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It’s been said that the third time’s the charm. Maybe that means that we’ll get it right this time.
Anyway, as regular readers of this blog know, Wyeth filed its principal merits brief in Wyeth v. Levine early last week. As night follows day, that means that all defense amicus briefs are due a week later.
As swine follow pearls, that means we’re going to read and comment on those briefs. We’re so blatantly predictable that the folks over at Overlawyered are just sitting around waiting for us to do this. Hey, we also provide direct links so you can just ignore what we say and read all the amicus briefs for yourselves. We’re not bothered by that. Our opponents ignore what we have to say all the time.
As usual, we give primacy of position to the amicus brief filed by the Department of Justice, on behalf of the FDA. That’s because, unlike any of the other defense side amici, the legal position of the government – because it’s the government – has at least arguable substantive weight in its own right, depending upon whatever label (Chevron, Auer, Skidmore, etc.) the Supreme Court’s inclined to apply in any particular case.
We find the government’s amicus brief particularly interesting this time around because the government flat out says that it’s making an attempt to add some overarching structure to its prior, somewhat ad hoc amicus filings concerning preemption. In particular, on page 27, the government goes beyond the six “non-exclusive” examples of preempted situations that the FDA offered in its 2006 Preemption Preamble (71 Fed. Reg. at 3935-36) to “articulate[e] a more general rule of decision” on when there is conflict preemption by reason of FDA drug labeling decisions:

In this brief, the government has articulated a more generally applicable rule of decision, consistent with those examples, based on the preamble’s explanation that (i) the labeling requirements are not a mere minimum safety standard, but rather strike a balance between risks and benefits, and (ii) FDA’s regulations permit changes in labeling without prior approval only in narrow circumstances.

DoJ br. at 27.
So let’s take a look in more detail at what that “rule,” as articulated by the government, is. The first criteria for preemption, under the FDA’s position, is that the Agency’s actions – here approval of drug labeling – represent a “balance between risks and benefits.” Id.

That proposition ties into, initially, the “rigor” with which the FDA evaluates the new drugs that it approves, and especially its review of the labeling for new drugs. See DoJ br. at 11 (“labeling is the centerpiece of risk management”). Thus there is a long and detailed, almost over-detailed, description of the FDA’s drug approval process on pages 11-14 of the government’s brief. That’s all prologue for the balancing proposition:

In determining whether to grant or continue its approval of a new drug application, FDA does not merely impose minimum standards of safety. . . . No drug is absolutely safe; all drugs have side effects. Thus, FDA weighs health benefits against health risks. And FDA generally considers a drug safe when the expected therapeutic gain
justifies the risk entailed by its use.

DoJ br. at 15 (omitting all sorts of citations). That’s balancing. FDA approval is as lengthy and involved as it is because the Agency balances risks and benefits in the context of each of the labeled indications for an approved drug.
Balancing is important because that’s the agency function that drove the Court’s preemption conclusion in Riegel – the conviction that that juries are inherently incapable of factoring the benefits of medical devices or drugs to persons not party to tort litigation into their liability evaluations. See DoJ br. at 19-20. Quite the opposite of juries, broad societal balancing is what the FDA does, and what it’s good at:

  • “FDA’s balancing of a drug’s risks and benefits is similar to the balancing it undertakes in the analogous context of Class III medical devices. DoJ br. at 15.
  • “In the course of weighing health risks and benefits, FDA considers the overall health consequences of including particular instructions or warnings in a drug’s labeling.” Id. at 16.
  • “[L]abeling must strike a balance between notifying users of potential dangers and not unnecessarily deterring beneficial uses through overwarning.” Id. at 17.

Labeling approval involves risk-benefit balancing, and once the FDA has done that, in the absence of new information, its decision controls:

Where, however, federal regulation is designed to strike a balance between competing considerations, state laws that strike a different balance are impliedly preempted because they interfere with the federal balancing.

DoJ br. at 18 (emphasis added).
The second criterion for preemption in the FDA’s “general rule of decision” is that there are only a few circumstances that permit drug manufacturers to bypass FDA pre-approval of label changes. Drug product liability “claims are preempted [when] they challenge labeling that FDA approved after being informed of the relevant risk.” DoJ br. at 17. That’s the trigger for preemption from the government’s standpoint. If the FDA has already reviewed the risk at issue and has approved labeling that deals with it, state law cannot deem inadequate the labeling that the FDA approved.
The key here is something we first posted about over a year ago, and that’s the clear regulatory history that limits to new information the “changes being effected” (“CBE”) exception to FDA pre-approval. The government comes out swinging on this point:

[L]iability under state law turns on whether a drug, as labeled, is “unreasonably dangerous.” Any such finding would directly conflict with FDA’s determination that the drug is safe and effective under the conditions prescribed, recommended, or suggested in the labeling. Indeed, respondent specifically urged the jury to second-guess FDA and reject the agency’s expert judgment.

DoJ br. at 19 (citations, as usual, omitted). As we mentioned in connection with Wyeth’s brief last week, one of the best facts the defense position has going for it in Levine is the explicit attack that plaintiff mounted upon the FDA in her closing argument.
The CBE regulation, the government argues, does not allow plaintiffs “to disregard FDA’s judgment concerning previously known risks.” DoJ br. at 21. The holding of the lower court in Levine that any label change adding or strengthening warnings could always be made unilaterally, without FDA pre-approval, would lead to absurd and unreasonable results:

If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval based on information that was previously available to the agency, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted.

Id. at 21-22.
This is a powerful practicality argument. Any contrary rule would require manufacturers to make the same CBE change over and over again – despite FDA rejection of the change – in order to avoid liability. This issue came up Colacicco, too, and the plaintiffs never articulated a persuasive response. The only way to prevent the CBE exception from becoming a vehicle for ignoring FDA labeling decisions is (as we argued last April) to limit it to new information:

[A]ny changes to a drug’s labeling without prior FDA approval must be. . .based on new information establishing that risks arising from use of the drug are of a different type or greater severity than the risks of which FDA had previously been made aware – not cumulative new information that does not add to the information that was previously available to the agency.

DoJ br. at 24. Moreover, since this argument merely interprets the scope of the FDA’s own CBE regulation (as opposed to, say, the Agency’s general views about preemption), the government has a stronger argument that its views concerning that regulation are entitled to substantial deference. Id.

Anyway, that’s the government’s main argument in Levine. Beyond that, there are a number of lesser points of interest. We note another interesting little twist in the government’s argument on pages 11-12. Among the citations for the otherwise (to us anyway) rather obvious proposition that new drug approvals are similar to those for Class III medical devices is Justice Ginsberg’s dissent otherwise opposing preemption in Riegel. We – well, actually guest blogger Adam Masin – had picked that nugget (“[t]he process for approving new drugs is at least as rigorous as the premarket approval process for medical devices,” Riegel, 128 U.S. at 1018) in a post written shortly after Riegel came down. We’re glad to see that silver lining to Justice Ginsberg’s otherwise dismal (at least to us preemption buffs) opinion being put to better use than just blog fodder.
The government also persuasively (and somewhat sarcastically) debunks the rather rigid argument that preemption applies only where the FDA has rejected the exact, word-for-word label change that the plaintiff advocates. That contention is a recipe for futility because it “underestimate[s] the post hoc imagination of lawyers to think such an exhaustion of potential variants by the manufacturer or the agency is even possible.” DoJ br. at 25. Rather, the minutiae of the FDA’s wordsmithing must take a back seat to the substantive risk involved:

[I]t is FDA’s approval decision – which, in this case, followed the disclosure of the relevant risk – not the specifics of the agency’s deliberations or speculation about whether the agency might have modified the label in some manner not expressly proposed at the time of the approval, that gives rise to preemption. Any state law liability would be premised on a re-weighing of the same risks and benefits that FDA already considered.

Id. at 25.
In connection with the excellent arguments made by Wyeth, we’ve already discussed the plaintiff-side reliance upon an uncodified 1962 quasi-savings/quasi-preemption clause predicating preemption upon “direct and positive conflict.” The government takes on this argument as well. It makes the following points: (1) since Phenergan was approved before 1962, the clause is of doubtful applicability; (2) the clause preserves, rather than limits conflict preemption; (3) “direct and positive conflict” is a longstanding judicial term describing and encompassing all conflict preemption; (4) the clause’s legislative history shows it was directed against field, not conflict, preemption; and (5) the Court has never read general savings clause to preclude application of ordinary conflict preemption principles. DoJ br. at 28-31.
Between Wyeth’s and the government’s briefs, there’s more than enough ammunition for any defense counsel facing this same argument to shoot it full of holes.
Lastly, the government responds to an argument that a “rule of construction” adopted as part of the 2007 FDAAA retroactively undermined conflict preemption. We blogged about this poor, tortured little rule shortly after the FDAAA became law. Like us, DoJ points out that that rule is limited to a particular “paragraph added in 2007.” DoJ br. at 32-33. Facially, the rule also applies only to “existing” federal requirements like those it lists – and not to state law, which the rule does not mention. Id. at 32. Finally, the brief points out that for every statement by an individual legislator that this rule was supposed to affect preemption, there’s an equal and opposite statement by some other legislator that it didn’t limit preemption. Id.
That’s the government’s brief. There’s also a bunch of amicus briefs by the usual pro-defense cast of characters in this sort of case. Because Bexis is a PLAC (Product Liability Advisory Council) member, we’ll start with PLAC’s brief.
Actually, we’re starting with PLAC’s brief because its lead argument is one that’s very near and dear to our hearts. PLAC challenges frontally the “presumption against preemption” that plaintiffs trot out indiscriminately in preemption cases. PLAC argues (as we did in our inaugural post on this blog) that this presumption is simply inapplicable to preemption that arises by reason of actual conflict:

The time has come for this Court to clarify once and for all that – contrary to the opinion below – the presumption against preemption simply does not apply to the analysis of whether state law conflicts with federal law.

PLAC br. at 2. We wish.
Like our post, PLAC demonstrates (only much more elegantly) that the Court has not applied the presumption in its implied conflict preemption cases since that presumption first reared its ugly little head (as a mere “assumption”) in 1947. PLAC br. at 5-8. Indeed, we’re grateful to PLAC for picking up something that we missed: In 2000 the Supreme Court specifically noted that application of the presumption against preemption remained open in conflict preemption cases. Crosby v. National Foreign Trade Council, 530 U.S. 363, 374 n.8 (2000) (“We leave for another day a consideration in this context of a presumption against preemption.”). See PLAC br. at 8.
Note to selves: Use this.
PLAC reviews the Supreme Court’s recent conflict preemption precedent and concludes that in at least three cases the Court’s stated preemption rationale is actually inconsistent with the existence of a presumption against preemption. PLAC br. at 8-10 (discussing Geier v. American Honda Motor Co., 529 U.S. 861 (2000); United States v. Locke, 529 U.S. 89 (2000); and Sprietsma v. Mercury Marine, 537 U.S. 51 (2002)).
After finishing its arguments against the presumption based on the lack of Supreme Court precedent applying that presumption in conflict preemption cases, PLAC turns to other reasons why the presumption should not extend to this situation:

  • There’s no textual basis in the Constitution for any presumption in cases where preemption arises by direct application of the Supremacy Clause. PLAC br. at 11-13.
  • The 10th Amendment doesn’t implicate preemption analysis where preemption exists pursuant to the exercise of a power expressly delegated to the federal government. PLAC br. at 12 n.8.
  • There’s no basis in constitutional history for any presumption in cases where preemption arises by direct application of the Supremacy Clause. Id. at 13-15 (to think, we’d never even heard of “non obstante” before).
  • The presumption only has logical application to situations where it’s necessary to infer positive congressional to preempt, and conflict preemption doesn’t depend on any such inference of intent. Id. at 15-18.
  • In implied preemption, the scope of preemption is delineated by the scope of the actual conflict. Id. at 18.

Any defense lawyer looking to preserve a similar existential challenge to the presumption against preemption in the conflict preemption context (and not just in pharmaceutical litigation) would do well to study the arguments PLAC has made in Levine very carefully.
Beyond the presumption against preemption, PLAC focuses on the policy reasons supporting preemption in the context of FDA approved products and labeling. Like the government, PLAC incorporates the FDA’s function in balancing the risks and benefits of drugs into a broad public health rationale. PLAC br. at 19-20. More than DoJ itself does (since the government, being the government, can simply declare its policy) PLAC supports this argument with copious citations to prior FDA amicus briefs and regulatory history. Id. at 20-22.
Once again, there’s lots of useful stuff for anybody who’s thinking about making a similar argument in another preemption case. After all, plagiarism is not a sin among lawyers – it’s a way of life.
PLAC also makes overwarning and uniformity arguments (br. at 22-23, 26-27), but since it plows no new ground that we can see, we’ll move on. Since Riegel, PLAC’s also added to its repertoire a version of the “juries don’t consider external benefits” argument. PLAC br. at 23-25. This argument is a little different from what we’ve seen elsewhere, so it’s worth a read, too.
Turning to the CBE issue, PLAC takes on the lower court’s “misconstruction” of that regulation. PLAC br. at 27-30. The argument’s not all that much different from one made by the DoJ (and by Wyeth, for that matter), but as is true throughout, the PLAC brief is chock full of useful citations for the defense practitioner.
PLAC follows with a useful discussion of the deference owed to the FDA’s previous pronouncements (the 2006 Preamble and various government amicus briefs) on preemption. Br. at 32-34. It finishes with a slightly different take on the 1962 savings/preemption clause that emphasizes Supreme Court precedent holding that express and implied preemption work separately, and thus an express savings clause does not affect the operation of implied preemption. Id. at 33-35.
Moving right along, the Pharmaceutical Manufacturers Ass’n (along with the Biotechnology Industry Organization) filed an amicus brief that contains, along with several of the arguments we have already discussed (risk/benefit balancing, overwarning, CBE/novelty), a useful historical analysis (br. at 10-14) of the ominous increase in product liability litigation involving FDA-regulated products in recent years. Lots of good statistics here. PhRMA/BIO point out that this far more intense litigation climate has resulted in more and more intrusions by common-law plaintiffs into the operation of the FDCA’s regulatory scheme. Increased litigation has resulted in increased opportunities for the tort system to come into conflict with the FDA’s administrative decisions. Hence the similar increase in the number of claims subject to dismissal on preemption grounds.

In recent years, there has been a sharp increase in the number of state-law tort suits in which juries are asked to second-guess FDA’s determinations concerning the appropriate warnings and instructions about pharmaceutical risks. Rather than challenging the absence of any warning about the risk at issue, many of these state-law suits – including this case – involve situations in which FDA has explicitly considered the risk at issue and approved labeling that expressly addresses the risk.

Id. at 11-12.
We are particularly gratified to see PhRMA/BIO bring to the Supreme Court’s attention how product liability litigation actually leads to increased harm in a situation that we’ve blogged about before – that more suicide warnings, added under litigation pressure to the labeling for anti-depressant drugs, has produced a statistically significant increase the number of suicides by causing depressed patients not to take their medicine:

[F]rom 2003 to 2005 [after the stronger warnings were added], prescriptions to those younger than age 15 declined by approximately 17 percent. Between 2003 and 2004, there was already a 14% increase in child adolescent suicide rates – the first increase of this magnitude in the child and adolescent suicide rate since the CDC began systematically collecting suicide data in 1979. As a result, the first systematic study of the effect of these new warnings concluded: If the intent of the pediatric black box warning was to save lives, the warning failed, and in fact it may have had the opposite effect; more children and adolescents have committed suicide since it was introduced.

PhRMA/BIO br. at 17 (emphasis added). Attorneys advocating ever-more and ever-stronger warnings don’t seem to think about the downside of what they do. Litigation, in and of itself, is killing the nation’s kids.
We’re pleased to see this point put squarely before the Supreme Court.
Also, since PhRMA and BIO are purely industry groups, we’re not surprised to find them arguing that all this tort litigation has an adverse effect on the development of new and better drugs. Br. at 18-25. It’s a well written argument, but we’re a little disappointed. Since we’ve made this argument ourselves, we were hoping (like the good plagiarists we are) to find new examples to add to our own lists. We didn’t find any. We’ve already got vaccines, Bendectin and contraceptives.
Let’s see some update action next time.
Another argument in the PhRMA/BIO brief that we haven’t encountered in the previous briefs – at least not in the same way – is their take on the practical effect of the lower court’s holding that even a CBE filing wouldn’t be preemptive unless the FDA rejected identical language. Their response, that such an approach would “encourage manufacturers to inundate FDA with requests for labeling changes that FDA has already rejected in substance” (br. at 36), seems right to us. Since preemption is such a powerful defense, there would be every incentive for defendants seeking the protection of preemption to increase their filings substantially if the lower court’s form-triumphs-over-substance rationale were to stand.
There’s also an argument to be made that, in response to litigation pressure, “defensive” drug warnings are multiplying to such a degree that the next wave of litigation will attack manufacturers for having too many warnings, so that the “important” (read: whatever is relevant to any plaintiff’s particular case) warnings are being buried in an avalanche of words. We’ve seen allusions to that argument in both the PLAC brief (at 29 n.15) and the PhRMA/BIO brief (at 16 n.7). This is one benefit of reading all of these briefs, because PLAC and PhRMA/BIO cite different things. There’s room here for a synthesis that could produce a more comprehensive argument than either has made separately – maybe enough to elevate the argument out of footnote status.
Continuing our review, our long-time fellow travelers at the Washington Legal Foundation (together with the American College of Emergency Physicians) also filed an amicus brief in Levine.
The distinctive feature of the WLF brief is its dramatic parade of horribles – we’ve already encountered one of them, the increase in suicide after suicide warnings on antidepressants were “strengthened” (see WLF br. at 16-17) – but WLF sets out several other specific examples in some detail:

  • A decrease in the IQ and other intelligence measures in babies whose pregnant mothers were scared away from eating fish due to overblown mercury warnings, and thus lost the beneficial effect that fish have on embryonic development. WLF br. at 18-19.
  • The increase in abortions that followed a “pill scare” caused by warnings about supposed increased risks of venous thrombosis associated with new (and more effective) types of oral contraceptives. Id. at 20-22.
  • The surge in measles cases caused by parents not getting their children vaccinated due to scientifically unsubstantiated fears that vaccines cause autism. Id. at 22-24.

There’s also an extensive discussion of the overwarning phenomenon in WLF’s brief (pp. 8-13) that we recommend due to its completeness.
Next on our list is the amicus brief filed by the Chamber of Commerce. Every amicus strives for a distinctive approach to case in question (for example, PLAC’s presumption analysis or WLF’s parade of horribles), and the Chamber is no exception. It takes the historical approach to preemption (something that should resonate with the original intent bloc on the Court) and explains in depth why and how we came to have a Supremacy Clause in our Constitution in the first place. Chamber br. at 12-18 If you want a history lesson, this brief is the place to start. Did you know that, at one point, the Founders considered giving Congress rather than the courts the power to veto state laws on preemption grounds? See Chamber br. at 16. Did you know that there was a proposal to use the army to enforce preemption? Id. at 15.
Nope, we didn’t either.
The point of the Chamber’s historical treatment of the Supremacy Clause is to demonstrate that “obstacle” preemption – which the lower court refused to recognize under the FDCA – is every bit as historically grounded in the Supremacy Clause as preemption by reason of impossibility. Chamber br. at 19-20.
We’ve learned more today about 18th Century non obstante clauses than we’d accumulated in over a quarter century each of practicing law. Of course that’s not saying much, since we hadn’t known anything about them before.
Having established that proposition, the Chamber goes on to discuss what must be every intermediate linguistic formulation of preemption (“conflicting; contrary to; repugnance; difference; irreconcilability; inconsistency; violation; curtailment; and interference”) known to man (or, at least, to lawyers). The point, of course, is to make more thoroughly than any of the other amicus briefs the argument that there is no hierarchy of preemption and that obstacle and impossibility preemption are of equal constitutional dignity:

This reluctance to create a hierarchy of theories of conflict preemption is understandable, not only because conflicts and inconsistencies between federal
and state law can take myriad forms but also because obstacle and impossibility preemption each serve a vital function in our constitutional scheme. Impossibility preemption addresses situations where both federal and state law impose mandates on a regulated party – and it is simply not possible to comply simultaneously with both mandates. . . . But federal laws and regulatory regimes can be severely undermined and even destroyed even in the absence of such diametrically opposed commands or requirements.

Chamber br. at 21-22 (citations, once again, omitted).
What the Chamber is leading up to with its scholarly, almost magisterial, discussion of constitutional history, is to induce the Court to decide a broader question – the nature of “obstacle” conflict preemption itself. Thus the Chamber urges a less “narrow” decision that would “clarify” (br. at 26) obstacle preemption in several important respects:

  • The inapplicability of the presumption against preemption to conflict preemption. Chamber br. at 27-28. This, of course, is essentially a shorter version of the argument that was the lead proposition in the PLAC brief.
  • The lower court attempted to draw distinctions between different types of implied preemption (obstacle and impossibility) that have no basis in law or policy. Chamber br. at 28-29.
  • An agency determination that obstacle preemption exists (only as to the scheme that that agency actually administers, of course) is entitled to substantial deference from the courts. Id. at 29-32.

It’s an ambitious agenda that the Chamber has mapped out, but that’s the point of amicus briefs. Because they are not parties, and do not have a direct state in litigation, amici are free to argue for more far-reaching results without the conservatism that comes from having one’s own life, liberty, or property at risk. Even if the Chamber only goes one for three, our side of the “v.” would be much better off.
Finally, there is the amicus brief filed by Dr. Calfee (whom we both had the pleasure of meeting a couple of weeks ago at the AEI (American Enterprise Institute) off-label use session at which we recently spoke), et al. It’s one of those “bunch of professors get together” type of amicus briefs. Since AEI’s Overlawyered blog had the cheek to anticipate this User’s Guide, we’ve retaliated by leaving their brief for last. Don’t tread on us! (not really, Ted – it’s just that somebody always ends up last – just like we did at the off-label use conference).
One thing for sure, we can’t let this post go by without acknowledging the ubiquitous Spriggs & Hollingsworth gang. They’re actually counsel of record for two different amicus briefs (WLF and AEI) in the same Supreme Court case. That’s something you don’t see every day.
The Calfee brief is devoted almost entirely to the issue of overwarning – touched upon to a greater or lesser extent by almost all of the other defense amici – but comprehensively addressed (and one might even say beaten into submission) here. The argument starts from the premise that, for reasons inherent to the bureaucratic imperatives of government agencies, the FDA naturally starts off as overly cautious with respect to drug approvals. Br. at 6-7. The brief goes on to argue that the FDA’s “sluggish” rate of drug approval doesn’t leave the public any safer – only without potentially better drugs:

[C]omparisons of drug approval regimes. . .demonstrate that the more rapid drug approval timelines in the European countries have not led to an increased rate of subsequent drug safety withdrawals in those countries, as would be expected if FDA’s cautious approach prevented the approval of unsafe drugs.

Br. at 9.
Particularly when aggravated by the effects of product liability litigation, the FDA’s general bureaucratic conservatism leads to a number of adverse effects: (1) fewer drugs being available to treat disease; (2) research and development disincentives; (3) loss of FDA control over labeling; and (4) defensive labeling/overwarning. Id. at 14-18.
Finally, of all the defense amici, the Calfee brief is the only one that focuses on the special problems created by this particular plaintiff’s claim, which as we’ve pointed out, does not merely involve alleged inadequate warnings – but rather, a claimed failure to contraindicate. That type of claim poses unique conflicts:

If failure-to-warn lawsuits cause unfounded or excessive warnings to be placed on the label, physicians can still exercise their usual role in balancing risks. . . . Contraindications work differently. Physicians are likely to view contraindications as outright bans, because to prescribe in the face of a labeled contraindication is to court a malpractice lawsuit and punitive damages if anything goes wrong. Contraindications therefore largely replace, rather than supplement, the usual balancing of risks and benefits.

Calfee br. at 19.
So that’s it – six defense amici in Levine, each with a different primary argument. There’s agency risk/benefit balancing and the CBE regulation limited to new information (DoJ); the presumption against preemption (PLAC); litigation created economic disincentives (PhRMA/BIO); adverse effects on public health (WLF); the history of conflict preemption (the Chamber); and overwarning (Dr. Calfee, et al.).
For preemption proponents, here’s everything on a silver platter.