Study: Generic Drug Label Warnings Are Often Different From the Brand-Name Labels on Which They Are (Supposedly) Based

by Brian Wolfman

Indiana University medical school professor Jon Duke and two co-authors have published this study entitled "Consistency in the safety labeling of bioequivalent drugs." The study could have been entitled "Inconsistency in the safety labeling of bioequivalent drugs" because it finds that the warnings on generic drug labels often deviate from the brand-name labels on which they are supposed to be based -- sometimes quite significantly. The study maintains that, overall, "68% of multi-manufacturer drugs [studied] had discrepancies in ADR [adverse drug reaction] labeling."

The problems identified by Duke raise concerns for patients and their prescribing doctors who, when labels are inaccurate, may be in the dark about a generic drug's adverse effects, contraindications, and other hazards. The study concludes that doctors prescribing generic drugs should review the branded label as well as the generic label. In a press statement, Duke also said that the best solution

may be a centralized listing of drug side-effects, maintained independently of individual manufacturer labels.  Drug labels would simply reference this common repository rather than attempting to maintain all the information within a single document.  Clinicians could refer to this resource for the most up-to-date safety information regardless of generic manufacturer.

Duke's study also raises legal concerns. Generic drugs are supposed to be bioequivalent to the brand-name drug on which they are based, and the FDA's marketing approval for a generic drug is premised largely on the FDA's finding of bioequivalence. When the FDA approves a generic drug, it requires the generic's label to ape the label on the equivalent branded drug. Although lawyers, drug companies, and advocacy groups have disagreed over the years about whether a generic manufacturer may make safety-related label changes without FDA pre-approval -- as the generic manufacturer learns over time about the drug's hazards -- the FDA takes the position that a generic manufacturer may not alter the label on its own. (In this regard, note that Public Citizen has filed a petition with the FDA asking that generic manufacturers be authorized to warn of drug hazards that come to their attention without prior FDA approval on the same or similar terms currently available to brand-name manufacturers.)

Last year, in PLIVA v. Mensing, the Supreme Court held 5-4 that state-law damages claims premised on generic drug manufacturers' failures to warn of a generic drug's hazards were preempted by federal law because federal law prohibited the generic manufacturers from changing their labels to meet the dictates of state law, but rather required that the labels stay the same as the branded labels. The Court explained that if the defendant generic drug manufacturers had

independently changed their labels to satisfy their state-law duty, they would have violated federal law. Taking [the plaintiffs'] allegations as true, state law imposed on the [generic] Manufacturers a duty to attach a safer label to their generic metoclopramide. Federal law, however, demanded that generic drug labels be the same at all times as the corresponding brand-name drug labels. See, e.g., 21 CFR §314.150(b)(10). Thus, it was impossible for the [generic] Manufacturers to comply with both their state-law duty to change the label and their federal law duty to keep the label the same.

PLIVA had an immediate impact, making it nearly impossible for a plaintiff to maintain a state-law damages claim based on a generic drug manufacturer's failure to warn. For more detail on PLIVA's reasoning and future implications, see this article I wrote with Dena Feldman.

Duke's study challenges the existence, in fact, of the "sameness" that formed the legal premise for the Court's decision in PLIVA. It also suggests that implementation of PLIVA is no easy task for the courts. If actual sameness is lacking between the generic label and the branded label with respect to an allegedly inadequate warning that a plaintiff says caused her generic-drug-based injury, what is the basis for preemption under PLIVA?  [Note: The Supreme Court recently granted review in Mutual Pharmaceutical Co. v. Bartlett, which presents the question whether FDA approval of a generic drug preempts a state-law damages claim premised on the drug's design defect. I wonder whether Duke's study will play a role in the briefing in Bartlett. For more on Bartlett, go here.]

Here are the Duke study's "Key Points":

• FDA mandates identical labeling between bioequivalent brand and generic medications, but
this consistency has never been validated

• Analyzing structured product labels, we found the majority of bioequivalent drugs show differences in safety warnings between manufacturers

• Reasons for these differences included missing tables, outdated post-marketing reports, and
formatting issues

• New strategies should be considered for harmonizing bioequivalent labels

Here is the study's conclusion:

Despite existing mandate, bioequivalent medications from different manufacturers often differ in their safety labeling. This variation stands in contrast to the expectations of providers, the FDA, and, more recently, the United States Supreme Court. While the clinical significance of such labeling discrepancies remains unclear, we suggest for now that physicians review branded drug labeling even when a patient is taking a generic version of a medication. Further research will be necessary to determine the clinical importance of these labeling discrepancies as well as to identify optimal solutions for ensuring ongoing harmonization of safety data across bioequivalent drugs.

The study's abstract is reproduced after the jump. You may also want to look at Indiana University's press release.

Intervention by Non-Class-Member Objectors

In Devlin v. Scardelletti, the Supreme Court held that a class member who objects in a federal district court to a proposed class-action settlement may appeal approval of that settlement without moving for (and being granted) intervention. As I explained in this article, despite efforts by settling parties to limit Devlin to members of non-opt-out classes, the right to appeal approval of a class settlement should extend to all class members.

Devlin proceeded on the (correct) assumption that a class member could object to a proposed settlement in a district court without intervening. But what about the rights of non-class members to object to a class certification and settlement that could adversely affect their interests? Those issues are addressed in a new decision of the Third Circuit, Benjamin v. Department of Public Welfare. There, the objectors were intellectually impaired residents of state-run care facilities who objected to a settlement that favored community placement. The class definition excluded people who opposed community placement. The district court denied the objectors' motion to intervene for the purpose of challenging class certification and the proposed settlement.

The Third Circuit reversed, holding that the objectors' interests were not adequately representated by the existing parties, including the state of Pennsylvania, which ran the care facilities. The court noted that although ordinarily a government is an adequate representative of the public, the objectors here had their own personal interests at stake and should not be forced to accede to Pennsylvania's position, which was "necessarily colored by its view of the public welfare."

The Third Circuit remanded to allow the objectors to raise their concerns with the class certification and settlement. Armed with intervention status, presumably the objectors will be able to appeal any adverse rulings on their merits. Worth reading.

Steubenville Rape Case and Libel Suit

by Paul Alan Levy

The New York Times carries an exceptionally detailed report of the controversy over the rape of a high school girl and the libel case brought by the parents of a player against an online blogger and several anonymous commenters, discussed here two weeks ago.  A reminder that reporting can be dangerous -- the football coach, who had been criticized for not benching the players involved in the rape, apparently threatened one of the reporters who was asking questions, saying  "you’re going to get yours. And if you don’t get yours, somebody close to you will."  One can understand why the anoymous commenters who live in the community are afraid about the consequences of being identified.

Calo's Against Notice Skepticism

by Jeff Sovern

I've moved on to the privacy chapter of our casebook, and in that regard I just finished reading M. Ryan Calo's (Calo is at the University of Washington and affilated with Stanford)  intriguing Against Notice Skepticism In Privacy (And Elsewhere), 87 Notre Dame Law Review 1027 (2012).  Before I add my two cents, here's the abstract:

What follows is an exploration of innovative new ways to deliver privacy notice. Unlike traditional notice that relies upon text or symbols to convey information, emerging strategies of “visceral” notice leverage a consumer’s very experience of a product or service to warn or inform. A regulation might require that a cell phone camera make a shutter sound so people know their photo is being taken. Or a law could incentivize websites to be more formal (as opposed to casual) wherever they collect personal information, as formality tends to place people on greater guard about what they disclose. The thesis of this Article is that, for a variety of reasons, experience as a form of privacy disclosure is worthy of further study before we give in to calls to abandon notice as a regulatory strategy in privacy and elsewhere.

Calo is clearly more a fan of notice than outright regulation.  At one point he paraphrases Winston Churchill and writes that “notice is the worst regulatory mechanism, except for all of the alternatives."  Regular readers of this blog know that I am less fond of notice as a way of conveying information to consumers.  Still, notice may yet have a role to play in privacy, in the form of the single letter-grade approach.  As I have blogged about before, restaurant grades have been effective to convey health department assessments to consumers, and have improved the health not only of consumers who pay attention to the grades, but also of those who don't.  Surely it would be possible for some external agency to devise criteria for privacy policies, so that companies that don't use consumer information at all would get an "A", those who use it only internally would get a "B", and so forth.  That way, consumers could continue to forego reading privacy policies, but still know what privacy choices they are making.  And just as restaurateurs strive for better health department grades, to attract the business of those who care about the grades, which helps all consumers, perhaps businesses would strive for better privacy grades.  It seems like such an obvious idea, I wonder if someone has already tried it. 

Calo calls for more research, and I agree.  We need to try different ways of providing notice to see what consumers actually use.  The CFPB is willing to do this with its notices. Perhaps the FTC will follow suit on privacy.  I would love to see one of those Innocentive contests for notices that convey privacy policies to consumers in such a way that consumers will actually use them.

Bruce Bartlitt on the Budget "Crisis"

In this piece, Bruce Bartlett has the audacity to bring facts to the discussion of the so-called budget crisis. It's mainly about how "entitlements" are a small part of the problem despite what we hear from the Republicans. Here's an excerpt about social security, where he explains that if we simply subjected the same percentage of wages to social security tax as we have historically (90%), concerns about the solvency of the social security system would be resolved:

To be sure, some restraint is needed in federal entitlement programs. But the idea that we are facing a crisis is complete nonsense. Spending for Social Security, in particular, is very stable. Relatively modest changes, such as raising the taxable earnings base slightly, would be sufficient to put the program on a sound footing virtually forever. As a Nov. 28 Congressional Research Service report explains, historically 90 percent of covered earnings was subject to the Social Security tax. In recent years, this percentage has fallen to 84 percent, as the bulk of wage gains has gone to those making more than the maximum taxable income, currently $110,100. Raising the share of covered earnings back to 90 percent would be sufficient to eliminate almost half of Social Security’s long-run actuarial deficit, according to the Social Security actuaries.

Positive step in police whistleblower case

This week, the Ninth Circuit agreed to rehear en banc a case about a cop who revealed the abuse of suspects inside his department. The Ninth Circuit has developed a troubling line of cases to the effect that, under the Supreme Court's 2006 decision in Garcetti v. Ceballos, any time a police officer in the state of California reports misconduct, he is just doing his job -- which means he is speaking as an employee not as a member of the public and is therefore not protected by the First Amendment. Most other circuits (and indeed some decisions within the Ninth Circuit) hold that whether a whistleblower is speaking as an employee is a question of fact and no categorical rule is appropriate. Hopefully the Ninth will resolve this conflict when it rehears the case in March.

Disclosure: Public Citizen is co-counsel on the petition for rehearing. The panel decision (criticizing but reluctantly following the reporting-misconduct-is-part-of-the-job rule) is here.

Victoria Secret Trademark Complaint — Another Hosting Company Finks Out

by Paul Alan Levy   

Amid the coverage of the feminist prank web site using Victoria Secret's name on a site promoting the concept of consent-themed underwear instead of underwear that portrays a woman’s readiness for sexual contact as a “sure thing,” I noted that in demanding the takedown of the web site on trademark infringement grounds, Victoria Secret “contacted our server, not us directly.” Apparently, the hosting service precipitously took the site down in response to the trademark holder's complaint, forcing the pranksters to move to a new host.

It would be nice to know which hosting service betrayed its customers instead of standing up for their free speech rights, so that other consumers would be warned not to do business with that ISP.

The Ninth Circuit's En Banc Argument in Kilgore v. Keybank

An 11-judge en banc panel of the Ninth Circuit heard oral argument this week in Kilgore v. Keybank, an important consumer arbitration case. Kilgore presents the question whether the Federal Arbitration Act and the Supreme Court's decision in AT&T v. Concepcion require courts to enforce arbitration clauses even when they would block consumers from pursuing their substantive statutory rights to a public injunction under California consumer-protection laws. The panel, consisting of Chief Judge Kozinski and Judges Pregerson, McKeown, Fletcher, Tallman, Callahan, Milan Smith, Murguia, Christen, Watford, Hurwitz, notably includes four new Obama appointees. Andy Pincus argued for the Chamber and Jim Sturdevant argued for the plaintiffs. You can read detailed accounts of the arguments at the UCL Practitioner blog here and here, read the papers at Public Justice's website, and go here or click on the embedded video below to watch the arguments:

Richard Frankel Paper on Arbitration Clauses

Richard Frankel of Drexel has written The Arbitration Clause as Super Contract.  Here's the abstract:

It is widely acknowledged that the purpose of the Federal Arbitration Act was to place arbitration clauses on “equal footing” with other contracts. Nonetheless,federal and state courts have placed arbitration clauses on a pedestal by creating special interpretive rules for arbitration clauses that do not apply to other contracts. In doing so, they have relied extensively on the Supreme Court’s adoption of a “federal policy favoring arbitration” in the case of Moses H. Cone Memorial Hosp., Inc. v. Mercury Constr. Corp., 463 U.S. 1 (1983).

While many scholars have focused attention on the public policy rationales for and against arbitration, few have explored how arbitration clauses should be interpreted. This article fills that gap and asserts that judicial reliance on the federal policy favoring arbitration unfairly deprives litigants of access to the courts by pushing cases into arbitration that do not belong there and in the process. By creating special rules favoring arbitration that deviate from state contract law, courts are enforcing arbitration agreements in situations where they would not enforce other agreements. This article questions the basis for the federal policy favoring arbitration and identifies several areas in which courts are relying on it to over-enforce arbitration clauses. Because the original purpose of the Federal Arbitration Act was to make arbitration clauses just like other contracts, this article proposes that courts should not rely on a poorly-conceived federal policy favoring arbitration, but instead should apply general contract principles to arbitration clauses. Doing so best ensures that litigants are not unfairly forced into arbitration in situations where they never agreed to it.

Looks Like Senator Warren is Heading to the Banking Committee

Read about it here in a piece by William Alden. We discussed the possibility right after her election. Now it looks like a certainty. An excerpt from Alden's piece:

Elizabeth Warren, the Harvard professor who won a Senate seat in November, is officially on track to join the Senate Banking Committee, after the Democratic Steering Committee approved her assignment on Wednesday. The appointment is subject to approval by the full Democratic caucus and a resolution by the full Senate after it convenes in January. Ms. Warren’s role on the banking committee would give her greater influence over laws and regulations affecting the financial industry. A noted consumer advocate, Ms. Warren had harsh words for Wall Street throughout her campaign, and she is expected to support tougher controls on the industry.