We posted Wyeth’s principal brief in Wyeth v. Levine as soon as we got it to ensure our readers’ “first on the web” priority (much like we did with today’s Vioxx decisions). That was a “sight unseen” post, something we don’t generally like doing. We’d much rather give you our take on things – we figure that’s why most of our visitors come here in the first place, since they can get pure “news” elsewhere – but sometimes things can’t be helped.

Anyway, that was then; this is now. Now we’ve read it. We’re impressed with the job Wyeth’s brief does defending the preemption principle in a critical case. And we still think, like we did before, that the case itself is an excellent bridgehead for establishing the $64,000 question – preemption, or not – in the prescription drug product liability field.

We won’t rehash our prior post, where we discussed the favorable facts of Levine in depth, but we want to emphasize one key point – this isn’t just a failure to warn case, this is a failure to contraindicate case.

That makes a big difference, and it makes the preemption argument all the much stronger than it would be in “just” a warning case.

The plaintiff’s position in Levine is not that the warning of the risk (gangrene and amputation) of the use (intravenous (“IV”) injection) wasn’t explicit or detailed enough. No, her position is much more extreme. That position is that nobody should be allowed to use this drug for this FDA-approved purpose – ever. The plaintiff argued at trial, quite explicitly, that the FDA goofed:

Dr. Harold Green, another of respondent’s witnesses, also criticized FDA’s approval of Phenergan’s labeling, testifying that, in his opinion, “somebody at the FDA made an administrative error and approved it.” JA 82. In his view, the drug should not have been approved for intravenous administration. JA 79-80. Respondent’s FDA expert similarly “disagree[d] with FDA’s conclusions” to approve Phenergan’s labeling. JA 98. . . . During closing arguments, respondent’s counsel. . .invited the jury to override FDA’s labeling approval decision: “Thank God we don’t rely on the FDA to. . .make the safe[ty] decision. You will make the decision.” Id. “The FDA doesn’t make the decision, you do.” JA 212.

Wyeth Pr. Br. at 22-23. That’s some heavy-duty FDA-bashing. It’s facts like this that make the defense preemption argument much easier than it might otherwise be. That’s what we want in what has become the industry’s “point of the spear” case.

The alternative argument, of course, is that facts like this make anything the Supreme Court might say distinguishable. We don’t think the distinctions are all that great in terms of whether there should be preemption or not, but no matter. We’ll happily litigate any claimed distinctions once we get the core proposition – that FDA labeling decisions preempt state product liability claims – established.

That the plaintiff in Levine explicitly made (and was allowed to make) the John C. Calhoun argument that a jury applying state law can nullify supreme federal law just makes our side’s “Job 1” that much easier.

How much easier?

Well, it’s not every preemption brief that can start off with an “impossibility,” rather than an “obstacle,” argument in the lead position. Wyeth’s brief does. See Wyeth Pr. Br. at pp. 29-40.

Whoa, whoa, whoa…. Slow down guys. Cool it with the inside baseball jargon already.

OK, what we’re talking about here is that there are two main flavors of implied (that is, not by virtue of statutory language) conflict preemption: The first kind arises when, in the words of innumerable (that means so many that we won’t bother with citations) Supreme Court decisions, “compliance with both federal and state regulations is a physical impossibility.” That’s yes/no or can/can’t preemption. The feds say one thing and the state says something else, and doing one means you can’t do the other. It’s the best kind of conflict preemption to assert because the conflict is both easily apparent and complete.

It’s what happens when counsel, in closing arguments, tells the jury that they should give the FDA the old Bronx cheer.

The second form of preemption occurs, in the words of equally numerous Supreme Court decisions, “when state law stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” That’s “obstacle” preemption. It’s broader, but does not involve as palpable a degree of conflict. It’s also the type of implied preemption most commonly invoked in product liability cases.

Does impossibility work in Levine? Well, the FDA, after evaluating IV injection of Phenergan, approved the drug for that use – not once but several times. It approved labeling including that use and addressing the risks at issue in Levine. As Wyeth points out in its brief, FDA approval is “conditioned upon” the manufacturer using the labeling approved by the FDA “exactly as directed” by the Agency. Br. at 30 (quoting 21 C.F.R. §314.105(b)). The plaintiff’s verdict is based upon the theory that the FDA approved use should be contraindicated – that is, never allowed under any circumstances.

It’s rather difficult to comply with “yes, you must” and “no, you can’t” at the same time. So we’d say the impossibility argument works pretty well. But we’re biased, of course. That, and the opposing argument would seem to have a hard time passing the red face test.

Unless “yes” can be interpreted as “maybe.”

Which brings us to all plaintiffs’ favorite toy in preemption cases – the “changes being effected” (“CBE”) regulation, §314.70(c)(6)(iii), that allows manufacturers to make certain changes to their warnings without prior FDA approval. Just what those changes are is one of the key issues in the Levine case. The Vermont Supreme Court held that anything that arguably “strengthens” a warning is permitted by the CBE regulation, even if the information has been known for decades and already brought to the FDA’s attention. Wyeth argues for a narrower interpretation, that to qualify for this exception to prior FDA labeling approval the information must be something that’s “new.” Wyeth Pr. Br. at 31-32.

The argument that the CBE exception can’t be expanded so far that it swallows the ostensible rule requiring prior FDA approval of labeling is a strong one. As we’ve discussed before, all of the regulatory history supports limiting the exception to novel information that the FDA has not previously had occasion to review. The Agency itself not only supports this interpretation, but is in the midst of rulemaking that would bring the regulation’s language into line with longstanding regulatory intent. See 73 Fed. Reg. 2848 (FDA Jan. 16, 2008). As we pointed out at the time, the effect of this regulatory change would take the plaintiffs’ favorite toy away from them. In Levine, plaintiff’s reading of the CBE regulation would put manufacturers under a state-law duty to change FDA-approved labels unilaterally, even if the Agency’s approval had rejected that change and no new facts had arisen in the interim. Wyeth, of course, makes all of these points in its brief. Br. at 34-40. Not only that, but Wyeth did a lot more digging in the Federal Register than we did, in our post, so we highly recommend this part of the brief to anyone confronted with a similar CBE-based anti-preemption argument.

Anyway, Wyeth has an additional arrow in its quiver – the Supreme Court’s holding earlier this year in Riegel v. Medtronic, Inc., rejecting the contention that manufacturers had broad discretion to make unilateral post-approval changes to FDA approved devices. 128 S. Ct. 999, 1007 (2008) (“the FDA requires a device that has received premarket approval to be made with almost no deviations from the specifications in its approval application”). That same quote was point number two in our own long Riegel post, a point that Wyeth drives home in its brief:

In Riegel, the Court held that once a Class III medical device receives premarket approval, the FDCA (as amended by the Medical Device Amendments of 1976 (MDA)) forbids the manufacturer to make any change without FDA permission, including a change to the approved labeling, that would “affect safety or effectiveness.” Id. at 1005. Any change must be submitted by supplemental application for FDA approval before implementation. Id. The Court thus held that FDA’s detailed, individualized review of the safety and effectiveness of each Class III medical device imposed a federal-law “requirement” that approved devices be made “with almost no deviations from the specifications in its approval application,” and preempted conflicting state-law requirements applicable to the device. Id. at 1006-1007.

Wyeth Pr. Br. at 31. After all, as Wyeth points out, medical devices are governed by a substantively identical CBE regulation. Id. at 32. See also id. at n.13 (describing how the medical device approval process – found preemptive in Riegel – was generally modeled after the approval process for prescription drugs).

In our own Riegel post, we called the kind of Riegel-based arguments that we’re seeing in Wyeth’s brief “spillover effects.” There’s another one on page 33 – Wyeth’s argument that “[n]o less than a state statute or regulation, this common-law claim is preempted if it imposed a duty that conflicts with federal law.” The first case cited, once again, is Riegel, for its holding that “common-law liability is premised on the existence of a legal duty, and a tort judgment therefore establishes that the defendant has violated a state-law obligation.” 129 S. Ct. at 1008.

After finishing with its preemption by impossibility argument, Wyeth goes on to make the more conventional preemption by obstruction argument that prevailed in Geier v. American Honda Motor Co., 529 U.S. 861 (2000), and Buckman Co. v. Plaintiffs’ Legal Committee, 531 U.S. 341 (2001) – and that we’ve seen be so successful in, inter alia, the SSRI warning cases. See Wyeth Pr. Br. at 40-51. This part of Wyeth’s brief makes the argument – now indelibly connected with Riegel (see the block quote in our post on that case), that allowing juries to disregard FDA drug approval decisions, puts such determinations in the hands of a legal system inherently incapable of properly balancing the benefits that drugs offer to society at large:

Vermont, by contrast, seeks to alter that balance by substituting the judgment of lay juries that focus on individual patients’ injuries on a case-by-case basis, effectively disregarding the countervailing benefits of the drug to the public as a whole. See Riegel, 128 S. Ct. at 1008. The Vermont judgment thus frustrates both Congress’s objective of having an expert agency serve as the ultimate regulator of the labeled conditions of use for which a drug is approved and FDA’s specific fulfillment of that objective.

Wyeth Pr. Br. at 40; see id. at 46. “The determination whether a drug is generally recognized as safe and effective. . .necessarily implicates complex chemical and pharmacological considerations” and is “peculiarly suited to initial determination by the FDA.” Id. at 43 (quoting Weinberger v. Bentex Pharmaceuticals, Inc., 412 U.S. 645, 653-654 (1973)).

Following a lengthy discussion (which we will leave to our readers, since it’s case specific) of everything the FDA did to evaluate the IV administration of Phenergan, Wyeth Pr. Br. at 43-44, the defense argument takes on frontally the lower court’s FDA as “minimum standards” rationale.

The regulatory scheme that Congress established in the FDCA and that FDA implemented in the specific case of Phenergan serves competing goals: to protect the public from unreasonable risk of harm, while ensuring the availability of beneficial treatments, all of which carry a certain degree of risk. And an approved drug’s labeling must provide sufficient instructions for safe and effective use, while avoiding limitations that foreclose beneficial use of a drug in an effort to avoid all risk of human error. For these reasons, as the United States has explained, “FDA interprets the [FDCA] to establish both a “floor” and a “ceiling”’ with respect to drug labeling,” and “FDA’s approval of labeling for a new drug reflects FDA’s expert judgment that the labeling strikes the appropriate balance.”

Wyeth Pr. Br. at 45 (quoting 2007 amicus brief of the United States in support of granting certiorari; other citations and quotation marks omitted). The FDA’s administrative balancing of competing objectives is thus equivalent to the kind of administrative process that supported preemption of no-airbag claims in Geier. Wyeth Pr. Br. at 47-48.

The final portion of Wyeth’s brief deals with an otherwise rather obscure (sufficiently so that we’ve only just touched on it before here and here) point about an uncodified preemption/savings clause (§202 of the bill) dating from the 1962 Amendments to the FDCA. It’s more important in Levine because the lower court held that the “direct and positive conflict” language in that section somehow eliminated the aforementioned “obstacle” form of implied conflict preemption.

In a couple of pages (pp. 52-54), Wyeth slices, dices, and purées that argument: (1) citing precedent (Geier) holding the express and implied preemption work independently; (2) demonstrating that the “direct and positive” language is simply a phrase the Supreme Court has used to describe conflict preemption generally (although there are more recent cases for this proposition – see Swift & Co. v. Wickham, 382 U.S. 111, 132 & n.3 (1965); Farmers Educational and Coop Union v. WDAY, 360 U.S. 525, 540-41 (1959)); and (3) establishing that all this language was intended to accomplish was to prevent any claim of preemption of the field.

Whew! We finally reached the end of it.

Anyway, it’s obvious to us that Wyeth has done the entire industry a favor while carrying the flag for our side in the Levine matter. We’re crossing our fingers in hopes that good facts, combined with good arguments (and good lawyering), will produce good law.