FDA to Reconsider Approval of Generic BAYTRIL; Court Gives Importance to Unresolved Citizen Petition; Will the Decision Affect FDA Petition Procedures?

By Kurt R. Karst –      

Bayer HealthCare, LLC’s (“Bayer’s”) court challenge to FDA’s approval of Abbreviated New Animal Drug Application (“ANADA”) No. 200-495 submitted by Norbrook Laboratories, Ltd. (“Norbrook”) for Enroflox™ 100, a generic version of Bayer’s fluroquinolone animal drug Baytril® 100 (enrofloxacin) Injectable Solution, has paid off.  FDA, following an April 12, 2013 Order from the U.S. District Court for the District of Columbia suspending the ANADA approval (and its associated labeling) for use in cattle (but not in swine), administratively suspended the cattle approval pending completion of the Agency’s consideration of issues raised by Bayer in a June 2006 Citizen Petition (Docket No. FDA-2006-P-0010, formerly FDA Docket No. 2006P-0249).  That stay was memorialized in a Stipulated Stay and Preliminary Injunction agreed to by the court, but opposed by Norbrook, and cited in an April 24, 2013 Order remanding the case to FDA for reconsideration.

As we previously reported, Bayer sued FDA on April 10th alleging that the Agency’s approval of ANADA No. 200-495 for use in cattle violates the Administrative Procedure Act (“APA”) and FDC Act § 512(c)(2)(A)(ii) – as added by the Generic Animal Drug and Patent Term Restoration Act of 1988 (“GADPTRA”), Pub. Law No. 98-417, 98 Stat. 1585 (1988), the Hatch-Waxman equivalent in the animal drug world – and served as a constructive denial of Bayer’s 2006 Citizen Petition in violation of the APA.  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)).  The Single-Dose Therapy use is covered by U.S. Patent No. 5,756,506 (“the ‘506 patent”), which expires on June 27, 2015, and claims the use of enrofloxacin in a single high dose to replace multiple lower doses in bovine respiratory disease and swine pneumonia.  FDC Act § 512(c)(2)(A)(ii), as amended by GADPTRA, states 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)).

Bayer’s 2006 Citizen Petition requested that FDA refrain from approving ANADAs for generic Baytril® 100 for Multiple-Day Therapy in cattle 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 the provisions of the GADPTRA and FDA regulations and undermine the incentives for discovery and innovation that GADPTRA and patent laws were intended to protect. 

Other than a boilerplate tentative response from FDA in December 2006 saying that the Agency “is currently considering the issues raised by your citizen petition,” and that “the agency will require additional time to issue a final response because of the complexity and the number of issues raised in your petition,” the petition docket has remained dormant.  In an April 17th Opinion made public last week granting in part and denying in part Bayer’s Motion for a Temporary Restraining Order, the DC District Court (Judge Rosemary Collyer), which has previously been critical of FDA Citizen Petition decisions (see, e.g., here at pages 21-24) criticized FDA’s failure to respond to Bayer’s petition.  Judge Collyer commented in her decision:

FDA recognizes that it erred by failing to respond to Bayer’s Citizen Petition before approving Enroflox but argues that the Court cannot conclude that FDA “knew” when making its decision that off-label use was reasonably certain to occur.  The Court rejects FDA’s formulation of the issue: resolution does not turn here on what FDA “knew” in a vacuum, but whether, based on all the facts before it, FDA had found that the conditions of use specified in the proposed labeling were not reasonably certain to be followed in practice.  Since FDA offers no evidence that it considered the full record before it or made the necessary finding, FDA presents an exceptionally weak position despite the excellence of its lawyering. . . .

The facts set forth in the Petition stand unchallenged and bereft of reasoned agency response.  Although counsel for FDA claimed that someone within FDA had prepared a tentative draft response denying the Citizen Petition, neither a “tentative draft” nor the prediction that a response is forthcoming can substitute for reasoned decisionmaking at the time FDA approved the Norbrook application for Enroflox.

At this juncture, FDA presents only legal argument that the Court should presume regularity and defer to its expertise.  But, while agency action may generally be “entitled to a presumption of regularity,” here FDA itself acknowledges that its action has not been regular: it failed to respond to the Citizen Petition for years and failed to provide a reasoned basis for rejecting it before approving Enroflox.  Further, the present record is devoid of any explanation at all for the basis for FDA’s decision to approve Enroflox. [(Emphasis in original; internal citations omitted)]

FDA’s failure to timely respond to citizen petitions (or to provide a substanstantive response and not just a denial without comment) before taking an action has been a sticking point with the FDA-regulated industry for years.  See, e.g., Warner-Lambert Co. v. Shalala, 202 F.3d 326 (D.C. Cir. 2000).  Indeed, Purdue Pharma L.P. (“Purdue”) recently submitted a Petition for Reconsideration (Docket No. FDA-2012-P-0939) after FDA denied without comment an August 2012 Citizen Petition concerning the approval of generic versions of reformulated OxyContin® (oxycodone HCl controlled-release tablets) approved under NDA No. 022272.  According to Purdue, FDA’s denial of the petition on non-substantive grounds was improper and based on a flawed interpretation of FDC Act § 505(q), which requires FDA to respond to certain petitions within 150 days of receipt.  Will companies now argue, in light of the Baytril® decision, that this kind of response is inadequate?  Will FDA have to change the way the Agency handles Citizen Petitions?  Something tells us that Judge Collyer’s Baytril® decision will show up again in litigation with FDA.