Treatment failure after substitution of generic pancrelipase capsules. Correlation with in vitro lipase activity

Pancreatic enzyme products are formulated, manufactured, and sold without submitting efficacy or bioavailability data to the Food and Drug Administration because of a quirk in the law. We documented therapeutic failures in three patients with cystic fibrosis after pharmacists substituted generic pancrelipase capsules for the Pancrease brand. Gastrointestinal symptoms and fat malabsorption rapidly resolved after therapy was reinstituted with brand name products. In vitro analysis indicated that after 1 hour of exposure to simulated gastric fluid, lipase activity was less than 200 U per capsule from all three generic capsules dispensed to the patients compared with 6820 U per capsule from Pancrease. These data indicate that the enteric coating of the generic product was defective and that the substituted product was not bioequivalent to the prescribed brand. We conclude that the Food and Drug Administration should institute regulations over this group of products.