By Kurt R. Karst –
In a notice that will publish in the Federal Register later this week, FDA, citing safety concerns, will announce the Agency’s plans to take enforcement action against all unapproved single-ingredient, immediate-release human drug products containing Oxycodone HCl for oral administration, and persons who manufacture or cause the manufacture or distribution of such products in interstate commerce. The announced move is part of FDA’s “Unapproved Drugs Initiative.” It follows a March 2009 FDA enforcement action concerning several marketed unapproved narcotic drug products, including unapproved single-entity, immediate-release oxycodone tablets (but specifically excluding oxycodone capsules). Since then, FDA has approved an NDA for Oxycodone HCl Capsules, 5 mg (NDA No. 200534), an NDA for Oxycodone HCl Oral Solution, 100 mg/5 mL (NDA No. 200535), and an NDA for Oxycodone HCl Oral Solution, 5 mg/5mL (NDA No. 201194).
According to FDA, unapproved drug products containing Oxycodone HCL, a derivative of opium and a Schedule II controlled substance, “pose particular safety concerns because of their potential for addiction.” FDA illustrates this point by citing several examples of marketed unapproved Oxycodone HCL drug products where the labeling allegedly omits “critical information,” such as information in the “Indications and Usage,” “Dosage and Administration,” and “Warnings and Precautions” labeling sections. Moreover, says FDA, the Agency “has received reports of medication errors associated with unapproved oxycodone products and the strength of the active ingredient,” such as cases where the wrong dose of Oxycodone HCl Oral Solution was administered “due to the visual similarity of the container labels and carton labeling of the two product strengths.”
As to the legal status of unapproved single-ingredient, immediate-release drug products containing Oxycodone HCl for oral administration, FDA has determined that they are “new drugs” requiring the approval of a marketing application. “In no case did FDA find literature sufficient to support a determination that any of these products is generally recognized as safe and effective.” Earlier this year, Lannett Company, Inc. and Cody Laboratories, Inc. (collectively “Lannett”) submitted a citizen petition to FDA (Docket No. FDA-2012-P-0189) requesting that the Agency affirm, pursuant to the 1938 “grandfather clause” of the FDC Act, the grandfather status of certain Oxycodone HCl and Cocaine HCl drug products, including Lannett’s Oxycodone HCL Oral CONCENTRATE Solution, 20 mg/mL (see our previous post here). On the same day FDA announced the Agency's plans to take enforcement action with respect to certain single-entity Ocycodone HCl drug products, FDA denied Lannett's petition with respect to Oxycodone HCl. FDA's decision discusses two principal grounds for denying the petition: “First, we reject your implicit contention that oxycodone HCI products as a class are 'grandfathered' under the 1938 grandfather clause. Furthermore, the evidence provided with your petition is inadequate to demonstrate that Lannett's Oxycodone HCI Product meets the requirements of the 1938 grandfather clause.”
Lannett has previously challenged FDA in court on the grandfather/new drug status of another product the company marketed without approval - Morphine Sulfate Oral Solution. In that case, the U.S. Court of Appeals for the Tenth Circuit affirmed a November 2010 decision from the U.S. District Court for the District of Wyoming granting FDA’s Motion to Dismiss the lawsuit. In doing so, the Tenth Circuit refused to reach the merits of Lannett’s grandfather drug claim, stating, in relevant part, that “we cannot reach the merits of [Lannett’s] grandfathering claim unless the FDA has engaged in 'final agency action' under the APA. . . . [Lannett’s] failure to avail itself of available administrative remedies [(i.e., use of the citizen petition process)] defeats its claim . . . ." Subsequently, Lannett petitioned FDA on the grandfather status of Morphine Sulfate Oral Solution, perhaps in an effort to obtain final agency action from which to launch a new lawsuit (see our previous post here). Although FDA has not yet substantively responded to that petition, now that Lannett has final agency action on its citizen petition with respect to Oxycodone HCl, a lawsuit challenging FDA on grandfather status might not be far off.
With respect to when and how FDA will take enforcement action against companies marketing unapproved Oxycodone HCl drug products subject to the Agency's notice, the Agency says that it “does not expect to issue a warning letter or any other further warning to firms marketing drug products covered by this notice before taking enforcement action.” Any drug product covered by FDA’s notice that a company (including a manufacturer or distributor) began marketing after September 19, 2011 – the proverbial “line in the sand” FDA drew in the Agency’s most recent iteration of its Marketed Unapproved Drugs Compliance Policy Guide – “is subject to immediate enforcement action.” Products first marketed on or before September 19, 2011, that are not listed with FDA in compliance with FDC Act § 510 before July 6, 2012, and that are introduced or delivered for introduction into interstate commerce after July 6, 2012 are subject to enforcement action. A product listed in full compliance with FDC Act § 510 that is not being “commercially used or sold” in the United States before July 6, 2012, but that is introduced or delivered for introduction into interstate commerce after July 6, 2012 is also subject to enforcement action.
The one caveat is that FDA will exercise limited enforcement discretion for what the Agency terms a “currently marketed and listed product,” which includes a drug product covered by the notice that a company began marketing in the United States on or before September 19, 2011. For such currently marketed and listed products, FDA says that the Agency intends to excercise enforcement discretion with respect to a product that is manufactured on or after the date that is 45 days after July 6, 2012, or that is shipped on or after the date that is 90 days after July 6, 2012. After those dates, FDA says that the Agency will take enforcement action (e.g., seizure, injunction, or other judicial or administrative proceeding).