FDA’s decision that Ranbaxy Laboratories Ltd. did not forfeit 180-day generic marketing exclusivity for Novartis AG’s Diovan (valsartan) was based on more than just the mere fact that publication of a U.S. Pharmacopeia monograph for the hypertension drug resulted in new review requirements, a federal court ruled Dec. 27 in a lawsuit brought by Mylan Laboratories Ltd.

Judge John Bates of the U.S. District Court for the District of Columbia said FDA’s conclusion that the publication of the new USP monograph caused first-filer Ranbaxy’s failure to secure ANDA tentative approval within the statutory 30-month forfeiture period followed a logical path and was based on reasoned decision-making.

The court denied Mylan’s request for a preliminary injunction requiring FDA to grant final approval of its valsartan ANDA. However, the decision sheds no new light on the status of Ranbaxy’s first-filed application or when the first single-ingredient valsartan generic might launch.

Mylan’s Quick Trip To Court

The court's decision has no impact on the commercial market, as the agency has yet to grant final approval to any generic versions of Diovan. Ranbaxy, Mylan and Ivax Pharmaceuticals Inc. (part of Teva Pharmaceutical Industries Ltd.), hold ANDA tentative approval for single-ingredient valsartan, but the latter two companies are blocked from coming to market by Ranbaxy’s 180-day exclusivity.

Pediatric exclusivity for Novartis’ valsartan compound patent expired in September, at which time Mylan launched the first generic version of Diovan HCT (valsartan/hydrochlorothiazide) with 180 days of marketing exclusivity ([A#14120925001]).

Less than two weeks after the valsartan patent expired, Mylan sued FDA requesting the court vacate the agency’s decision that Ranbaxy retained 180-day exclusivity rights on single-ingredient valsartan even though it had failed to timely secure ANDA tentative approval Also see "Mylan vs. FDA (And Ranbaxy): Diovan Exclusivity Forfeiture Edition" - Pink Sheet, 4 October, 2012..

Under the Medicare Modernization Act of 2003, a first-filer forfeits exclusivity if it fails to obtain tentative approval within 30 months after the date on which the application is filed, unless that failure is caused by a change in, or a review of, the approval requirements imposed after the date on which the application was filed.

New Standards Vs. Existing Requirements

FDA determined that Ranbaxy had not forfeited its eligibility for 180-day exclusivity because the company’s efforts to comply with the new USP monograph for valsartan (published in May 2007, about two months before the 30-month forfeiture deadline) and FDA’s subsequent review were a cause of Ranbaxy’s failure to secure tentative approval in a timely fashion.

In its lawsuit, Mylan did not challenge the agency’s determination that there was a change in the requirements for approval. However, it challenged the causation determination, arguing that FDA had given no reasoned explanation for determining that publication of the USP monograph caused Ranbaxy’s delay in getting tentative approval.

In a September 2012 memo on the valsartan forfeiture issue, FDA said it takes into consideration seven factors in deciding whether publication or change of a USP monograph has caused a failure to obtain tentative approval. However, Mylan said that FDA failed to discuss or apply one of these factors – the consistency of the new or changed monograph with pre-existing approval requirements.

Judge Bates said that during a hearing in the case, FDA counsel asserted this factor was not relevant because prior to the May 2007 publication of the USP monograph, there were no official standards for valsartan set forth in any USP monograph of other compendium. Rather, the pre-existing requirements were matters the agency and Ranbaxy had agreed upon in a back-and-forth process.

The court agreed with Mylan that a forfeiture assessment must include an analysis of whether the new approval standards are consistent with pre-existing requirements.

Nevertheless, the judge agreed with Mylan that this consistency factor should be considered in the causation analysis.

“If this factor is not part of the analysis, and only the other factors need be considered, then the causation analysis approaches a bright-line test,” the court said. “Considering those factors alone, nearly any publication of a new, official USP monograph close to the 30-month forfeiture date would be sufficient to ‘cause’ a delay in tentative approval. The Court will not give the forfeiture exception this interpretation. Causation in this context requires a showing of something more than just the fact and timing of a USP monograph publication.”

FDA’s Clear Path To Determining Causation

However, the administrative record shows that FDA’s decision was based on more than the mere fact and timing of the monograph’s publication, the court said, noting that the agency’s September 2012 memo discusses Ranbaxy’s efforts to comply with the monograph.

“FDA’s ‘path’ to its conclusion on causation is not difficult to decipher,” the court said. “A new, final USP monograph was published; Ranbaxy made an initial effort to comply with the monograph; FDA then asked for more data; Ranbaxy gave FDA more data; and because FDA had to review Ranbaxy's amendments and the additional data to ensure that Ranbaxy's drug substance specifications and test methods met the standards set forth in the new monograph, tentative approval was delayed. This connection between the specific facts and FDA's conclusion is apparent from the face of the Forfeiture Memo and is both logical and rational.”

The court rejected Mylan’s argument that the May 2007 monograph publication could not have caused the delay in tentative approval because an almost identical proposed monograph had been published more than a year earlier. Ranbaxy was not required to comply with the proposed monograph, the court said, adding that the agency generally requires ANDA applicants to comply with official, final monographs.

Where’s Ranbaxy’s ANDA?

The judge also declined to consider Mylan’s assertion that Ranbaxy is not actively pursuing approval of its ANDA, saying the plaintiff had raised this argument too late.

Notably, the decision is silent on the current status of Ranbaxy’s tentatively approved ANDA and the impact, if any, of the company’s consent decree on that application.

The consent decree resulted from a multi-year investigation by FDA and the Department of Justice into Good Manufacturing Practice violations and data integrity problems at Ranbaxy facilities in India and New York. The decree contains unusual provisions governing the relinquishment of generic marketing exclusivity on up to eight products that have not been publicly identified ([A#00120130016]).

It is unclear if valsartan is among those eight products. Ranbaxy told “The Pink Sheet” DAILY that the company is working with FDA and will launch generic valsartan upon final approval.

Diovan Generic Exclusivity Mystery Deepens After Judge Tosses Mylan Lawsuit

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