The Supreme Court’s Continued Frustration with the Prescription Drug Legal Framework – And Forthcoming FDA Regulatory Action in Response to Mutual Pharmaceuticals v.s Barlett

I. Overview

The United States Supreme Court’s now well-known trio of cases on implied preemption — Wyeth v. Levine,¹ PLIVA v. Mensing,² and Mutual Pharmaceuticals v. Bartlett ³ — has generated sweeping change in pharmaceutical litigation. Condensed to their most simplistic results (perhaps unfairly so), the scorecard can be summarized as follows:

• Implied conflict preemption for brand manufacturers? By and large, NO — unless the brand manufacturer can show clear evidence that the FDA considered, and rejected, proposed warnings on the same risks and injuries (Wyeth v. Levine);
• Implied conflict preemption for generic manufacturers based on a theory of failure to warn/adequacy of the warnings? Generally, YES — because generic manufacturers must ask FDA for permission (and get it) before changing a label beyond that authorized for the brand version (PLIVA v. Mensing); and
• Implied conflict preemption for generic manufacturers based on a theory of design defect? Generally, YES — under the rationale of Mensing, a generic manufacturer cannot unilaterally change the design of a product that was FDA-approved, and further, the manufacturer should not be forced to make a Hobson’s choice of ceasing sales of the product altogether to avoid conflict (Mutual Pharmaceuticals v. Bartlett).

So we have what we have: three cases, with essentially two different results, that turn on one issue: whether the product in question is a brand or generic.

Other articles — including discussions in our very own Pro Te: Solutio — have considered how plaintiffs’ firms are seeking to use the above cases as shields or swords. This article, by contrast, looks at an issue that the Supreme Court has raised in each of these three preemption cases: Congress’s attention (or lack thereof ) to the laws that have, according to the Supreme Court, directly resulted in seemingly disparate results, and the FDA’s actions in response.

The Court’s unabashed frustration at the prescription drug regulatory arena is perhaps best revealed in the following statement, penned by Justice Alito near the conclusion of the majority opinion in Bartlett:

Suffice to say, the Court would welcome Congress’ “explicit” resolution of the difficult pre-emption questions that arise in the prescription drug context. That issue has repeatedly vexed the Court — and produced widely divergent views — in recent years. […] In the absence of [such an] “explicit” expression of congressional intent, we are left to divine Congress’ will from the duties the statute imposes.⁴

II. The FDA Response to Bartlett: Step 1

The above statement in Bartlett was issued on June 24, 2013. Less than two weeks later, FDA announced its intention to ultimately “create parity” for those plaintiffs who took generic products and found their state claims barred under Mensing and Bartlett. In early July 2013, the FDA took the first administrative step for a rule change by formally notifying the Office of Management and Budget (OMB) that it would propose new rules on this issue. That notice states⁵:

T I T L E : Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

A B S T R A C T : This proposed rule would amend the regulations regarding new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs) to revise and clarify procedures for changes to the labeling of an approved drug to reflect certain types of newly acquired information in advance of FDA’s review of such change. The proposed rule would describe the process by which information regarding a “changes being effected” (CBE) labeling supplement submitted by an NDA or ANDA holder would be made publicly available during FDA’s review of the labeling change. The proposed rule also would clarify requirements for the NDA holder for the reference listed drug and all ANDA holders to submit conforming labeling revisions after FDA has taken an action on the NDA and/or ANDA holder’s CBE labeling supplement. These proposed revisions to FDA’s regulations would create parity between NDA holders and ANDA holders with respect to submission of CBE labeling supplements.

The FDA has stated that “It is premature to cite what changes in the regulations might be,” and that “[d]iscussions are under way.”⁶ More information was announced to be forthcoming in September 2013, but nothing has been released as of yet. The likely translation of the notice, however, is this: if promulgated, the rules would modify FDA regulations that define the circumstances under which generic manufacturers can change a label prior to formal FDA approval. Presumably, this would require generic manufacturers to change the label at the same time brand manufacturers do (i.e., before receiving formal FDA approval to make a label change when important new safety information is received about the drug). Stated colloquially, it could impose a “make the label safer first, get formal permission from FDA second” regime for generic manufacturers.

III. Let’s Not Get Ahead of Ourselves: Lots of “Ifs,” “Whens,” and “Hows” Will Have to be Sorted Out

Even if the imposed rulemaking process proceeds as expected, the future of an actual change to the rules is hazy at best. The length of the rulemaking process and timing, questions about the validity of such measures, and the prospective relief such a rule change would effectuate (if at all) are important and contemporary concerns — which stakeholders will want to keep in mind as the process unfolds.

A THE RULEMAKING PROCESS WILL TAKE YEARS.

The rulemaking process is far from a quick run through a bureaucratic park. Years of wrangling are more likely. As OMB explains, “[f]ederal regulations are created through a process known as ‘rulemaking,’ which is governed by the Administrative Procedure Act.”⁷ When a federal agency determines that regulatory action is needed, it develops and publishes a proposed rule in the Federal Register (the official daily publication for agency rules, proposed rules, and notices of federal agencies and organizations), solicits comments from the public on the proposal, and after the agency considers public feedback, it implements changes where appropriate and publishes a final rule, including its effective date, in the Federal Register. When an agency issues a “final rule,” the agency must describe and respond to the public comments that were received.⁸ As specific to the FDA, before a proposed or final rule is published in the Federal Register, it may be reviewed by “other parts” of the federal government, such as the Department of Health and Human Services (HHS), of which FDA is a part.⁹

Even assuming the absence of any unusual federal government obstacles (think: sequestration, budget cuts), new proposed rules should not be expected anytime soon — or any time in the reasonably foreseeable future.¹⁰

B ANY RULE CHANGE WOULD BE PROSPECTIVE.

If and/or when new rules are promulgated, these changes will affect how FDA acts/enforces in the future — it will not change the validity of Mensing or Bartlett, both of which were (necessarily) evaluated under the regulatory scheme in place at their respective points in time. Indeed, the FDA’s amicus brief in Bartlett — while advocating that the claims in Bartlett were preempted pursuant to current regulations and the holding in Mensing — nevertheless noted that “FDA is considering a regulatory change that would allow generic manufacturers, like brand-name manufacturers, to change their labeling in appropriate circumstances. If such a regulatory change is adopted, it could eliminate preemption of failure-to-warn claims against generic-drug manufacturers.”¹¹ Any reach of the new rules will be prospective.

C FDA’S AUTHORITY TO MAKE THE PROPOSED CHANGES IS NOT A SLAM DUNK.

A final issue involves the validity of a change to the rules — specifically, whether FDA has the authority to do what it proposes to do through the rulemaking process, as opposed to the need for Congressional action.

According to OMB, “Congress enacts the legislation that mandates or authorizes agencies to issue regulations. Through the Administrative Procedure Act (APA) and other laws, Congress also establishes the procedures that govern agency rulemaking. Congress may use a variety of processes as part of its oversight of agency action, including holding hearings or informal meetings, issuing reports, or adopting legislation. In addition, Congress, through the Congressional Review Act (CRA) (5 U.S.C. Chapter 8), may review and choose to reject new regulations issued by federal agencies. The CRA requires federal agencies to submit all new final rules to both the House and Senate. After submission, Congress may begin a process to reconsider and vote to overturn the rule.”¹²

The above explanation begs the question: what are the boundaries of the authority of FDA (vis-à-vis Congress) regarding a generic manufacturer’s ability to change a label prior to receiving FDA approval? A comprehensive (or even sufficiently abbreviated) recitation of the full authority Congress has vested with FDA is far beyond this article. For these purposes, consider the statements contained in the United States’ amicus brief in Bartlett: “Congress has vested FDA with the responsibility to determine when a new drug is ‘safe’ and ‘effective’ under the conditions of use stated in its labeling, so as to warrant the drug entering the interstate market.”¹³ Yet of extreme importance is that the “sameness in labeling” obligation for generic manufacturers is statutory,¹⁴ and regulations must conform to the governing statute.

A detailed analysis of whether FDA would exceed the boundaries of its authorization in this rulemaking process is a topic left to legal scholars. Yet if FDA proceeds down the current path, consider that (a) its actions could be invalid if not based on a valid exercise of its authority, and/or (b) Congress could (if it so chose) overturn such rulemaking. If nothing else, this situation may result in a protracted administrative wrest for power.

It is notable that when Justice Alito commented in Bartlett that the Court would welcome resolution on the “difficult preemption questions that arise in the prescription drug context,” the Court specifically said it would welcome “Congress’ ‘explicit’ resolution” — so as to not have to “divine Congress’ will from the duties the statute imposes” (emphasis added).¹⁵ Perhaps one should not make too much of the Court calling on Congress as opposed to the FDA — in fact, Congress has not enacted any legislation since Mensing, which was more than two years ago — but maybe not. Perhaps Congress acting to resolve the lack of “parity” is precisely what the Court expects.

IV. Conclusion

The issuance of yet another generic implied preemption case in Bartlett, followed almost instantly by the FDA’s announcement that it seeks to implement the rulemaking process to “create parity” in the generic versus brand labeling processes, has created a maelstrom of speculation of the continued validity of Mensing and Bartlett. Stakeholders should unquestionably be engaged in and educated about the rulemaking process. To that end, new information on the terms of the proposed rule should be soon forthcoming, a public comment period will follow, and advocates on every side of the issue should (and certainly will) be heavily involved. In the meantime, bear in mind that the feeling may not, in fact, be as “Mutual ” as it appeared immediately post-Bartlett. Rule changes may well be coming. But no time soon. And not without a fight.

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[1] Wyeth, Inc. v. Levine, 555 U.S. 555 (2009).

[2] PLIVA, Inc. v. Mensing, — U.S. –, 131 S. Ct. 2567 (U.S. 2011).

[3] Mutual Pharm. Co. v. Bartlett, — U.S. –, 133 S. Ct. 2466, 2013 U.S. LEXIS 4702 (U.S. 2013).

[4] Mut. Pharm. Co. v. Bartlett, 133 S. Ct. at 2480.

[5] HHS/FDA. Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products. <http://www.reginfo.gov/public/servlet/ForwardServlet?SearchTarget=Agenda&textfield=0910-AG94>. Last accessed Sept. 22, 2013.

[6] Thomas, Katie, “F.D.A. Rule Could Open Generic Drug Makers to Suits,” New York Times, July 3, 2013. Available at <http://www.nytimes.com/2013/07/04/business/fda-rule-could-open-generic-drug-makers-to-suits.html?_r=0>. Last accessed Sept. 22, 2013.

[7] Office of Information and Regulatory Affairs, FAQs/Resources, “Regulations and the Rulemaking Process,” <http://www.reginfo.gov/public/jsp/Utilities/faq.jsp>. Last visited Sept. 22, 2013.

[8] Administrative Procedure Act (APA), 5 U.S.C. ch. 5. See also <http://www.reginfo.gov/public/jsp/Utilities/faq.jsp>. Last visited Sept. 22, 2013. See also <http://www.reginfo.gov/public/reginfo/Regmap/index.jsp>. Last visited Sept. 22, 2013.

[9] FDA explanation of rulemaking process: <http://www.fda.gov RegulatoryInformation/RulesRegulations/default.htm>. Last visited Sept. 22, 2013.

[10] This is certainly not to suggest that stakeholders should not be involved with the process; to the contrary, the system can only work if public comment is robust and interaction with FDA close.

[11] Mut. Pharm. Co. v. Bartlett, No. 12-142, Brief for United States as Amicus Curiae Supporting Petitioner, at fn. 2. Available at <http://www.scotusblog.com/case-files/cases/mutual-pharmaceutical-co-v-bartlett>. Last accessed Sept. 22, 2013.

[12] Office of Information and Regulatory Affairs, FAQs/Resources, “Regulations and the Rulemaking Process,” <http://www.reginfo.gov/public/jsp/Utilities/faq.jsp>. Last visited Sept. 22, 2013.

[13] United States amicus brief, supra, at p. 24 (citing 21 U.S.C. § 355).

[14] 21 U.S.C. § 355. The “sameness” requirement for generic drugs is indeed statutory. As explained in Bartlett, 133 S. Ct. at 2471:
First, the proposed generic drug must be chemically equivalent to the [**616] approved brand-name drug: it must have the same “active ingredient” or “active ingredients,” “route of administration,” “dosage form,” and “strength” as its brand-name counterpart. 21 U. S. C. §§ 355(j)(2)(A)(ii) and (iii). Second, a proposed generic must be “bioequivalent” to an approved brand-name drug. § 355(j)(2)(A) (iv). That is, it must have the same “rate and extent of absorption” as the brand-name drug. § 355(j)(8)(B). Third, the generic drug manufacturer must show that “the labeling proposed for the new drug is the same as the labeling approved for the [approved brand-name] drug.” § 355(j)(2)(A)(v).

[15] Mut. Pharm. Co. v. Bartlett, 133 S. Ct. at 2480.

Finis