Brent Nyitray
Fairlington Blade
Let the mutherfuker burn!
jnc4p
Kevin S. Willis
Michigoose
lmsinca
markinaustin
Arcanaut
novahockey
quarterback
ScottC
yellojktIt is currently the state of the law that if you think you were injured by a brand name Rx you can sue, claiming failure to warn of the consequences absent a label warning, but if you think you were injured by a generic Rx you cannot sue, claiming failure to warn absent a label warning.
In 2009, the Supremes decided Wyeth v. Levine, 6-3. It held that the approval of the label by the FDA does not immunize the drug company from failure to warn, basically because drug companies can provide more info than FDA approves.
In June, the Supremes decided Pliva v. Mensing, 5-4. The Hatch-Waxman Amendments allow generics to gain FDA approval if they are equal to brand named drugs. FDA regs state that because the generic’s approval is based on the listed drug’s approval, its “labeling must be the same”. The majority said that therefore, unlike brand name drugs, generics can not change their warnings. Thus “failure to warn” cases against generics are precluded by the generics’ duty to a fixed label, under federal law.
The opinion recognizes the oddity. It says that this makes no sense to the plaintiff, who would have had a lawsuit if she had been prescribed the named brand. It also says it is up to Congress not to make unusual and bizarre laws.
On its face, it is an odd result dictated by judicial restraint, in both cases. However, legal critics say the majority overlooked the fact that the generic maker can ask FDA for permission to upgrade the warning label. Sotomayor seized on this in her dissent calling it a “dilution of the impossibility standard.” Another criticism is that if Congress intended for brand name drugs to be liable for failure to warn, then Congress would have had to affirmatively state that this rule did not apply to generics in H-W. A final criticism is that the whole case relies on pre-emption of state tort law by the federal regulation. Sotomayor addressed that in her dissent, saying that H-W did nothing to address preemption and thus the 2009 case should be seen as controlling on that issue.
Kennedy voted with the majority both times but did not write.
These cases are in QB’s area, not mine, and I look forward to his comments. I also want to know from NoVaH if there is an effort to get Congress to clarify. You would think the industry had an interest here, but the interest is obviously divided between the brand names and the generics.
I know Mike and ‘goose probably have some good points to offer. But all are welcome to fill my insight gaps, here.
Filed under: Uncategorized |
All Things in Moderation 
I know that there's some work being done on the regulatory side. The changes-being-effected (CBE) regulation was promulgated before Hatch-Waxman, so some public advocacy types are pushing for the FDA to clarify through regulation, but FDA isn't really in my wheelhouse so i'm not sure of the status. Can poke around to see if anything is kicking around in Congress, but I don't know
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That's a good summary except for a couple of quibbles, Mark. I'll comment in more detail later. It probably won't surprise you that I find Levine to be the decision that makes less sense, but there is a statutory distinction on which they decided Mensing. Btw, I know several of the lawyers in the Mensing case very well and have heard that Mensing's lawyers are trying effectively to gut the decision back in the 8th. That doesn't seem promising. But I am in litigation in which there are hundreds if not thousands of claims that should eventually be dismissed under Mensing.I think one basic point that people should understand about this is that, when the FDA approves a drug application, it is actually an approval of an application to market the drug pursuant to specific labeling, and by law drug companies may not change that labeling. The FDA says not just that "you may market under this label" but that "you may market ONLY under this label." Drug companies thus may neither diminish the warnings nor strengthen them. The reason for this is that overwarning is a problem as undesirable as underwarning. If the company wants to change the label, it has to apply for approval support its request, in a case like this with scientific studies.Anyone familiar with the process in the drug industry can tell you that slapping an extra warning on the label and submitting a CBE supplement is completely impractical and risky to the point of being reckless. CBEs are normally used for things that are relatively innocuous like changing a batch mixing time or sourcing for an ingredient. You are playing with fire if you add a warning to the label and submit a CBE telling the FDA you are doing it. You put your company at risk of a finding that you've marketed an adulterated drug, among other things. And, if your change isn't approved, you've just changed your label and have to change it back. It just can't be and isn't done. More later.
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Btw, the biggest quibble I have with your summary, Mark, is that Mensing does not mean that brand makers are liable for generic drugs. That is a theory that the plaintiffs bar has pursued for a number of years now, but it has only ever been accepted by one court in California (naturally!) and has been rejected by numerous others. I think it is a stillborn theory, and while plaintiffs are arguing that Mensing should somehow give it life, Mensing in fact in no way implies such a result. Thus, I don't think brand and generic companies had quite the adverse interests you post might suggest. Branded companies might secretly have favored the generics' losing Mensing, so as not to create renewed impetus for the theory that branded companies should be liable for generic products, but that question really is not involved in Mensing, and plaintiffs are still getting no traction with it as far as I have seen.
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QB, I figured the application to change the label was a regulatory gotcha and am glad you confirmed.Why did you think I suggested branders would be liable for generics? I sure did not mean to do so!
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QB:Can you submit a CBE supplement that will be effective only after approval? In other words, if some side effect of a drug becomes apparent only after the brand name drug has come off patent, can the generic manufacturer propose changing the label without having to actually do it until the change is approved?It is an interesting conundrum. Brand name drugs are more expensive, but then you can sue more easily for failure to warn. Generics are cheaper, but, well, caveat emptor.Lots of doctors prescribe drugs off-label too. FDA regs are pretty tight — if something works well for a 5 y.o., you'd think that a 4 y.o. might benefit too. But that would be off-label in some cases. Using a non-recommended dose is off-label. And some drugs have additional effects beyond their initial disease target, but cannot be marketed for those purposes.Off-topic: As a small insight into Mark's brain, I'll point out that he named the author of the dissent in Mensing, but not the author of the opinion. IIRC, the author of the opinion also switched sides (with Kennedy) from his vote in Levine.
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NoVA:Did you learn anything interesting at MedPAC? I'd be interested in a post on that if you are so inclined.
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Hi Mike — I'm actually turning to MedPAC now for my client work. I can do a post later this week on it.
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Me too NoVA. I think I remember you promised me a summary at least. 🙂
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I did promise a post. Most of the sessions were pretty technical payment reform stuff. not that you aren't interested in that, but i think the best one for our purposes in the benefit redesignslides at http://www.medpac.gov/transcripts/benefit%20design.pdfI'll get a summary up by the end of the week.
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Mike,I'm not sure of the answer to that question without looking into it, but I think the answer is no as to CBEs. As a practical matter, though, it was agreed by all sides that a drug company could propose a prospective label change (it just isn't a CBE).It was largely the "unilateral" nature of a CBE and its availability only to branded drug makers for label changes that led Kennedy and Thomas to reach a different conlusion in Mensing. The dissent said, that isn't a real distinction, since a CBE change can be rescinded by the FDA and hence is not really unilateral, which is true and which is why Levine seems wrong to me.Your noting that cheaper generic drugs now come at the price of not being able to sue for failure to warn is perceptive, although as I said, I don't think warning claims against branded drugs should be allowed either (when the approved warnings were given).Off-label use is another interesting topic that leads to different and also interesting preemption issues. Plaintiffs often try to pursue economic loss lawsuits claiming that off-label use was illegally promoted, but there is a twin problem with these claims. First, the FDCA expressly bars private enforcement (and thus raises another form of preemption), and, second, as various courts have recognized, off-label promotion isn't inherently fraudulent (because, as you note, sometimes off-label use is quite safe and effective, indeed sometimes is standard of care). An ultimate policy problem that people should think about is this. If you want to have a federal FDA regime like we have, in which drugs can only be marketed with FDA approval under FDA mandated-labels, what will happen if you have a rule of law that says the drug company can still be sued for marketing the drug with the label the FDA requires? Do you want the FDA to decide what drugs are safe and effective for what, and sold under what kind of labels, or do you want state courts and juries to decide this after the fact? How are companies supposed to satisfy both legal obligations? This is what these cases are about.
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Thanks for the knowledge, QB. I've noticed that the drug reps are very, very careful when talking about off-label uses for their products — until you put a couple of drinks into them, of course.The next frontier for generics is the biologics. Big ones coming off patent in the next couple of years include Remicade and Enbrel. There's already a Korean company with a biosimilar to Enbrel just itching to hit the US market. 2015(?), I think. Of course, the extent of testing necessary for these biosimilar is of great interest to Big Pharma as well as generic makers. I don't think the FDA has sorted that out yet.
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At conferences I attend (lawyers), biosimilars and biologics are the rage. Lawyers are racing to become knowledgable. It is a formative field for lawyers. In truth, there are few who know much about it yet.I am a litigator and not a regulatory counselor, so my knowledge tends to be spotty and follow my experience. There are a few corners of FDA regulation that I probably as well as anyone in the country, but they aren't always the areas directly involved in the drug development and approval process, or are not comprehensive anyway.
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Mark,Re your question to me, perhaps I misinterpreted these two sentences to imply that Mensing results in branded liability for generics:"Another criticism is that if Congress intended for brand name drugs to be liable for failure to warn, then Congress would have had to affirmatively state that this rule did not apply to generics in H-W.""You would think the industry had an interest here, but the interest is obviously divided between the brand names and the generics."To me, what is persuasive in the Mensing majority opinion is that, if compliance with a legal requirement isn't impossible so long as there is a theoretical possibility of asking the federal government to change its conflicting requirement, then we really have gutted the Supremacy Clause as it applies to statutory and regulatory requirements. When the FDA has said, "You must use this label," and a state says, "You may not use that label," this seems to me as clear an impossibility conflict as there could be.If any nonlawyers are interested in more thorough explanation of what is happening in these cases, I'm sure we can oblige, but I'll leave it there for now.
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QB:Well, as a scientist, my knowledge of laws and regulatory affairs is spotty and tends to follow my experience as well. Perhaps we'll learn something from each other … :-)I have worked some on vaccine development and preclinical testing of drugs (Enbrel, among them). But the closest to regulatory affairs I've gotten is my friends' labs in the FDA (CBER).
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