Case 1:18-cv-00303-RGA Document 23-1 Filed 05/01/18 Page 1 of 206 PageID #: 633
`Case 1:18-cv—00303-RGA Document 23-1 Filed 05/01/18 Page 1 of 206 PageID #: 633
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`EXHIBIT 1
`FDA DECISION LETTER (AUG. 18, 2014)
`FDA DECISION LETTER (AUG. 18, 2014)
`DOCKET NO. FDA-2014-N-0087
`DOCKET NO. FDA-2014-N-0087
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`EXHIBIT 1
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`Case 1:18-cv-00303-RGA Document 23-1 Filed 05/01/18 Page 2 of 206 PageID #: 634
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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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` Food and Drug Administration
` Rockville, MD 20857
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`Docket No. FDA-2014-N-0087
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`SENT VIA EMAIL
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`Dear Dexmedetomidine Hydrochloride Injection NDA Holder/ANDA Applicant:
`
`On January 15, 2014, the U.S. Food and Drug Administration (FDA or the agency) established a
`public docket to solicit comment on certain legal and regulatory issues that pertain to Precedex
`(dexmedetomidine hydrochloride injection, 100 mcg (base)/mL packaged in 200 mcg (base)/2
`mL single-dose vials). As described in detail below, FDA also sent a letter describing the issue
`to Hospira, Inc. (Hospira), the holder of New Drug Application (NDA) No. 21-038 for Precedex
`and to all applicants that submitted Abbreviated New Drug Applications (ANDAs) to FDA
`referencing Precedex. The letter also was posted on the website for FDA’s public dockets at
`http://www.regulations.gov.
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`Today’s letter reflects FDA’s determinations with respect to permissibility of labeling carve outs
`for ANDAs referencing Precedex. For the reasons set forth below, FDA concludes that
`regardless of whether the original use code or the revised use code applies, the agency can
`approve an ANDA that submits a “section viii” statement and omits labeling that discloses the
`protected use (as identified by Hospira). FDA further concludes that such omissions do not
`render the drug less safe or effective for the remaining non-protected conditions of use.
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`I.
`
`In the letters sent to NDA holder Hospira and ANDA applicants and posted to the docket, FDA
`noted the following:
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`Precedex is approved for the following indications:
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`1. Sedation of initially intubated and mechanically ventilated patients during treatment in an
`intensive care setting. Administer Precedex by continuous infusion not to exceed 24
`hours.
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`2. Sedation of non-intubated patients prior to and/or during surgical and other procedures.
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`FACTUAL BACKGROUND
`
`
`Hospira has, over time, listed several patents covering the Precedex product referenced above.
`Only a method-of-use patent remains: U.S. Patent No. 6,716,867 (the ‘867 patent), which
`expires (including a pediatric exclusivity period) on October 1, 2019.1
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`1 U.S. Patent No. 4,910,214 expired on July 15, 2013, and an associated pediatric exclusivity period expired on
`January 15, 2014.
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`Reference ID: 3611876
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`Hospira originally listed the ‘867 patent in May 2004 with the following use code (U-572):
`“Intensive care unit sedation.” In November 2008, Hospira listed U.S. Patent No. 5,344,840 (the
`‘840 patent) with the following use code (U-912) in the Orange Book: “Sedation of non-
`intubated patients prior to and/or during surgical and other procedures.” That patent expired on
`September 6, 2011. On January 6, 2014, Hospira sought to amend the ‘867 patent use code to
`“intensive care unit sedation, including sedation of non-intubated patients prior to and/or during
`surgical and other procedures.” FDA, in accordance with the ministerial manner in which it
`implements patent use code information, changed the use code on January 8, 2014.
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`FDA sought comments on the following issues:
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`1. Does the breadth of the new use code description for the ‘867 patent foreclose ANDA
`applicants from gaining approval for any of the approved indications (or for any subset of
`those indications) before the ‘867 patent expires? For example, would it be permissible
`as a scientific, regulatory, and legal matter for an ANDA applicant to submit a statement
`under 21 U.S.C. §355(j)(2)(A)(viii) and a corresponding carve out that results in an
`approval for a subset of the second approved indication, i.e., an approval explicitly
`limited to procedures outside of an intensive care setting? In this context, is it acceptable
`to add new words to the approved indication to limit the indication to exclude only that
`portion of the indication that is covered by the use code (i.e., to exclude sedation of non-
`intubated patients in the ICU setting only)? If you believe a carve out of this type is
`permissible, if you wish, you may submit a side by side of the indication section of the
`labeling for dexmedetomidine hydrochloride injection showing the carve out that you
`believe would be acceptable.
`
`2. Whether the fact that Hospira changed the use code information outside of the 30-day
`window after the patent issued means that the use code change is late listed as to any
`ANDAs pending with a section viii statement at the time the use code was changed. See
`21 C.F.R. § 314.53(c), (d). If so, would any ANDA with an existing section viii
`statement be entitled to retain that statement (and corresponding carve out) under 21
`C.F.R. § 314.94(a)(12)(vi), notwithstanding the change in use code?
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`3. What relevance, if any, to a determination of whether the use code change was timely
`submitted is the fact that Hospira previously listed the ‘840 patent with very similar use
`code information to that now listed for the ‘867 patent, and did not change the use code
`for the ‘867 patent until after the ‘840 patent expired?2
`
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`FDA requested a response by close of business on January 24, 2014. Commenters submitting in
`the initial comment period had an opportunity to respond to comments from other commenters
`by close of business January 31, 2014. The agency received 22 comments, which can be
`accessed at http://www.regulations.gov.
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`2 Dear Applicant Letter from FDA Center for Drug Evaluation and Research to Hospira Inc. re. Dexmedetomidine
`Hydrochloride Injection NDA ANDA , Docket No. FDA-2014-N-0087 (Jan. 15, 2014).
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`2
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`Reference ID: 3611876
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`II.
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`LEGAL AND REGULATORY BACKGROUND
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`A.
`
`The Statutory and Regulatory Framework for Patent Protection for NDAs and for
`Labeling Differences for ANDAs
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`
`The Federal Food, Drug, and Cosmetic Act (the FD&C Act) and FDA regulations require that a
`sponsor seeking to market an innovator drug submit an NDA. NDAs contain, among other
`things, extensive scientific data demonstrating the safety and effectiveness of the drug for the
`indication for which approval is sought.3 Under the statute, an NDA applicant also must submit
`to FDA a list of patents claiming the approved drug substance or drug product, or claiming an
`approved method of using the drug product in the NDA. Specifically, section 505(b)(1) of the
`FD&C Act requires an NDA applicant to file as part of the NDA “the patent number and the
`expiration date of any patent which claims the drug for which the applicant submitted the
`application or which claims a method of using such drug and with respect to which a claim of
`patent infringement could reasonably be asserted if a person not licensed by the owner engaged
`in the manufacture, use, or sale of the drug.”4 FDA is required to publish this patent
`information5 and does so in the publication titled Approved Drug Products with Therapeutic
`Equivalence Evaluations, commonly known as the Orange Book.
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`The statute also provides that if a relevant patent is issued after NDA approval, the NDA sponsor
`must file the required patent information with FDA not later than 30 days after the date the
`patent is issued.6 FDA’s regulations further require that an applicant seeking approval of certain
`supplements, including a supplement for a new indication, submit with its supplement the patent
`information required for NDA approvals for a patent that claims the drug, drug product, or
`method of use.7
`
` A
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` drug product with an effective approval under section 505(c) or 505(j) of the FD&C Act is
`known as a “listed drug.”8 Under the Drug Price Competition and Patent Term Restoration Act
`of 1984 (Public Law 98-417) (the Hatch-Waxman Amendments), an applicant may submit an
`ANDA under section 505(j) of the FD&C Act for approval of a generic version of a listed drug
`previously approved under section 505(c).9 The ANDA approval process shortens the time and
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`3 Section 505(b)(1) of the FD&C Act.
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` 4
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` Sections 505(b)(1) of the FD&C Act (emphasis added). See also 21 CFR 314.53(c)(2)(ii).
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` Section 505(b)(1), (c)(2) and (j)(7) of the FD&C Act.
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` Section 505(c)(2) of the FD&C Act; 21 CFR 314.53.
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` 21 CFR 314.53(d)(2).
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` Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.
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`3
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` Under 21 CFR 314.3(b), “[l]isted drug means a new drug product that has an effective approval under section
`505(c) of the act for safety and effectiveness or under section 505(j) of the act, which has not been withdrawn or
`suspended under section 505(e)(1) through (e)(5) or (j)(5) of the act, and which has not been withdrawn from sale
`for what FDA has determined are reasons of safety or effectiveness.” A listed drug is identified as having an
`effective approval in the Orange Book, which includes patent information for each drug approved under 505(c). 21
`CFR 314.53(e).
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`Reference ID: 3611876
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`effort needed for approval by, among other things, allowing an ANDA applicant to rely on
`FDA’s previous finding of safety and effectiveness for a listed drug rather than requiring the
`ANDA applicant to independently demonstrate the safety and effectiveness of its proposed drug.
`To rely on such a finding, the ANDA applicant must show that its proposed drug product is the
`same as the listed drug in many respects (including active ingredient, dosage form, strength,
`route of administration, and, with certain exceptions, labeling), and that its product is
`bioequivalent to the listed drug.
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`The ANDA applicant must identify the listed drug on which it seeks to rely for approval. As
`described in more detail below, the timing of ANDA approval depends on, among other things,
`any patent protection for the listed drug that the ANDA references and whether the ANDA
`applicant challenges those patents.10 In general, an ANDA may not obtain final approval until
`listed patents and marketing exclusivity have expired or until NDA holders and patent owners
`have had the opportunity to defend relevant patent rights in court.
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`Specifically, with respect to each patent submitted by the sponsor for the listed drug and listed in
`the Orange Book, the ANDA applicant generally must submit to FDA one of four specified
`certifications under section 505(j)(2)(A)(vii) of the Act. The certification must state one of the
`following:
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`(I) that such patent information has not been filed (a paragraph I certification),
`(II) that such patent has expired (a paragraph II certification),
`(III) the date on which such patent will expire (a paragraph III certification), or
`(IV) that such patent is invalid or will not be infringed by the manufacture, use, or sale of
` the new drug for which the application is submitted (a paragraph IV certification).11
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`The purpose of this requirement is “to give notice, if necessary, to the patent holder so that any
`legal disputes regarding the scope of the patent and the possibility of infringement can be
`resolved as quickly as possible.”12
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`If an applicant files a paragraph I or II certification, the patent in question (there is none in the
`case of a paragraph I certification) will not be a barrier to ANDA approval. If an applicant files
`a paragraph III certification, the applicant agrees to wait until the relevant patent has expired
`before seeking final approval of its ANDA. If, however, an applicant wishes to seek approval
`of its ANDA before a listed patent has expired by challenging the validity of a patent or
`claiming that a patent would not be infringed by the product proposed in the ANDA or is
`unenforceable, the applicant must submit a paragraph IV certification to FDA. An applicant
`submitting a paragraph IV certification to a listed patent must provide the NDA holder and each
`patent owner with notice of its patent certification, including a description of the legal and
`factual basis for the ANDA holder’s assertion that the patent is invalid or not infringed.13
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`10 See section 505(b), (c), (j)(2)(A)(vii), and (j)(5)(B) of the FD&C Act.
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`11 Section 505(j)(2)(A)(vii) of the FD&C Act; see also 21 CFR 314.94(a)(12)(i)(A).
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`12 Torpharm, Inc. v. Thompson, 260 F. Supp. 2d 69, 71 (D.D.C. 2003).
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`13 Section 505(j)(2)(B) of the FD&C Act.
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`Reference ID: 3611876
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`If a patent is listed at the time an ANDA is submitted and, in response to a paragraph IV
`certification, the NDA holder or patent owner initiates a patent infringement action against the
`ANDA applicant within 45 days of receiving the required notice, approval of the ANDA
`generally will be stayed for 30 months from the date of the notice or such shorter or longer time
`as the court might order.14 When the 30-month period has expired, the patent ceases to be a
`barrier to final ANDA approval, even if the patent litigation is ongoing. Similarly, if the NDA
`holder and patent owner receive notice of paragraph IV certification and decline to sue within
`45 days of receipt of notice, the patent will not be a barrier to ANDA approval. FDA plays a
`ministerial role in patent listing and any method-of-use descriptions submitted by the NDA
`sponsor, meaning FDA does not review the patent to confirm or deny the appropriateness of the
`listing or the accuracy of the descriptions.15
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`The four patent certifications described above are not the only way in which an ANDA applicant
`may address all relevant patents. When a patent is listed only for a method of use, an ANDA
`applicant seeking to omit that approved method of use covered by the listed patent need not file a
`paragraph III or IV certification for that patent. Instead, the applicant may submit a “section viii
`statement” acknowledging that a given method-of-use patent has been listed, but stating that the
`patent at issue does not claim a use for which the applicant seeks approval. Specifically, section
`505(j)(2)(A)(viii) of the FD&C Act provides that “if with respect to the listed drug referred to in
`[section 505(j)(2)(A)(i)] information was filed under subsection (b) or (c) for a method of use
`patent which does not claim a use for which the applicant is seeking approval under this
`subsection, [the ANDA must contain] a statement that the method of use patent does not claim
`such a use.”16
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`Such a statement requires the ANDA applicant to omit from its labeling information pertaining
`to the protected use.17 If an ANDA applicant files a section viii statement (and makes the
`requisite labeling carve out), the patent claiming the protected method of use will not serve as a
`barrier to ANDA approval, nor will any 180-day exclusivity for which another ANDA applicant
`may be eligible with respect to that patent serve as such a barrier to approval of the section viii
`applicant’s product.18 Under the FD&C Act, an ANDA applicant must submit either a patent
`
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`14 Section 505(j)(5)(B)(iii) of the FD&C Act.
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`15 See, e.g., Apotex, Inc. v. Thompson, 347 F.3d 1335, 1349 (Fed. Cir. 2003); aaiPharma v. Thompson, 296
`F.3d 227, 242-43 (4th Cir. 2002).
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`16 When a patent is submitted that claims both the drug product and a method of using the drug, and if a sponsor
`does not seek approval for the method of use claimed by the patent but seeks approval of the drug product for a
`different use before the patent expires, FDA allows a split certification to that patent. This permits a paragraph IV
`certification to the drug product claim and a section viii statement to the method-of-use claim (and an accompanying
`labeling carveout). See, e.g., Letter fr. J. Woodcock to R. Wilk-Orescan and J. Hurst re. Docket Nos. FDA-2008-P-
`0343 and -0411 (Dec.4, 2008) (Repaglinide Citizen Petition Response), at 18. The current circumstances do not
`involve a split certification.
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`17 21 CFR 314.92(a)(1) and 314.94(a)(12)(iii).
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`18 See also H.R. REP. NO. 857 (Part I), 98th Cong., 2d sess. 21.
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`...The [ANDA] applicant need not seek approval for all of the indications for which the
`listed drug has been approved. For example, if the listed drug has been approved for
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`certification or a section viii statement for each listed patent. FDA implementing regulations
`describe when a section viii statement is required:
`
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`If patent information is submitted under section 505(b) or (c) of the [A]ct and
`§ 314.53 for a patent claiming a method of using the listed drug, and the labeling
`for the drug product for which the applicant is seeking approval does not include
`any indications that are covered by the use patent, [the ANDA applicant must
`submit] a statement explaining that the method of use patent does not claim any of
`the proposed indications.19
`
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`Accordingly, FDA regulations also expressly recognize that by submitting a section viii
`statement, an ANDA applicant may omit from the proposed labeling a method of use protected
`by a listed patent, and therefore need not seek approval for that use.20
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`The right to file a section viii statement and carve out from labeling method-of-use information
`protected by a patent has been upheld by the courts. Thus, in Purepac Pharmaceutical Company
`v. Thompson, the D.C. Circuit stated that a “section viii statement indicates that a patent poses no
`bar to approval of an ANDA because the applicant seeks to market the drug for a use other than
`the one encompassed by the patent.”21 Similarly, in Torpharm, the D.C. District Court stated
`that a section viii statement “avers that the patent in question has been listed, but does not claim
`a use for which the applicant seeks FDA approval.”22 These courts have upheld the Agency’s
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`hypertension and angina pectoris, and if the indication for hypertension is protected by
`patent, then the applicant could seek approval for only the angina pectoris indication.
`
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`19 21 CFR 314.94(a)(12)(iii). FDA regulations implementing this statutory provision use the term
`“indications” to refer to information an ANDA applicant omits from its labeling in the context of submitting
`a statement that a protected use of a drug is not claimed in a listed patent. 21 CFR 314.94(a)(l2)(iii).
`However, the preambles for the proposed rule and final rule on patent and exclusivity provisions related to
`ANDA approval express no intent to distinguish between method of use and indication, using the terms
`interchangeably (see, e.g., Abbreviated New Drug Application Regulations; Patent and Exclusivity
`Provisions; Final Rule, 59 FR 50338, 50347 (Oct. 3, 1994)). FDA has consistently allowed use codes and
`labeling carve outs that correspond to methods of use other than indications (e.g., dosing schedules).
`Moreover, when the ANDA labeling proposes not to include the indication or other method of use, only the
`section viii statement is appropriate. The preamble to the final rule emphasizes that such an ANDA applicant
`does not have the option of choosing between a paragraph IV certification and a section viii statement
`where the patent claims only a single method of use. Id. The preamble to the proposed rule states that where
`“the labeling for the applicant’s proposed drug product does not include any indications that are covered by the use
`patent,” the ANDA applicant would submit a section viii statement rather than a paragraph IV certification
`(Abbreviated New Drug Application Regulations; Proposed Rule, 54 FR 28872, 28886 (July 10, 1989)).
`20 See also Applications for FDA Approval to Market a New Drug: Patent Submission and Listing
`Requirements and Application of 30-Month Stays on Approval of Abbreviated New Drug Applications
`Certifying That a Patent Claiming a Drug Is Invalid or Will Not Be Infringed; Final Rule (68 FR 36676
`(June 18, 2003) (Patent Submission and Listing Rule). In the preamble to this final rule, we stated that the
`section viii statement permits an ANDA applicant to “avoid certifying to a patent by stating that it is not
`seeking approval for the use claimed in the listed patent.” Id. at 36682. We stated, “[o]ur position has been
`that, for an ANDA applicant to file a section viii statement, it must ‘carve-out’ from the proposed ANDA
`labeling, the labeling protected by the listed patent.” Id.
`21 Purepac Pharmaceutical Company v. Thompson, 354 F.3d 877, 880 (D.C. Cir. 2004).
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`22 Torpharm Inc. v. Thompson, 260 F. Supp. 2d at 73.
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`interpretation that an ANDA applicant may choose not to seek approval for a method of use
`protected by a listed patent, and under those circumstances, that patent will not be a barrier to
`ANDA approval.
`
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`B. Requirements Regarding ANDA Labeling
`
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`Section 505(j)(2)(A)(i) of the FD&C Act requires that an ANDA contain “information to show
`that the conditions of use prescribed, recommended, or suggested in the labeling proposed for the
`new drug have been previously approved for a [listed drug].” This language reflects Congress’s
`intent that the generic drug be safe and effective for each “condition of use” prescribed,
`recommended, or suggested in the generic drug labeling. However, it does not require that an
`ANDA be approved for each condition of use for which the reference listed drug is approved. In
`21 CFR 314.92(a)(l), FDA explicitly states that a proposed generic drug product must have the
`same conditions of use as the listed drug, except that “conditions of use for which approval
`cannot be granted because of ... an existing patent may be omitted.”23
`
`The FD&C Act also requires that an ANDA contain “information to show that the labeling
`proposed for the new [generic] drug is the same as the labeling approved for the listed drug...
`except for changes required because of differences approved under a petition filed under [section
`505(j)(2)(C) of the FD&C Act] or because the new drug and the listed drug are produced or
`distributed by different manufacturers.”24 Similarly, 21 CFR 314.94(a)(8)(iv) requires that:
`
`Labeling (including the container label, package insert, and, if applicable,
`Medication Guide) proposed for the [generic] drug product must be the same as
`the labeling approved for the reference listed drug, except for changes required
`because of differences approved under a petition filed under § 314.93 [21 CFR
`314.93] or because the drug product and the reference listed drug are produced or
`distributed by different manufacturers.
`
`
`This subparagraph also sets forth examples of permissible differences in labeling that may result
`because the generic drug product and RLD are produced or distributed by different
`manufacturers. These differences include “differences in expiration date, formulation,
`bioavailability, or pharmacokinetics, labeling revisions made to comply with current FDA
`labeling guidelines or other guidance, or omission of an indication or other aspect of labeling
`protected by patent or accorded exclusivity under section 505(j)(5)(F) of the [FD&C Act].”
`FDA’s regulations at 21 CFR 314.127(a)(7) further provide that to approve an ANDA containing
`proposed labeling that omits “aspects of the listed drug’s labeling [because those aspects] are
`
`
`23 To note, an ANDA applicant may not carve out a condition of use for a product that is not protected by patent or
`exclusivity.
`
`24 Section 505(j)(2)(A)(v) of the FD&C Act. See also Section 505(j)(4)(G) of the FD&C Act (providing
`that FDA must approve an ANDA unless, among other things, the “information submitted in the application
`is insufficient to show that the labeling proposed for the drug is the same as the labeling approved for [the
`reference listed drug] except for changes required because of differences approved under [an ANDA
`suitability petition] or because the drug and the listed drug are produced or distributed by different
`manufacturers”).
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`protected by patent” the agency must find that the “differences do not render the proposed drug
`product less safe or effective than the listed drug for all remaining, non-protected conditions of
`use.”
`
`Case law affirms an ANDA applicant’s ability to carve out protected labeling in a manner
`consistent with the “same labeling” requirement. For example, in Bristol-Myers Squibb v.
`Shalala, 91 F.3d 1493, 1500 (D.C. Cir. 1996), the D.C. Circuit ruled that “the statute expresses
`the legislature’s concern that the new generic be safe and effective for each indication that will
`appear on its label; whether the label for the new generic lists every indication approved for the
`use of the pioneer is a matter of indifference.” Similarly, in Sigma-Tau Pharmaceuticals, Inc. v.
`Schwetz, 288 F.3d 141, 148, fn. 3 (4th Cir. 2002), the Fourth Circuit upheld the right of an
`ANDA applicant to carve out an indication protected by orphan drug exclusivity as a permissible
`difference due to difference in manufacturer. Thus, under the statute, regulations, and applicable
`case law, the carve out of patent and exclusivity-protected labeling is generally permitted as a
`permissible difference due to difference in manufacturer if the omission does not render the
`proposed drug product less safe or effective for the conditions of use that remain in the labeling.
`
`III. DISCUSSION
`
`As indicated above, FDA received numerous comments from the NDA holder and ANDA
`applicants and other interested parties to the public docket. The comments generally fell
`within one of two categories: those asserting that FDA should not approve an ANDA for
`dexmedetomidine hydrochloride injection that contains a section viii statement to the ‘867
`patent and carves out labeling associated with the patent because the use code precludes any
`such approvals; and those that assert that any protected information in the use code does not
`foreclose approval of an ANDA under the applicable statute, regulations, and the agency’s
`past practice. FDA has carefully reviewed these comments in considering the issues, but will
`not separately address each comment. Rather, the agency will address the various positions
`asserted where appropriate to explain FDA’s conclusions on this issue.
`
`
`A. FDA’s Authority to Determine Permissible Labeling Carve Out
`
`
`As a threshold matter, Hospira asserts that FDA’s ministerial role in patent listing and use
`code matters requires FDA to accept Hospira’s view of its use code, as well as Hospira’s view
`that no ANDAs are approvable.25 While Hospira is correct that, as described above, FDA
`takes a ministerial role in listing patent information and we do not independently evaluate the
`information provided in the use code in relation to the patent, we nevertheless regularly
`evaluate what portions of labeling appropriately correspond to the use code provided and
`whether ANDAs may be approvable with labeling that carves out protected information that
`corresponds to the use code provided. Such determinations fall squarely within the ambit of
`FDA’s scientific expertise.
`
`
`
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`25 Letter to FDA fr. R. Bedward, Hospira, Inc. re Docket No. FDA 2014-N-0087 (Jan. 24, 2014) (Hospira Jan. 24
`Letter), at 3, 8-9.
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`In particular, we evaluate, in light of the patented method of use as described by the NDA
`sponsor, whether an ANDA can be approved by omitting protected information and what
`information must be omitted, as well as whether the product with the protected information
`omitted will be rendered less safe or effective for its remaining non-protected conditions of
`use without that information.26 In accordance with our statutory and regulatory authority and
`past practice, we have determined that in this instance, we can approve an ANDA that omits
`the information Hospira has identified as protected by the use code because we have
`concluded that such omissions do not render the drug less safe or effective for the remaining
`non-protected conditions of use. As described below, this is true regardless of whether the
`carve out is done with reference to the original use code or the revised use code that Hospira
`submitted to the agency on January 6, 2014.27 Because we are not independently assessing the
`scope of the patent but instead are relying on the information that Hospira has provided, our
`decision-making process is consistent with our ministerial role in patent listing matters.
`
`
`B. ANDA Sponsors May Carve Out the Use Protected by the ‘867 Patent
`
`
`As described above, Hospira originally listed the ‘867 patent in May 2004 with the use code
`(U-572): “Intensive care unit sedation.” In November 2008, Hospira listed the ‘840 patent
`with the following use code (U-912) in the Orange Book: “Sedation of non-intubated patients
`prior to and/or during surgical and other procedures.” On January 6, 2014, without making
`any other changes to its approved drug product or approved labeling, Hospira sought to amend
`the ‘867 use code to “intensive care unit sedation, including sedation of non-intubated patients
`prior to and/or during surgical and other procedures.” Consistent with its ministerial role,
`FDA changed the use code on January 8, 2014.
`
`Hospira asserts that both its original and its revised use code overlap not only with the first
`indication for Precedex but also with the second indication for that drug because there is a
`subset of non-intubated patients that may receive Precedex for procedural sedation (the second
`indication) in the ICU setting. Hospira argues that because its use code(s) for the ‘867 patent
`fully cover the first indication and may overlap with the second indication, an applicant with a
`section viii statement to the ‘867 patent must carve out both the first and the second
`indications in their entirety, thereby precluding approval of any ANDAs with carved out
`labeling.28 In support of this position, Hospira cites the Supreme Court’s decision in Caraco
`Pharm. Labs., Ltd. v. Novo Nordisk A/S, 132 S. Ct. 1670, 1677 (2012), in which the Court
`summarized its understanding of FDA’s practice: “the FDA will not approve an ANDA if the
`generic’s proposed carve out label overlaps at all with the brand’s use code” (citing the Patent
`Submission and Listing Rule, 68 Fed. Reg. at 36682-83).
`
`
`
`
`26 See, e.g., Repaglinide CP response, at 9-14.; Letter to Macdonald, Apotex Corp. fr. J. Woodcock, FDA re. Docket
`Nos. 01P-0495/CP1, 02P-191/CP1, & 02P-0252/CP1, at 7-11 (June 11, 2001) (Tramadol CP Response).
`
`27 Because the outcome is the same regardless of whether the original or revised use code is used, FDA is not
`addressing separately whether the revised use code is late-listed and the consequences, if any, of the timing of its
`submission.
`
`28 Hospira Jan. 24 Letter, at 5, 7-9.
`
`
`
`9
`
`Reference ID: 3611876
`
`

`

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`Case 1:18-cv-00303-RGA Document 23