The Ascension of FDA’s September 19, 2011 Marketed Unapproved Drugs Compliance Policy Guide

By Kurt R. Karst –      

FDA’s recent announcement that the Agency seized more than $11,185,000 worth of unapproved drugs marketed by Ascend Laboratories (“Ascend”) is the latest, and most clear example yet of FDA taking action pursuant to the Agency’s September 19, 2011 Marketed Unapproved Drugs Compliance Policy Guide, Sec. 440.100, Marketed New Drugs Without Approved NDAs or ANDAs (“Unapproved Drugs CPG”) (Docket No. FDA-2011-D-0633), which is the cornerstone of FDA’s Unapproved Drugs Initiative.  FDA’s Unapproved Drugs CPG is specifically called out in the Verified Complaint for Forfeiture In Rem filed in the U.S. District Court for the Southern District of Ohio last month. 

As we previously reported (here and here), the September 2011 Unapproved Drugs CPG revised a previous version of the document issued in June 2006.  In that previous version, FDA articulated the Agency’s risk-based enforcement approach to taking enforcement action with respect to the manufacture and distribution of marketed unapproved drugs.  Under that policy, FDA gives higher priority to enforcement action against unapproved drugs in certain categories, including drugs that present direct challenges to the “new drug” approval and over-the-counter drug monograph systems.  The September 2011 Unapproved Drugs CPG also drew a new line in the sand for enforcement discretion purposes.  In it FDA states:

The enforcement priorities and potential exercise of enforcement discretion discussed in this guidance apply only to unapproved drug products that are being commercially used or sold as of September 19, 2011.  All unapproved drugs introduced onto the market after that date are subject to immediate enforcement action at any time, without prior notice and without regard to the enforcement priorities set forth below.  In light of the notice provided by this guidance, we believe it is inappropriate to exercise enforcement discretion with respect to unapproved drugs that a company (including a manufacturer or distributor) begins marketing after September 19, 2011.

Over the nearly three years since issuance of the September 2011 Unapproved Drugs CPG, FDA has cited it on occasion in Federal Register notices concerning particular drugs or categories of drugs for purposes of explaining how the Agency intends to approach enforcement actions (see, e.g., here, here, and here).  In one Warning Letter issued in February 2012, FDA cited the Unapproved Drugs CPG in relation to certain marketed unapproved drugs; however, because the names of those products is redacted, it is unclear whether FDA’s enforcement action was specifically targeted to products initially marketed after September 19, 2011.

FDA’s seizure action with respect to Ascend, however, leaves little doubt that the Agency’s September 2011 Unapproved Drugs CPG is the basis for FDA’s decision to take enforcement action and not to exercise enforcement discretion.  According to the Complaint, the unapproved articles at issue – Pramoxine-HC Otic Drops, Hydrocortisone Acetate Suppositories, and Urea Cream –

are new drugs that are not the subjects of approved NDAs or ANDAs.  On September 21, 2011, in a Federal Register notice, FDA revised a 2006 Comp[liance Policy Guide (CPG), Sec. 440.100, “Marketed New Drugs Without Approved NDAs or ANDAs.”  According to this revision, any unapproved new drug product that is introduced into interstate commerce after September 19, 2011 is subject to immediate enforcement action without prior notice.

Although the Complaint does not say exactly when the Ascend products were first marketed or how FDA makes such a determination, we think FDA referenced the National Drug Code (“NDC”) Directory, which includes a Start Marketing Date field.  According to the NDC Directory, Ascend identified a start date for each of the products subject to the Complaint that is after September 19, 2011: Pramoxine-HC Otic Drops show a date of 09-26-2011; Hydrocortisone Acetate Suppositories show a date of 10-01-2013; and the Urea Cream products show dates of 06-01-2013 and 01-16-2012.

Interestingly, FDA took action against Ascend’s Urea Cream products notwithstaning the  inclusion of urea products in the OTC Drug Review.  FDA has a long-standing regulatory compliance policy for OTC drugs under which the Agency generally defers action on products that contain active ingredients and bear label claims that are included in the OTC Review.  In June 2008, FDA issued a proposed rule in response to a December 2003 notice.  In the June 2008 notice, FDA proposes that “[a]ny drug products containing urea for any labeled claims” are not Generally Recognized as Safe and Effective (“GRASE”) and are misbranded in the absence of an approved NDA.  At least one comment submitted to FDA in response to the proposed rule argues that urea is GRASE.  That proceeding is pending to this day.  FDA’s enforcement action against Ascend at least suggests that even in the face of other compliance policies, companies that begin marketing after September 19, 2011 any product FDA considers an unapproved new drug may be subject to immediate enforcement action.