In PLIVA v. Mensing, the Court ruled that generic drug companies should comply with federal regulations instead of conflicting state regulations when it comes to updating warning labels. Federal law prohibits generic companies from updating the warning labels, while some states require generic companies to include updated safety information. For pharmaceutical sales representatives, though, all eyes were riveted on the Sorrell v. IMS Health case, which pitted rep free speech vs. physician privacy.

In a 6 to 3 decision, the Court roundly came down on the side of pharmaceutical marketing as predicted during a recent Pharma Faceoff debate on the topic. “The State may not burden the speech of others in order to tilt public debate in a preferred direction,” Justice Anthony Kennedy argued in writing for the majority. “The capacity of technology to find and publish personal information, including records required by the government, presents serious and unresolved issues with respect to personal privacy and the dignity it seeks to secure. In considering how to protect those interests, however, the State cannot engage in content-based discrimination to advance its own side of a debate.”

In essence, the Court dismissed the privacy concerns, and utilizing ample evidence from the Vermont legislature, insisted that the real goal was to decrease the effectiveness of branded pharma sales efforts and increase generic utilization. Kennedy insisted that the case really was about free speech and just because the state of Vermont does not like the marketing practices of pharma doesn’t mean it can place an additional burden on it. The state should instead enter the “marketplace of ideas” and offer its own perspective on equal footing.

The case could be considered something of a landslide. Typically the court breaks down 5 to 4 along ideological lines, but in this case Justice Sotomayor, joined her more conservative colleagues, Alito, Scalia, Thomas and Roberts.

Not surprisingly, PhRMA and the data mining companies crowed over the decision. PhRMA claimed it was “not only a victory for free speech, but also a triumph for patients and future research and development by biopharmaceutical companies. SDI predicted that “existing laws in Maine and New Hampshire also will likely be declared unconstitutional or repealed in light of this Supreme Court decision.”

In dissenting, though, Justice Breyer raised some interesting challenges. Arguing that the state was not counter-detailing as implied in the decision, Breyer worried that the Court was opening up all state and federal regulation that impinges upon speech. “At best the Court opens a Pandora’s Box of First Amendment challenges to many ordinary regulatory practices that may only incidentally affect a commercial message,” he argued. “At worst, it re-awakens… pre-New Deal threat of substituting judicial for democratic decision making where ordinary economic regulation is at issue.”

Since the law’s passage, Vermont has created the nation’s most significant effort to create a universal health program, which only increases the state’s interest in drug marketing and healthcare costs and raising the stakes for the next showdown.

So, the question for pharma is more basic: Will there be a backlash as Frank Pasquale predicted in Pharma Faceoff? Will states like Vermont take a different approach that restricts pharmaceutical marketing in a way that is less likely to draw the ire of the court?

“Today’s decision introduces a critical distinction between brand-name and generic drugs. Consumers of brand-name drugs can sue manufacturers for inadequate warnings; consumers of generic drugs cannot,” writes Sotomayor. “These divergent liability rules threaten to reduce consumer demand for generics, at least among consumers who can afford brand-name drugs.”

In an article published in Pharmaceutical Executive’s May issue, John Brenner, a partner at Pepper Hamilton, suggested that it’s not inconceivable for plaintiffs seeking “failure to warn” protection to take up their grievances with the brand drug manufacturer, the originator of a given drug label. Generics companies must, by law, use a verbatim copy of the original brand drug label, regardless of new risk information or adverse events reports.

Commenting today on the Supreme Court’s decision, Brenner noted that two state courts, an appellate court in California (Conte v. Wyeth, November 2008), and a Vermont District Court (Kellogg v. Wyeth, October 2010), have ruled that brand drug companies could be held liable for the labeling on a generic drug, and therefore be subject to claims. While the California and Vermont decisions don’t necessarily constitute a consensus, Brenner said that “there are 50 states out there, and a lot of them have a great penchant for saying, ‘We really don’t like to leave our injured citizens without a remedy.’”

Writing for the majority, Justice Clarence Thomas acknowledges “the unfortunate hand that federal drug regulation has dealt [the plaintiffs],” leading Brenner to surmise that “there can’t be any question about the fact that the majority knew exactly what it was doing.” In her dissenting opinion, Sotomayor writes that “a drug consumer’s right to compensation for inadequate warnings now turns on the happenstance of whether her pharmacist filled her prescription with a brand-name drug or a generic…if she takes a generic drug, as occurs 75% of the time, she now has no right to sue.” Brenner says Sotomayor may want to check with the plaintiff’s bar about that one. “[Sotomayor] doesn’t know how clever these folks are,” said Brenner.

UPDATE: Brenner points to a statement released yesterday by metoclopramide (the generic form of Wyeth’s Reglan) claimants, including Elizabeth Conte of Conte v. Wyeth, announcing plans to take their cases to the brand manufacturer, in this case, Wyeth (now Pfizer). If generics companies can’t be held liable for what Reglan users consider an insufficient warning label, then Wyeth/Pfizer itself must be liable, according to the statement. “This ruling puts the responsibility back in the lap of brand name manufacturers,” said Michelle Schwartz, a metoclopramide victim who is also a spokesperson for the Reglan Metoclopramide Victims Organization, in the statement.

The case as heard by the Supreme Court deals in a great deal of legal complexity, but the underlying lawsuit that inspired it is based on a fairly simple idea: Diana Levine was severely injured when she was given Wyeth’s Phenergan by a physician’s assistant who was attempting to inject the drug directly into the vein but instead either got it into the artery or injected it in such a way that it leaked out of the vein (”perivascular extravasation”) and mixed with arterial blood. The labeling for the drug warns what can happen, but Levine and her lawyers argued that Wyeth should have acted independently of FDA and contraindicated injection directly into the vein (or “IV push).

Well there are warnings, and there are warnings, so we took a look at the Phenergan PI to see what it had to say. It’ll no doubt make you feel even more sympathy for Diana Levine, but if you’re like me, it will make you wonder whether it makes sense to prevent problems with warnings when a warning like this didn’t suffice:

From the “Contraindications” section of the label:

Under no circumstances should PHENERGAN Injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS—Injection Site Reactions).</b>

PHENERGAN Injection should not be given by the subcutaneous route; evidence of chemical irritation has been noted, and necrotic lesions have resulted following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.

Under “Injection Site Reactions”:

PHENERGAN Injection can cause severe chemical irritation and damage to tissues, regardless of the route of administration. Irritation and damage can also result from perivascular extravasation, unintended intra-arterial injection, and intraneuronal or perineuronal infiltration.

Signs, Symptoms, and manifestations of severe tissue irritation include burning, pain, erythema, swelling, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, and gangrene. Administration of PHENERGAN Injection has resulted in nerve damage ranging from temporary sensory loss to palsies and paralysis. Injection into or near a nerve may result in permanent tissue damage. In some cases, surgical intervention (including fasciotomy, skin graft, and/or amputation) may be required (see ADVERSE REACTIONS).

Inadvertent Intra-Arterial Injection
Due to the close proximity of arteries and veins in the areas most commonly used for intravenous injection, extreme care should be exercised to avoid perivascular extravasation or unintentional intra-arterial injection. Reports compatible with unintentional intra-arterial injection of PHENERGAN Injection, usually in conjunction with other drugs intended for intravenous use suggest that pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation are likely under such circumstances. Intravenous injection was intended in all the cases reported but perivascular extravasation or arterial placement of the needle is now suspect. There is no proven successful management of unintentional intra-arterial injection or perivascular extravasation after it occurs. Sympathetic block and heparanization have been employed during the acute management of unintentional intra-arterial injection, because of the results of animal experiments with other known arteriolar irritants. Aspiration of dark blood does not preclude intra-arterial needle placement, because blood is discolored upon contact with PHENERGAN Injection. Use of syringes with rigid plungers or of small-bore needles might obscure typical arterial backflow if this is relied upon alone.

When used intravenously, PHENERGAN Injection should be given in a concentration of no greater than 25 mg per mL, and at a rate not to exceed 25 mg per minute. When administering any irritant drug intravenously, it is usually preferable to inject it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended intravenous injection of PHENERGAN Injection, the injection should be stopped immediately to provide for evaluation of possible arterial placement or perivascular extravasation.

Under “Adverse Reactions”:

INTRA-ARTERIAL INJECTION MAY RESULT IN GANGRENE OF THE AFFECTED EXTREMITY.

Under “Dosage and Administration”:

The preferred parenteral route of administration for PHENERGAN Injection is by deep intramuscular injection. The proper intravenous administration of this product is well tolerated, but use of this route is not without some hazard. Not for subcutaneous administration.

UNINTENTIONAL INTRA-ARTERIAL INJECTION CAN RESULT IN GANGRENE OF THE AFFECTED EXTREMITY (see CONTRAINDICATIONS, WARNINGS—Injection Site Reactions). SUBCUTANEOUS INJECTION IS CONTRAINDICATED, AS IT MAY RESULT IN TISSUE NECROSIS (see CONTRAINDICATIONS, WARNINGS—Injection Site Reactions, and ADVERSE REACTIONS).

 

For the first time, the highest court in the land is weighing in on whether federal approval of a drug preempts tort claims against a drugmaker, such as an injured consumer might bring in a state court. A decision for Wyeth upholding preemption could help end the proliferation of product liability and class-action lawsuits at the state level—as seen in the massive Vioxx litigation.

The details of the case verge on melodrama. A Vermont musician, Diana Levine, lost part of her right arm to gangrene after Wyeth’s anti-nausea drug Phenergan (mistakenly) came into contact with arterial blood.

Although the drug’s label carries a warning about this bizarre potential side effect, which can result from an improper emergency “IV push,” the plaintiff has argued that the drugmaker should have either made the warning more prominent or not sought approval for this specific technique. A Vermont court agreed with the plaintiff, ordering Wyeth to pay Levine $6 million in damages. Wyeth appealed.

Following the arguments, Pharm Exec spoke to James Huston, a San Diego–based litigator at Morrison & Foerster, who has scored some big victories defending major manufacturers of drugs and medical devices. (He is also a bestselling crime-thriller novelist.)

We asked Huston for his take on how the arguments went, how the judges might decide, and other aspects of the case.

What can you tell us about the judges’ demeanor during questioning?
I talked to someone who was there, and I have read the briefs in the case as well as the questions that the judges asked. The lawyers on both sides seemed to be on their heels a lot of the time, and Wyeth was getting the more aggressive questioning from the judges, even some of the so-called “pro-business” judges.

They were asking fundamental questions—Judge Alito asked, “How in the world could the FDA approve an IV push for this [anti-nausea] drug when there is a risk of developing gangrene?”
Based on all the questioning, it seems clear that the court is very troubled by this case. And they should be. It’s not a good test case for preemption.

Why not?
Because it’s really a case of medical malpractice. The woman who got the IV push was a victim of medical error, not a regulatory or liability error. Whoever injected the IV push committed medical malpractice.

The plaintiff is arguing that FDA shouldn’t have allowed this type of drug administration at all. And I tend to agree with her. And that’s the problem with this case: We’re all left wondering why neither Wyeth nor FDA can tell us about the potential medical event that is so critical as to make the severe risk associated with this IV push worth it—rather than experiencing 15 minutes of nausea waiting for the regular [and safe] IV drip to take effect.

Wyeth didn’t give a single example in their brief of why this was medically necessary.

What’s the pro-preemption answer to Alito’s question?
The answer is, how FDA came to the conclusion is not up to us or a jury to second guess. The point is that it went to a medical committee, and FDA determined that the warning that this drug carried about this particular risk was adequate.

What does a jury know that medical experts do not know, and that enables them to and say, “No, the warning is not adequate”? And then another jury in another state says, “Yes, it is.” And then another jury says, “No, it isn’t.” And we skip across the country making some lawyers very rich. It’s a crazy patchwork of decisions and an awful waste of money.

Does that mean that under preemption, people who are injured by an FDA-approved drug will no longer be able to sue the drugmaker?
The short answer is yes. A decision supporting preemption would probably cover the vast majority of liability issues related to the design or warning label of a drug. You could probably still sue for manufacturing problems.

Could you sue FDA?
That’s exactly what Judge Scalia said today during the arguments: “If you have a problem with FDA’s decision, sue ’em.” But that’s a crazy idea. You’d have to bring a claim for negligence under the Federal Torts Claims Act, and it would almost certainly be struck down.

If it’s a case of medical malpractice, why is the drugmaker held responsible?
Because of limitations and restrictions in the state medical malpractice rules. If Ms. Levine brought her case in California against her medical professional or the clinic, the amount of money she could recover is very limited. She would never get the $6 million a jury awarded her.

The drug company gets hit for $6 million for a risk that they knew about, identified, and warned against. That’s a problem—and addressing that problem would make a very interesting footnote. We’ll see if it makes it into the opinion. None of the briefs filed with the case mentioned it.

How do you think the Supreme Court will decide the case?
I think the decision, when it comes in three months, will be a very narrow affirmation of the lower court’s result and yet confirming that preemption does apply sometimes. The court will probably say that preemption only applies when we have actual knowledge that FDA considered the specific risk/benefit at issue.

The problem is that you don’t get that proof because FDA never reveals how it comes to its decisions. So I think the decision will ultimately leave us with a big conundrum.

Basically, the judges will decide narrowly both for and against. They may give Ms. Levine her judgment and say, “In this case preemption does not apply because Wyeth should have proposed a change in the warning on the label. But don’t get us wrong, we’re not saying preemption doesn’t apply in general.”

Would that set some kind of precedent for preemption?
It would be a very narrow extension of implied preemption. But even if the court recognized a broad preemption application, I think that Senator Waxman and others in Congress will, on the day after the decision, issue an amended Food and Drug Act saying that nothing in this act is intended to preempt any tort claim in any state anywhere. And given the Democratic majority, that law is likely to be enacted.

But we’re seeing the courts pushing on preemption in a lot of different arenas right now.

For example, in the Ninth Circuit here in California, there was a recent case where the court said, “We’ve got the Federal Aviation Association regulating airports and aircraft and aircraft design already, so how can you—a jury—come in and tell us that the way an international airplane is designed is more likely to cause deep vein thrombosis injuries? The Ninth Circuit said you can’t—that the entire field of aviation is preempted by the FAA.

Is there a potential solution beyond the issue of preemption?
Congress could probably come up with a better solution. They passed a law for medical devices saying that state torts laws do not work, but they didn’t extend it to drugs. Still, there has never been a federal tort standard on anything, and Congress isn’t about to start generating one.