Purpose: In 2004, under pressure from patient advocacy groups to ensure safety, effectiveness, and most importantly safe product interchange, the Food and Drug Administration (FDA) mandated that all pancreatic enzyme products (PEPs) be approved under a New Drug Application (NDA) by 2010. As a result of this requirement, the number of PEPs marketed in the United States for treatment of cystic fibrosis, pancreatic surgery, and chronic pancreatitis declined from approximately 30 different products in 2008 to currently only six. The aim of this study was to determine the effect of this intervention on the cost of and access to PEP prescriptions in the United States. Methods: Using the IMS Health Product Report 5.0 database, the total annual number of United States prescriptions and sales (U.S. dollars) from the years 2008-2012 for relevant PEPs were obtained. The study focused on three PEPs: Creon (AbbVie, North Chicago, IL), Pancrease/Pancreaze (Janssen Pharmaceuticals, Inc. Raritan, NJ), and Zenpep (Aptalis, Inc. Bridgewater, NJ), because all were approved prior to 2011, and thus, 1-year post-approval cost data were available. Prescription costs for each medication were calculated by dividing the annual total number of prescriptions by total sales. The primary outcome was the cost of each medication (with the exception of Zenpep, which was new in 2009) 1 year before and 1 year after FDA approval. Results: In the year prior to approval (2008), the mean prescription cost for Creon 10 and 20 formulations was $262 and $488, respectively. In 2010, the year after approval, prices were $350 for Creon 12 and $683 for Creon 24. Similarly, Pancreaze increased in price after its approval (2010) from $336 to $538. Zenpep, which debuted in 2009, was initially priced at $580. The total number of prescriptions for the most common PEP formulations (Creon, Pancrease/Pancreaze, Ultrase, Viokase/Viokace, Zenpep, Pancrelipase) was 631,291 in 2008, 876,226 in 2009 and 1,118,774 in 2010. No comparative efficacy or post-marketing surveillance studies have been published since the FDA requirement was enacted to ensure safe product interchange. Conclusion: The FDA NDA requirement for pancreatic enzyme products resulted in universal prescription price increases. No studies to ensure safe product interchange, the original goal of the NDA requirement, have been performed.