FDA Prevails in PRADAXA Patent Term Extension Regulatory Review Period Challenge

August 22, 2016

By Kurt R. Karst –  

Last month, while this blogger was on vacation enjoying the fine beers of Germany during a tour of that country, the U.S. District Court for the District of Columbia issued a Memorandum Opinion in a rather interesting Hatch-Waxman Patent Term Extension (“PTE”) dispute. As we previously posted, the case at bar offers up a new twist on the question: “When is an NDA subject to a rolling review initially submitted to FDA?”

As we previously reported (here and here), in April 2015, Boehringer Ingelheim Pharma GmbH & Co. KG and Boehringer Ingelheim Pharmaceuticals, Inc. (collectively “Boehringer”) filed a Complaint alleging that FDA and the PTO unlawfully shorted by about two months a PTE for U.S. Patent No. 6,087,380 (“the ‘380 patent) covering Boehringer’s PRADAXA (dabigatran etexilate) Capsules (NDA 022512). The Complaint was prompted by a December 2014 PTE regulatory review period decision in which FDA refused to revise the Agency’s previous determination published in the Federal Register.   In that May 2012 Notice, FDA commented that:

[Boehringer] claims December 15, 2009, as the date the new drug application (NDA) for PRADAXA (NDA 22-512) was initially submitted. However, FDA records indicate that NDA 22-512, received December 15, 2009, was incomplete.  FDA refused to file this application and notified the applicant of this fact by letter dated February 12, 2010.  The completed NDA was then submitted on April 19, 2010, which is considered to be the NDA initially submitted date.

Boehringer alleged that FDA violated the Administrative Procedure Act (“APA”) and the Hatch-Waxman Amendments and regulations – as well as inconsistency with a PTE precedent from concerning TONOCARD (tocainide HCl) Tablets – when the Agency unlawfully relied on the NDA “filing” standard instead of an “initially submitted” standard in the Agency’s PTE calculation for the ‘380 patent.

In her 26-page July 2016 ruling, Judge Colleen Kollar-Kotelly granted FDA’s Motion for Summary Judgment and denied Boehringer’s Motion for Summary Judgment.  “Ultimately, the question before the Court is narrow,” wrote Judge Kollar-Kotelly: “whether the agency’s determination of the date on which the approval phase begins is lawful under the [FDC Act], as amended, not whether Congress has chosen the best statutory scheme or whether the agency has implemented that scheme through the best set of regulations” (emphasis in original). 

With respect to Boehringer’s first argument – “that [FDA’s] determination of the start date of the approval phase of the FDA’s regulatory review period is inconsistent with the statute” – the court addressed that argument through the familiar two-step Chevron framework, ultimately concluding under Step Two that FDA’s determination is consistent with the statute.

Plaintiffs argue that the phrase “the date an application was initially submitted” is unambiguous. Defendants respond that the phrase is ambiguous because the statute does not specify exactly what must be “submitted” to satisfy that requirement.  The Court agrees with Defendants.  Plaintiffs emphasize the use of the word “initially” in the phrase “initially submitted,” suggesting talismanic importance to the use of that word.  But the fact that the statute refers to the initial submission—as opposed to a later or final submission—does not resolve the question at hand.  Notwithstanding Plaintiffs’ arguments to the contrary, the Court concludes that the statute simply does not specify what must be submitted initially to satisfy the statutory requirements.  It is clear that the application must include several components—enumerated immediately above. See 21 U.S.C. § 355(b)(1).  But it is not clear from the statutory language what must actually be submitted to qualify. That is, the statute is ambiguous as to whether a deficient application qualifies as an application that was “initially submitted” or whether materials submitted must be sufficient for substantive review in order to qualify as an application that was “initially submitted”. . . .

[T]he agency’s interpretation of the statutory language, as stated in the regulations, warrants deference and is reasonable. As a regulation duly promulgated with notice and comment there is no dispute such an interpretation is the sort of agency pronouncement that warrants deference.  Similarly, this interpretation is plainly reasonable.  The agency determined that, in order to qualify as “initially submitted,” an application must have sufficient information to allow the agency to commence a substantive review.  This is sensible. The purpose of the agency’s review process is for the agency to be able to review the application to determine whether the proposed product satisfies the several complex statutory criteria.  Any application that would not allow the FDA to begin a substantive review would not fulfill the purpose of the substantive review process.  Therefore, it is proper not to consider any such deficient application to have been “initially submitted.” [(Emphasis in original)]

Boehringer also argued that FDA’s action was inconsistent with the Agency’s regulations, and specifically with 21 C.F.R. § 60.22, which provides that the approval phase of the PTE regulatory review period begins “on the date [the application] contains sufficient information to allow FDA to commence review of the application.” But like Boehringer’s statutory argument, Judge Kollar-Kotelly deferred to FDA’s interpretation of the PTE regulation, concluding that “it was reasonable for [FDA] to determine that the materials provided to the agency as of December 15, 2009, did not ‘contain[] sufficient information to allow FDA to commence review of the application’ because they were fatally deficient and would not allow a full substantive review of the proposed product.”

Finally, Judge Kollar-Kotelly dismissed Boehringer’s argument that the Agency’s determination with respect to the ‘380 patent covering PRADAXA violated the APA in light of the TONOCARD precedent (which we discussed in a previous post). That instance appears to have been a one-off for FDA. “Ultimately, the question comes down to whether, in each individual case, the applicant has provided sufficient information for the agency to commence its substantive review,” wrote Judge Kollar-Kotelly.

Interestingly, Judge Kollar-Kotelly notes in her Opinion, and which FDA raised in the Agency Motion for Summary Judgment, that Boehringer did not avail itself of the opportunity – see 21 C.F.R. § 314.101(a)(3) – to have the PRADAXA NDA filed over protest and reviewed by FDA.  Instead, the company accepted FDA’s refuse-to-file letter and responded to the deficiencies identified therein a couple of months later, after which FDA accepted the NDA as filed.  In hindsight, would that have been the better option?  Perhaps – at least for PTE purposes – but who knows what delays (if any) might have resulted in final NDA approval.  In any case, it highlights the importance of communication between a company’s regulatory and intellectual property counsel to maximize a product’s protections.