Source: http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2017/08/index.html
Timestamp: 2017-10-22 20:57:28
Document Index: 543454658

Matched Legal Cases: ['§ 505', '§ 314', '§ 355', '§ 355', '§ 355', 'art 117', '§ 256']

DC Circuit Rules for FDA in 3-Year Exclusivity Dispute; Hashes Out ABILIFY’s “Zone of Exclusivity” vis-à-vis ARISTADA
Earlier this week, the U.S. Court of Appeals for the District of Columbia Circuit isued a 31-page Opinion handing FDA a victory in a dispute kicked off by Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceuticals Co., Ltd. (collectively “Otsuka”) after FDA’s October 5, 2015 approval of Alkermes plc’s (“Alkermes”) 505(b)(2) NDA 207533 for ARISTADA (aripiprazole lauroxil) Extended-release Injectable Suspension, a prodrug of N-hydroxymethyl aripiprazole (and which N-hydroxymethyl aripiprazole is a prodrug of aripiprazole), for the treatment of schizophrenia. Otsuka is the sponsor of several NDAs for aripiprazole drug products marketed under the proprietary name ABILIFY, including ABILIFY MAINTENA (NDA 202971), which is currently listed in the Orange Book with two unexpired periods of 3-year exclusivity expiring on December 5, 2017 (identified in an Orange Book addendum as “ADDITION OF THE RESULTS OF A CONTROLLED CLINICAL STUDY TREATING ADULT PATIENTS WITH SCHIZOPHRENIA EXPERIENCING AN ACUTE RELAPSE”) and July 27, 2020 (identified in the Orange Book as “NEW INDICATION OF MAINTENANCE MONOTHERAPY TREATMENT OF BIPOLAR I DISORDER IN ADULTS”).
As we previously reported (see our previous posts here , here, and here), Otsuka alleged in its October 2015 Complaint that FDA violated the FDC Act’s 3-year exclusivity provisions (FDC Act § 505(c)(3)(E)(iii) and (iv), and referred to as “romanette iii” and “romanette iv” throughout the case), the Agency’s regulations governing 3-year exclusivity (21 C.F.R. §§ 314.108(b)(4) and (5)), and the Administrative Procedure Act (“APA”) in approving ARISTADA in light of unexpired 3-year exclusivity applicable to ARISTADA. As Judge Ketanji Brown Jackson of the U.S. District Court for the District of Columbia noted in her July 2016 57-page Memorandum Opinion granting summary judgment for FDA, all three allegations boil down to a single issue:
What is at issue in the instant case is the scope of the exclusivities that were conferred to Abilify Maintena and its supplement by statute. . . . In essence, Otsuka maintains that the FDA was plainly prohibited from approving Alkermes’s drug Aristada during the relevant time period, and thus the agency’s authorization of the marketing of Aristada was arbitrary, capricious, and in violation of the law, because the three-year periods of marketing exclusivity that Abilify Maintena and its supplement received under romanettes iii and iv (and their accompanying regulations) were broad enough to block the approval of subsequent drug applications that have the same “conditions of approval.”
But the FDA has taken the position that the exclusivity provisions in the FDCA and the agency’s regulations only prohibit approval of a subsequent new drug application that pertains to a drug that has the same active moiety as the drug that received exclusivity, regardless of any overlap with respect to the conditions of approval, and so, the FDA argues, because Aristada and Abilify Maintena have different active moieties, the agency was permitted to approve the Aristada NDA within Abilify Maintena’s exclusivity periods. [(emphasis in original)]
In ruling for FDA (and intervenor Alkermes), Judge Jackson held that the FDC Act “does not unambiguously prevent the FDA from determining that the [statute’s] three-year exclusivity bar blocks only subsequent applications for drugs with the same active moiety,” and that “it was not unreasonable for the FDA to have employed that interpretation” in the context of approving ARISTADA.
On appeal to the DC Circuit, and in affirming Judge Jackson’s decision, the Court set up the dispute in a rather simple and elegant manner:
When a drug earns a period of exclusivity, [FDA] must withhold approval of certain competing drugs if various conditions are satisfied. But how does the FDA determine if a new drug bears a sufficiently close relationship to a pioneering drug to fall within the latter’s zone of exclusivity? This case concerns the FDA’s test for making that determination.
According to Otsuka, 3-year exclusivity “broadly covers any two drugs that are ‘legal equivalents,’” which the Court notes is “a term of Otsuka’s invention that draws an equivalence between two drugs whenever one relies upon the other to receive approval.” In contrast, FDA argued that 3-year exclusivity “applies as between two drugs sharing the same active moiety.”
Citing the familiar deference principles articulated by the U.S. Supreme Court in Chevron, U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837 (1984), the Court concluded that it “must sustain the FDA’s interpretation of the scope of exclusivity afforded by romanettes iii and iv as long as it is consistent with the statutory terms and is reasonable,” and that FDA’s “understanding comfortably meets those standards.” Although we won’t get into the nuances of all of the arguments Otsuka raised, suffice it to say that the 3-judge panel was not convinced by any of them:
Congress perhaps could have written a statute under which, if one drug relies on the safety or efficacy of a previously approved drug to obtain approval, the two drugs must be considered “legally equivalent” for purposes of defining the previously approved drug’s zone of exclusivity. But the statutory romanettes nowhere expressly set out any concept of legal equivalence in describing the scope of marketing exclusivity. Instead, Otsuka claims to find a footing for its theory in the FDCA’s provisions governing new drug applications, which in turn, the company contends, informs the proper interpretation of the romanettes. . . .
For Otsuka’s theory to prevail, it would need to show not only that its interpretation is permissible, but that the agency’s alternative understanding is not. Otsuka falls far short of making that showing. . . .
[T]he agency’s reading of “made to show”/“such drug” in § 355(b)(1) is fully reasonable, and considerably more straightforward than Otsuka’s. And because the agency understands “such drug” to refer solely to the applied-for drug, its reading, unlike Otsuka’s, does not involve any concept of legal equivalence between an applied-for drug and other drugs on which it may rely.
Even if we assume Otsuka’s reading of “such drug” in § 355(b)(1) is controlling, Otsuka again falls short in its effort to transport its preferred understanding of “such drug” from § 355(b)(1) into the statutory romanettes. Because Otsuka cannot make that essential showing, its statutory argument, independent of any other shortcomings, must fail. [(internal citation omitted)]
The DC Circuit’s decision caps off a recent spate of disputes and FDA decisions concerning the scope of 3-year exclusivity, including some recent decisions in the abuse-deterrent drug product space (see our previous post here).
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From the enforcement perspective, the outlines of Dr. Gottlieb’s approach are also salutary, as FDA appears to have taken on paper tiger status because the agency has issued several Warning Letters (as well as numerous untitled letters) in the area of Human Cells, Tissues, and Cellular and Tissue-based Products (HCT/Ps) over many years, and has almost never taken enforcement action against recalcitrant firms that the agency claims continue to violate the law and put the public health at risk (the sole exception to this statement being the case of Regenerative Sciences - see here).
Posted at 10:49 PM in Prescription Drugs and Biologics | Permalink | Comments (0)
By Serra J. Schlanger & Jeffrey N. Wasserstein –
Posted at 12:46 PM in Enforcement, Health Care | Permalink | Comments (0)
Posted at 10:26 PM in Foods, Foods and Dietary Supplements | Permalink | Comments (0)
In a blog posting that cited the agency’s goal of educating while regulating, FDA released the Food Safety Plan Builder (FSPB) – a software program “designed to assist owners/operators of food facilities with the development of food safety plans that are specific to their facilities and meet the requirements of the Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food regulation (21 CFR Part 117).” The FSPB web page makes clear that use of the FSPB is voluntary and does not necessarily ensure compliant food safety procedures. Nonetheless, the FSPB can be expected to find an audience, especially among smaller manufacturers that are subject to extended compliance dates and might not have yet invested substantial resources in developing a food safety plan. Even larger manufacturers who have already developed their plans may be tempted to delve into the FSPB as a point of reference.
In conjunction with the software, FDA released 16 (!) training videos on YouTube that address various aspects of FSPB. FDA also released a user guide with more detailed information. Perhaps not surprising in light of the subject matter, the user guide includes a lengthy legal disclaimer putting users on notice that FDA makes no warranties of any kind and admits of no liability for any damages, and that “[r]esponsibility for the interpretation and use of the [FSPB] and of the accompanying documentation lies solely with users.”
Posted at 11:12 PM in Foods, Foods and Dietary Supplements | Permalink | Comments (0)
HHS Proposes Longer Delays to Implementation of the 340B Final Rule
On August 21, 2017, the Health Resources and Services Administration (“HRSA”), the federal agency responsible for overseeing the 340B Drug Discount Program, published in the Federal Register a Notice of Proposed Rulemaking (“NPRM”) that would delay until July 1, 2018 the implementation of the Final Rule establishing the methodology for calculating the 340B ceiling price (including the so-called penny pricing policy) and civil monetary penalties (“CMPs”) for knowing and intentional overcharges of 340B covered entities (see our original post regarding the Final Rule here).
Similar to the reason given for previous delays (see our posts here and here), HRSA indicated that this latest delay to mid-2018 will “allow for necessary time to more fully consider the substantial questions of fact, law, and policy raised by the rule.” 82 Fed. Reg. 39,554. The impetus for HRSA’s delay to the effective date of the Final Rule expressly derives from both the “Regulatory Freeze Pending Review” memorandum issued by the Trump administration on January 20, 2017 as well as the Executive Order issued the same day entitled, “Minimizing the Economic Burden of the Patient Protection and Affordable Care Act [(‘ACA’)] Pending Repeal.” See our post here that described the Regulatory Freeze memorandum. The Regulatory Freeze memorandum provided time for the Trump administration to review and reconsider regulations implemented during the Obama administration. The Executive Order directed Trump appointees, including the heads of the U.S. Department of Health and Human Services (“HHS”) and other executive offices to “utilize all authority and discretion available to delay the implementation of certain provisions or requirements of the [ACA].” Id. The ACA required HHS to improve aspects of 340B program integrity with a statutory mandate to develop a system to enable HHS to verify the accuracy of ceiling prices calculated and reported by manufacturers, including the implementation of “precisely defined standards and methodology for the calculation of ceiling prices,” and to impose CMPs for manufacturer overcharges to covered entities. 42 U.S.C. § 256b(d)(1)(B)(i)(I), (vi). The 340B Final Rule was HRSA’s long-overdue rulemaking aimed at implementing those ACA provisions. Despite unsuccessful attempts by Congress to repeal and replace the ACA since that Executive Order was issued, the Executive Order appears, nevertheless, to continue to affect certain rulemaking implementing the ACA, including this 340B Final Rule.
Unlike the previous delays, this one raises the possibility that substantive changes may be made to the Final Rule. This NPRM states that, more than merely delaying implementation, HRSA “intends to engage in additional rulemaking on these issues” and will take additional time to consider a “more deliberate rulemaking process.” As a further signal that regulatory changes may be forthcoming, HRSA stated that the agency did not want manufacturers to invest time and expense coming into compliance with a Final Rule “that is under further consideration and for which substantive questions have been raised . . . .” Id. However, the NPRM contains no information on what substantive questions have been raised or what the new rulemaking would entail.
Public comments on the delay to the effective date of the Final Rule are also being solicited by HRSA in this NPRM. They are due to the agency on or before September 20, 2017.
We will continue to track and report on further developments regarding implementation of the Final Rule or other updates concerning the 340B Drug Pricing Program.
Posted at 07:25 PM in Health Care | Permalink | Comments (0)
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