2009 BIOL503 Class 3 Supporting document: Wyeth V Levine Scotus Oral Argument Transcript 06 1249

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Slide 1: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 IN THE SUPREME COURT OF THE UNITED STATES -----------------x WYETH, Petitioner v. DIANA LEVINE. : : : : No. 06-1249 -----------------x Washington, D.C. Monday, November 3, 2008 The above-entitled matter came on for oral argument before the Supreme Court of the United States at 10:06 a.m. APPEARANCES: SETH P. WAXMAN, ESQ., Washington, D.C.; on behalf of the Petitioner. EDWIN S. KNEEDLER, ESQ., Deputy Solicitor General, Department of Justice, Washington, D.C.; on behalf of the United States, as amicus curiae, supporting the Petitioner. DAVID C. FREDERICK, ESQ., Washington, D.C.; on behalf of the Respondent. 1 Alderson Reporting Company Slide 2: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 ORAL ARGUMENT OF SETH P. WAXMAN, ESQ. C O N T E N T S PAGE On behalf of the Petitioner EDWIN S. KNEEDLER, ESQ. On behalf of the United States, as amicus curiae, supporting the Petitioner DAVID C. FREDERICK, ESQ. On behalf of the Respondent REBUTTAL ARGUMENT OF SETH P. WAXMAN, ESQ. On behalf of the Petitioner 3 14 24 51 2 Alderson Reporting Company Slide 3: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 PROCEEDINGS (10:06 a.m.) CHIEF JUSTICE ROBERTS: We'll hear argument first this morning in Case 06-1249, Wyeth v. Levine. Mr. Waxman. ORAL ARGUMENT OF SETH P. WAXMAN ON BEHALF OF THE PETITIONER MR. WAXMAN: please the Court: This case concerns conflict pre-emption under the Supremacy Clause, and the conflict presented here is stark. Repeatedly over the years, the FDA Mr. Chief Justice, and may it approved Phenergan injection as safe and effective under all the conditions and methods of use described in the labeling, including what is referred to as "IV push" injection. Yet a State jury, evaluating the same risk that the FDA had considered, determined that the precise labeling that FDA had required Wyeth to use in fact rendered Phenergan "unreasonably dangerous." JUSTICE KENNEDY: just make one comment. That -- Just at the outset, I'll You argue that it's impossible for Wyeth to comply with the State law and at the same time the Federal label. As a textual matter, as a I logical matter, I just -- I don't understand that. think I could design a label that's completely 3 Alderson Reporting Company Slide 4: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 consistent and that meets the requirements that the Respondents wish to urge. Now, if you want to say that any alteration of the label violates Federal law, that's something else. But as a textual matter, as a logical matter, as a semantic matter, I don't agree with it. MR. WAXMAN: Well, let me make sure, because I do think we do agree, and I want to make sure that I'm understood, Justice Kennedy. I think what you've articulated is the test which is, is it possible for a regulated party to comply at the same time with both Federal law and State law? In other words, could they use, as they were required by Federal law to do, to use the precise label that in approving the application in 1998 the FDA required Wyeth to use, and also use the label that the Vermont jury determined should be used, and that was stated in the complaint and in the opening and the closing a statement that you may not, should not use IV administration or IV push, in other words that you should contra -- the label should contra-indicate something -JUSTICE GINSBURG: MR. WAXMAN: Mr. Waxman -- -- that -It didn't say -- it It said IV push is the JUSTICE GINSBURG: didn't say IV across the board. 4 Alderson Reporting Company Slide 5: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 claim, and that was -- as I understand this, the FDA was aware of the IV use and a certain risk. But did it ever, ever discreetly consider IV push versus IV administered the usual way by a drip bag? MR. WAXMAN: Yes it did, Justice Ginsburg, and I want to cite you to the portions of the record that demonstrate that it did. But before I do so, I just want to underscore a point that I think is clear from both our brief and the Solicitor General's brief, which is that isn't the test of preemption in any event. The question is what did the labeling say and upon what information was the labeling decision made. But as to your particular question, there are -- first of all, there was testimony in the record from multiple parties, including experts from both sides, that the FDA was aware of all of the forms of administration and the risk, including IV push. Their experts simply disagreed with the judgment that the labeling requires. But most saliently, the labeling in this case, which is reproduced, in sort of microscopic size unfortunately, on the last two pages of the petitioner appendix and the last two pages of the joint appendix, have four separate reference that, as we explained in footnote 11 of our reply brief, only apply to IV push. 5 Alderson Reporting Company Slide 6: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 system. There is a reference to the use of the Tubex That is a direct IV push system. There is a reference to rigid plungers and small-bore needles. Again nothing to do with drip. There is a reference to Drip is gravity. The a maximum rate of administration. testimony in the case was that an instruction that a particular rate of administration not be exceeded only referred to IV push. And finally, there are cautions on the label about how the ordinary aspiration of blood to see if its bright or dark, which is only done in the context of a needle that is being used to push something into a vein, is not reliable in the context of this case because Phenergan discolors arterial blood immediately. So the labeling plainly comprehended and warned about the specific risks of IV push administration, and that's not all. There is an advisory -- an advisory committee in 1976 was asked to look at precisely the risk of arterial exposure to Phenergan injection or any other irritant drug that is administered intravenously and it made specific recommendations, including recommendations that go directly to IV push. JUSTICE ALITO: How could the -- how could the FDA concluded that IV push was safe and effective when on the benefit side of this you don't have a 6 Alderson Reporting Company Slide 7: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 life-saving drug, you have a drug that relieves nausea, and on the risk side you have the risk of gangrene? MR. WAXMAN: I mean, there was testimony -- Justice Alito, I can go over the testimony, but there is -- there was testimony in this very case about those very circumstances in which direct IV injection is indicated. And there is also test -- there is also evidence in the FDA record, including if you look at the 1987 correspondence that the FDA sent to Wyeth in the context of talking about what warnings had to be provided. The FDA provided Wyeth 20 citations to 20 medical journals that addressed this problem, and in footnote 13 of our reply brief we've cited the ones that specifically address the circumstances in which IV push administration is an important tool. I think, that -JUSTICE GINSBURG: But that doesn't answer The point here is, the question of was it -- the risk of gangrene and amputation is there. No matter what benefit there was, how could the benefit outweigh that substantial risk? MR. WAXMAN: Justice Ginsburg, this is It labeling that is directed at medical professionals. is labeling that is directed at physicians, who have to be able to determine what method, what pharmaceutical and what method of administration to use, given the 7 Alderson Reporting Company Slide 8: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 constellation of risks and benefits that a particular patient -JUSTICE KENNEDY: The FDA was never concerned with risks versus benefit? MR. WAXMAN: certainly is. The FDA -- well, the FDA And the issue, Justice Kennedy, here is the FDA has to decide what information to provide to clinicians so that they can make judgments about what to use. And it -- what it did here is it provided ample, lavish warnings about the risk of intra-arterial injection and exposure of an irritant drug like Phenergan to arterial blood. It provided in the labeling to the physicians a cascading hierarchy of methods of administration. It said intramuscular It then said with injection is the preferred method. respect to intravenous injection that it is, as with any irritant drug, it is usually preferable to inject it into an IV infusion set that is known to be running properly, in other words where a line has already been established into the vein and the IV push occurs into the line that's already established. All that information was available to physicians and the FDA has to understand and does understand that in labeling to allow medical professionals to make their judgments, taking options 8 Alderson Reporting Company Slide 9: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 away from physicians is not always better. not -- it may not even often be better. It may What the FDA has to decide in terms of telling physicians what's on the table and what's off the table and in terms of what's on the table what the relevant risks are is, is this ever -- would this ever be medically warranted? The testimony in this case and in the administrative record was yes, there are circumstances -CHIEF JUSTICE ROBERTS: I'd like you to address the distinction between the medical device area and the drug area because in the medical device area, of course, you have an express pre-emption clause, while here in contrast you don't. MR. WAXMAN: Yes. I mean, I think, Mr. Chief Justice, you've identified the respect in which this is difference than the medical device area. But for the salient purposes, I think the Riegel case directly points the Court to the nature of the determination that the FDA makes with respect to class 3 drugs. It goes through the same preclearance process. As we pointed out in our brief and as I think Justice Scalia's opinion in Riegel points out, the balancing time-intensive, data- intensive inquiry for medical devices was patterned after what is done for drugs, and it reflects a balancing of risks and benefits of the 9 Alderson Reporting Company Slide 10: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 particular drug in light of the conditions and methods of administration prescribed in the labeling. CHIEF JUSTICE ROBERTS: If that's true you would have expected the Federal Drug Act to have a similar express pre-emption provision. And one reason perhaps that it didn't is that when the Drug Act was passed you had an established background of State actions; when the Medical Device Act was passed you didn't. MR. WAXMAN: Well, let me address both the established background of State actions and then the pre-emption clause difference, if I may. The Respondent and her amici have identified 97 cases going back 150 years in which tort actions have been brought with respect to pharmaceuticals. Very few of those cases -- and they are recent -- are implicated by the rule that the Vermont Supreme Court applied in this case, which is where a fully informed FDA, informed of all the information that Wyeth had, approved a labeling standard, but a court looking at the same evidence can reach a different conclusion about what is on the label. The most -- those cases I believe all post-date Cipollone. Many of them postdate Geier. And by my count, there are fewer than 20 such cases out of all of the cases that have been decided and those issues -10 Alderson Reporting Company Slide 11: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that issue had never come up and never could have come up when Congress enacted the 1938 Act, because it was only the 1938 Act that established a drug-specific, preclearance regime, and really in 1962, in which the FDA was required not just to evaluate safety in terms of licensing the distribution of the drug, but to balance safety against effectiveness. And so the -- the constellation of common law cases -- I mean, let me just say we are -- we are not seeking here a rule of field preemption. We are not seeking to preclude tort remedies for conduct that violates Federal law. What we are saying here is -- and this goes, I think, finally to your point about the express pre-emption clause -- the presence of expressed pre-emption clauses or the absence, the presence of a savings clause or the absence, does not and cannot affect the operation of conflict pre-emption under the Federal Constitution. Now, members of this Court are concerned about applying a broad, vague, or free-wheeling analysis of implied conflict pre-emption, but this case is heartland. A jury was asked to look at the same information and conclude that the precise language that the FDA just didn't allow, the FDA required Wyeth to 11 Alderson Reporting Company Slide 12: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 use, rendered that drug unreasonably unsafe. JUSTICE SOUTER: Well, it required it because that is what the FDA had approved as a label. But as -- excuse me -- as I understand it, the -- the company, Wyeth, could have gone back to the FDA at any time and said, either based on experience or just our rethinking of the data that we have, we think the label ought to be changed to say "Don't use IV push." Wyeth could have done that at any time, and it simply didn't do it. And the -- the reason I raise this is because it could have done it at any time, where, going back to Justice Kennedy's first question, where is the conflict? MR. WAXMAN: The liability in this case was not predicated on the fact that Wyeth didn't go to the -- remember, the FDA had approved this label two years before Miss Levine was injured. In approving the label, it rejected stronger proposed language that Wyeth had presented. There was nothing that was -- Wyeth was -JUSTICE SOUTER: But as I understand it, Wyeth is not Wyeth's argument is not this argument. saying the reason there is a conflict here is that we tried to give the kind of warning that the Vermont jury, in effect, says we should have given and the FDA didn't 12 Alderson Reporting Company Slide 13: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 allow us to do it, so that, in fact, there is a conflict between a specific rejection by the FDA of the Vermont rule and the rule that the Vermont jury applied. MR. WAXMAN: Right. As I understand it, Wyeth's JUSTICE SOUTER: argument is: Whatever is on the label, in fact, is the It doesn't matter whether we You simply standard of conflict. tried or could have tried or didn't try. look at the label and you look at what the Vermont jury did; and if there is a -- if there is a difference between them, there is a conflict. your argument? MR. WAXMAN: Yes, you are right. We -- we Am I right about have both an impossibility form of conflict because, in the absence of any new information or new analyses of old information, we could not make the change in advance of getting approval. And we also have an -- an objects-and-purposes form of conflict pre-emption because the Vermont jury decided on the same information that the labeling that the FDA had approved and required was unreasonably unsafe. And we cannot have a world in which the very day after an intensive process -- the FDA says you may distribute this drug, but you must use this specific language -- either, A, manufacturers can just run in and 13 Alderson Reporting Company Slide 14: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 change the label and ask for permission down the road; or, B, that a State jury -- let's take the easier case -- a State legislature or 50 State legislatures can decide: Because you could have gone back and asked, we can impose an obligation on you that you must have done so or must have changed the labeling. inconsistent with -JUSTICE SOUTER: liability or negligence? Well, is it -- is it strict That just is In other words, are they saying you must have done so, or are they saying because you could have done so and didn't you did not conform to the standard of care? MR. WAXMAN: Either a negligence theory or a strict-liability theory would be pre-empted. May I reserve the balance of my time. CHIEF JUSTICE ROBERTS: Mr. Kneedler. ORAL ARGUMENT OF EDWIN S. KNEEDLER ON BEHALF OF THE UNITED STATES, AS AMICUS CURIAE, SUPPORTING THE PETITIONER MR. KNEEDLER: please the Court: The State law duties on which Respondent's tort claims are based are pre-empted because they 14 Alderson Reporting Company Thank you, counsel. Mr. Chief Justice, and may it Slide 15: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 conflict with the FDA's determination that Phenergan injection is safe and effective under the conditions of use recommended or suggested in the labeling. JUSTICE GINSBURG: Mr. Kneedler, at the outset, would you clarify something that is central, I think, to this case? Some of the briefs tell us that this represents a change of policy on the part of the FDA, that in fact the FDA once approved and said torts were -- tort suits were a helpful adjunct to the FDA's own efforts to protect consumers. They helped because they prodded manufacturers to -- to disclose risks that were either unknown or under- evaluated. Was that once the FDA's policy; and, if so, when did it change? MR. KNEEDLER: The -- the FDA, to my knowledge, has never taken the position that -- that, as a general matter, a manufacturer may change a label without -- without the existence of new information that justifies a revision. The Respondents and the amici relied primarily on some snippets of rule-making proceedings and things like that in which FDA has referred to the existence of tort remedies. But we are not arguing for the proposition that tort remedies are -- are pre-empted as a general matter. JUSTICE SCALIA: there be a tort remedy? But when -- when would What -- what situation would 15 Alderson Reporting Company Slide 16: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you envision? MR. KNEEDLER: As Mr. Waxman mentioned, if -- if the State standard was the same as the Federal standard, there wouldn't be any conflict. And, for example, if -- and not to mention the fact if there was adulteration of -- of the product or if the -- if the product in the box was not the same -JUSTICE SCALIA: What if they found out about new information which would, if properly considered, alter what the labeling ought to be? Would there be a tort remedy for the failure to bring that new information to the attention of -MR. KNEEDLER: Well, the position we are arguing for here would not cover that situation, but -but there could be a further situation of pre-emption, if I could just explain why. JUSTICE SCALIA: I think -You mean if you failed to provide the FDA the new information that you think negates the provisions on the -- on the label, you still couldn't be sued? MR. KNEEDLER: No. If you -- if you failed to provide it altogether, there would not be a -- a pre-emption defense if there were -- if your failure-to-warn claim was based on the new information that you didn't furnish. 16 Alderson Reporting Company Slide 17: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 I was -- I was going to identify the situation where -- and this has come up in the antidepressant drug situation, for example, where there is evolving information. There has been a rule- making petition, in fact several over the years, to the FDA to change the labeling to warn against -- to warn about the possibility of suicidal ideation. And FDA has rejected that even though it's -- it's new information arising after the drug was approved. If the information is brought to the FDA's attention and FDA rejects the proposed change, then you would you have conflict pre-emption again. But if the information was never brought to the FDA's attention in the first place, then -- then there would -- it would be not inconsistent with Federal law to have a tort suit based on that. If it's -- if it's been proposed and rejected, then you're back with a conflict. JUSTICE SCALIA: What if -- what if you brought it to the FDA's attention and the FDA just hasn't acted on it? You would be authorized to change the label on your own. MR. KNEEDLER: You would be authorized, but if FDA then rejects -- rejects the labeling -JUSTICE SCALIA: I understand, but in the interim, you could -- could you be subject to a State 17 Alderson Reporting Company Slide 18: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tort suit for not changing the label when -- when you had the power to do so? MR. KNEEDLER: I -- if -- if FDA has taken I no action at all, then I think you -- you could be. this it's very likely that FDA would have acted by the -- by the time that -- I mean, I suppose there could be a window in there before it was approved. JUSTICE GINSBURG: But why is that -- why is I that likely, considering the huge number of drugs? mean, one figure said that there are 11,000 drugs that have this approval. Is the FDA really monitoring every one of those to see if there is some new information that should change the label? MR. KNEEDLER: about that: If I could make two points The first is, as I said, we are not arguing that there is pre-emption in a situation where there is new information that is not brought to FDA's attention. But the second point is that in the 2007 amendments to the Act, Congress recognized the difficulties with this and gave FDA important new enforcement tools and resources to go after the problem of things that arise after a drug is improved -approved, that has given FDA the authority to direct a change in the label, which it did not have before. It has given the FDA the authority to order 18 Alderson Reporting Company Slide 19: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 new clinical studies, and it has ordered FDA to set up a data system where it will get electronic notification of -- of adverse events. I -- I should point out in the -- in the one year since these amendments were passed, FDA has, I -- I think, in 21 instances ordered clinical trials. instances it has ordered a revision of labeling. hired 430 new employees in the Center for Drug Evaluation and Research to address the post-marketing situation. JUSTICE BREYER: Why isn't -- why isn't the In four It has fact that some certain number of people are getting gangrene, why isn't that new information? MR. KNEEDLER: The risk -- the way FDA -- and this is set forth in the changes being affected regulation amendment that was -JUSTICE BREYER: That was all passed long after the events here took place, I think. MR. KNEEDLER: JUSTICE BREYER: But -- but -So at the time, you read the regulation, I think a person would think that he was free drug manufacturer if he learned something new to strengthen -- strengthens the contraindication, put it in. MR. KNEEDLER: As FDA explained in 2008, 19 Alderson Reporting Company Slide 20: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 when it promulgated this regulation, it's been FDA's long-standing interpretation that only new information would justify a change. JUSTICE BREYER: MR. KNEEDLER: Why wouldn't that be new? New information means new information about a risk that is greater in severity or frequency. If you have -JUSTICE BREYER: of cases. MR. KNEEDLER: There is no claim -- there is If you get a certain number no claim here that either of those -- in the record in this case, that either of those was true. JUSTICE BREYER: That's because nobody So if nobody brought up this new information point. brought up the new information point at the trial and if the burden is on the manufacturer to show that it's pre-empted, isn't that the manufacturer's fault, because if you simply read the regulation, you wouldn't find any of all this complicated stuff about certain kinds of new information. MR. KNEEDLER: factual. That's a legal question not a And it was argued to the Vermont -JUSTICE BREYER: MR. KNEEDLER: Yes it's a legal question. It was argued to the Vermont Supreme Court, and I don't think -- I don't think that 20 Alderson Reporting Company Slide 21: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Respondent -- Respondent has noted that it wasn't raised, but I don't think it's argued that it's waived. And I think for the Court to fully address this situation, I think it would be good to take into account FDA's -- certainly going forward that is the regulatory regime -JUSTICE BREYER: advisory opinion. But we are not making an And this We are deciding this case. case here you say new information of a certain kind would be okay, nobody argued it. You read the reg, and it doesn't seem to make all these distinctions end of case. Since the manufacturer has the burden of going So, now we into this, which apparently it didn't do. have decided this case, and we go on to the next one. MR. KNEEDLER: one further -JUSTICE BREYER: that? MR. KNEEDLER: point about that. If I could make one further What's your response to Okay. If I could make just And that is the -- this act sets up a In other words, Congress prior approval situation. wanted the FDA to look at the drug in advance, balance -- against benefits as this Court said in Rutherford, and -- Brown & Williamson, strike a balance and approve it. 21 Alderson Reporting Company Slide 22: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 It would be fundamentally inconsistent with a prior approval system to have a regime in which the very next day State law could require the manufacturer to change the very labeling that FDA has struck a balance -JUSTICE KENNEDY: we're talking about here. I don't understand what The new information was not brought up by either side -MR. KNEEDLER: Right. -- showing increased JUSTICE KENNEDY: frequency or increased severity? MR. KNEEDLER: That's correct. Right? JUSTICE KENNEDY: And supposedly, it was burden of the drug company to show -MR. KNEEDLER: No. The drug company says it's pre-empted, and the only escape hatch from the preemption is new information. JUSTICE KENNEDY: You agree with -- you agree with Mr. Waxman that the FDA specifically addressed the risks and benefits of IV push as opposed to the risks of arterial exposures? MR. KNEEDLER: It specifically addressed in the labeling that the FDA approved, and I think that's all that needs to be looked at in -- it's just as in 22 Alderson Reporting Company Slide 23: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Riegle, where the preemption turns on that device, in that case, and the labeling that was presented. Here the preemption turns on the labeling and the drug that was presented. And FDA regulations prohibit the change unless there is new information. If I could make one other point about Riegle. Riegle does contain an FDA -- an expressed But the reason why this Court preemption provision. found preemption in Riegle under that provision is very instructive here, because as Mr. Waxman pointed out, the premarket approval process in the two situations are essentially the same. And what you had on the one hand was Federal action having the force of law like under the file rate doctrine or some administrative determination having the force of law approving a license or -- or a drug, a legal prohibition against changing that without new information. And on the state side, you have a rule of law under the common law of torts imposing a different obligation. Those are squarely termed -JUSTICE KENNEDY: You're talking about changing but you can supplement without changing the label. MR. KNEEDLER: No -- no, you cannot. Any -- any change in the wording of -- of the label is a change 23 Alderson Reporting Company Slide 24: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that requires FDA approval unless it is -JUSTICE SCALIA: You can supplement only when there is new information? MR. KNEEDLER: When there is new information and even then, it has to be in the form of a new drug -a supplemental drug application to the agency. CHIEF JUSTICE ROBERTS: Mr. Kneedler. Mr. Frederick. ORAL ARGUMENT OF DAVID C. FREDERICK ON BEHALF OF THE RESPONDENT MR. FREDERICK: Justice. I'd like to start with regulation 201.80, which is set forth in an addendum to our brief at 19-A. The second sentence of which reads: "The labeling shall Thank you, Mr. Chief Thank you, be revised -- this is after an applicant, a sponsor has obtained approval of the drug label -- "it shall be revised to include a warning as soon as there is reasonable evidence of an association of a serious risk with a drug. proved." The testimony at trial established that Wyeth knew or should have known from at least the '70s that there was a significance issue concerning IV push 24 Alderson Reporting Company A causal relationship need not have been Slide 25: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 risks. And, Justice Alito, in answer to your question -JUSTICE SCALIA: Excuse me. Those -- those risks were set forth on the labeling approved by the FDA. Surely that sentence means it shall be revised to include a warning as soon, as soon as there is reasonable evidence of an association of a serious hazard that the FDA has not considered. already addressed on the labeling. And that is not I mean to read it as -- as opening up stuff that's already been considered by the FDA would -- would -- would make a -- a mush out of it. MR. FREDERICK: FDA never considered any The comparative risks of IV push versus IV drip. evidence on this was clear. Wyeth had a -- CHIEF JUSTICE ROBERTS: What about the various portions of the label in the record that Mr. Waxman addressed and Mr. Kneedler, representing the FDA, said they specifically considered IV push risks? MR. FREDERICK: What the evidence showed was that FDA certainly was aware that there are different forms of intravenous administration of drugs, but it never considered that the risk of IV push so greatly increased the risks of a catastrophic injury -25 Alderson Reporting Company Slide 26: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CHIEF JUSTICE ROBERTS: Well, they have to. When they determine that it's safe to use it under those circumstances that necessarily includes a consideration of the risk. People can say it's safe for you to walk That doesn't mean there is no risk It down the sidewalk. that you get hit by lightning or something else. just means in evaluating them together, they determine that it's worth the candle in particular cases where a physician determines that that's the indicated method. MR. FREDERICK: Mr. Chief Justice, here there was no way FDA could have made this determination because the risks of IV push are so catastrophic compared to the benefit which the testimony at trial showed -JUSTICE SCALIA: contradicting the label. Well, you're just The fact is they could not have approved that label unless they made that determination. Now, if you're telling me the FDA acted irresponsible -- irresponsibly, then sue the FDA. MR. FREDERICK: JUSTICE SCALIA: No. But the labeling made it very clear that the preferred method of administering this medicine was -- was -- was muscular and -- and that there were serious risks involved in -- in the IV push. 26 Alderson Reporting Company Slide 27: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 serious? Moreover, your client didn't follow the labeling or your client's physician didn't follow the labeling prescription for IV push, did he? MR. FREDERICK: The testimony at trial showed that the doctor acted with a standard of care that was not negligent, and that was based on expert testimony. JUSTICE SCALIA: No. No. Wait, wait. He administered a -- a level of the drug that was vastly in excess of -- of -- of what the labeling said could safely be used for IV push. MR. FREDERICK: And the testimony at trial showed that that had no bearing on her injury, because -JUSTICE SCALIA: Had no bearing. Are you MR. FREDERICK: Yes. It did. The testimony Both at trial from Dr. Green disputed that point. courts below rejected that notion. But the idea that a label is set in stone for all time misunderstands the way the process works. When FDA approves a drug with a drug label, it does so on the basis of small clinical trials with very few, sometimes as few as a thousand or a couple of thousand people. And when the drug is marketed and goes to lots 27 Alderson Reporting Company Slide 28: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 and lots of people that are not healthy, that are in different conditions, new problems arise. That's why the general -- the GAO found that over 51 percent of drugs have adverse drug events not known. JUSTICE SCALIA: were new problems? You established that there I mean, if there were new problems, then -- then they could have simply supplemented the labeling. But did you establish that there were problems that had not been considered already by the FDA? I mean, the labeling says, you know, that this is dangerous to use -- use IV push. very clear that it's dangerous. MR. FREDERICK: That was not our burden and But as It made it that was not how the testimony came in at trial. the amicus brief by Dr. Budhwani, et al. at pages 54 establishes had Wyeth been a reasonably prudent manufacturer over the years, it would have known that the risks of IV push so far outweigh any bearing negligible benefits, that it would have offered a stronger instruction, it would have moved to revise its label either with FDA approval or -JUSTICE SCALIA: It proposed a more And the FDA restrictive label to the FDA, didn't it? said, no, you use this label. 28 Alderson Reporting Company In other words, it's -- Slide 29: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 what you're saying was not its call. the FDA. MR. FREDERICK: It was the call of Footnote one of the Vermont Supreme Court's opinion disputes that point, because it says the label was different. And if you compare what was submitted to FDA versus what FDA looked at, there was no reference to IV push risks creating the risk of catastrophic harm versus negligible, Justice Scalia. CHIEF JUSTICE ROBERTS: I thought your -- I thought your theory was that this type of administration of the drug should not be allowed. The label should not You -- say here are the risks, here are the benefits. your jury theory was you cannot suggest in the labeling that physicians should have this available. MR. FREDERICK: Well, as the jury was instructed, Mr. Chief Justice, and the evidence came in at trial, it was -- it was somewhat larger than that in the sense that a State failure to warn claim doesn't prescribe particular wording. existing wording is inadequate. to this Court -CHIEF JUSTICE ROBERTS: Well, it simply says It simply says that the And if the case comes that if you go ahead with the label like this, you don't have to pay $10 million whenever it comes wrong. That's having the effect, as our case has established, imposing 29 Alderson Reporting Company Slide 30: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 a limitation on the label. MR. FREDERICK: But the label itself is not Manufacturers change set in stone, Mr. Chief Justice. their labels all the time as new drug risks come in. And the regulations provide that the manufacturer is responsible not only for the label, but for monitoring post-market information. CHIEF JUSTICE ROBERTS: So your case depends upon us determining that the risk at issue here that was presented to the jury was a new risk that the FDA did not consider? MR. FREDERICK: No. It's not dependent on It is dependent on a that at all, Mr. Chief Justice. finding that the manufacturer had a duty of due care and it didn't live up to that. JUSTICE SCALIA: What if it referred to new drug risks, then, in your preceding sentence, where you are saying manufacturers change it all the time as new drug risks become apparent? MR. FREDERICK: JUSTICE SCALIA: The testimony -What you mean is whether or not new drug risks become apparent, they have to change, right? MR. FREDERICK: The question is what does the manufacturer know and when did this manufacturer 30 Alderson Reporting Company Slide 31: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know it? And here, the testimony at trial showed that an antinausea drug called Vistrol -- this is at page 79 of the joint appendix -- caused amputations in two cases. Pfizer voluntarily removed IV push injection for This was information in Wyeth's files; Wyeth that drug. knew this from the 1970s; and yet it did nothing to change the Phenergan label. CHIEF JUSTICE ROBERTS: JUSTICE SOUTER: Suppose -- With respect to the obligation in this case, may I go back to an earlier question that Justice Scalia asked you? And I -- I -- if you responded to this particular point, I didn't get it. He said that he understood that Wyeth had in fact asked the FDA to modify the label, at least to strengthen the warning against IV push, and that request was -- was denied, so that in fact that -- that created the conflict. What is your response to -- to the factual basis for that -- for that comment? MR. FREDERICK: Well, the FDA itself said in the Solicitor General's brief at page 25 that it was deemed to be a nonsubstantive change. changes that were being made -JUSTICE SOUTER: Well, regardless of what These were their, their semantic label was, was there a request at 31 Alderson Reporting Company Slide 32: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 least to -- to beef up the warning against using IV push? And if so, did the -- did the FDA reject it and say no, you can't do that. MR. FREDERICK: It was a different label and it was a different strength of warning, but it didn't have to do with the relative risks and benefits of IV push versus IV drip. JUSTICE SOUTER: MR. FREDERICK: JUSTICE SOUTER: MR. FREDERICK: What would it -That was the crucial point. What would it have said? This is set out at footnote 1 of the Vermont Supreme Court opinion, which is set out in the joint -- in the petition appendix at pages 4a to 5a, and it goes on for two pages. But essentially what the -- what the comparison was was talking about the preferability of injecting it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily, which would suggest to most medical practitioners and was it the case in the trial testimony given by Dr. Green below, that that would suggest an IV drip, not IV push. When FDA then rejected it for -- for nonsubstantive reasons, it went back to the prior verbiage which is set out at 5a, which simply says if you put this drug in an artery the concentration can be 32 Alderson Reporting Company Slide 33: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 such that it will -- it will cause harm. But our point is that these kinds of risks come to light frequently with drugs that are on the market and the need to revise these labels is the duty of the manufacturer. Section 314. -But you -- you also, to be JUSTICE SOUTER: clear on it, as I understand it, you do not accept the position that the FDA puts forward, that the obligation depends upon the accrual of new information. MR. FREDERICK: JUSTICE SOUTER: Well, how you -Any information, new or old, as I understand it, on your argument raises this obligation to -- to act. MR. FREDERICK: I think that the dispute is -- is what constitutes new information, because we don't take issue with the notion that new information can be new analysis of prior submitted data; and what the amicus brief by Dr. Budhwani et al. Points out is that there was a lot of unpublished information about the harms of Phenergan that was known to Wyeth or should have been known to Wyeth in the '80s and '90s that would have justified a change under the CEE regulations. JUSTICE ALITO: Well, suppose the record showed that the FDA clearly considered whether IV push should be contraindicated and concluded it should not be 33 Alderson Reporting Company Slide 34: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 and prescribed the label that now appears on the drug; and then, as some of the other arguments have referenced, the very day after the FDA made that ruling, Ms. Levine was injured. Would you still -- would she still have a claim in your view, a non-pre-empted claim? MR. FREDERICK: That be pre-empted. And the reason it would be pre-empted is because the FDA would have considered and rejected on the basis of the same information or similar information the very duty that underlies the State claim. JUSTICE ALITO: So your argument is -- is If predicated on the existence of new information. there was no new information, then the claim is pre-empted? MR. FREDERICK: No, it's -- well, it is not -- I think there are two things to keep analytically clear. One is can the manufacturer come forward with a label change on the basis of -- of information that is assessing the risk or reassessing the risk, and under the -- under the regulations it's absolutely clear it can do that before FDA has approved it. to FDA disapproval. JUSTICE SCALIA: And -- and is entitled to It is subject amend the labeling automatically. MR. FREDERICK: That's correct. 34 Alderson Reporting Company Slide 35: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 JUSTICE SCALIA: I envision a -- a scheme under which manufacturers who are worried about jury liability of -- of the magnitude that occurred in this case saying, gee, why should we take chances? And every time there is a jury verdict on some -- on some other -some other ground not -- not prohibited by the label, they just add that to the label; and they submit it to -- to the FDA and the -- and until -- unless and until the FDA conducts an investigation and disapproves that label, that labeling change occurs. How many -- how many -- you mentioned a number of -- of times that -- that label alterations are -- are proposed. I mean, this is going to be a massive operation for the FDA. MR. FREDERICK: Justice Scalia, that would promote public safety, because it puts into the hands of doctors the information that enables them to make individualized risk determinations. JUSTICE SCALIA: It would not promote public safety if you believe that the name of this game is balancing benefits and costs. MR. FREDERICK: JUSTICE SCALIA: And Congress said -And if you are simply eliminating certain drugs which people who -- who have real desperate need for could -- could be benefited by, 35 Alderson Reporting Company Slide 36: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you're not benefiting the public. MR. FREDERICK: No, and in fact that's In contrary to the policy determination Congress made. the misbranding provision, which is Section 352(f), it calls -- that the label is misbranded unless its labeling bears adequate directions for use and such adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health or against unsafe dosage or methods or duration of administration or application. JUSTICE SCALIA: it's approved by the FDA? MR. FREDERICK: in the 1979 -JUSTICE SCALIA: You're saying FDA approval Yes. It's misbranded. And And that applies even if doesn't -- doesn't give you any protection at all? MR. FREDERICK: It -- it provides you a basis for marketing your --- your product. JUSTICE SCALIA: But -- but -- but the marketing may be a misbranding? MR. FREDERICK: In -- the FDA itself said so in 1979 in 44 Federal Register, which we cite in our brief, that even an original label may be misbranded if the drug manufacturer subsequently learns that it was not adequate for the safe use of the drug. 36 Alderson Reporting Company Slide 37: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 JUSTICE SCALIA: Well then, gee, then all of the qualifications you were making earlier about whether it's new information or a new assessment, that's irrelevant. MR. FREDERICK: JUSTICE SCALIA: No, it's -You're saying whenever it's unsafe, whatever the FDA has approved, you have a lawsuit. MR. FREDERICK: No. What I'm saying is that the information developed after the original label is approved, and it is not a floor and a ceiling -JUSTICE SCALIA: There -- there was nothing You said about new information in what you just said. it's misbranded if it's not safe, new information or not. MR. FREDERICK: JUSTICE SCALIA: that your position? MR. FREDERICK: Our position is that the And that's -Is that -- is that -- is duty is on the manufacturer to make a safe label, and if the label is -JUSTICE SOUTER: But getting to Justice Scalia's point, as I understand your answer to an earlier question, on the day that the FDA approves the label, if there is no further information indicating 37 Alderson Reporting Company Slide 38: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 danger, then any liability that is based upon what the -- the kind of information that the FDA knew would be pre-empted. The only time -- you're saying pre-emption does not occur when there is -- forget the word "new" for a moment -- when there is further information, information in addition to what the FDA was told, whether it's 1,000 years old or discovered yesterday; and if there is liability predicated on further information beyond what the FDA was told, then there is not pre-emption. Is that a fair statement of your position? MR. FREDERICK: That's fair, but let me just make clear that our test would require the FDA to consider and reject the specific basis on which the State law -JUSTICE SCALIA: If that's a fair statement then you have to retract your -- your earlier assertion that whenever it's not safe it's misbranded. MR. FREDERICK: that, Justice Scalia. JUSTICE SCALIA: -- which is it? Whenever I mean -- I'm not going to retract it's not safe, it's misbranded, or what you just responded to Justice Souter? MR. FREDERICK: The basis -- the basis of the FDA's approval is on the basis of limited 38 Alderson Reporting Company Slide 39: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 information, which Congress has said for public safety reasons -- we are not doing a balancing here; we are doing this for public safety -And if the label is not adequate for public safety it is a misbranded drug. JUSTICE SOUTER: Okay, but if -- if the so-called misbranding is determined to be misbranding, based upon information which was given to the FDA, as I understand your position, you would admit that there was pre-emption. MR. FREDERICK: I -- I think there is pre-emption, but that does not mean -JUSTICE SOUTER: MR. FREDERICK: JUSTICE SOUTER: Okay. So there -- Maybe there is no -In other words, there is that one exception at least to the broad statement that you gave in answer to Justice Scalia? MR. FREDERICK: this way. Let me try to untangle it The fact that there is pre-emption and you cannot bring as State law failure-to-warn claim doesn't mean that the drug isn't misbranded under the Federal standard the FDA -JUSTICE SOUTER: But the -- but the misbranding is of no consequence to liability. MR. FREDERICK: Well, if -39 Alderson Reporting Company Slide 40: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 yes. point -- JUSTICE SOUTER: In other words, I think you're saying if there -- if there would be pre-emption it may be misbranded, but there cannot be any recovery in a State tort suit. MR. FREDERICK: That's correct. The -- the JUSTICE SOUTER: Okay. So misbranding under those circumstances is a purely theoretical concept. MR. FREDERICK: In that very hypothetical, JUSTICE SOUTER: MR. FREDERICK: Okay. But the point is that the failure is that the failure-to-warn claim tracks the misbranding provision; and if you look at the jury instructions in this case, the wording is very close to the wording of the misbranding provision in terms of the adequacy of the warning that must be provided. JUSTICE STEVENS: MR. FREDERICK: Mr. Frederick -All State law is doing is providing a remedy that is absent from Federal law. JUSTICE STEVENS: Mr. Frederick, I'd like to put the misbranding point to one side and just concentrate on pre-emption. And I understood you to agree with Justice Alito that there is a hypothetical case in which there would be pre-emption, and would you 40 Alderson Reporting Company Slide 41: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tell me what particular fact distinguishes your case from his hypothetical? MR. FREDERICK: The fact is there was no consideration and rejection of a stronger IV push warning. There was no consideration by the FDA of IV push as a means of administration distinct from other intravenous forms that would lead to a different kind of risk-benefit balancing. So with the -- in the case where there would be pre-emption, FDA would be asked, we -- we want to put a stronger warning as against this -FDA says: We don't think there is scientific evidence. Do not put that warning on the label. CHIEF JUSTICE ROBERTS: So now, your friends on the other side said there was specific consideration of IV push as opposed to simply arterial exposure, and that that is laid forth in the labeling. So, as I understood your answer to be, all we have to do is simply look at the record, and if we think the FDA considered specifically IV push risks as opposed to general arterial exposure, then you lose, and if we determine that they did not, then they lose. MR. FREDERICK: And the Vermont Supreme Court was quite emphatic about this, Mr. Chief Justice. CHIEF JUSTICE ROBERTS: Well, I don't know I if the Vermont Supreme Court was emphatic about it. 41 Alderson Reporting Company Slide 42: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 mean, the record is either -- addresses the FDA -- I'm more interested in what the FDA was emphatic about, and they either address IV push separately or they don't. MR. FREDERICK: And you search in the joint appendix in vain for communications between Wyeth and FDA communicating about the particular risks of IV push. JUSTICE GINSBURG: What -- can you turn to the references that Mr. Waxman and Mr. Kneedler made? They said oh, yes, IV push was considered discretely from IV drip bags. MR. FREDERICK: I will acknowledge that the There is references in some instances suggest IV push. no doubt that the FDA knew that IV push was a method of intravenous administration, but our point is a starker one, and that is that the FDA never was put to the test of deciding comparative risks and benefits of IV push versus IV drip. And it's that point that is crucial, because the catastrophic risks of IV push are so dramatic, no reasonable person could have made a safety determination to allow this drug with its risks when there are corresponding benefits that create exactly the same kind of treatment of care for the patient. JUSTICE SOUTER: Well, is your argument that they couldn't have considered these comparative risks, because if they had, they would have come out 42 Alderson Reporting Company Slide 43: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 differently; because they didn't come out differently, we have to infer that they didn't consider it? MR. FREDERICK: It's two things: One, they didn't consider it and that's clearly -JUSTICE SOUTER: MR. FREDERICK: JUSTICE SOUTER: No, I -Second, Apart from your analysis that they couldn't have or they would have come out differently, how did we know that they didn't consider it? MR. FREDERICK: There are communications These are that went back and forth between the company. set out in the joint appendix. They make no reference to IV push risks as distinct from -JUSTICE SOUTER: And do these -- when you say "communications," do you mean starting with the original application for approval of the label? MR. FREDERICK: actually is not known. The original application It wasn't in Wyeth's files. We don't know where the This drug was approved in 1955. original label was, Justice Souter. JUSTICE SOUTER: So, you are saying all the correspondence that we do know about, that is extant, fails to mention comparative risk. MR. FREDERICK: That's correct. 43 Alderson Reporting Company And -- Slide 44: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 opinion? JUSTICE SCALIA: But the label doesn't. I mean, the label ask discusses the high risk from IV push and sets forth particular cautions for that -- for that specific means of administration. MR. FREDERICK: It does not, Justice Scalia. The label says -- it's talking about intravenous administration. and IV push. It does not distinguish between IV drip And Dr. Matthew testified at trial that, based on the label, he would not have been able to make a treatment determination to distinguish between the two, and that had he had that information, he clearly would have given this drug to Diana Levine through the intravenous drip method. The label simply didn't -If we conclude that new JUSTICE KENNEDY: information is the criterion for deciding this case, if we reject the argument that misbranding at the outset allows State law to supplement the duty, but that if there's new information, then the label has to be changed -- if it that's the line we draw, can this verdict be sustained? MR. FREDERICK: sustained on the basis of -JUSTICE KENNEDY: And the Vermont court's Yes, I think it can be MR. FREDERICK: I don't think that the 44 Alderson Reporting Company Slide 45: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Vermont Supreme Court's opinion totally, because it does go into the area that you're talking about, Justice Kennedy, but if I could refer the Court to trial record testimony, which is set out in the joint appendix and more elaborately in the trial record itself, which makes clear that Wyeth knew or should have known about these comparative risks. It should have had a basis for changing its label or proposing to FDA a different label, and that would be sufficient to satisfy the Federal standards as well as the State duty of due care. And we think the judgment on that basis could be sustained. JUSTICE STEVENS: May I ask this: When did the duty on the part of Wyeth to have a different label arise, in your view? MR. FREDERICK: I think it probably arose in the early '70s when a -- when there was a published -or there was an incident -JUSTICE STEVENS: Did it arise before or after submitting the original drug application? MR. FREDERICK: A strong argument can be made that it would have been before the 1970s application when they were reformatting. drugs. These are old We don't have evidence from the 1950s that would have suggested that the original label determination in 45 Alderson Reporting Company Slide 46: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1955 would have caused a difference but certainly by the 1970s when -- when Wyeth was reformatting this as an old drug to comply with new standards, it should have known and it certainly should have known by the 1990s when several amputations had occurred from IV push Phenergan, which were in Wyeth's files. The people who analyzed these records, you know, were emphatic that Wyeth knew or should have known by the 1990s. And that was clear by the testimony of experts that -- that showed the comparison between Vistrol and Phenergan and on the basis of the IV push injuries that had occurred that were nonpublished. They appeared to have been reported to FDA, but Wyeth never took the trouble to do the synthesis, to connect the dots between these very terrible tragedies that had occurred from its drug, to bring about a labeling change or a modification that would have saved lives. And that is a failure on the part of the manufacturer not to comply with its standards of due care and with the regulations which require health risk information to be the basis of modifications to the labeling. JUSTICE STEVENS: Does that boil down to a claim that there was new information that was available between the original approval and the time of the lawsuit? 46 Alderson Reporting Company Slide 47: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MR. FREDERICK: Well, by "original approval," do you mean 1955 or do you mean in 1998 and 2000? JUSTICE STEVENS: Either one. But is your theory really a theory based on new information or new judgment about old information? MR. FREDERICK: think, of both. It would be on the basis, I I think we would be able to establish that there was a justification on the basis of information before the reformatted labeling took place, and that was testimony by Dr. Green at trial on the basis of Vistrol, the other amputation that had occurred with Phenergan in 1965. And the -- the important point here is that on the basis of new information, if you are going to conclude that there is a standard that has to be met, I would urge you to consider two things: One is that the burden of showing absence of new information is going to fall on the manufacturer because it is asserting a pre-emption defense, but the way pre-emption gets argued in the courts, it is done oftentimes before discovery is permitted. So, if there is information in the drug manufacturer's files that would be relevant to a determination of the breach of duty by the drug manufacturer, if you decide pre-emption has to be done 47 Alderson Reporting Company Slide 48: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 before discovery can be done, there would be no way to get that information. JUSTICE KENNEDY: Well, to put the burden on the manufacturer seems to me inconsistent with what 10 States have said, that there is a rebuttable presumption and inconsistent also with the instructions the jury received in this case, that you can consider the FDA label. So, I think, to me, what you say there is not borne out by what happened in this case or by those other States' -MR. FREDERICK: Well, let me -- let me address that question because your question goes to the regulatory compliance defense and that is not a pre-emption defense. It is a defense based on State law that the manufacturer in fact was not negligent because it complied with the applicable regulations. In that -- under that scenario, Justice Kennedy, the plaintiff is going to be able to obtain discovery and make arguments to the trial court about whether or not that compliance negated or did not negate negligence. But pre-emption is a Federal defense that would be asserted typically at the outset of the lawsuit before information is obtained. And notably, before 2000, FDA did not have It did not have It didn't even subpoena power of drug manufacturers. the power to force labeling changes. 48 Alderson Reporting Company Slide 49: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 have the power to force drug manufacturers to make post-marketing studies. JUSTICE BREYER: to figure out is this: The --the part I'm trying I Suppose it was before trial. The plaintiff comes in That's don't care, before or after. with a claim. pre-empted. All right. Manufacturer: The claim is that you should have told the FDA and added something to your label. Manufacturer: That's preempted. Plaintiff: Well, you haven't read this reg here. The reg here which has been in existence since 1965 says that we can go and add something. I mean you can go and add something to show a contra indication, and that's the end of it. Now, in fact, 30 years later, I guess, without the horrible things happening that Justice Scalia mentioned, or maybe they did -- I don't know. But 30 years later the FDA makes another mention of new information. I take it that's in 1982. That's the first time that happened. Now, if I'm right about that, what happens when no one says a word about that? Of course, if the manufacturer had said something about that, then maybe the plaintiff would have said: And it was new. It was Are you new, but the manufacturer doesn't say a word. following what I'm saying? 49 Alderson Reporting Company Slide 50: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 about that. MR. FREDERICK: I'm not totally, Justice Breyer, I confess, but let me try to address it this way. JUSTICE BREYER: what happens. I mean, I'm wondering still I believe what happened here is that in the argument in the lower courts, in the trial court, nobody said anything about the FDA's claim that the information necessary to just go ahead and change the label had to be new. Am I right about that? You are absolutely right MR. FREDERICK: JUSTICE BREYER: So what I'm trying to figure out -- and I don't know if "burden of proof" is the right word -- where nobody says a word about it, who wins? If they had said a word about it, you need new information, maybe the manufacturer -- the plaintiff could have shown that the manufacturer had new information. MR. FREDERICK: I think the duty is always going to be on the manufacturer, Justice Breyer. The regulations at 314.80(b) establish that the -- that the manufacturer has the responsibility to do postmarketing analysis and post-marketing surveys to determine the continuing safety of its drugs. If the manufacturer doesn't do that, it isn't complying with 50 Alderson Reporting Company Slide 51: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the Federal regulations which have an ongoing duty on them. And so in the case where there is silence, I would respectfully submit the manufacturer is not complying with its regulatory duty to ensure that there is current information about all of the side- effect risks of its drugs. Thank you. CHIEF JUSTICE ROBERTS: Thank you, counsel. Mr. Waxman, you have three minutes remaining. REBUTTAL ARGUMENT OF SETH P. WAXMAN ON BEHALF OF THE PETITIONER MR. WAXMAN: Thank you, Mr. Chief Justice. I want to make -- I do want to go to -- make a preliminary point about all the talk about misbranding here. The statute has two criminal prohibitions. One is misbranding, which is the original 1906 reactive penalty. If the FDA subsequently finds that something is false or misleading, it CAN come after you for misbranding. But this case involves the criminal prohibition against distributing drugs for which there is not an approved, effective application. what's at stake here. Now, the notion that there was any -- any misunderstanding in the trial court about whether there 51 Alderson Reporting Company And that's Slide 52: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was new information or whether there was -- there were incidents that the FDA didn't know about, or it didn't evaluate the risk, is just flat wrong. The plaintiff tried this -- the plaintiff's experts said the FDA knew about this risk. decades. That is what is so wrong. That is why he Wyeth knew about this risk for stood up and said the FDA doesn't decide this question. You decide this question. And there was never, ever a suggestion in the record in this case, nor could there have been, that Wyeth ever failed to bring every single adverse-event report to the FDA's attention, every analysis that it did to the FDA's attention. And what the record does show is that after -- between the time of the 1955 approval of the new-drug application and the 1998 rejection of the SDNA, the Supplemental New -- SNDA, the Supplemental New Drug Application, that did have more extensive, stronger warnings in this case, Wyeth filed five -- and these are all in the joint appendix -- five supplemental, new-drug applications, each one asking for more language, more warnings, about direct IV injection. "push." It's not called It's IV injection versus drip, which is a And, in fact, Mr. Frederick gravity method. says: Well, you know, in this case there could have 52 Alderson Reporting Company Slide 53: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 been stronger warnings, and that -- and this case wasn't really about -- the jury wasn't really asked to -- it didn't really say that the label had to contra indicate something that the FDA-labeling required. That is exactly the opposite of what the trial lawyer told the jury at opening and at closing. What he said is this was unreasonably unsafe because it didn't say: Do not use by intravenous administration. With respect to whether or not the warning -- the last SNDA which we submitted, which was in 1987 and is reprinted in the joint appendix -- not only is it an original, but there is a typewritten version that actually has the text in the type size that one can actually read. At the summary-judgment stage that the pre-emption issue was decided -- may I finish my answer? CHIEF JUSTICE ROBERTS: MR. WAXMAN: Sure. Summary judgment was decided at the -- pre-emption was decided at summary judgment before trial. So there was no evidence about what was In Ms. Levine's motion for summary new or wasn't new. judgment, she uses the word "new" information about labeling change. And, with respect to the proposed 1987 language, the '88 change that we asked for, she said -and I'm reading from page 24 of her motion for summary judgment -- "In 1988, Wyeth drafted changes to the 53 Alderson Reporting Company Slide 54: Official - Subject to Final Review 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 warning which advised that the use of a free-flowing IV would ensure adequate dilution and reduce the risk of arterial injectia. Although not strong enough, this improved the labeling instruction; if followed, would have prevented the inadvertent administration of Phenergan into an artery for the reasons described." CHIEF JUSTICE ROBERTS: The case is submitted. (Whereupon, the case was submitted.) Thank you, counsel. 54 Alderson Reporting Company Slide 55: Official - Subject to Final Review A able 7:24 44:9 47:8 48:18 above-entitled 1:11 absence 11:16 11:17 13:15 47:18 absent 40:20 absolutely 34:20 50:10 accept 33:7 account 21:4 accrual 33:9 acknowledge 42:11 act 10:4,6,8 11:2 11:3 18:19 21:20 33:13 acted 17:20 18:5 26:19 27:5 action 18:4 23:14 actions 10:8,11 10:14 add 35:7 49:11 49:12 added 49:8 addendum 24:15 addition 38:6 address 7:14 9:10 10:10 19:9 21:3 42:3 48:12 50:2 addressed 7:12 22:21,23 25:10 25:19 addresses 42:1 adequacy 40:17 adequate 36:6,7 36:25 39:4 54:2 adjunct 15:9 administered 5:4 6:20 27:9 administering 26:23 administration 4:19 5:17 6:5,7 6:16 7:15,25 8:14 10:2 25:23 29:10 36:10 41:6 42:14 44:4,7 53:8 54:5 administrative 9:7 23:15 admit 39:9 adulteration 16:6 advance 13:16 21:22 adverse 19:3 28:4 adverse-event 52:12 advised 54:1 advisory 6:17,17 21:8 affect 11:18 agency 24:6 agree 4:6,8 22:19,20 40:24 ahead 29:23 50:8 al 28:16 33:18 Alito 6:23 7:4 25:2 33:23 34:11 40:24 allow 8:24 11:25 13:1 42:20 allowed 29:11 allows 44:17 alter 16:10 alteration 4:3 alterations 35:12 altogether 16:22 amend 34:24 amendment 19:16 amendments 18:19 19:5 amici 10:13 15:18 amicus 1:19 2:6 14:20 28:16 33:18 ample 8:9 amputation 7:19 47:12 amputations 31:3 46:5 analyses 13:15 analysis 11:21 33:17 43:7 50:23 52:13 analytically 34:16 analyzed 46:6 answer 7:17 25:2 37:23 39:17 41:17 53:15 anti 17:2 antinausea 31:2 Apart 43:7 apparent 30:19 30:22 apparently 21:13 APPEARAN... 1:14 appeared 46:12 appears 34:1 appendix 5:22 5:23 31:3 32:13 42:5 43:13 45:4 52:20 53:11 applicable 48:16 applicant 24:17 application 4:14 24:6 36:10 43:17,18 45:20 45:23 51:22 52:16,18 applications 52:21 applied 10:17 13:3 applies 36:11 apply 5:24 applying 11:21 approval 13:17 18:11 21:21 22:2 23:11 24:1,18 28:22 36:15 38:25 43:17 46:24 47:2 52:15 approve 21:25 approved 3:13 10:19 12:3,17 13:20 15:8 17:9 18:7,23 22:24 25:5 26:17 34:21 36:12 37:7,11 43:20 51:22 approves 27:22 37:24 approving 4:14 12:18 23:16 area 9:10,11,11 9:16 45:2 argue 3:21 argued 20:22,24 21:2,10 47:20 arguing 15:22 16:14 18:15 argument 1:12 2:2,10 3:3,6 12:22,22 13:6 13:12 14:18 24:10 33:12 34:11 42:23 44:16 45:21 50:6 51:11 arguments 34:2 48:18 arising 17:9 arose 45:16 arterial 6:13,18 8:12 22:22 41:15,20 54:3 artery 32:25 54:6 articulated 4:10 asked 6:17 11:23 14:4 31:11,15 41:9 53:2,23 asking 52:21 aspiration 6:9 asserted 48:21 asserting 47:19 assertion 38:17 assessing 34:19 assessment 37:3 association 24:20 25:8 attention 16:12 17:10,13,19 18:17 52:12,13 authority 18:23 18:25 authorized 17:20,22 automatically 34:24 available 8:22 29:14 46:23 aware 5:2,16 25:22 a.m 1:13 3:2 B B 14:2 back 10:13 12:5 12:13 14:4 17:16 31:10 32:23 43:12 background 10:7,11 bag 5:4 bags 42:10 balance 11:6 14:15 21:23,24 22:5 balancing 9:22 9:25 35:21 39:2 41:8 based 12:6 55 Alderson Reporting Company Slide 56: Official - Subject to Final Review 14:25 16:24 17:15 27:6 38:1 39:8 44:9 47:5 48:14 basis 27:23 31:19 34:8,18 36:18 38:14,24 38:24,25 44:22 45:7,11 46:11 46:20 47:7,9 47:12,15 bearing 27:13 27:15 28:19 bears 36:6 beef 32:1 behalf 1:15,18 1:21 2:4,6,9,12 3:7 14:19 24:11 51:12 believe 10:22 35:20 50:5 benefit 6:25 7:19,20 8:4 26:13 benefited 35:25 benefiting 36:1 benefits 8:1 9:25 21:23 22:21 28:20 29:12 32:6 35:21 42:16,21 better 9:1,2 beyond 38:9 blood 6:9,13 8:12 board 4:25 boil 46:22 borne 48:9 box 16:7 breach 47:24 Breyer 19:11,17 19:20 20:4,8 20:13,23 21:7 21:17 49:3 50:2,4,12,20 brief 5:9,9,24 7:13 9:21 24:15 28:16 31:21 33:18 36:23 briefs 15:6 bright 6:10 bring 16:11 39:20 46:16 52:11 broad 11:21 39:16 brought 10:14 17:10,13,19 18:17 20:14,15 22:8 Brown 21:24 Budhwani 28:16 33:18 burden 20:16 21:12 22:14 28:14 47:18 48:3 50:13 C C 1:21 2:1,8 3:1 24:10 call 29:1,1 called 31:2 52:22 calls 36:5 candle 26:8 care 14:12 27:5 30:14 42:22 45:10 46:19 49:5 cascading 8:13 case 3:4,10 5:20 6:6,12 7:5 9:7 9:17 10:17 11:22 12:15 14:2 15:6 20:12 21:8,9 21:12,14 23:2 29:20,25 30:8 31:10 32:19 35:4 40:15,25 41:1,8 44:15 48:7,9 51:3,20 52:10,19,25 53:1 54:8,9 cases 10:13,15 10:22,24,25 11:9 20:9 26:8 31:4 catastrophic 25:25 26:12 29:8 42:18 causal 24:21 cause 33:1 caused 31:3 46:1 cautions 6:8 44:3 CEE 33:22 ceiling 37:11 Center 19:8 central 15:5 certain 5:2 19:12 20:8,19 21:9 35:24 certainly 8:6 21:5 25:22 46:1,4 chances 35:4 change 13:16 14:1 15:7,13 15:16 17:6,11 17:20 18:13,24 20:3 22:4 23:4 23:25,25 30:3 30:18,22 31:7 31:22 33:22 34:18 35:10 46:16 50:8 53:22,23 changed 12:8 14:6 44:19 changes 19:15 31:23 48:25 53:25 changing 18:1 23:17,22,22 45:8 Chief 3:3,8 9:9 9:15 10:3 14:16,22 24:7 24:12 25:17 26:1,10 29:9 29:16,22 30:3 30:8,13 31:8 41:13,23,24 51:9,13 53:16 54:7 children 36:8 Cipollone 10:23 circumstances 7:6,14 9:8 26:3 40:8 citations 7:11 cite 5:6 36:22 cited 7:13 claim 5:1 16:24 20:10,11 29:18 34:5,5,10,13 39:20 40:13 46:23 49:6,7 50:7 claims 14:25 clarify 15:5 class 9:19 clause 3:11 9:12 10:12 11:15,17 clauses 11:16 clear 5:8 25:16 26:23 28:13 33:7 34:17,20 38:13 45:6 46:8 clearly 33:24 43:4 44:11 client 27:1 client's 27:2 clinical 19:1,6 27:23 clinicians 8:8 close 40:15 closing 4:18 53:6 come 11:1,1 17:2 30:4 33:3 34:17 42:25 43:1,8 51:19 comes 29:20,24 49:5 comment 3:21 31:19 committee 6:17 common 11:8 23:19 communicating 42:6 communicatio... 42:5 43:11,16 company 12:5 22:15,16 43:12 comparative 25:15 42:16,24 43:24 45:7 compare 29:5 compared 26:13 comparison 32:15 46:10 complaint 4:17 completely 3:25 compliance 48:13,19 complicated 20:19 complied 48:16 comply 3:22 4:11 46:3,18 complying 50:25 51:5 comprehended 6:14 concentrate 40:23 concentration 32:25 concept 40:8 concerned 8:4 11:20 concerning 24:25 concerns 3:10 conclude 11:24 44:14 47:16 concluded 6:24 33:25 conclusion 56 Alderson Reporting Company Slide 57: Official - Subject to Final Review 10:21 conditions 3:14 10:1 15:2 28:2 36:8 conduct 11:11 conducts 35:9 confess 50:2 conflict 3:10,11 11:18,22 12:14 12:23 13:1,7 13:11,14,18 15:1 16:4 17:11,17 31:18 conform 14:11 Congress 11:2 18:19 21:21 35:22 36:3 39:1 connect 46:14 consequence 39:24 consider 5:3 30:11 38:14 43:2,4,9 47:17 48:7 consideration 26:3 41:4,5,14 considered 3:17 16:10 25:9,11 25:14,20,24 28:9 33:24 34:8 41:19 42:9,24 considering 18:9 consistent 4:1 constellation 8:1 11:8 constitutes 33:15 Constitution 11:19 consumers 15:10 contain 23:7 context 6:11,12 7:10 continuing 50:24 contra 4:20 49:13 53:3 contradicting 26:16 contraindicated 33:25 contraindicati... 19:23 contrary 36:3 contrast 9:13 contra-indicate 4:20 correct 22:12 34:25 40:5 43:25 correspondence 7:9 43:23 corresponding 42:21 costs 35:21 counsel 14:16 51:9 54:7 count 10:24 couple 27:24 course 9:12 49:21 court 1:1,12 3:9 9:18 10:17,20 11:20 14:23 20:25 21:3,23 23:8 29:21 32:12 41:23,25 45:3 48:19 50:6 51:25 courts 27:19 47:21 50:6 court's 29:4 44:23 45:1 cover 16:14 create 42:21 created 31:17 creating 29:7 criminal 51:16 51:20 criterion 44:15 crucial 32:9 42:17 curiae 1:19 2:7 14:20 current 51:6 9:19 15:1 23:15 26:11,18 36:3 42:20 44:10 45:25 47:24 determinations D 35:18 D 3:1 determine 7:24 danger 38:1 26:2,7 41:21 dangerous 3:19 50:24 28:12,13 36:8 determined 3:17 dark 6:10 4:16 39:7 data 9:23 12:7 determines 26:9 19:2 33:17 determining DAVID 1:21 2:8 30:9 24:10 developed 37:10 day 13:23 22:3 device 9:10,11 34:3 37:24 9:16 10:8 23:1 decades 52:6 devices 9:24 decide 8:7 9:3 Diana 1:6 44:12 14:4 47:25 difference 9:16 52:8,9 10:12 13:10 decided 10:25 46:1 13:19 21:14 different 10:21 53:15,17,18 23:19 25:22 deciding 21:8 28:2 29:5 32:4 42:16 44:15 32:5 41:7 45:8 decision 5:12 45:14 deemed 31:22 differently 43:1 defense 16:23 43:1,9 47:20 48:13,14 difficulties 48:14,21 18:20 demonstrate 5:7 dilution 54:2 denied 31:17 direct 6:2 7:6 Department 18:23 52:22 1:18 directed 7:22,23 dependent directions 36:6 30:12,13 directly 6:22 depends 30:8 9:18 33:9 disagreed 5:18 depressant 17:3 disapproval Deputy 1:17 34:22 described 3:14 disapproves 54:6 35:9 design 3:25 disclose 15:11 desperate 35:25 discolors 6:13 determination discovered 38:7 discovery 47:21 48:1,18 discreetly 5:3 discretely 42:9 discusses 44:2 dispute 33:14 disputed 27:18 disputes 29:4 distinct 41:6 43:14 distinction 9:10 distinctions 21:11 distinguish 44:7 44:10 distinguishes 41:1 distribute 13:24 distributing 51:21 distribution 11:6 doctor 27:5 doctors 35:17 doctrine 23:15 doing 39:2,3 40:19 dosage 36:9 dots 46:14 doubt 42:13 Dr 27:18 28:16 32:20 33:18 44:8 47:11 drafted 53:25 dramatic 42:19 draw 44:19 drip 5:4 6:4,5 25:15 32:7,21 42:10,17 44:7 44:13 52:23 drug 6:19 7:1,1 8:11,17 9:11 10:1,4,6 11:6 12:1 13:24 17:3,9 18:22 19:8,22 21:22 22:14,16 23:3 57 Alderson Reporting Company Slide 58: Official - Subject to Final Review 24:18,21 27:9 27:22,22,25 28:4 29:11 30:4,17,19,22 31:2,5 32:25 34:1 36:24,25 39:5,21 42:20 43:20 44:12 45:20 46:3,15 47:22,24 48:24 49:1 52:17 drugs 9:20,24 18:9,10 25:23 28:4 33:3 35:24 45:24 50:24 51:7,21 drug-specific 11:3 due 30:14 45:10 46:19 duration 36:10 duties 14:24 duty 30:14 33:4 34:9 37:20 44:17 45:10,14 47:24 50:19 51:1,5 D.C 1:8,15,18 1:21 E E 2:1 3:1,1 earlier 31:10 37:2,24 38:17 early 45:17 easier 14:2 EDWIN 1:17 2:5 14:18 effect 12:25 29:25 51:6 effective 3:13 6:24 15:2 51:22 effectiveness 11:7 efforts 15:10 either 12:6 13:25 14:13 15:12 20:11,12 22:8 28:22 42:1,3 47:4 elaborately 45:5 electronic 19:2 eliminating 35:24 emphatic 41:23 41:25 42:2 46:7 employees 19:8 enables 35:17 enacted 11:2 enforcement 18:21 ensure 51:5 54:2 entitled 34:23 envision 16:1 35:1 escape 22:17 ESQ 1:15,17,21 2:3,5,8,11 essentially 23:12 32:14 establish 28:8 47:8 50:21 established 8:20 8:21 10:7,11 11:3 24:23 28:5 29:25 establishes 28:17 et 28:16 33:18 evaluate 11:5 52:3 evaluated 15:12 evaluating 3:16 26:7 Evaluation 19:9 event 5:10 events 19:3,18 28:4 evidence 7:8 10:20 24:20 25:8,16,21 29:16 41:11 45:24 53:19 evolving 17:4 exactly 42:21 53:5 example 16:5 17:3 exceeded 6:7 exception 39:16 excess 27:10 excuse 12:4 25:4 existence 15:17 15:21 34:12 49:11 existing 29:20 expected 10:4 experience 12:6 expert 27:6 experts 5:15,18 46:9 52:4 explain 16:16 explained 5:24 19:25 exposure 6:18 8:11 41:15,20 exposures 22:22 express 9:12 10:5 11:14 expressed 11:15 23:7 extant 43:23 extensive 52:18 F fact 3:18 12:16 13:1,6 15:8 16:5 17:5 19:12 26:16 31:15,17 36:2 39:19 41:1,3 48:15 49:14 52:24 factual 20:22 31:19 failed 16:17,21 52:11 fails 43:24 failure 16:11 29:18 40:13 46:17 failure-to-warn 16:24 39:20 40:13 fair 38:11,12,16 fall 47:19 false 51:19 far 28:19 fault 20:17 FDA 3:12,17,18 4:15 5:1,16 6:24 7:8,9,11 8:3,5,5,7,23 9:2,19 10:18 11:5,25,25 12:3,5,17,25 13:2,20,23 15:8,8,14,20 16:18 17:5,7 17:10,19,23 18:3,5,11,20 18:23,25 19:1 19:5,14,25 21:22 22:4,20 22:24 23:4,7 24:1 25:6,9,12 25:14,20,22 26:11,19,20 27:22 28:10,22 28:24,24 29:2 29:6,6 30:10 31:15,20 32:2 32:22 33:8,24 34:3,7,21,22 35:8,9,14 36:12,15,21 37:7,24 38:2,6 38:9,13 39:8 39:22 41:5,9 41:11,18 42:1 42:2,6,13,15 45:8 46:13 48:7,23 49:8 49:17 51:18 52:2,4,8 FDA's 15:1,9,13 17:10,13,19 18:17 20:1 21:5 38:25 50:7 52:12,13 FDA-labeling 53:4 Federal 3:23 4:4 4:12,13 10:4 11:12,19 16:3 17:15 23:13 36:22 39:21 40:20 45:10 48:21 51:1 fewer 10:24 field 11:10 figure 18:10 49:4 50:13 file 23:14 filed 52:19 files 31:5 43:19 46:6 47:23 finally 6:8 11:14 find 20:18 finding 30:14 finds 51:18 finish 53:15 first 3:4 5:14 12:13 17:13 18:15 49:19 five 52:19,20 flat 52:3 floor 37:11 follow 27:1,2 followed 54:4 following 49:25 footnote 5:24 7:13 29:3 32:11 force 23:14,16 48:25 49:1 forget 38:4 form 13:14,18 24:5 forms 5:16 25:23 41:7 forth 19:15 24:15 25:5 58 Alderson Reporting Company Slide 59: Official - Subject to Final Review 41:16 43:12 44:3 forward 21:5 33:8 34:17 found 16:8 23:9 28:3 four 5:23 19:6 Frederick 1:21 2:8 24:9,10,12 25:14,21 26:10 26:21 27:4,12 27:17 28:14 29:3,15 30:2 30:12,20,24 31:20 32:4,9 32:11 33:10,14 34:6,15,25 35:15,22 36:2 36:13,17,21 37:5,9,16,19 38:12,19,24 39:11,14,18,25 40:5,9,12,18 40:19,21 41:3 41:22 42:4,11 43:3,6,11,18 43:25 44:5,21 44:25 45:16,21 47:1,7 48:11 50:1,10,19 52:24 free 19:22 free-flowing 54:1 free-wheeling 11:21 frequency 20:7 22:11 frequently 33:3 friends 41:13 fully 10:18 21:3 functioning 32:17 fundamentally 22:1 furnish 16:25 further 16:15 21:16,19 37:25 ground 35:6 38:5,8 guess 49:14 H G 3:1 hand 23:13 game 35:20 hands 35:16 gangrene 7:2,18 happened 48:9 19:13 49:19 50:5 GAO 28:3 happening gee 35:4 37:1 49:15 Geier 10:23 happens 49:20 general 1:17 50:5 15:16,23 28:3 harm 29:8 33:1 41:20 harms 33:20 General's 5:9 hatch 22:17 31:21 hazard 25:9 getting 13:17 health 36:9 19:12 37:22 46:20 Ginsburg 4:22 healthy 28:1 4:24 5:5 7:17 hear 3:3 7:21 15:4 18:8 heartland 11:23 42:7 helped 15:10 give 12:24 36:16 helpful 15:9 given 7:25 12:25 hierarchy 8:13 18:23,25 32:20 high 44:2 39:8 44:12 hired 19:8 go 6:21 7:4 hit 26:6 12:16 18:21 horrible 49:15 21:14 29:23 huge 18:9 31:10 45:2 hypothetical 49:11,12 50:8 40:9,24 41:2 51:14 I goes 9:20 11:13 idea 27:20 27:25 32:14 ideation 17:7 48:12 identified 9:15 going 10:13 10:13 12:12 17:1 21:5,12 35:13 identify 17:1 38:19 47:15,18 immediately 6:13 48:18 50:20 implicated good 21:4 10:16 gravity 6:5 implied 11:22 52:24 important 7:15 greater 20:6 18:20 47:14 greatly 25:24 impose 14:5 Green 27:18 imposing 23:19 32:20 47:11 G 29:25 impossibility 13:14 impossible 3:21 improved 18:22 54:4 inadequate 29:20 inadvertent 54:5 incident 45:18 incidents 52:2 include 24:19 25:7 includes 26:3 including 3:15 5:15,17 6:21 7:8 inconsistent 14:7 17:14 22:1 48:4,6 increased 22:10 22:11 25:25 indicate 53:3 indicated 7:7 26:9 indicating 37:25 indication 49:13 individualized 35:18 infer 43:2 information 5:12 8:7,22 10:19 11:24 13:15,16,19 15:17 16:9,12 16:18,24 17:4 17:8,9,12 18:12,17 19:13 20:2,5,6,14,15 20:20 21:9 22:7,18 23:5 23:18 24:3,4 30:7 31:5 33:9 33:11,15,16,19 34:9,9,12,13 34:18 35:17 37:3,10,13,14 37:25 38:2,5,6 38:9 39:1,8 44:11,15,18 46:20,23 47:5 47:6,10,15,18 47:22 48:2,22 49:18 50:8,16 50:18 51:6 52:1 53:21 informed 10:18 10:18 infusion 8:18 32:17 inject 8:17 injectia 54:3 injecting 32:16 injection 3:13 3:16 6:19 7:6 8:11,15,16 15:2 31:4 52:22,23 injured 12:18 34:4 injuries 46:11 injury 25:25 27:13 inquiry 9:23 instances 19:6,7 42:12 instructed 29:16 instruction 6:6 28:21 54:4 instructions 40:15 48:6 instructive 23:10 intensive 9:23 13:23 interested 42:2 interim 17:25 interpretation 20:2 intramuscular 8:14 intravenous 8:16 25:23 59 Alderson Reporting Company Slide 60: Official - Subject to Final Review 32:17 41:7 42:14 44:6,13 53:8 intravenously 6:20 intra-arterial 8:10 investigation 35:9 involved 26:25 involves 51:20 irrelevant 37:4 irresponsible 26:20 irresponsibly 26:20 irritant 6:19 8:11,17 issue 8:6 11:1 24:25 30:9 33:16 53:15 issues 10:25 IV 3:15 4:19,19 4:25,25 5:2,3,3 5:17,25 6:2,8 6:15,22,24 7:6 7:14 8:18,20 12:8 22:21 24:25 25:15,15 25:20,24 26:12 26:25 27:3,11 28:12,19 29:7 31:4,16 32:1,6 32:7,20,21 33:24 41:4,5 41:15,19 42:3 42:6,9,10,12 42:13,16,17,18 43:14 44:2,7,8 46:5,11 52:22 52:23 54:1 J joint 5:22 31:3 32:13 42:4 43:13 45:4 52:20 53:11 journals 7:12 judgment 5:18 45:11 47:6 53:17,18,21,25 judgments 8:8 8:25 jury 3:16 4:16 11:23 12:24 13:3,9,19 14:2 29:13,15 30:10 35:2,5 40:14 48:6 53:2,6 Justice 1:18 3:3 3:8,20 4:9,22 4:24 5:5 6:23 7:4,17,21 8:3,6 9:9,15,21 10:3 12:2,13,21 13:5 14:8,16 14:22 15:4,24 16:8,17 17:18 17:24 18:8 19:11,17,20 20:4,8,13,23 21:7,17 22:6 22:10,13,19 23:21 24:2,7 24:13 25:2,4 25:17 26:1,10 26:15,22 27:8 27:15 28:5,23 29:8,9,16,22 30:3,8,13,16 30:21 31:8,9 31:11,24 32:8 32:10 33:6,11 33:23 34:11,23 35:1,15,19,23 36:11,15,19 37:1,6,12,17 37:22,22 38:16 38:20,21,23 39:6,13,15,17 39:23 40:1,7 40:11,18,21,24 41:13,23,24 42:7,23 43:5,7 43:15,21,22 44:1,5,14,23 45:2,13,19 46:22 47:4 48:3,17 49:3 49:15 50:1,4 50:12,20 51:9 51:13 53:16 54:7 justification 47:9 justified 33:22 justifies 15:18 justify 20:3 49:16 50:13 34:24 35:10 52:2,25 36:6 41:16 knowledge 46:16,21 47:10 15:15 48:25 53:22 known 8:18 54:4 24:24 28:4,18 labels 30:4 33:4 32:17 33:20,21 laid 41:16 43:19 45:6 language 11:24 46:3,4,8 12:19 13:25 52:21 53:23 L larger 29:17 label 3:23,25 4:4 lavish 8:10 4:14,16,20 6:9 law 3:22 4:4,12 10:21 12:3,7 4:12,13 11:9 12:17,18 13:6 11:12 14:24 K 13:9 14:1 17:15 22:3 keep 34:16 15:16 16:19 23:14,16,19,19 Kennedy 3:20 17:21 18:1,13 38:15 39:20 4:9 8:3,6 22:6 18:24 23:23,25 40:19,20 44:17 22:10,13,19 24:18 25:18 48:14 23:21 44:14,23 26:16,17 27:20 lawsuit 37:8 45:3 48:3,17 27:22 28:22,24 46:25 48:22 Kennedy's 28:25 29:5,11 lawyer 53:6 12:13 29:23 30:1,2,6 lead 41:7 kind 12:24 21:9 31:7,15,25 learned 19:22 38:2 41:7 32:4 34:1,18 learns 36:24 42:22 35:6,7,10,12 legal 20:21,23 kinds 20:19 33:2 36:5,23 37:10 23:17 Kneedler 1:17 37:20,21,25 legislature 14:3 2:5 14:17,18 39:4 41:12 legislatures 14:3 14:22 15:4,14 43:17,21 44:1 let's 14:2 16:2,13,21 44:2,6,9,13,18 level 27:9 17:22 18:3,14 45:8,9,14,25 Levine 1:6 3:4 19:14,19,25 48:8 49:8 50:9 12:18 34:4 20:5,10,21,24 53:3 44:12 21:15,19 22:9 labeling 3:15,18 Levine's 53:20 22:12,16,23 5:11,12,19,19 liability 12:15 23:24 24:4,8 6:14 7:22,23 14:9 35:3 38:1 25:19 42:8 8:13,24 10:2 38:8 39:24 knew 24:24 31:6 10:19 13:20 license 23:16 38:2 42:13 14:6 15:3 licensing 11:6 45:6 46:7 52:4 16:10 17:6,23 life-saving 7:1 52:5 19:7 22:4,24 light 10:1 33:3 know 28:11 23:2,3 24:16 lightning 26:6 30:25 31:1 25:5,10 26:22 limitation 30:1 41:24 43:9,20 27:2,3,10 28:8 limited 38:25 43:23 46:7 28:11 29:13 line 8:19,21 60 Alderson Reporting Company Slide 61: Official - Subject to Final Review 44:19 live 30:15 lives 46:17 logical 3:24 4:5 long 19:17 long-standing 20:2 look 6:18 7:8 11:23 13:9,9 21:22 40:14 41:18 looked 22:25 29:6 looking 10:20 lose 41:20,21 lot 33:19 lots 27:25 28:1 lower 50:6 M magnitude 35:3 making 17:4 21:7 37:2 manufacturer 15:16 19:22 20:16 21:12 22:3 28:18 30:5,14,25,25 33:5 34:17 36:24 37:20 46:18 47:19,25 48:4,15 49:6,9 49:22,24 50:16 50:17,20,22,25 51:4 manufacturers 13:25 15:11 30:3,18 35:2 48:24 49:1 manufacturer's 20:17 47:23 market 33:4 marketed 27:25 marketing 36:18,20 50:23 massive 35:14 matter 1:11 3:23 3:24 4:5,5,6 7:19 13:7 15:16,23 Matthew 44:8 maximum 6:5 mean 7:3 9:14 11:9 16:17 18:6,10 25:10 26:5 28:6,11 30:21 35:13 38:18 39:12,21 42:1 43:16 44:2 47:2,2 49:12 50:4 means 20:5 25:6 26:7 41:6 44:4 medical 7:12,22 8:24 9:10,11 9:16,23 10:8 32:18 medically 9:6 medicine 26:24 meets 4:1 members 11:20 mention 16:5 43:24 49:17 mentioned 16:2 35:11 49:16 met 47:16 method 7:24,25 8:15 26:9,23 42:13 44:13 52:24 methods 3:14 8:14 10:1 36:9 microscopic 5:20 million 29:24 minutes 51:10 misbranded 36:5,13,23 37:14 38:18,22 39:5,21 40:3 misbranding 36:4,20 39:7,7 39:24 40:7,14 40:16,22 44:16 51:15,17,20 46:13 52:9 misleading new 13:15,15 51:19 15:17 16:9,11 misunderstan... 16:18,24 17:8 51:25 18:12,17,20 misunderstands 19:1,8,13,22 27:21 20:2,4,5,5,14 modification 20:15,19 21:9 46:16 22:7,18 23:5 modifications 23:17 24:3,4,5 46:21 28:2,6,6 30:4 modify 31:15 30:10,16,18,22 moment 38:5 33:9,11,15,16 Monday 1:9 33:17 34:12,13 monitoring 37:3,3,13,14 18:11 30:6 38:4 44:14,18 morning 3:4 46:3,23 47:5,5 motion 53:20,24 47:15,18 49:17 moved 28:21 49:23,24 50:9 multiple 5:15 50:15,17 52:1 muscular 26:24 52:17,17 53:20 mush 25:12 53:20,21 new-drug 52:15 N 52:20 N 2:1,1 3:1 nonpublished name 35:20 46:12 nature 9:18 nonsubstantive nausea 7:1 31:22 32:23 necessarily 26:3 non-pre-empted necessary 50:8 34:5 need 24:21 33:4 notably 48:23 35:25 50:15 noted 21:1 needle 6:11 notification 19:2 needles 6:3 notion 27:19 needs 22:25 33:16 51:24 negate 48:20 November 1:9 negated 48:20 number 18:9 negates 16:19 19:12 20:8 negligence 14:9 35:12 14:13 48:20 O negligent 27:6 O 2:1 3:1 48:15 negligible 28:20 objects-and-p... 13:18 29:8 never 8:3 11:1,1 obligation 14:5 23:20 31:10 15:15 17:12 33:8,13 25:14,24 42:15 obtain 48:18 obtained 24:18 48:23 occur 38:4 occurred 35:3 46:5,11,15 47:12 occurs 8:20 35:10 offered 28:20 oftentimes 47:21 oh 42:9 okay 21:10,15 39:6,13 40:7 40:11 old 13:16 33:12 38:7 45:23 46:2 47:6 once 15:8,12 ones 7:13 ongoing 51:1 opening 4:17 25:11 53:6 operation 11:18 35:14 opinion 9:22 21:8 29:4 32:12 44:24 45:1 opposed 22:21 41:15,19 opposite 53:5 options 8:25 oral 1:11 2:2 3:6 14:18 24:10 order 18:25 ordered 19:1,6,7 ordinary 6:9 original 36:23 37:10 43:17,18 43:21 45:20,25 46:24 47:1 51:17 53:12 ought 12:8 16:10 outset 3:20 15:5 61 Alderson Reporting Company Slide 62: Official - Subject to Final Review 44:16 48:22 outweigh 7:20 28:19 P P 1:15 2:3,11 3:1 3:6 51:11 page 2:2 31:2,21 53:24 pages 5:21,22 28:16 32:13,14 part 15:7 45:14 46:18 49:3 particular 5:13 6:7 8:1 10:1 26:8 29:19 31:12 41:1 42:6 44:3 parties 5:15 party 4:11 passed 10:7,8 19:5,17 pathological 36:7 patient 8:2 42:22 patterned 9:24 pay 29:24 penalty 51:18 people 19:12 26:4 27:25 28:1 35:24 46:6 percent 28:3 permission 14:1 permitted 47:22 person 19:21 42:19 petition 17:5 32:13 petitioner 1:4,16 1:20 2:4,7,12 3:7 5:22 14:21 51:12 Pfizer 31:4 pharmaceutical 7:24 pharmaceutic... 10:15 Phenergan 3:13 3:19 6:13,19 8:12 15:1 31:7 33:20 46:5,10 47:13 54:6 physician 26:9 27:2 physicians 7:23 8:13,23 9:1,3 29:14 place 17:13 19:18 47:10 plainly 6:14 plaintiff 48:17 49:5,9,23 50:16 52:3 plaintiff's 52:4 please 3:9 14:23 plungers 6:3 point 5:8 7:15 11:14 18:18 19:4 20:14,15 21:20 23:6 27:18 29:4 31:12 32:9 33:2 37:23 40:6,12,22 42:14,17 47:14 51:15 pointed 9:21 23:10 points 9:18,22 18:14 33:18 policy 15:7,13 36:3 portions 5:6 25:18 position 15:15 16:13 33:8 37:18,19 38:11 39:9 possibility 17:7 possible 4:10 post 50:22 postdate 10:23 post-date 10:22 post-market 30:7 post-marketing 19:9 49:2 50:23 power 18:2 48:24,25 49:1 practitioners 32:19 preceding 30:17 precise 3:17 4:14 11:24 precisely 6:18 preclearance 9:20 11:4 preclude 11:11 predicated 12:16 34:12 38:8 preempted 49:9 preemption 5:10 11:10 22:18 23:1,3,8 23:9 preferability 32:16 preferable 8:17 preferred 8:15 26:23 preliminary 51:15 premarket 23:11 prescribe 29:19 prescribed 10:2 34:1 prescription 27:3 presence 11:15 11:16 presented 3:11 12:20 23:2,4 30:10 presumption 48:5 prevented 54:5 pre-empted 14:14,25 15:23 20:17 22:17 34:6,7,14 38:3 49:7 pre-emption 3:10 9:12 10:5 10:12 11:15,16 11:18,22 13:18 16:15,23 17:12 18:16 38:3,10 39:10,12,19 40:2,23,25 41:9 47:20,20 47:25 48:14,20 53:15,18 primarily 15:19 prior 21:21 22:2 32:23 33:17 probably 45:16 problem 7:12 18:21 problems 28:2,6 28:6,9 proceedings 15:20 process 9:20 13:23 23:11 27:21 prodded 15:11 product 16:6,7 36:18 professionals 7:22 8:25 prohibit 23:4 prohibited 35:6 prohibition 23:17 51:21 prohibitions 51:16 promote 35:16 35:19 promulgated 20:1 proof 50:13 properly 8:19 16:9 proposed 12:19 17:11,16 28:23 35:13 53:22 proposing 45:8 proposition 15:22 protect 15:10 protection 36:16 proved 24:22 provide 8:7 16:18,22 30:5 provided 7:11 7:11 8:9,12 40:17 provides 36:17 providing 40:20 provision 10:5 23:8,9 36:4 40:14,16 provisions 16:19 prudent 28:17 public 35:16,19 36:1 39:1,3,4 published 45:17 purely 40:8 purposes 9:17 push 3:15 4:19 4:25 5:3,17,25 6:2,8,11,15,22 6:24 7:14 8:20 12:8 22:21 24:25 25:15,20 25:24 26:12,25 27:3,11 28:12 28:19 29:7 31:4,16 32:2,7 32:21 33:24 41:4,6,15,19 42:3,6,9,12,13 42:16,18 43:14 44:2,8 46:5,11 52:23 put 19:23 32:25 40:22 41:10,12 42:15 48:3 puts 33:8 35:16 62 Alderson Reporting Company Slide 63: Official - Subject to Final Review recommendat... Q 6:21,21 qualifications recommended 37:2 15:3 question 5:11,13 record 5:6,14 7:18 12:13 7:8 9:8 20:11 20:21,23 25:3 25:18 33:23 30:24 31:11 41:18 42:1 37:24 48:12,12 45:3,5 52:10 52:8,9 52:14 quite 41:23 records 46:7 R recovery 40:3 reduce 54:2 R 3:1 refer 45:3 raise 12:11 reference 5:23 raised 21:2 6:1,3,4 29:7 raises 33:12 43:13 rate 6:5,7 23:14 referenced 34:3 reach 10:21 references 42:8 reactive 51:17 42:12 read 19:20 referred 3:15 20:18 21:10 6:8 15:21 25:10 49:10 30:16 53:14 reflects 9:25 reading 53:24 reformatted reads 24:16 47:10 real 35:25 reformatting really 11:4 45:23 46:2 18:11 47:5 reg 21:10 49:10 53:2,2,3 49:10 reason 10:5 12:11,23 23:8 regardless 31:24 regime 11:4 34:7 21:6 22:2 reasonable Register 36:22 24:20 25:8 regulated 4:11 42:19 regulation 19:16 reasonably 19:21 20:1,18 28:17 24:14 reasons 32:23 regulations 23:4 39:2 54:6 30:5 33:22 reassessing 34:20 46:19 34:19 48:16 50:21 rebuttable 48:5 51:1 REBUTTAL regulatory 21:5 2:10 51:11 48:13 51:5 received 48:7 reject 32:2 recognized 38:14 44:16 18:19 rejected 12:19 17:8,16 27:19 32:22 34:8 rejection 13:2 41:4 52:16 rejects 17:10,23 17:23 relationship 24:21 relative 32:6 relevant 9:5 47:23 reliable 6:12 relied 15:19 relieves 7:1 remaining 51:10 remedies 11:11 15:21,22 remedy 15:25 16:11 40:20 remember 12:17 removed 31:4 rendered 3:19 12:1 Repeatedly 3:12 reply 5:24 7:13 report 52:12 reported 46:12 representing 25:19 represents 15:7 reprinted 53:11 reproduced 5:20 request 31:16,25 require 22:3 38:13 46:20 required 3:18 4:13,15 11:5 11:25 12:2 13:20 53:4 requirements 4:1 requires 5:19 24:1 Research 19:9 reserve 14:15 resources 18:21 respect 8:16 9:15,19 10:15 31:9 53:9,22 respectfully 51:4 responded 31:12 38:23 Respondent 1:22 2:9 10:12 21:1,1 24:11 Respondents 4:2 15:18 Respondent's 14:24 response 21:17 31:18 responsibility 50:22 responsible 30:6 restrictive 28:24 rethinking 12:7 retract 38:17,19 revise 28:21 33:4 revised 24:17,19 25:6 revision 15:18 19:7 Riegel 9:17,22 Riegle 23:1,7,7,9 right 13:4,11,13 22:9,13 30:23 49:6,20 50:9 50:10,14 rigid 6:3 risk 3:16 5:2,17 6:18 7:2,2,18 7:20 8:10 19:14 20:6 24:20 25:24 26:4,5 29:7 30:9,10 34:19 34:19 35:18 43:24 44:2 46:20 52:3,5,5 54:2 risks 6:15 8:1,4 9:5,25 15:11 22:21,22 25:1 25:5,15,20,25 26:12,25 28:19 29:7,12 30:4 30:17,19,22 32:6 33:2 41:19 42:6,16 42:18,20,24 43:14 45:7 51:7 risk-benefit 41:8 road 14:1 ROBERTS 3:3 9:9 10:3 14:16 24:7 25:17 26:1 29:9,22 30:8 31:8 41:13,24 51:9 53:16 54:7 rule 10:16 11:10 13:3,3 17:4 23:18 rule-making 15:19 ruling 34:3 run 13:25 running 8:18 Rutherford 21:24 S S 1:17 2:1,5 3:1 14:18 safe 3:13 6:24 15:2 26:2,4 36:25 37:14,20 38:18,22 safely 27:11 safety 11:5,7 35:16,20 39:1 39:3,5 42:19 50:24 salient 9:17 63 Alderson Reporting Company Slide 64: Official - Subject to Final Review saliently 5:19 satisfactorily 32:18 satisfy 45:9 saved 46:17 savings 11:17 saying 11:13 12:23 14:10,10 29:1 30:18 35:4 36:15 37:6,9 38:3 40:2 43:22 49:25 says 12:25 13:23 22:16 28:11 29:5,19,22 32:24 41:11 44:6 49:11,21 50:14 52:25 Scalia 15:24 16:8,17 17:18 17:24 24:2 25:4 26:15,22 27:8,15 28:5 28:23 29:8 30:16,21 31:11 34:23 35:1,15 35:19,23 36:11 36:15,19 37:1 37:6,12,17 38:16,20,21 39:17 44:1,5 49:16 Scalia's 9:22 37:23 scenario 48:17 scheme 35:1 scientific 41:11 SDNA 52:16 search 42:4 second 18:18 24:16 43:6 Section 33:5 36:4 see 6:10 18:12 seeking 11:10,11 semantic 4:6 31:25 sense 29:18 sent 7:9 sentence 24:16 25:6 30:17 separate 5:23 separately 42:3 serious 24:20 25:8 26:25 27:16 set 8:18 19:1,15 24:15 25:5 27:20 30:3 32:11,12,17,24 43:13 45:4 SETH 1:15 2:3 2:11 3:6 51:11 sets 21:20 44:3 severity 20:6 22:11 show 20:16 22:15 49:12 52:14 showed 25:21 26:14 27:5,13 31:1 33:24 46:9 showing 22:10 47:18 shown 50:17 side 6:25 7:2 22:8 23:18 40:22 41:14 51:6 sides 5:16 sidewalk 26:5 significance 24:25 silence 51:3 similar 10:5 34:9 simply 5:18 12:9 13:8 20:18 28:7 29:19,22 32:24 35:23 41:15,18 44:13 single 52:11 situation 15:25 16:14,15 17:2 17:3 18:16 19:10 21:4,21 situations 23:11 size 5:21 53:13 small 27:23 small-bore 6:3 SNDA 52:17 53:10 snippets 15:19 Solicitor 1:17 5:9 31:21 somewhat 29:17 soon 24:19 25:7 25:7 sort 5:20 Souter 12:2,21 13:5 14:8 31:9 31:24 32:8,10 33:6,11 37:22 38:23 39:6,13 39:15,23 40:1 40:7,11 42:23 43:5,7,15,21 43:22 so-called 39:7 specific 6:15,20 13:2,24 38:14 41:14 44:4 specifically 7:14 22:20,23 25:20 41:19 sponsor 24:17 squarely 23:20 stage 53:14 stake 51:23 standard 10:20 13:7 14:12 16:3,4 27:5 39:22 47:16 standards 45:10 46:3,19 stark 3:12 starker 42:14 start 24:14 starting 43:16 state 3:16,22 4:12 10:7,11 14:2,3,3,24 16:3 17:25 22:3 23:18 29:18 34:10 38:15 39:20 40:4,19 44:17 45:10 48:14 stated 4:17 statement 4:18 38:11,16 39:16 States 1:1,12,19 2:6 14:19 48:5 48:10 statute 51:16 STEVENS 40:18,21 45:13 45:19 46:22 47:4 stone 27:20 30:3 stood 52:8 strength 32:5 strengthen 19:23 31:16 strengthens 19:23 strict 14:8 strict-liability 14:14 strike 21:24 strong 45:21 54:3 stronger 12:19 28:21 41:4,10 52:18 53:1 struck 22:4 studies 19:1 49:2 stuff 20:19 25:11 subject 17:25 34:21 submit 35:7 51:4 submitted 29:6 33:17 53:10 54:8,9 submitting 45:20 subpoena 48:24 subsequently 36:24 51:18 substantial 7:20 sue 26:20 sued 16:20 sufficient 45:9 suggest 29:13 32:18,20 42:12 suggested 15:3 45:25 suggestion 52:10 suicidal 17:7 suit 17:15 18:1 40:4 suits 15:9 summary 53:17 53:18,20,24 summary-jud... 53:14 supplement 23:22 24:2 44:17 supplemental 24:6 52:17,17 52:20 supplemented 28:7 supporting 1:19 2:7 14:21 suppose 18:6 31:8 33:23 49:4 supposedly 22:14 Supremacy 3:11 Supreme 1:1,12 10:17 20:25 29:4 32:12 41:22,25 45:1 sure 4:7,8 53:16 Surely 25:6 surveys 50:23 64 Alderson Reporting Company Slide 65: Official - Subject to Final Review sustained 44:20 44:22 45:12 synthesis 46:14 system 6:2,2 19:2 22:2 43:3 47:17 49:15 think 3:25 4:8,9 5:8 7:16 9:14 9:17,21 11:14 12:7 15:6 T 16:16,18 18:4 T 2:1,1 19:6,18,21,21 table 9:4,4,5 20:25,25 21:2 take 14:2 21:4 21:3,4 22:24 33:16 35:4 33:14 34:16 49:18 39:11 40:1 taken 15:15 18:3 41:11,18 44:21 talk 51:15 44:25 45:11,16 talking 7:10 47:8,8 48:8 22:7 23:21 50:19 32:15 44:6 thought 29:9,10 45:2 thousand 27:24 tell 15:6 41:1 27:24 telling 9:3 26:19 three 51:10 termed 23:20 time 3:23 4:11 terms 9:3,4 11:5 12:6,9,12 40:16 14:15 18:6 terrible 46:15 19:20 27:21 test 4:10 5:10 30:4,18 35:5 7:7 38:13 38:3 46:24 42:15 49:19 52:15 testified 44:8 times 35:12 testimony 5:14 time-intensive 6:6 7:3,4,5 9:7 9:23 24:23 26:13 told 38:6,9 49:7 27:4,7,12,17 53:6 28:15 30:20 tool 7:15 31:1 32:19 tools 18:21 45:4 46:9 tort 10:14 11:11 47:11 14:25 15:9,21 text 53:13 15:22,25 16:11 textual 3:23 4:5 17:15 18:1 Thank 14:16 40:4 24:7,12 51:8,9 torts 15:8 23:19 51:13 54:7 totally 45:1 50:1 theoretical 40:8 tracks 40:13 theory 14:13,14 tragedies 46:15 29:10,13 47:5 treatment 42:22 47:5 44:10 things 15:20 trial 20:15 24:23 18:22 34:16 26:13 27:4,12 27:18 28:15 29:17 31:1 32:19 44:8 45:3,5 47:11 48:19 49:4 50:6 51:25 53:6,19 trials 19:6 27:23 tried 12:24 13:8 13:8 52:4 trouble 46:13 true 10:3 20:12 try 13:8 39:18 50:2 trying 49:3 50:12 Tubex 6:1 tubing 32:16 turn 42:7 turns 23:1,3 two 5:21,22 12:17 18:14 23:11 31:3 32:14 34:16 43:3 44:11 47:17 51:16 type 29:10 53:13 typewritten 53:12 typically 48:21 W wait 27:8,8 waived 21:2 walk 26:4 want 4:3,8 5:6,8 41:10 51:14,14 wanted 21:22 warn 17:6,6 29:18 warned 6:15 warning 12:24 24:19 25:7 31:16 32:1,5 40:17 41:5,10 41:12 53:9 54:1 warnings 7:10 8:10 36:7 52:19,22 53:1 V warranted 9:6 v 1:5 3:4 Washington 1:8 vague 11:21 1:15,18,21 vain 42:5 wasn't 21:1 various 25:18 43:19 53:1,2 vastly 27:9 53:20 vein 6:12 8:20 Waxman 1:15 U verbiage 32:24 2:3,11 3:5,6,8 underlies 34:10 verdict 35:5 4:7,22,23 5:5 underscore 5:8 44:20 7:3,21 8:5 9:14 understand 3:24 Vermont 4:16 10:10 12:15 5:1 8:23,24 10:17 12:24 13:4,13 14:13 12:4,21 13:5 13:2,3,9,19 16:2 22:20 17:24 22:6 20:22,24 29:3 23:10 25:19 33:7,12 37:23 32:12 41:22,25 42:8 51:10,11 39:9 44:23 45:1 51:13 53:17 understood 4:9 version 53:12 way 5:4 19:14 31:14 40:23 versus 5:3 8:4 26:11 27:21 41:17 25:15 29:6,8 39:19 47:20 unfortunately 32:7 42:17 48:1 50:3 5:21 52:23 went 32:23 United 1:1,12,19 view 34:5 45:15 43:12 2:6 14:19 violates 4:4 We'll 3:3 unknown 15:12 unpublished 33:19 unreasonably 3:19 12:1 13:21 53:7 unsafe 12:1 13:21 36:9 37:7 53:7 untangle 39:18 urge 4:2 47:17 use 3:14,18 4:13 4:13,15,15,19 5:2 6:1 7:25 8:9 12:1,8 13:24 15:3 26:2 28:12,12 28:25 36:6,7,8 36:25 53:8 54:1 uses 53:21 usual 5:4 usually 8:17 11:12 Vistrol 31:2 46:10 47:12 voluntarily 31:4 65 Alderson Reporting Company Slide 66: Official - Subject to Final Review we're 22:7 we've 7:13 Williamson 21:24 window 18:7 wins 50:15 wish 4:2 wondering 50:4 word 38:4 49:21 49:24 50:14,14 50:15 53:21 wording 23:25 29:19,20 40:15 40:16 words 4:12,19 8:19 14:9 21:21 28:25 39:15 40:1 works 27:21 world 13:22 worried 35:2 worth 26:8 wouldn't 16:4 20:4,18 wrong 29:24 52:3,7 Wyeth 1:3 3:4 3:18,22 4:15 7:9,11 10:19 11:25 12:5,8 12:16,19,20,22 24:24 25:16 28:17 31:5,14 33:20,21 42:5 45:6,14 46:2,7 46:13 52:5,11 52:19 53:25 Wyeth's 12:22 13:5 31:5 43:19 46:6 X x 1:2,7 12:17 17:5 28:18 38:7 49:14,17 yesterday 38:7 $ $10 29:24 0 06-1249 1:5 3:4 1 1 32:12 1,000 38:7 10 48:4 10:06 1:13 3:2 11 5:24 11,000 18:10 13 7:13 14 2:7 150 10:13 19-A 24:15 1906 51:17 1938 11:2,3 1950s 45:24 1955 43:20 46:1 47:2 52:15 1962 11:4 1965 47:13 49:11 1970s 31:6 45:22 46:2 1976 6:17 1979 36:14,22 1982 49:18 1987 7:9 53:10 53:22 1988 53:25 1990s 46:4,8 1998 4:15 47:2 52:16 21 19:6 24 2:9 53:24 25 31:21 3 3 1:9 2:4 9:19 30 49:14,17 314 33:5 314.80(b) 50:21 352(f) 36:4 4 4a 32:13 430 19:8 44 36:22 5 5a 32:14,24 50 14:3 51 2:12 28:3 54 28:16 7 70s 24:24 45:17 79 31:2 8 80s 33:21 88 53:23 9 90s 33:21 97 10:13 2 20 7:11,11 10:24 2000 47:3 48:23 Y 2007 18:18 year 19:5 years 3:12 10:14 2008 1:9 19:25 201.80 24:14 66 Alderson Reporting Company