Wyeth Sues FDA over Generic ZOSYN Approvals; Lawsuit Challenges FDA Inactive Ingredient Policy and Same Labeling Requirement

September 23, 2009

By Kurt R. Karst –      

Late yesterday (Sept. 22nd), Wyeth Pharmaceuticals (“Wyeth”) sued FDA in the U.S. District Court for the District of Columbia over the Agency’s recent decision to approve two ANDAs for generic versions of ZOSYN (piperacillin sodium; tazobactam sodium) Injection.  Both ANDAs are owned by Orchid Healthcare (“Orchid”) and were approved (here and here) on September 15, 2009 following FDA’s decision on several related citizen petitions.  As we previously reported, FDA’s decision to grant petitions submitted by generic manufacturers (and largely deny a Wyeth petition) and approve ANDAs reaffirmed an Agency policy that FDA will, in the context of discontinued drug product formulations, waive its so-called “exception excipient regulations” to permit the receipt and approval of an ANDA for a drug product containing a so-called “non-exception excipient” change from the Reference Listed Drug.

By way of background, in September 2005, FDA approved an NDA supplement for a new formulation of ZOSYN containing edetate disodium dihydrate (“EDTA”) and citric acid monohydrate, which reportedly function in the drug product as a chelator (a non-exception excipient) and a buffer, respectively.  Several petitions were submitted to FDA requesting that the Agency: (1) determine that the formulation of ZOSYN originally approved by FDA was not discontinued for safety or efficacy reasons; and (2) accept ANDAs for generic versions of ZOSYN duplicating the discontinued formulations (i.e., without EDTA and citric acid).  FDA granted the petitions in its September 15th response, and commented that “experience with Wyeth's original Zosyn formulation and FDA’s recent analysis has shown that the inactive ingredients in the ANDA for piperacilin and tazobaetam for injection duplicating the original Zosyn formulation are safe. . . .”   Wyeth contended in its own citizen petition that the new formulation of ZOSYN was essential to its safe use – specifically that EDTA and citric acid are essential to the safe co-administration of ZOSYN with Lactated Ringers Solution (“LRS”) – and that ANDAs should not be approved with the discontinued formulation.  Alternatively, Wyeth requested that FDA require any generic appliant whose drug could not safely be co-administered with LRS to implement a Risk Management Action Plan (“RiskMAP”) “to ensure that healthcare professionals were aware of and understood the [product] differences.”

Wyeth’s September 22nd complaint challenges FDA’s petition decision and ANDA approval decisions as a violation of the Administrative Procedure Act, as well as violations of FDA’s ANDA exception excipient regulations (21 C.F.R. § 314.94(a)(9)(iii); 21 C.F.R. § 314.127(a)(8)(ii)(A)) and the statutory and regulatory same labeling requirement (FDC Act § 505(j)(2)(A)(v); 21 C.F.R. § 314.94(a)(8)(iv)).  According to Wyeth’s complaint:

FDA’s decision to approve a generic formulation that lacks two inactive ingredients that are essential to the safe co-administration of Zosyn with LRS was wrong as a matter of fact and law.  That decision was based on an impermissibly narrow view of generic drug safety, which focused only on the intrinsic safety of the product under the labeled conditions for use and ignored the risks of confusion and medication error that could result in the product being used in a manner contrary to the labeled warnings.  Given the evident purpose of the Hatch-Waxman Act and the related body of law governing generic approvals, statutory and regulatory requirements that products be the “same” can only be waived where the evidence demonstrates not only that the differences do not undermine the intrinsic safety of the generic product viewed in isolation, but also that they will not compromise patient health and safety under the likely conditions of actual use by clinicians.  The evidence is directly to the contrary with respect to the approved generic formulation. 

Wyeth also filed a Motion for a Preliminary Injunction or a Temporary Restraining Order (and a supporting Memorandum of Points and Authorities) that would, if granted, require FDA to withdraw or suspend the Orchid ANDA approvals.  Wyeth is seeking a hearing on or before Friday, September 25th.

Wyeth’s lawsuit – filed on the first day of Fall 2009 – follows a rather active summer in which FDA was sued several times, including over generic drug approvals for ELOXATIN (oxaliplatin) and PROGRAF (tacrolimus).


  • US court denies Wyeth bid to halt Zosyn generic-India's Orchid (Reuters).
  • A copy of the district court's September 24th Memorandum Opinion is available here.
Categories: Hatch-Waxman