Boehringer Ingelheim Pharma GMBH & Co. KG v. FDA

The FDA’s interpretation of the statutory language determining when an NDA is “initially submitted” is due deference, is reasonable, is consistent, and is not arbitrary or capricious.

October 25, 2016

GENERICally Speaking

Case Name: Boehringer Ingelheim Pharma GMBH & Co. KG v. FDA, Civ. No. 15-656 (CKK), 2016 U.S. Dist. LEXIS 86952 (D.D.C. July 6, 2016) (Kollar-Kotelly, J.) 

Drug Product and Patent(s)-in-Suit: Pradaxa® (dabigatran etexilate mesylate); U.S. Patent No. 6,087,380 (“the ’380 patent”)

Nature of the Case and Issue(s) Presented: Boehringer Ingelheim (“BI”) owns the ’380 patent, which covers dabigatran. On August 6, 2003, the FDA granted BI permission to begin clinical trials on Pradaxa. On August 17, 2009, BI told the FDA that it intended to request priority review and the FDA responded that it “believe[d] it likely” the application for Pradaxa would receive priority. The FDA instructed BI to submit its application modules to the FDA on a rolling basis and “[a]t the time the last module of the [New Drug Application] is received, the decision will be made regarding a priority review, and the review clock will start.” On December 15, 2009, BI submitted its eleventh submission and notified the FDA that it was the last submission in its dabigatran NDA and BI requested priority designation for its application. On January 5, 2010, the FDA sent BI a letter acknowledging that it had received the application on December 15, 2009, and that it would be dated December 15, 2009. Within 60 days after the FDA receives an application, the agency will determine whether the application may be filed. The filing of an application means that the FDA has made a threshold determination that the application is sufficiently complete to permit a substantive review. On February 12, 2010, the FDA sent BI a letter stating “[a]fter a preliminary review, we find that your application is not sufficiently complete to permit a substantive review” and refused to file the application. The letter also noted that the FDA would refund 75% of the total user fee associated with the application, and further informed BI of its ability to seek review of the agency’s “refusal to file” decision.

BI and the FDA continued to exchange e-mails regarding the materials that had already been submitted. In addition, on February 18, 2010 the FDA met with BI regarding steps for moving forward. Following that meeting BI provided additional materials on February 19, 2010, which had been requested by the agency. That same day, by a separate submission, and subsequently thereafter, BI provided additional information that responded to the FDA’s request for information in light of the deficiencies in the materials previously submitted. BI provided another submission on April 19, 2010, stating that it “provides the final documents to the complete the original new drug application” for the drug in question, and again requested priority designation for the application, as it had done with respect to the application materials submitted on December 15, 2009. On June 3, 2010, the FDA sent a letter to BI indicating that the application was “sufficiently complete to permit a substantive review” and deemed filed 60 days after the application was received (April 19, 2010). The FDA also determined that the review classification for the application was “priority.”

On December 10, 2010, BI applied for a patent-term extension for the ’380 patent in connection with the FDA review and approval of Pradaxa. BI sought an extension of 1,469 days—in light of its claim of a 2,322-day testing phase, beginning on August 7, 2003, and ending on December 15, 2009, and its claim of a 308-day approval phase, beginning on December 15, 2009, and ending on October 19, 2010. The FDA determined that the regulatory review period was 2,633 days—2,449 days during the testing phase and 184 days in the approval phase. In the FDA’s letter to the PTO notifying it of the length of the regulatory review period, the FDA explained that FDA records indicated that NDA 22-512, received December 15, 2009, was incomplete, the FDA refused to file this application and notified the applicant of this fact by letter dated February 12, 2010, and that the completed NDA was then submitted on April 19, 2010, which was considered to be the NOA initially submitted date. This determination was published in the Federal Register as required by law, and the FDA presented there the same explanation regarding the lengths of the testing and approval phases. On June 27, 2012, BI requested that date dividing the testing and approval phases be shifted earlier to December 15, 2009, the date that it first claimed it had submitted all materials necessary for FDA review. The FDA denied BI’s request with a lengthy explanation of why it determined that the beginning of the approval phase was April 19, 2010.

BI brought suit challenging the FDA’s determination of the regulatory review period. Specifically, BI argued that the approval phase ought to be considered to begin on December 15, 2009, rather than on April 19, 2010, and that the agency’s contrary conclusion was legally flawed. The legal issue before the court was as follows: the legal sufficiency of the FDA’s interpretation of the statutory reference to “the date an application was initially submitted for such [approved] drug product” and its implementation of that interpretation. Plaintiffs moved for summary judgment while defendants moved to dismiss, or in the alternative cross-motion for summary judgment. Plaintiffs argue that the FDA violated the relevant statutory provisions, that the action violated the agency’s own regulations, and the FDA acted arbitrarily and capriciously because this action was inconsistent with prior agency practice. Defendants responded that the FDA’s interpretation of the relevant statutory language is due deference, that its interpretation of that language was reasonable, that its action in this case was consistent with its regulations and the statutory language, and that it did not act arbitrarily or capriciously. The court found in favor of the FDA.

Why the FDA prevailed: The court conducted its analysis per Chevron U.S.A. Inc. v. NRDC, 467 U.S. 837 (1984). First, the court asks “whether Congress has directly spoken to the precise question at issue, in which case we must give effect to the unambiguously expressed intent of Congress.” If the statute is silent or ambiguous with respect to the specific issue, however, the court moves to the second step and defer to the agency’s interpretation as long as it is based on a permissible construction of the statute. Moreover, it is a fundamental principle of administrative law that a court reviews the agency’s interpretation of its own regulations with “substantial deference” allowing that interpretation to control unless “plainly erroneous or inconsistent with the regulation.”

Plaintiffs first argued that the FDA’s determination of the start date of the approval phase of the regulatory review period was inconsistent with the statute. Plaintiffs argued that the phrase “the date an application was initially submitted” was unambiguous. Defendants responded that the phrase is ambiguous because the statute did not specify exactly what must be “submitted” to satisfy that requirement. The court agreed with Defendants, finding that the statute simply did not specify what must be submitted initially to satisfy the statutory requirements. It was clear that the application must include several components, but it was not clear from the statutory language what must actually be submitted to qualify. The court concluded that, as the agency argued, Congress has not spoken to the question at issue. Therefore, it proceeded to analyze the statutory provisions under Chevron Step Two.

Under Chevron Step Two, court decided the following issue: whether the FDA’s answer was based on a permissible construction of the statute. Under FDA regulations, an application “is initially submitted on the date it contains sufficient information to allow FDA to commence review of the application.” The FDA’s interpretation of the statutory language, as stated in the regulations, warranted deference and was reasonable. As a regulation duly promulgated with notice and comment there was no dispute such an interpretation was the sort of agency pronouncement that warranted deference. Moreover, the FDA determined that, in order to qualify as “initially submitted,” an application must have sufficient information to allow the agency to commence a substantive review. The court found this sensible. Furthermore, the FDA’s approach minimized the risk of applicants’ strategically filing applications before they are fully ready for review for the express purpose of obtaining longer patent-term extensions. For those reasons, it was reasonable for the FDA to consider an application to be “initially submitted” only when the application is ready for substantive review.

The court also concluded that the FDA’s implementation of the statutory scheme was reasonable. It was true that the FDA began some review shortly after receiving the application in order to determine whether the application was sufficiently complete to begin its substantive review. But the mere assessment of the application for completeness was not tantamount to the FDA’s substantive review. How else could the FDA determine that the application was deficient in order to inform the applicant of the deficiency and of the necessity of submitting additional materials in order to move forward in the review process? Here, the FDA determined that the application as delivered on December 15, 2009 was deficient. The issues that the FDA based its decision on were not minor issues that could be resolved as the substantive review process proceeded; rather, the errors discovered “called into question the overall quality of these datasets.” Moreover, BI did not exercise its right to have its December 15, 2009, application filed over protest. Instead, it accepted the refund of 75% of the filing fees that it had paid for its earlier filings and proceeded to provide additional information required by the FDA in order to remedy the deficiencies in the submissions to that point. Additionally, the determination of whether a submission is sufficient to permit the FDA’s statutorily-mandated substantive review is the sort of issue that warrants agency deference. Thus, the FDA’s implementation of the statutory and regulatory scheme in this case was reasonable.

Finally, the court found that the FDA’s determination was consistent with numerous similar determinations made in other cases.

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