FDA Continues Aggressive Marketed Unapproved Drugs Enforcement Initiative

May 1, 2007

As we previously reported, FDA has promised to accelerate its enforcement efforts against marketed unapproved drugs in 2007.  Indeed, in the past month, FDA has announced two enforcement actions, and future actions are likely.

In early April 2007, FDA announced that companies must stop manufacturing and distributing unapproved suppository drug products containing trimethobenzamide hydrochloride as of May 9, 2007, because such drug products lack evidence of effectiveness. Trimethobenzamide is used to treat nausea and vomiting in adults and children. FDA’s Federal Register notice outlines the Agency’s order to manufacturers and distributors.  The notice concludes all outstanding issues for drugs containing trimethobenzamide under the Drug Efficacy Study Implementation program (“DESI”) proceeding FDA began for such drug products in 1971.

In 1979, FDA announced in a DESI notice that the Agency was classifying trimethobenzamide hydrochloride suppositories as lacking substantial evidence of effectiveness, and proposed to withdraw approval of the NDAs for trimethobenzamide hydrochloride suppositories.  During the past 28 years, FDA has evaluated efficacy data on trimethobenzamide hydrochloride suppositories and has been in discussions with companies marketing such drug products. After one company notified FDA that it had decided not to pursue additional studies of its drug product, TIGAN Suppositories, FDA decided to take action to prevent the continued marketing of such drug products.

On April 25, 2007, FDA announced the entry of a Consent Decree of Permanent Injunction against PharmaFab Inc., its subsidiary, PFab LP, and two company officials to stop the illegal manufacture and distribution of various prescription and OTC drug products.  The Consent Decree follows two FDA Warning Letters sent to PharmaFab in October 2002 and June 2004 noting serious deviations from Current Good Manufacturing Practice (“CGMP”) and the lack of required FDA approval for several drug products.

According to FDA’s Complaint For Permanent Injunction, PharmaFab failed to comply with CGMP by not investigating manufacturing failures and by not recording and justifying why it deviated from written manufacturing procedures. PharmaFab also lacked an effective quality control unit and failed to establish reliable expiration dates for products.  FDA’s complaint also adds unapproved new drug charges with respect to 8 drug products:

1.         De-Congestine Sustained Release Capsules;

2.         GFN 1200lDM 60/PSE 60 Extended-Release Tablets;

3.         Rhinacon A Tablets;

4.         Sudal 12 Chewable Tablets;

5.         Histex PD 12 Suspension;

6.         Atuss HX CIII;

7.         Ergotrate Tablets; and

8.         Hyoscyamine Sulfate Time-Release Capsules

FDA stated in its June 2006 Marketed Unapproved Drugs Compliance Policy Guide that the Agency will follow a risk-based approach with regard to enforcement against marketed unapproved products. Under this approach, FDA gives higher priority to enforcement action against unapproved drugs in several categories, including unapproved new drugs that are also violative of the FDC Act in other ways (e.g., CGMP violations).  FDA relies on the decision in United States v. Sage Pharma., Inc., 210 F.3d 475 (5th Cir. 2000), to permit the addition of unapproved new drug charges after finding CGMP violations. In Sage, the United States Court of Appeals for the Fifth Circuit agreed that FDA was permitted “to address the unapproved status of a particular drug outside the established priorities in the same enforcement proceeding as other violations of the [FDC Act.].”

Categories: Enforcement