Our recent post on the outcome of the plaintiffs’ in limine motions in the Guenther Aredia/Zometa case prompted a volcanic retort from one of the plaintiffs’ counsel (who will remain anonymous) that “all was not beer and skittles” (yech – not an appetizing combination) for the defense, specifically listing the court’s rejection of a defense “paper storm” and “preemption based in limines.” Attached to counsel’s emails were an order striking an original set of defense in limines as too darn long and a second order resolving a choice of law dispute in favor of Florida, rather than Georgia, law.  Why a plaintiff would prefer
Florida law in prescription drug product liability litigation case escapes us; some of us remember the excellent Florida law on causation and the learned intermediary rule that led to huge defense wins in the Seroquel litigation.

At about the same time as that email, one of our automatic searches pulled up the opinion on the Guenther defense in limines, which counsel had referenced but did not attach.  See Guenther v. Novartis Pharmaceutical Corp., 2013 WL 4648449 (M.D. Fla. Aug. 29, 2013).  Because (as counsel noted) we are interested in preemption issues – even hard ones for our side, which certainly includes preemption in innovator drug cases post-Wyeth v. Levine, 555 U.S. 555 (2009) –
we took a look.
For a post-Levine decision, we actually don’t think the rulings are all that bad.  In fact, since the opinion provides a road map for possible future preemption inroads, we think this Guenther decision is worthy of comment.

The first preemption argument in Guenther involves
allegations that the defendant should have included a black box warning.  We’ve blogged on black box preemption before
(way back in 2006) and ever since we’ve continued to believe the preemption argument is a good one.  New favorable cases include Fulgenzi v. PLIVA, Inc., 711 F.3d 578, 584-85 (6th Cir. 2013) (generic drugs); Ray v. Allergan, Inc., 2012 WL 2120018, at *7 (E.D. Va. June 1, 2012); In re Avandia Marketing, Sales Practices & Products Liability Litigation, 817 F. Supp.2d 535, 553 n.97 (E.D. Pa. 2011); cf. Ray v. Allergan, Inc., 863 F. Supp.2d 552, 560-61 (E.D. Va. 2012) (allowing plaintiff to argue for a black box change only on a “take steps” rationale rejected in PLIVA v. Mensing, 131 S. Ct. 2567 (2011)).

In Guenther “Plaintiffs [did] not directly respond to this point.”  2013 WL 4648449, at *3.  Instead they fed the court a lot of Levine-related blather, which the court duly waded through.  But in the end the requirement of FDA pre-approval won out:
Despite the foregoing, the Plaintiffs never directly dispute [defendant’s] contention that the FDA regulations preclude a manufacturer from adding a black box warning without preapproval.  Accordingly, the Plaintiffs will not be permitted to argue at trial that [defendant] should have done so.
Id. at *5.  It appears from the opinion, id., that the defendant tried to extend Mensing/Mutual Pharmaceutical Co. v. Bartlett, 133 S. Ct. 2466 (2013), preemption to all warnings –which would be nice, but is unlikely to happen without another Supreme Court decision.  While Guenther did reject that argument, it did apply the fundamental “independence principle” (see our discussion here) to black box warnings involving innovator drugs, which is the most we reasonably could hope for.

The next preemption argument in Guenther had to do with state-law claims that the dosage of A/Z should be changed.  There’s a regulation that, once again, requires prior FDA approval of dosage changes.
21 C.F.R. §314.70(b) (requiring FDA pre-approval of, among other things, changes to the “strength” of all drugs). We mentioned this reg (although not this precise point) in our post-Bartlett  Major Changes post discussing where FDA prior approval is required with respect to innovator drugs.  In response, to the defense argument in Guenther it looks like plaintiffs abandoned any claim attacking the actual dosage of the drug, and limited themselves to changing warnings about dosage.  2013 WL 4648449, at *5.  Since a warning change on this subject may be made unilaterally, the defendant lost.  Id.  As long as Levine is on the books, that’s unfortunately the likely result.

However, the implication of this aspect of Guenther is clear– at least to us.  To the extent that a plaintiff were to argue for a change in the per-pill dose of an innovator drug, that claim, which goes to the design of the drug, should be preempted.  That’s entirely in accordance with Bartlett, which pointed out that, with respect to design changes, “[o]nce a drug − whether generic or brand-name − is approved, the manufacturer is prohibited from making any major changes to the
‘qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved application’.”  133 S. Ct. at 2471 (also quoting §314.70(b)) (emphasis added).

There are a lot of warning-related claims that, after Levine, aren’t going to be preempted as to innovator drugs like A/Z, but there are more claims against which preemption survives than a lot of us initially feared.

The next preemption argument involves comparative labeling – a plaintiff claiming that a manufacturer should warn that a competing product is in some way “safer” than its own product.  We previously presented a large amount of common-law precedent rejecting this type of claim here while discussing In re Baycol Products Litigation, 532 F. Supp.2d 1029 (D. Minn. 2007).  However, there’s also an on-point FDA regulation (actually two), prohibiting a manufacturer from comparing its drug to another unless it has “substantial evidence derived from adequate and well-controlled studies.”  See 21 C.F.R. §§201.57(c)(2)(iii), 201.80(c)(3)(v); see also 21 C.F.R.  §314.126(b) (defining “adequate and well-controlled study”).  Thus in our Major Changes post, we pointed out that the FDA requires prior approval of label changes involving comparative labeling.

Now, there’s also some bad law on this subject, but it’s from the Levaquin litigation, and we think it has been superseded.  See Schedin v. Ortho-McNeil-Janssen Pharmaceuticals, Inc., 808 F. Supp.2d 1125, 1143 (D. Minn. Aug. 26, 2011) (finding comparative labeling claim not preempted; defendants should have “applied for a waiver from the well-controlled studies requirement”).  Schedin is another example of a court relying on a “take steps” rationale that’s no longer valid after Mensing. The Eighth Circuit, in a post-Mensing Levaquin appeal, pointedly refused to endorse the lower court’s permitting a comparative labeling claim.  See In re Levaquin Products Liability Litigation, 700 F.3d 1161, 1166 (8th Cir. 2012) (“we need not address whether the district court erred in denying [defendant’s] motions based upon Schedin’s comparative toxicity theory”).

Once again, we’re encouraged by what we see in Guenther:

The Plaintiffs argue that there were comparative studies
. . . because [defendant] referenced Aredia as a control during the Zometa trials. . . .  The Plaintiffs then argue that “[w]hen [defendant] had indications that Aredia’s safety profile . . . was better than Zometa’s . . . it had carte blanche through the CBE to say so on the label.” However, having “indications” that one drug is safer than another is a far cry from having “adequate and well-controlled studies” reaching that conclusion, which the Plaintiffs appear to admit is the applicable standard.  At this juncture, the Court does not know
enough about the comparison(s) to be made or the evidence backing them to reach a final conclusion.  But it appears that the Plaintiffs’ evidence would not satisfy the [FDA] standard.

2013 WL 4648449, at *6 (emphasis added).  It’s not definitive, but we doubt that plaintiffs have necessary studies (no other plaintiffs ever have).  The implication is that, once again, the court is willing (as it should be) to apply the “independence principle” developed in LevineMensing, and Bartlett to preemption issues involving an innovator drug.

The next preemption argument in Guenther involves allegations that the “format” of the defendants labeling should be altered.  2013 WL 4648449, at *6.  This is an argument that the A/Z defense already won in Hill v Novartis Pharmaceuticals Corp., ___ F. Supp.2d ___, 2013 WL 1953753 (E.D. Cal. May 10, 2013):

[Defendant] contends [plaintiff] should be precluded “from suggesting that [it] should have formatted the Zometa labeling differently. . . .
[Defendant] contends that because the FDA “comprehensively regulates the formatting of prescription drug labeling,” any “challenges to the FDA-approved formatting [would] undermine FDA’s considered judgments[.]”  Against this background, [defendant] moves the Court to bar [plaintiff] from arguing “that the FDA-approved label [for Zometa] should have placed the warning . . . in a different section of the label, or should have utilized a different font size or bolded text. The Court agrees. FDA regulations for prescription drug labeling extend not only to content but to formatting.  While the case law is clear that manufacturers may modify the contents of a brand-name drug label without FDA approval by adding to or strengthening the warnings, [plaintiff] has provided no authority − and the Court’s research reveals no authority − to suggest manufacturers may do the same with the label’s formatting

Id. at *10 (citations omitted).  Guenther denied essentially the same motion, but its rationale doesn’t come to grips with the sort of claims at issue – moving information (such as warnings) from one section of the drug’s labeling to another, or changing the font in which information is presented.  What follows is the entire analysis of the formatting issue in Guenther:

[Defendant] argues that the Plaintiffs should be barred from arguing that the company should have formatted the Zometa label differently, such as by moving the ONJ warning to a different section.  However, the FDA also regulates the content of such labels and drug manufacturers can add warning language, and it makes no sense to hold the formatting sacrosanct where the actual content is not. The CBE regulations that permit manufacturers to add or strengthen warnings impose no limitations on the formatting of such warnings.


2013 WL 4648449, at *6.

Instead of addressing FDA regulations and guidance (which are excruciatingly detailed) mandating what type of information belongs in which titled section of a drug’s warnings, Guenther adopts the attitude that “a word is a word is a word,” with a blanket citation to CBE regulations.  From Hill it appears that this motion was actually directed to something like moving what the FDA considers to be “warnings” into the “contraindications” section of the labeling, or adding bolded text or larger fonts where the FDA doesn’t demand them.  From the FDA guidance we discussed in our Major Changes post, it’s readily apparent that the FDA has never considered formatting as within the scope of the CBE regulations. Indeed, we went back and searched the entire guidance document that we discussed in that post for any references to “format” “font” or “section” to see if the FDA said anything that might be pertinent.  We found no references to this type of change.  The closest thing we found was something the FDA considered a “minor” label change (one that didn’t even require a CBE):

Changes in the layout of the package or container label that are consistent with FDA regulations (e.g., 21 CFR part 201) without a change in the content of the labeling.

FDA Guidance document at 26. We note the FDA’s caveat that any “layout” change must be “consistent with FDA regulations.”  This caveat gives us reason to believe that a label change that is not “consistent with FDA regulations” cannot be made without FDA approval (and probably a change in the regulations). Certainly the issue is worthy of greater treatment than the couple of sentences Guenther devoted to it.

This argument may be one area where the court’s prior order limiting the defendant’s in limine briefing to an absurd 20 pages (granted, the prior 131 pages that the court complained about strikes us as high) cheated the analysis of the issue. We’re not sure from Guenther whether the plaintiffs are even intent on making real formatting claims. Anyway, if the A/Z plaintiffs are actually attacking FDA-regulated formatting (as opposed to language changes allowed by the CBE regulation) then we think that the minimal treatment such allegations have been given in Guenther hardly forecloses the defense from raising preemption against something the FDA wouldn’t allow.

The final preemption argument in Guenther involves “failure to report.”  We consider claims of this nature to be disguised fraud on the FDA claims barred under the discussion in Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341 (2001), concerning exclusive governmental enforcement of the FDCA.  While not citing Buckman, it appears that Guenther does too:

[Defendant] argues that the Plaintiffs should be barred from contending that the company violated FDA regulatory requirements by failing to report some information about [risk] to the agency.  Novartis argues that such arguments are constitutionally preempted.  The Plaintiffs offer no response to this argument.  The question of whether certain information was reported to the FDA may still be relevant here, but the Plaintiffs will not be permitted to argue that [defendant] violated FDA regulations by withholding information from the agency.

2013 WL 4648449, at *6 (emphasis added).

So let’s see, that’s (1) black box warnings; (2) dosage/design changes; (3) comparative labeling; (4) formatting; and (5) failure to report.  This list covers, if not every aspect of innovator drug preemption that we think survives Levine, at least a high percentage of those issues. Except for the two-sentence discussion of formatting, the defense didn’t lose any preemption argument on the merits in Guenther and appears to have won, or be on its way to winning, on items (1), (3), and (5).

We’re a defense-related blog – we make no bones about it – so anything you read here will have a pro-defense spin, but based on the above, we have to take issue with plaintiffs’ counsel’s characterization of Guenther as a “rejection of the preemption based limines.”

You be the judge.