On November 13, 2012, Cumberland Pharmaceuticals Inc. (“Cumberland”) sued FDA, the Commissioner of Food and Drugs, and the Secretary of Health and Human Services in federal district court for the District of Columbia for denying Cumberland’s Citizen Petition and approving InnoPharma, Inc.’s (“InnoPharma’s”) abbreviated new drug application (“ANDA”) for an acetylcysteine injection. Cumberland asserted that the denial of the Citizen Petition and the approval of InnoPharma’s ANDA were “arbitrary, capricious, and abuse of discretion, and not in accordance with law, all in violation of the APA [Administrative Procedure Act]” and “violated the Federal Food, Drug, and Cosmetic Act (‘FDCA’),” according to its complaint.
Cumberland holds the approved new drug application (“NDA”) for the reference listed drug (“RLD”), Acetadote®, indicated to prevent or lessen hepatic injury in adults and children when administered intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen. The original formulation of Acetadote® contained edentate disodium (“EDTA”) as a chelating agent that was believed to be necessary for the stability of the product. FDA approved Acetadote® in January of 2004, but conditioned its approval on Cumberland’s agreement to perform post-approval studies to evaluate whether EDTA could be removed from the formulation in view of safety concerns. EDTA has been associated with a significant drop in serum calcium levels, which may result in fatality, hypokalemia, hypomagnesaemia, or hypotension as well as allergic reactions.
As a result, Cumberland developed and obtained approval in January 2011 from FDA for a new EDTA-free formulation after, according to the complaint, surprisingly demonstrating that EDTA was unnecessary to maintain drug stability. Cumberland then withdrew the EDTA-containing formulation from the market.
Cumberland filed a Citizen Petition with FDA to confirm that FDA would not approve a generic version of Acetadote® in which the formulation contained ETDA. Under the Federal Food, Drug, and Cosmetic Act (“FD&C Act”) and FDA’s rules implementing it, FDA generally will not approve an ANDA for a injectable drug product, such as the InnoPharma’s ANDA, if the drug product does not contain the same inactive ingredients and in the same concentration as the RLD. Moreover, FDA regulations require an ANDA for a product that refers to a listed drug that has been withdrawn voluntarily from sale to be accompanied by a petition seeking to determine whether the listed drug was withdrawn for safety or effectiveness reasons.
On November 7, 2012, FDA denied Cumberland’s Citizen Petition and granted approval for InnoPharma’s ANDA for a formulation containing EDTA. FDA concluded that the original Acetadote® was not withdrawn from the market for reasons of safety or efficacy and that it would waive the generally applicable requirement that the ANDA drug product have the same inactive ingredients at the same concentrations as the RLD.
According to Cumberland’s complaint, FDA granted a waiver without requiring InnoPharma to demonstrate that its formulation containing EDTA is as safe as Cumberland’s EDTA-free formulation. The complaint asserted that FDA’s actions amounted to treating “two similarly situated parties differently” noting that adverse events were reported for the EDTA-containing formulations.