Generic BAYTRIL Approval Suspended; Bayer Alleges ANADA Approval Violates GADPTRA and APA

April 15, 2013

By Kurt R. Karst –      

“GADPTRA” – Now there’s an acronym you don’t see very often on this blog.  It stands for the Generic Animal Drug and Patent Term Restoration Act of 1988, Pub. Law No. 98-417, 98 Stat. 1585 (1988), which is the Hatch-Waxman equivalent for generic animal drugs.  Our only specific reference to GADPTRA in the 6+ years we have been blogging was in a June 2011 post concerning the extension of a 30-month litigation stay of approval of an Abbreviated New Animal Drug Application (“ANADA”) submitted by Norbrook Labs. for a generic version of Bayer’s Baytril® 100 (enrofloxacin) Injectable Solution.  Baytril® 100, a fluroquinolone, is covered under New Animal Drug Application (“NADA”) No. 141-068 and is listed in the Green Book (the animal drug equivalent of the Orange Book) with U.S. Patent No. 5,756,506 (“the ‘506 patent”), which expires on June 27, 2015.  The ‘506 patent covers methods of treating bacterial infections by the administration of a single high dose of the drug.  FDA initially approved Baytril® 100 on July 24, 1998 for the treatment of Bovine Respiratory Disease (“BRD”) associated with Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus.  Subsequent supplemental NADA approvals have added conditions of use of the product.  Importantly, Baytril® 100 is approved for two different dosing regimens: (1) Single-Dose Therapy (7.5 to 12.5 mg/kg of body weight (3.4 to 5.7 mL/100 lb)); and (2) Multiple-Day Therapy (2.5 to 5.0 mg/kg of body weight (1.1 to 2.3 mL/100 lb)).

Why so much detail about our prior post on Baytril® 100 and GADPRTA?  Because it just so happens that Bayer sued FDA last week in the U.S. District Court for the District of Columbia after the Agency approved Norbrook’s ANADA No. 200-495 for a generic version of Baytril® 100 called Enroflox™ 100.  Bayer alleges in its Complaint that FDA violated the Administrative Procedure Act (“APA”) and the FDC Act, as amended by GADPTRA, when the Agency approved Norbrook’s ANADA No. 200-495.  Bayer also filed a motion seeking a Temporary Restraining Order and Preliminary Injunction.  Bayer asks the court to enter judgment declaring, among other things, that FDA’s approval of ANADA No. 200-495 violates the APA and FDC Act § 512(c)(2)(A)(ii) and that FDA constructively denied a 2006 Bayer Citizen Pettion (more on that below) in violation of the APA.  Bayer asks the court to enter judgment vacating the ANADA approval and enjoining FDA from aproving any ANADA for a generic version of Baytril® 100 not indicated for Single-Dose Therapy of BRD. 

Unfortunately, Bayer’s legal memorandum accompanying the company’s Motion for a Temporary Restraining Order and Preliminary Injunction is under seal, so there’s not a lot for us to go on.  The Complaint does reference, however, a June 2006 Citizen Petition (Docket No. FDA-2006-P-0010, formerly FDA Docket No. 2006P-0249) to which FDA has not yet substantively responded, and says that FDA’s approval of Norbrook’s ANADA No. 200-495 is a constructive denial of the citizen petition in violation of the APA, and that the court should order FDA to “issue a well-reasoned response to Bayer’s Citizen Petition that considers all aspects of the issues raised therein, in advance of approval of any application to market a generic version of Baytril® 100.”  (FDA also failed to issue a substantive response on a second Citizen petition – Docket No. FDA-2009-P-0581 – concerning a 30-month patent litigation stay on ANADA approval, although that petition is not at issue in the case.)

Bayer asks FDA in the company’s 2006 petition to refain from approving ANADAs for generic Baytril® 100 for Multiple-Day Therapy with labeling that omits information on Single-Dose Therapy protected by the ‘506 patent.  According to Bayer, any generic approved for Multiple-Day Therapy only will be promoted and used extralabel for the protected Single-Dose Therapy, which would directly conflict with express provisions of the GADPTRA and FDA regulations and undermine the incentives for discovery and innovation that GADPTRA and patent laws were intended to protect. 

The GADPTRA amended the FDC Act to state, at Section 512(c)(2)(A)(ii), that FDA will approve an ANADA unless, among other things, the Agency finds that “the conditions of use prescribed, recommended, or suggested in the proposed labeling are not reasonably certain to be followed in practice . . . .”  FDA’s regulations prohibit the extralabel use of fluoroquinolones in food-producing animals (21 C.F.R. § 530.41(a)(10)), and, in particular, extralabel use of enrofloxacin in food-producing animals (21 C.F.R. §522.812(d)(2)(iii)).  In addition, FDA published an advisory in September 1998 notifying industry about the prohibition against extralabel use of enrofloxacin (see here).  According to Bayer, “[i]t is reasonable to conclude that any generic approved for the [Multiple-Day Therapy] dosing regimen would likely be used as a [Single-Dose Therapy].”  As such, says Bayer, approving generic Baytril® 100 for Multiple-Day Therapy only would conflict with the statute. 

Last Friday, the D.C. District Court (Judge Rosemary M. Collyer) issued an Order granting in part and denying in part  Bayer’s motion for a Temporary Restraining Order and suspended the approval of Norbrook’s ANADA No. 200-495.  According to press reports, Judge Collyer “blasted the FDA for failing to provide any evidence to the court that it considered Bayer's allegations that Norbrook's Enroflox 100 would unavoidably infringe on its Baytril patent” before approving the ANADA.  A hearing on Bayer’s Motion for a Preliminary Injunction is scheduled for April 25, 2013 at 1:30 PM.