzymes than what is stated on their labels; they differ in ability to resist inactivation by stomach acid; and the pH required for release of enzymes differs between products.(3)
Because of reports of treatment failures in patients with cystic fibrosis after pharmacists substituted generic products for Pancrease(4) and the association of fibrosing colonopathy with high daily doses,(5) FDA initiated the process to require firms to obtain an approved application to market their products.
Since pancreatic enzymes are life-sustaining for patients with cystic fibrosis, the FDA allowed all brands that were on the market on April 25, 1995 to continue to be sold while the new drug application process was being completed. Implicit in such a regulatory action is that no new products can be marketed without FDA approval. Since the generic products were recently introduced, after FDA’s final rule was issued, they violate the intent of the agency’s Federal Register notice and as new products without an approved application are subject to regulatory action.
FDA’s Office of Compliance has been notified about the illegal products but it will take some time before they are removed from the market place. This process is likely to speed up, however, if there are reports of patients being harmed by illegal generics.
1. Pharmacists should not substitute a generic for a brand name pancreatic enzyme until such time that FDA approved bioequivalent generic products become available.
2. Forward a copy of this memo to prescription benefit plans who insist that the patient must have a generic product. It is unlikely that they will continue to insist on the dispensing of an illegal product.
3. Report any treatment failures to the FDA Medical Product Reporting Program (MedWatch): www.fda.gov/medwatch/report/hcp.htm; fax: 800-FDA-0178 or by phone: 800-FDA-1088.
1. FDA. Exocrine pancreatic insufficiency drug products for over-the-counter human use: Final Rule. Federal Register 1995;60:20162-5.
2. Hendeles L, Hochhaus G, Kazerounian S. Generic and alternative brand-name pharmaceutical equivalents: select with caution. Am J Hosp Pharm 1993;50:323-9.
3. Kraisinger M, Hochhaus G, Stecenko A, Bowser E, Hendeles L. Clinical pharmacology of pancreatic enzymes in patients with cystic fibrosis and in vitro performance of microencapsulated formulations. J Clin Pharmacol 1994;34:158-66.
4. Hendeles L, Dorf A, Stecenko A, Weinberger M. Treatment failure after substitution of generic pancrelipase capsules. JAMA 1990;263:2459-61.
5. FitzSimmons SC, Burkhart GA, Borowitz D, Grand RJ, Hammerstrom T, Durie PR, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med 1997;336:1283-9.
*Contact Information:
Leslie Hendeles, Pharm.D.
University of Florida (Box 100486)
Gainesville, FL 32610-0486
Phone: 352-392-5677
Fax: 352-846-2498
E-mail: hendeles@cop.ufl.edu