Boehringer Ingelheim Pharma Gmbh & Co. Kg v. United States Food and Drug Administration

UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLUMBIA

BOEHRINGER INGELHEIM PHARMA
GMBH & CO. KG, et al.,
Plaintiffs
v. Civil Action No. 15-656 (CKK)
UNITED STATES FOOD AND DRUG
ADMINISTRATION, et al.,
Defendants

MEMORANDUM OPINION
(July 6, 2016)
In this challenge to an action of the United States Food and Drug Administration

(“FDA”) under the Administrative Procedure Act, the underlying facts are complex, the related

science even more so. But the legal issue before this Court is relatively narrow: 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 the agency’s implementation of that

interpretation. 1 Before the Court are Plaintiffs’ [23] Motion for Summary Judgment, and

Defendants’ [26] Motion to Dismiss, or in the Alternative Cross-Motion for Summary Judgment.

Plaintiffs argue that the FDA’s action 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 respond that the agency’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.

1
In practical terms, what is at stake is approximately 62 additional days of a patent term
extension.

1
Upon consideration of the pleadings, 2 the relevant legal authorities, and the record for

purposes of this motion, the Court GRANTS Defendants’ [26] Motion for Summary Judgment,

DENIES Plaintiffs’ [23] Motion for Summary Judgment, and DENIES AS MOOT Defendants’

[26] Motion to Dismiss. 3 The Court concludes the agency’s interpretation of the statutory

language is due deference in the Chevron framework, that the interpretation is reasonable, that

the agency reasonably applied that interpretation, and that the agency did not act arbitrarily or

capriciously. The Court also concludes that Plaintiffs have identified no other legal shortcomings

with the agency’s application of that interpretation in this case. This case is dismissed in its

entirety.

I. BACKGROUND

A. Statutory and Regulatory Framework
Under the Food, Drug, and Cosmetic Act, approval of the Food and Drug Administration

(“FDA”) is required before a new drug can be distributed in interstate commerce. See

AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1045 (Fed. Cir. 2010) (citing 21 U.S.C. § 355(a)).

“To obtain approval for a new drug, an applicant may file a New Drug Application … that

2
The Court’s consideration has focused on the following documents:
• Pls.’ Mot. for Summary Judgment (“Pls.’ Mot.”), ECF No. 23;
• Defs.’ Mot. to Dismiss, or in the Alt. Cross-Mot. for Summary Judgment and Opp’n to
Pls.’ Mot. (“Defs.’ Mot.”), ECF No. 26;
• Pls.’ Comb. Opp’n to Defs.’ Mot. & Reply (“Pls.’ Opp’n”), ECF No. 28; and
• Defs.’ Reply in Support of their Mot. (“Defs.’ Reply”), ECF No. 30.
The Court refers throughout this Memorandum Opinion only to materials in the redacted version
of the Joint Appendix. In an exercise of its discretion, the Court finds that holding oral argument
in this action would not be of assistance in rendering a decision. See LCvR 7(f).
3
The Court concludes that it is best to resolve the issues presented under the framework of the
cross-motions for summary judgment on the full record before the Court rather than on the basis
of Defendants’ motion to dismiss, presented in the alternative to its motion for summary
judgment.

2
includes examples of the proposed label for the drug and clinical data demonstrating that the

drug is safe and effective for use.” Id. (citing 21 U.S.C. § 355(b)(1)(A), (b)(1)(F)). The statute

requires that certain informational components be included in an application:

Such person shall submit to the Secretary as a part of the application (A) full
reports of investigations which have been made to show whether or not such drug
is safe for use and whether such drug is effective in use; (B) a full list of the
articles used as components of such drug; (C) a full statement of the composition
of such drug; (D) a full description of the methods used in, and the facilities and
controls used for, the manufacture, processing, and packing of such drug; (E) such
samples of such drug and of the articles used as components thereof as the
Secretary may require; (F) specimens of the labeling proposed to be used for such
drug, and (G) any assessments required under section 355c of this title.

21 U.S.C. § 355(b)(1).

To compensate patent holders for time lost regarding the use of their patents while a drug

is undergoing FDA review, Congress has provided for certain extensions of patent duration

associated with the FDA approval process. Congress promulgated these provisions in 1984

through what are often described as the Hatch-Waxman Amendments or the Hatch-Waxman Act.

See Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. 98-417, 98 Stat.

1585 (1984). The Hatch-Waxman Amendments provide for an extension of a patent’s term to

account for a portion of the time consumed by regulatory review before the FDA. See id. Under

the statute, the “regulatory review period” for a new drug such as the one whose approval is at

the center of this case consists of

(i) the period beginning on the date an exemption under subsection (i) of section
505 or subsection (d) of section 507 became effective for the approved product
and ending on the date an application was initially submitted for such drug
product under section 351, 505, or 507, and

(ii) the period beginning on the date the application was initially submitted for the
approved product under section 351, subsection (b) of section 505, or section 507
and ending on the date such application was approved under such section.

3
35 U.S.C. § 156(g)(1)(B); see Astra v. Lehman, 71 F.3d 1578, 1579 (Fed. Cir. 1995). Only drug

products submitted under section 505, codified at 21 U.S.C. § 355, are relevant to this case. In

other words, the first phase of the “regulatory review period,” which is commonly referred to as

the testing phase, ends when “an application was initially submitted for such drug product”; the

second phase of the “regulatory review period,” known as the approval phase, begins on this

same date and ends when the application is approved. For the reasons explained below, it is only

the proper calculation of the “initially submitted date”—and thus the boundary between the

testing and the approval phases—that is at issue in this case.

Subject to other exceptions not relevant here, the patent term extension is equal to half of

the length of the testing period plus the entire length of the approval period. See 35 U.S.C.

§ 156(c) (explaining that the extension equals the regulatory review period with a reduction for

half of the length of the period under section 156(g)(1)(B)(i), the testing period applicable in this

case). 4 Under regulations promulgated by the FDA regarding the determination of a patent term

extension, an application “is initially submitted on the date it contains sufficient information to

allow FDA to commence review of the application.” 21 C.F.R. § 60.22. Plaintiffs agree that this

definition is consistent with Congress’s intent in passing the Hatch-Waxman Amendments. Pls.’

Mot. at 4.

To receive a patent term extension, a patent holder must submit a timely application to

the Director of the United States Patent and Trademark Office. 35 U.S.C. § 156(d)(1); see also

4
To understand how this formula is applied, take an example of a regulatory review period of
100 days. If the period is evenly divided with 50 days in a testing phase and 50 days in the
approval phase, the patent term extension would be 75 days: half of the 50 testing days (25 days)
plus 50 approval days. Similarly, a testing phase of 52 days and an approval phase of 48 days
yields a patent term extension of 74 days: half of 52 days (26 days) plus 48 approval days. In
other words, for each day shifted from the approval phase to the testing phase, the patent term
extension is reduced by half a day.

4
Astra, 71 F.3d at 1580. For drugs such as the one at issue in this case, the Director of the Patent

and Trademark Office refers the application to the Secretary of Health and Human Services who

“determine[s] the applicable regulatory review period.” 35 U.S.C. § 156(d)(2)(A)). The Secretary

of Health and Human Services has the sole authority to determine the length of the regulatory

review period and, concomitantly, the patent term extension. Astra, 73 F.3d at 1581. The

Secretary of Health and Human Services must then communicate this information to the Patent

and Trademark Office. 35 U.S.C. § 156(d)(2)(A). Under the applicable regulations, these

responsibilities of the Secretary of Health and Human Services are delegated to the FDA. See 21

C.F.R. § 60.20; Patent Term Restoration Regulations, 53 Fed. Reg. 7,298, 7,298 (Mar. 7, 1988).

After the FDA determines the regulatory review period, it publishes that determination in

the Federal Register. 21 C.F.R. § 60.20(c). “Any person may request a revision of the regulatory

review period determination within 60 days after its initial publication in the Federal Register.”

Id. § 60.24(a). The FDA then considers such a request and makes a definitive determination of

the regulatory review period.

B. Factual Background
Plaintiff Boehringer holds all rights in U.S. Patent No. 6,087,380 (“the ’380 patent”),

which covers the active ingredient in Pradaxa. On August 6, 2003, the FDA granted Boehringer

an exemption under 21 U.S.C. § 355(i) to begin clinical trials on Pradaxa. See AR 5404; see also

Determination of Regulatory Review Period for Purposes of Patent Extension; PRADAXA, 77

Fed. Reg. 26,289, 26,289 (May 3, 2012). There is no dispute that this date—August 6, 2003—

marks the beginning of the testing phase in this case.

On August 17, 2009, the FDA officials participated in a meeting with representatives of

Boehringer regarding the development of Pradaxa. AR 5636. Certain proposed drugs are eligible

5
for priority review by the FDA. 5 AR 8192. For drugs under priority review, the agency sets a

target of approving a drug within six months rather than within 10 months. AR 8192. At the

August 2009 meeting, Boehringer indicated that it intended to request priority review for the

drug in development. AR 5637. In response, the FDA representatives indicated that they

“believe[d] it likely” the application for Pradaxa would receive priority review if Boehringer

requested one. Id. The FDA further indicated that its “ability to complete [its] review within six

months is critically dependent on the quality of your application.” Id. The agency further

indicated that “[i]n order for us to complete our review of your [New Drug Application] in a

timely fashion, we request that you submit each module as you complete it.” Id. Finally, the

agency indicated that, “[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.” Id.

In the aftermath of that meeting, Boehringer submitted portions of its applications on a

rolling basis throughout the Fall of 2009, as agreed, with the first submission on September 17,

AR 5645-46; the second and third submissions on September 30, AR 5682-83, 5685-86; the

fourth submission on October 13, AR 5699-5700; the fifth on October 27, AR 5705-06; the sixth

on November 4 and November 9, AR 5707-08 6, 5711-12; the seventh on November 13, AR

5716-17; the ninth on November 30, AR 5735-46; and the tenth on December 8, AR 5752-53. On

December 15, 2009, Boehringer submitted its eleventh submission. AR 5770. In the letter

5
See AR 8192 (“Products regulated by [the Center for Biologics Evaluation and Research] are
eligible for priority review if they provide a significant improvement in the safety or
effectiveness of the treatment, diagnosis, or prevention of a serious or life-threatening disease.”);
see also Abigail Alliance for Better Access to Dev. Drugs v. von Eschenbach, 495 F.3d 695, 699
n.4 (D.C. Cir. 2007) (“The FDA categorizes some new drugs, including nearly all cancer drugs,
as ‘priority drugs’ and seeks to accelerate their availability.”).
6
It appears that the seventh submission was mistakenly labeled as the sixth, resulting in two
submissions labeled sixth, and that the eighth was mistakenly labeled as the seventh. These
differences are immaterial to the issues presented in this case.

6
accompanying the eleventh submission, Boehringer represented that “[t]his submission provides

the final documents to complete the original new drug application for dabigatran etexilate (NDA

22-512) for the prevention of stroke and systemic embolism in patients with atrial fibrillation.”

AR 5769. Through that letter, Boehringer also requested priority designation for its application.

Id. On January 5, 2010, the FDA sent Boehringer a letter in response, acknowledging that it had

received the application denominated as NDA 22-512 on December 15, 2009, and that the

application was dated December 15, 2009. 7 AR 5794-96. That letter noted that, “[u]nless we

notify you within 60 days of the receipt date that the application is not sufficiently complete to

permit a substantive review, we will file the application on February 13, 2010 in accordance with

21 CFR 314.101(a).” 8 AR 5694.

On February 12, 2010, the agency sent Boehringer a follow-up letter stating that, “[a]fter

a preliminary review, we find that your application is not sufficiently complete to permit a

substantive review.” AR 5961 (emphasis added). Therefore, the agency refused to file the

application. Id. (citing 21 C.F.R. 314.101(d)). The agency explained why it deemed the

application insufficient as follows:

7
Contrary to Plaintiff’s position, the Court does not read any legal significance into the fact that
the agency’s letter noted that the application that was received on December 15, 2009, was dated
that same day.
8
The relevant regulations provide as follows:
Within 60 days after FDA receives an application, the agency will determine
whether the application may be filed. The filing of an application means that FDA
has made a threshold determination that the application is sufficiently complete to
permit a substantive review.
21 C.F.R. § 314.101(a)(1) (2009). If the agency does not “refuse to file” the application, the
“date of filing will be the date 60 days after the date FDA received the application.” Id.
§ 314.101(a)(2).

7
In support of the proposed indication, you conducted a single phase 3 trial titled
“Randomized Evaluation of Long term anticoagulant therapy comparing the
efficacy and safety of two blinded doses of dabigatran etexilate with open label
warfarin for the prevention of stroke and systemic embolism in patients with non-
valvular atrial fibrillation: prospective, multi-centre, parallel-group, non-
inferiority trial (RE-LY).” The primary objective of RE-LY was to demonstrate
the efficacy and safety of dabigatran etexilate in subjects with non-valvular atrial
fibrillation for the prevention of stroke and systemic embolism.

We note that you claim an overall data error rate of 0.1% or less for primary
outcome data and 0.25% or less for all other data. However, we found data errors
in five out of six subjects in our initial analysis of your INR.xpt data. These errors
are described in Tables 1 and 2. These errors include transcription errors,
transposition errors, and auditing errors.

[Data tables omitted]

We note that you closed site 6; therefore, we do not comment on problems evident
in the data from that site.

We recognize that that there may be occasional inaccuracies in a large trial
database; however, the frequency of errors in the data sets impedes our ability to
perform an adequate review, and undermines our confidence in your data.

In recognition of the importance of this priority application, we proposed a rolling
review. We will, of course, continue our review of parts of your application that
are complete and reviewable, such as the chemistry and pharmacology toxicology
sections. In addition, the clinical reviewers will work with you to evaluate further
data integrity issues and to provide comment on your plans to respond to these
issues. Please note that the above comments are only a partial listing of
deficiencies, and that there may be additional deficiencies with your submission
that are not included in this letter.

AR 5961-62. The letter also noted that the agency would refund 75% of the total user fee

associated with the application. AR 5962. Finally, the letter informed Boehringer of its ability to

seek review of the agency’s “refusal to file” decision. Id.

After the “refusal to file” decision, Boehringer and the FDA continued to exchange

emails regarding the materials that had already been submitted. AR 5970-71, 5982-83. In

addition, agency representatives met with Boehringer representatives regarding steps for moving

8
forward on February 18, 2010. AR 5984-86. The internal meeting notes from that meeting

summarized the shortcomings with Boehringer’s application as follows:

Preliminary review revealed a number of errors in the blood transfusion dataset
and the INR dataset. These errors included transcription errors, transposition
errors, and auditing errors. Though the Agency recognizes that that there will be
some errors in the datasets of large trials, the errors found by relatively
unsophisticated means in clinically important datasets during preliminary review
called into question the overall quality of those datasets.

AR 5985 (emphasis added). The agency and company representatives discussed the issues with

the data and the other materials submitted and set out a roadmap to resolve those issues. AR

5985-5986. Boehringer did not seek to have the agency file its December 15, 2009, application

over protest. See 21 C.F.R. § 314.101(a)(3) (“If, following the informal conference, the applicant

requests that FDA file the application (with or without amendments to correct the deficiencies),

the agency will file the application over protest … , notify the applicant in writing, and review it

as filed.”). Accordingly, Boehringer accepted the refund of 75% of the filing fees that it had paid

for the earlier filings. See AR 5624-5632, 5962.

Following the February, 2010, meeting between Boehringer and the agency, Boehringer

provided additional materials on February 19, 2010, which had been requested by the agency.

AR 5988-90 (“Reference is made to the communication from the Division to the Sponsor on

February 16, 2010 requesting the 85 case report forms (CRFs) from RE-LY that have been

identified in review of the transfusion page … . This submission provides the 7 additional [case

report forms] that have not been previously submitted.”). That same day, by a separate

submission, Boehringer provided additional information that responded to the agency’s request

for information in light of the deficiencies in the materials previously submitted. AR 5998-6000

(“Reference is made to the communication from the Division to the Sponsor on February 16,

2010 requesting documentation on what would trigger the investigator to complete the RE-LY

9
[case report form] 122. The medical reviewer has requested details surrounding what the

investigators were told and how they were told to fill this out. Additionally, it was requested that

this documentation be provided for all the outcome events.”). One week later, on February 26,

2010, Boehringer provided additional materials again responding to deficiencies in its earlier

submissions. AR 5998-99 (“Reference is made to the February 23, 2010 telephone conversation

from Sharon Gershon (Division of Scientific Investigations) identifying Site 0006 – Patrick

Simpson, M.D. and Site 0351 – Initially Melvin Tonkon, M.D. replaced by Charles Morcos,

M.D. as for cause inspections and requesting the following documents to be provided on 2 CDs

per site for the inspectors …. This submission provides the documents as outlined in the table

below.”). A month later, Boehringer provided yet another set of materials responding to the

agency’s “requesting additional information to assist in the medical review.” AR 6069.

More than two months after the “refusal to file” decision, Boehringer provided another

submission on April 19, 2010, and represented that that submission “provides the final

documents to the complete the original new drug application” for the drug in question. AR 6082

(emphasis added); see also id. (“Included in this submission are [case report forms] (CRFs),

narratives, updated CRF datasets, analysis datasets, PK/PD datasets, SAS programs for review

and executable SAS programs with a data Reviewer's Guide (provided in the Module 5.3.5.1

tabulations folder) to re-create the efficacy analysis dataset.”). Boehringer explained how the

new submitted information resolved deficiencies previously identified by the agency regarding

the materials that had been submitted through December 15, 2009. See AR 6082-83 (“We have

completed the additional data quality checks agreed to during the February 18, 2010 meeting

with the Agency. To the extent possible, the deficiencies noted during the initial FDA review and

those identified by the quality checks have been corrected. Based on re-analyses of the update

10
data, the primary efficacy and safety conclusions of RE-LY remain unchanged.”). Boehringer

once again requested priority designation for the application submitted on April 19, 2010, as it

had done with respect to the application materials submitted on December 15, 2009. AR 6083.

Several days in advance of the April 19, 2010, filing, Boehringer paid the filling fee for that

application. AR 5629 (Letter dated April 13, 2010, including check with filing fee).

Boehringer continued to provide additional materials after the April 19, 2010,

submission, including materials submitted on April 20, 28 and 30; May 3-7, 10, 13-14, 17, 21,

24, and 26-28; and June 1, 2010. AR 6247. On June 3, 2010, the agency sent a letter to

Boehringer indicating that the application as “originally submitted on December 15, 2009 and

resubmitted on April 19, 2010,” together with the materials submitted in April, May, and June of

that year, was “sufficiently complete to permit a substantive review.” Id.; see AR 6248.

Therefore, the agency considered the application filed 60 days after the application was received

(April 19, 2010). Id. The agency also determined that the review classification for the application

was “priority,” as requested by Boehringer, and it set a goal of completing the approval process

by October 19, 2010. See id. Boehringer continued to provide additional material amending the

application through October 19, 2010. AR 8149. On October 19, 2010, the application, as

amended, was approved by the FDA. AR 8148-49.

On December 10, 2010, Boehringer applied for a patent term extension of patent ’380 in

connection with the FDA review and approval of Pradaxa. AR 5001-5012. Boehringer 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. AR 5111-5113. The FDA determined

that the regulatory review period was 2,633 days—2,449 days during the testing phase

11
(beginning on August 6, 2003, and ending on April 19, 2010), and 184 days in the approval

phase (beginning on April 19, 2010, and ending on October 19, 2010). AR 5250. In the FDA’s

letter to the Patent and Trademark Office notifying it of the length of the regulatory review

period, the FDA explained why it determined that April 19, 2010, was the date for the transition

from the testing phase to the approval phase:

The applicant 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 Februa1y 12, 2010. The completed NDA was then submitted on April 19,
2010, which is considered to be the NOA initially submitted date.

AR 5250. 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. See 77 Fed. Reg. at 26,290.

Under the applicable regulatory provision, “[a]ny person may request a revision of the

regulatory review period determination within 60 days after its initial publication in the Federal

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. AR 5255-5273; see also

AR 5769. The FDA denied Boehringer’s request with a lengthy explanation of why it determined

that the beginning of the approval phase was April 19, 2010. See AR 5524-5532.

Boehringer brings this civil action challenging the FDA’s determination of the regulatory

review period. Specifically, Boehringer continues to argue, as it did in its initial patent term

extension request, 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 is legally flawed.

12
II. LEGAL STANDARD

Under Rule 56(a) of the Federal Rules of Civil Procedure, “[t]he court shall grant

summary judgment if the movant shows that there is no genuine dispute as to any material fact

and the movant is entitled to judgment as a matter of law.” However, “when a party seeks review

of agency action under the APA [before a district court], the district judge sits as an appellate

tribunal. The ‘entire case’ on review is a question of law.” Am. Bioscience, Inc. v. Thompson, 269

F.3d 1077, 1083 (D.C. Cir. 2001). Accordingly, “the standard set forth in Rule 56[ ] does not

apply because of the limited role of a court in reviewing the administrative record.... Summary

judgment is [ ] the mechanism for deciding whether as a matter of law the agency action is

supported by the administrative record and is otherwise consistent with the APA standard of

review.” Southeast Conference v. Vilsack, 684 F. Supp. 2d 135, 142 (D.D.C. 2010).

The APA “sets forth the full extent of judicial authority to review executive agency

action for procedural correctness.” FCC v. Fox Television Stations, Inc., 556 U.S. 502, 513

(2009). It requires courts to “hold unlawful and set aside agency action, findings, and

conclusions” that are “arbitrary, capricious, an abuse of discretion, or otherwise not in

accordance with law.” 5 U.S.C. § 706(2)(A). “This is a ‘narrow’ standard of review as courts

defer to the agency’s expertise.” Ctr. for Food Safety v. Salazar, 898 F. Supp. 2d 130, 138

(D.D.C. 2012) (quoting Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State Farm Mut. Auto. Ins. Co.,

463 U.S. 29, 43 (1983)). An agency is required to “examine the relevant data and articulate a

satisfactory explanation for its action including a rational connection between the facts found and

the choice made.” Motor Vehicle Mfrs. Ass’n, 463 U.S. at 43 (internal quotation omitted).

“Moreover, an agency cannot ‘fail[ ] to consider an important aspect of the problem’ or ‘offer[ ]

an explanation for its decision that runs counter to the evidence’ before it.” Dist. Hosp. Partners,

13
L.P. v. Burwell, 786 F.3d 46, 57 (D.C. Cir. 2015) (quoting Motor Vehicle Mfrs. Ass’n, 463 U.S. at

43). The reviewing court “is not to substitute its judgment for that of the agency.” Id.

Nevertheless, a decision that is not fully explained may be upheld “if the agency’s path may

reasonably be discerned.” Bowman Transp., Inc. v. Arkansas–Best Freight Sys., Inc., 419 U.S.

281, 286 (1974).

III. DISCUSSION

Plaintiffs argue that the FDA’s determination of the patent term extension—specifically

the agency’s determination of the date of the beginning of the approval phase—contradicts the

terms of the statute, violates the agency’s own regulations, and is inconsistent with the agency’s

own past treatment of similarly situated applicants. In response, Defendants argue that the

agency’s action is consistent with the statute, consistent with its regulations, and consistent with

its past treatment of other applications. With respect to the statute, Defendants argue that, under

the familiar two-step Chevron analysis, the statute is ambiguous and that Defendants’

determination was based on a reasonable interpretation of the statute. The Court agrees with

Defendants with respect to each issue presented.

Before proceeding to evaluate the parties’ arguments on the several issues presented to

the Court, the Court emphasizes the fundamental principles of this Court’s review of agency

actions such as the one at issue in this case. To evaluate Plaintiffs’ claim that the agency’s

determination is inconsistent with the language of the Food, Drug, and Cosmetic Act, as

amended, the Court applies the framework established in Chevron U.S.A., Inc. v. NRDC, 467

U.S. 837 (1984). The Court first 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.” Deppenbrook v. Pension Benefit Guar. Corp, 778 F.3d 166, 172 (D.C. Cir. 2015)

14
(citation omitted). “If the statute is silent or ambiguous with respect to the specific issue,

however, we move to the second step and defer to the agency's interpretation as long as it is

based on a permissible construction of the statute.” Id. “To trigger deference,” an agency must

show that Congress has “ ‘delegated authority to the agency generally to make rules carrying the

force of law’ ” and that “ ‘the agency interpretation claiming deference was promulgated in the

exercise of that authority.’ ” Fogo De Chao (Holdings) Inc. v. U.S. Dep’t of Homeland Sec., 769

F.3d 1127, 1136 (D.C. Cir. 2014) (quoting United States v. Mead Corp., 533 U.S. 218, 226–27

(2001)). Moreover, with respect to the agency’s interpretation of its own regulations, it is a

fundamental principle of administrative law that the 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.’ ” U.S. Postal Serv. v. Postal Regulatory

Comm’n, 785 F.3d 740, 750 (D.C. Cir. 2015) (quoting Thomas Jefferson University v. Shalala,

512 U.S. 504, 512, 514 (1994)).

Ultimately, the question before the Court is narrow: whether the agency’s determination

of the date on which the approval phase begins is lawful under the Food, Drug, and Cosmetic

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. See Ark Initiative v.

Tidwell, 816 F.3d 119, 126-27 (D.C. Cir. 2016) (“The question before us is of a type ubiquitous

to administrative law: Whether the Colorado rule is permissible under federal law, not whether

we believe as a matter of environmental policy it is the best rule, or even a good one.”). With that

in mind, the Court turns first to the question of consistency with the statute raised by Plaintiffs.

15
A. Consistency with the Statute
As noted above, Plaintiffs first argue that the agency’s determination of the start date of

the approval phase of the FDA’s regulatory review period is inconsistent with the statute. The

Court addresses that argument through the framework of Chevron’s two steps and, ultimately,

concludes that the agency’s determination is consistent with the statute.

a. Chevron Step One
“Under step one, the court must determine ‘whether Congress has directly spoken to the

precise question at issue.’ ” W. Minnesota Mun. Power Agency v. Fed. Energy Regulatory

Comm’n, 806 F.3d 588, 591 (D.C. Cir. 2015) (quoting Chevron, 467 U.S. at 842). “If so, then the

court and the agency must ‘give effect to the unambiguously expressed intent of Congress.’ ” Id.

(quoting Chevron, 467 U.S. at 842–43). “In addressing a question of statutory interpretation, the

court begins with the text.” Id. As presented above, the statute delineates the “approval phase” of

the regulatory review period as follows:

the period beginning on the date the application was initially submitted for the
approved product under [21 U.S.C. § 355] and ending on the date such application
was approved under such section.

35 U.S.C. § 156(g)(1)(B)(ii). In addition, section 355 requires the following components for an

application:

(A) full reports of investigations which have been made to show whether or not
such drug is safe for use and whether such drug is effective in use;

(B) a full list of the articles used as components of such drug;

(D) a full description of the methods used in, and the facilities and controls used
for, the manufacture, processing, and packing of such drug;

(E) such samples of such drug and of the articles used as components thereof as
the Secretary may require;

16
(F) specimens of the labeling proposed to be used for such drug, and

(G) any assessments required under section 355c of this title.

21 U.S.C. § 355(b)(1) (paragraph breaks added).

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.”

Plaintiffs suggest in their reply, for the first time, that “the applicant’s intent is what

matters.” Pls.’ Reply at 6. But surely the language of the statute does not unambiguously mean

that the applicant’s intent governs agency’s determination as to whether sufficient information

has been submitted in order to satisfy the statute’s requirements. Nor does the legislative history

to which Plaintiffs refer unambiguously indicate that such subjective intent is the proper standard

for determining whether the statutory requirements had been satisfied. See id. (citing AR 5562).

And it is difficult to imagine, absent more explicit direction from Congress, that the statutory

17
language means that Congress intended for the agency—and in turn this Court—to embark into

an inquiry into an applicant’s subjective state of mind in order to apply the statutory

requirements in the first instance.

In short, the Court is presented with a classic case of statutory ambiguity. The statute

states that the approval phase begins on “the date the application was initially submitted for the

approved product.” 35 U.S.C. § 156(g)(1)(B)(ii). The statute further enumerates certain

components that must be included in the application. See 21 U.S.C. § 355(b)(1). But the statute

includes no more details. It remains ambiguous, therefore, as to exactly what materials must be

submitted in order to satisfy these requirements and whether the application must be sufficient

for substantive review in order to be considered “initially submitted.” Having fully considered

the parties’ arguments regarding the statute, the Court concludes that, as the agency argues,

Congress has not spoken to the question at issue. Therefore, the Court proceeds to analyze the

statutory provisions under Chevron Step Two. 9

b. Chevron Step Two
Under Chevron Step Two, the question for the Court is “whether the agency’s answer is

based on a permissible construction of the statute.” Chevron, 467 U.S. at 843.

“Chevron deference is appropriate ‘when it appears that Congress delegated authority to

the agency generally to make rules carrying the force of law, and that the agency interpretation

claiming deference was promulgated in the exercise of that authority.’ ” Mayo Found. for Med.

Educ. & Research v. United States, 562 U.S. 44, 57 (2011) (quoting Mead Corp., 533 U.S. at

9
This Court’s conclusion that the statutory provision is ambiguous is bolstered by the decision of
the United States Court of Appeals for the Federal Circuit regarding a distinct but analogous
patent term extension provision in Wyeth Holdings Corp. v. Sebelius, 603 F.3d 1291, 1298 (Fed.
Cir. 2010).

18
226–27). “An interpretation is permissible if it is a ‘reasonable explanation of how an agency’s

interpretation serves the statute’s objectives.’ ” Council for Urological Interests v. Burwell, 790

F.3d 212, 219 (D.C. Cir. 2015) (citing Northpoint Tech., Ltd. v. FCC, 412 F.3d 145, 151 (D.C.

Cir. 2005)).

Under regulations promulgated by the FDA, for the purpose of determining a patent term

extension, an application “is initially submitted on the date it contains sufficient information to

allow FDA to commence review of the application.” 21 C.F.R. § 60.22 (emphasis added). In other

words, the application is not considered “initially submitted” if the materials provided by the

applicant are insufficient for the commencement of the FDA’s substantive review. Notably,

Plaintiffs agree that this definition is consistent with Congress’s intent in passing the Hatch-

Waxman Amendments. Pls.’ Mot. at 4. Accordingly, the Court concludes that, insofar that there is

any contrary suggestion by Plaintiffs that the regulatory language is inconsistent with the

statute’s text or purpose, such an argument is waived as a result of Plaintiffs’ explicit concession

to the contrary.

Moreover, even absent any waiver or forfeiture by Plaintiffs, the 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

19
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.”

Furthermore, the agency’s approach minimizes the risk of applicants strategically filing

applications before they are fully ready for review for the express purpose of obtaining longer

patent term extensions. Plaintiffs protest that no reasonable applicant would submit a

purposefully deficient application in order to obtain a longer patent term extension. However, the

Court concludes that it is reasonable for the agency, in light of its long experience in

administering this complex statute, to arrive at a contrary assessment and to conclude that there

is a risk of parties filing applications prematurely for strategic reasons. Moreover, even if

Plaintiffs were correct that strategic filing behavior is unlikely or infrequent, it is reasonable for

the agency to interpret the statutory framework to encourage applicants to carefully ensure that

their applications are complete and ready for substantive review prior to submitting them. For

that reason as well, it is reasonable for the agency to consider an application to be “initially

submitted” only when the application is ready for substantive review. In short, the FDA’s

interpretation of the statutory requirements is reasonable.

The Court also concludes that the agency’s implementation of the statutory scheme, as

interpreted through the agency’s regulations, is reasonable as well. As an initial matter, the Court

notes that the 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.’ ” U.S. Postal Serv., 785 F.3d at 750 (citation omitted). The agency here

determined that the materials submitted on December 15, 2009, were not sufficient to permit the

agency to commence its substantive review. It is true that the agency began some review shortly

thereafter in order to determine whether the application was sufficiently complete to begin its

20
substantive review. See AR 5794-96 (letter acknowledging receipt of application and indicating

that the agency would assess the materials submitted in order to determine whether the

application was sufficiently complete for the substantive review to begin). The agency

determined that the mere assessment of the application for completeness is not tantamount to the

agency’s substantive review of the application, and the Court concludes that this determination is

reasonable. Indeed, a contrary conclusion would vitiate the standard promulgated through the

agency’s regulations. That is, even a deficient application must be assessed to determine its

completeness. How else could the agency determine that it 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? In other words, such an initial review does not constitute

the “commencement” of the agency’s substantive review and the fact of such review does not

mean that the agency had received an application that was sufficient to permit the

commencement of its substantive review.

In this case, the agency determined that the application as delivered on December 15,

2009—when the applicant claimed it was complete—was woefully deficient. The agency later

summarized the deficiency as follows:

AR 5985 (emphasis added). The Court need not review once again the lengthy set of reasons that

justified the agency’s refusal to file the application as of December 15, 2009, reproduced in full

above, because it is clear that the issues were not simply minor issues that could be resolved as

the substantive review process proceeded. As the agency noted, the errors discovered “called into

21
question the overall quality of these datasets.” Id. Plaintiffs’ attempt to whitewash these data

quality issues, see, e.g., Pls.’ Mot. at 6, Pls.’ Reply at 8, cannot hide the serious and significant

deficiencies that the agency found with the materials submitted.

Notably, Boehringer did not exercise its right to have its December 15, 2009, application

filed over protest. See 21 C.F.R. § 314.101(a)(3) (“If, following the informal conference, the

applicant requests that FDA file the application (with or without amendments to correct the

deficiencies), the agency will file the application over protest … , notify the applicant in writing,

and review it as filed.”). Instead, it accepted the refund of 75% of the filing fees that it had paid

for its earlier filings, see AR 5624-5632, 5962, and proceeded to provide, incrementally, the

additional information required by the agency in order to remedy the deficiencies in the

submissions to that point. Boehringer provided several supplementary submissions with

additional information before stating, with its April 19, 2010, submission that “[t]his submission

provides the final documents to complete the original new drug application for dabigatran

etexilate (NDA 22-512) for the prevention of stroke and systemic embolism in patients with

atrial fibrillation.” AR 5769; see AR 5988-90 (first February 19, 2010, submission); AR 5998-

6000 (second February 19, 2010, submission); AR 5998-99 (February 26, 2010, submission); AR

6069-70 (March 30, 2010, submission). Boehringer only then paid the filing fee on April 13,

2010, shortly in advance of the April 19, 2010, submission. AR 5629. In short, after the agency

identified various deficiencies with the submissions provided through December 15, 2009, it was

necessary for Boehringer to submit substantial new data and other material before even

Boehringer itself claimed that it had provided the documents necessary to “complete” the

application. It was therefore reasonable for the agency to conclude that the application was

22
sufficient to permit a substantive review only as of the April 19, 2010, submission and not as of

the December 15, 2009, submission.

In any event, the determination of whether a submission is sufficient to permit the

agency’s statutorily-mandated substantive review is precisely the sort of issue that warrants

agency deference. It is not for this Court to second-guess the determination of the expert agency

that the data was insufficient for the agency’s subject matter experts to begin their substantive

review of the product. Therefore, the Court defers to the agency’s interpretation of its regulations

and its implementation of those regulations in this case, and it concludes that the agency’s

determinations were reasonable in that light. Having considered all of parties’ arguments, the

Court concludes that none of Plaintiffs’ arguments to the contrary are persuasive, and the Court

finds no need to address them any further. 10 In short, the agency’s implementation of the

statutory and regulatory scheme in this case was reasonable. 11

B. Consistency with the Agency’s Regulations
Plaintiffs also argue that the agency’s action was inconsistent with its own regulations,

specifically with the requirement that the approval phase begins “on the date [the application]

contains sufficient information to allow FDA to commence review of the application.” 21 C.F.R.

§ 60.22. This argument largely parallels the parties’ arguments regarding consistency with the

statute. Indeed, because it was necessary under Chevron to analyze the question of statutory

10
Plaintiffs emphasize that the date an application is “initially submitted” must be different from
the filing date. See Pls.’ Mot. at 4 (discussing legislative history). But pursuant to the agency’s
determination, the date of initial submission is different than the filing date. The former was
April 19, 2010, whereas the filing date was deemed to be June 19, 2010.
11
Although this case does not pertain to the same precise provision as the one considered by the
Federal Circuit in Wyeth, this Court’s conclusion that the FDA’s determination is reasonable is
consistent with and bolstered by the Federal Circuit’s similar conclusion in that case. See Wyeth,
603 F.3d at 1300.

23
consistency through the lens of the agency’s regulations, the analysis presented above resolves

this argument as well in Defendants’ favor. As explained above, the Court is bound to defer to

the agency’s interpretation of its own regulation in this case given that the interpretation is

neither plainly erroneous nor inconsistent with the statute. Accordingly, for the reasons stated at

length above regarding consistency with the statute, the Court concludes that agency’s

determination is consistent with its regulations, as well. Specifically, the Court concludes that it

was reasonable for the agency 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. For that reason, the Court rejects Plaintiffs’ argument regarding

consistent with the agency’s own regulations, as well.

C. Consistent Treatment with Other Applicants
Finally, Plaintiffs argue that the agency’s determination was arbitrary and capricious

because it was inconsistent with a single determination regarding a patent term extension dating

from 1985. As an initial matter, it is far from clear that any putative consistency in comparison to

a single determination dating from over 30 years ago would be enough, standing on its own, to

mark the agency’s Pradaxa determination as arbitrary and capricious. In any event, the agency

has shown—and Plaintiffs have not rebutted—that the agency’s determination in this case is

consistent with numerous similar determinations made in other cases. See Defs.’ Mot. at 27-28

(citing other determinations). In addition, the agency has persuasively explained the differences

between this case and the 1985 Tonocard Tablet case, which is the sole case on which Plaintiffs

rely for this argument. The Court is persuaded by the differences highlighted by the agency. See

id. at 28-30. Ultimately, the question comes down to whether, in each individual case, the

24
applicant has provided sufficient information for the agency to commence its substantive review.

As noted above, this question is particularly appropriate for deference to an expert agency. The

expert agency is well-suited to determine whether, in a particular set of circumstances, the data

provided by an applicant is sufficient for the agency’s substantive review to commence.

Fundamental principles of administrative law indicate that it is not for this Court to substitute its

view for that of the agency. This Court’s review is therefore appropriately limited to whether, on

the basis of the record before the Court, the agency’s determination is arbitrary and capricious.

Having reviewed the record and all of the parties’ arguments, the Court concludes that the

agency’s determination was not arbitrary and capricious.

* * *

In short, this is the type of case for which deference to the expert agency is particularly

appropriate. The Court concludes that the relevant statutory provisions are ambiguous, that the

agency’s interpretation warrants deference and is reasonable, and that the agency’s application of

that interpretation in this case is reasonable. None of the Plaintiffs’ arguments to the contrary—

ranging from their linguistic arguments to their reliance on snippets of legislative history to their

comparison with a single case from more than three decades ago—are persuasive. Accordingly,

the Court concludes that the agency’s determination of the patent term extension for Pradaxa

survives this Court’s deferential review under the Administrative Procedure Act.

IV. CONCLUSION

For the foregoing reasons, the Court GRANTS Defendants’ [26] Motion for Summary

Judgment and DENIES Plaintiffs’ [23] Motion for Summary Judgment. The Court also DENIES

Defendants’ [26] Motion to Dismiss as MOOT. This case is dismissed in its entirety.

25
An appropriate Order accompanies this Memorandum Opinion.

Dated: July 6, 2016
/s/
COLLEEN KOLLAR-KOTELLY
United States District Judge