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We here at the DDL Blog try to stay on top of the goings on at the FDA. We’ve learned that on September 14, 2016, the FDA will hold an advisory committee meeting to review the results of a recently completed, randomized, placebo-controlled clinical trial (Evaluating Adverse Events in a Global Smoking Cessation Study or “EAGLES”), as well as findings from other studies that have assessed the neuropsychiatric effects of Chantix (varenicline).  See September 14, 2016: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee.  The committee will consider whether data from these studies supports changing the Chantix product labeling, including potentially removing the boxed warning regarding serious neuropsychiatric events.  The meeting comes approximately three years after Pfizer agreed to pay nearly $300 million to settle thousands of lawsuits filed by plaintiffs alleging that they experienced adverse neuropsychiatric effects while taking Chantix.  See Pfizer 2012 Financial Report, at 107.

This chain of events seems to be a clear cut example of litigation marching ahead of the science, and at that cost, we thought we’d probe the situation a little deeper. Chantix was approved by FDA in May 2006.  It was the first new smoking cessation medication to come to market in more than a decade, and was recognized at the time to be one of the most effective treatments available to help smokers break their addiction to nicotine.  The following, year, however, a highly publicized incident involving a Texas musician named Carter Albrecht raised concerns about potential adverse neuropsychiatric effects of the medication.  The musician, who was taking Chantix and was heavily intoxicated at the time, was shot and killed by a neighbor who thought that Mr. Albrecht was burglarizing his home.  Mr. Albrecht’s girlfriend publicly blamed Mr. Albrecht’s behavior on his use of Chantix.  The incident sparked national media attention, which led to an increasing number of anecdotal reports of patients experiencing neuropsychiatric events while taking Chantix.

Based largely on these anecdotal reports, the FDA instructed Pfizer to include warnings about potential neuropsychiatric effects in the Chantix product labeling, and, in July 2009, mandated the addition of a boxed warning.  The boxed warning advised that patients being treated with Chantix should be monitored for neuropsychiatric symptoms “including changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide” and recommended stopping Chantix if any of these symptoms are observed.   To further evaluate this issue, FDA also asked Pfizer to conduct a clinical trial—the recently completed EAGLES study—to assess the neuropsychiatric safety of Chantix.Continue Reading Chantix: A Lesson in Why Litigation Should Not Be Allowed to Get Ahead of Science

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It’s been over two years since the FDA – in March, 2014 Draft Guidelines and then in its June 2014 “grant” of an industry-submitted citizen’s petition – promised to review its restrictions on so-called “off-label promotion” by regulated drug and medical device manufacturers.  We were skeptical at the time that all we would get is “still more agency bobbing and weaving.”

Then two years with zilch – save more Agency First Amendment losses in off-label promotion cases.  Then industry gets sufficiently frustrated by FDA inaction on off-label communication issues that it starts to take matters into its own hands.

So, a month later, we finally hear from the FDA again.

Finally, some action?

Don’t bet on it.

On August 31, 2016, a notice appeared in the Federal Register entitled “Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products; Public Hearing; Request for Comments.”

Wonderful.  More talk, and the FDA kicks the can further down the road.  Once again the Agency refuses to recognizes the constitutional bind in which it finds itself.  Indeed, the term “First Amendment” doesn’t appear anywhere – not even once – in the notice.  Nor does the FDA so much as utter the phrase “off-label.”  Except for citations, the FDA uniformly uses the more pejorative term “unapproved.”

If not the First Amendment, then, what do we have?Continue Reading More Talk – No Action – From FDA on Off-Label “Communication”

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Earlier this month the FDA issued a draft guidance entitled “Deciding When to Submit a 510(k) for a Change to an Existing Device.” It’s long, and anyone interested in reviewing the whole thing can download it from the FDA’s website here.  Our interest in this draft guidance, as product liability litigators defending FDA-regulated products, is primarily due to the Agency’s numerous statements about when changes to the design and warnings of 510(k) medical device obligates their manufacturers to resubmit their products for additional FDA clearance prior to marketing.

As we’ve already discussed in much more detail in our September, 2015 “In Case of Good Judge, Break Glass” post, if a product change requires prior FDA review and assent, then that change cannot be mandated by common law tort actions.  The Supreme Court stated in PLIVA v. Mensing, 564 U.S. 604 (2011), “The question for ‘impossibility’ [preemption] is whether the private party could independently do under federal law what state law requires of it.” Id. at 620.  The new FDA draft guidance is all about when product changes to 510(k) devices require prior submission and Agency clearance:

This guidance, when finalized, will aid manufacturers of medical devices subject to premarket notification requirements who intend to modify a 510(k)-cleared device or a preamendments device subject to 510(k) (also referred to together as “existing devices”) during the process of deciding whether the modification exceeds the regulatory threshold of 21 C.F.R. §807.81(a)(3) for submission and clearance of a new 510(k).

Draft Guidance at 3 (“Scope”) (emphasis added).

Initially, we remind everyone that this document is both a “guidance” and a “draft.” It is subject to comment and is not final.  Even when final it has no legally binding effect.  But the guidance does interpret legally binding regulations that, as we discussed in our “Break Glass” post, mandate prior FDA review and clearance of changes to 510(k) devices.  The guidance is useful in that it provides a more comprehensive explication of the regulations, and thus more useful understanding of when a requirement for prior FDA submission of a device change gives rise to implied impossibility preemption under Mensing, Mutual Pharmaceutical Co. v. Bartlett, 133 S. Ct. 2466 (2013), and Wyeth v. Levine, 555 U.S. 555 (2009).

Here are the principles that we think are most important to that determination.Continue Reading New FDA Draft Guidance Helps Define the Scope of §510(k) Medical Device Preemption

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We have been waiting, literally for years, for the FDA to revise, clarify, update, or simply pay attention to, its off-label promotion regulatory position in light of repeated governmental First Amendment losses in Sorrell v. IMS Health Inc., 564 U.S. 552 (2011); Thompson v. Western States Medical Center, 535 U.S. 357 (2002); United States v. Caronia, 703 F.3d 149 (2d Cir. 2012); and Amarin Pharma, Inc. v. FDA, 119 F. Supp.3d 196 (S.D.N.Y. 2015), to name the most notable.  The FDA has promised action on a number of occasions, but has never delivered.  This stonewalling has even caused the Pharmaceutical Research & Manufacturers of America (“PhRMA”) to force the issue by filing amicus curiae briefs in litigation, as we discussed here a couple of years ago.

The longstanding disconnect remains. What the FDA purports to prohibit, and what the First Amendment actually allows, in terms of truthful communications by regulated manufacturers about off-label uses are two very different things.  So PhRMA, joined this time by the Biotechnology Innovation Organization (“BIO”), is charging once more unto the breach, this time with its own industry-practice “principles” concerning off-label communications.  Here’s a link to the document itself, which is called “Principles on Responsible Sharing of Truthful & Non-Misleading Information about Medicines with Health Care Professionals and Payers.”  That’s a mouthful, so we’ll just call it “Industry Principles” in this post.

Essentially, these industry organizations are drawing a line in the FDA’s regulatory sand – telling the Agency, and their own members, that they will fill the gap caused by administrative dithering themselves. Notably, since PhRMA has already shown its willingness to litigate First Amendment issues against the FDA, we would not be surprised to see these guidelines form the basis of industry’s First Amendment position in future court challenges.

The Principles’ introduction first states the reason off-label communication is needed: “Scientific knowledge and new findings go far beyond . . . clinical trials, often are outside the scope of [FDA] parameters . . ., and often outdate the FDA-approved labeling.”  Industry Principles, at 1.  The introduction then explains why the industry cares so much.  “Biopharmaceutical companies are uniquely positioned to help health care professionals achieve the best outcomes for patients, because companies can provide timely, accurate, and comprehensive information about both approved and unapproved uses of [their] medications.” Id. Finally, it states what the industry is doing about it from this day forward.

These Principles are intended to form the basis for defining new and clear regulatory standards governing responsible, truthful and non-misleading communications to inform health care professionals about the safe and effective use of medicines.

Id. In other words, in default of FDA action, industry will set its own standards for off-label communications (including those that the FDA calls “promotion”), and will defend them in whatever fora are necessary, including in court.Continue Reading Off-Label Marketing – Industry Groups Step into the Breach

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We ran across a Ninth Circuit decision last week that, while non-precedential, made interesting rulings. See Fisher v. Monster Beverage Corp., 2016 U.S. App. Lexis 12608 (9th Cir. July 8, 2016). It was a class-action filed under California’s trio of plaintiffs-lawyer-attracting statutes, the Consumer Legal Remedies Act (CLRA), the False Advertising Laws (FAL) and the Unfair Competition Law (UCL). While the court allowed portions of these class action claims to move forward under these incredibly plaintiff-friendly statutes, its ruling on off-label promotion and failure to warn claims may be helpful in drug and device product liability litigation.

The three named plaintiffs alleged that the defendant manufacturers made all sorts of misrepresentations about the safety of its products, certain Monster energy drinks. Only one named plaintiff made an off-label claim. But he couldn’t get out of the gate with it. He claimed that the defendants’ marketing of its energy drinks targeted kids. Id. at *2. He claimed to have seen this alleged marketing and to have come away believing that the Monster energy drinks were safe—yet, according to him in his lawsuit, they were not. These allegations may or may not have been true. But they didn’t matter. He failed to allege that he ever relied on this alleged off-label marketing. With no injury caused by a misrepresentation, he lacked standing: “That is not a sufficient allegation of injury-in-fact to support standing.” Id. at *3 (citing Kwikset Corp. v. Superior Court, 246 P.3d 877, 890 (Cal. 2011)). Accordingly, the Ninth Circuit upheld the trial court’s dismissal of this off-label claim with prejudice. Id. at *3, 8.Continue Reading The Ninth Circuit Issues Helpful Decision Addressing Standing and Preemption

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Not that our readers are dying for a glimpse behind the curtain into the making of the sausage (and mixed metaphors) of the blog, but we do try to first figure out what decisions may be blogworthy before we start writing up the posts each week. We cannot say how blogworthiness relates to spongeworthiness, but we do know that the former involves asking a few questions, one of which is “is this just the same old same old?” In other words, even if the decision comes from a product liability case with a drug or device and addresses something that we think matters, we will not write about it if it adds nothing more than being another decision like we have seen many times before. Maybe it will be added to some cheat sheet or other compilation post, but it will not be worthy of its own post on this illustrious blog. (So illustrious are we that have noticed other blogs trying to rip off our name in the hopes that they will confuse search engines into directing traffic their way.)

When Levine came out with its misreading of the CBE regulation and novel “clear evidence” standard for impossibility preemption, we certainly did not think it would become so commonplace for prescription drug manufacturers—branded, in particular, although the liability of generics was not much of a concern then—to win warnings claims based on preemption. We are not yet there, but we can envisage a day where wins like in Seufert v. Merck Sharp & Dohme Corp., No. 13cv2928, 2016 WL 3369512 (S.D. Cal. May 11, 2016), just end up in our handy-dandy Levine cheat sheet.  For now, Seufert is still blogworthy.

Here are the basic facts. Plaintiffs sued over allegedly inadequate (absent) warnings on a purported risk of pancreatic cancer with two anti-diabetes drugs—the same compound is in each, with one adding metformin—within a class of drugs called incretin mimetics or incretin-based therapies. There are a number of approved drugs in this class, including one with its active ingredient derived from Gila monster venom. The two at issue were approved in 2009 and 2010 and there has been some degree of attention by FDA to a proposed risk of pancreatic cancer since they came on the market. It is not clear if plaintiffs contended that there was pre-marketing evidence of a pancreatic cancer risk specific to these two drugs, but we assume they did not have much if anything. In 2009, FDA reviewed adverse event data for the class of drugs and concluded “a causal association . . . is indeterminate as this time.” In 2013, FDA issued a “Drug Safety Communication” stating that it was analyzing the issue of pancreatitis and pancreatic cancer with the class of drugs, but that “it had not reached a new conclusion regarding whether incretin mimetics cause pancreatic cancer, and advised health care professionals to continue following the prescribing recommendations in the drug labeling”—which did not mention pancreatic cancer. Based on the plaintiffs’ case numbers, it looks like this Communication started them suing.

Continue Reading Another Prescription Drug Warnings Preemption Decision

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We blogged a couple of years ago about the beginnings of what has become a wave of state “Right to Try laws” – laws that purport to give terminal patients with no other medical options the right to seek investigational drugs for their conditions from manufacturers who have yet to obtain full FDA approval.  Mostly, these laws are motivated by the unwieldy nature of the FDA’s “compassionate use” regulations, which are directed at the same problems.  Given that these laws originated with a “states’ rights group” called the Goldwater Institute, we strongly suspect that a second motive of gratuitously poking the FDA in the eye was also at work.

Whatever their provenance, we were deeply skeptical of their practicality. Three large obstacles loomed.  Number one:

For one thing, there’s the FDA. States can pass all the laws they want, but unless the FDA gives its okay to programs more expansive than its compassionate use (“expanded access”) program, nothing’s going to happen.

Number two:

The reason, as is the case for so many things these days, is the threat of liability. . . . You won’t induce a manufacturer to participate in a voluntary program by painting a target on its back.

Number three:

There’s no upside. These statutes are for use by very ill people, and if (as is unfortunately likely) the statutory participant died, then there’s an adverse event that must be reported to the FDA.  Companies investigate drugs in the hope of obtaining approval.  Adverse events definitely don’t help get approval.

Indeed, despite a couple dozen Right to Try statutes enacted over the last few years, we are unaware of even a single instance in which anybody successfully obtained treatment with an investigational drug under any of these state laws.Continue Reading Developments in Compassionate Use and Right To Try Laws

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There is a lawyer we worked with at another firm who had a standard move, kind of the way that Jerry Seinfeld had a standard “move” – and, come to think of it, with a similar intention. (“The Move” shows up in “Fusilli Jerry,” the 107th episode of Seinfeld.)   In the face or fear of a hostile action against our client, this lawyer would file a declaratory judgment action in a friendly federal court.  The concept, of course, was to seize the initiative and do some forum-shopping.  Sometimes the action would be preemptive and sometimes it would be reactive. One would think that the timing would make a difference.  But as today’s case, Monster Beverage Corp., v. Herrera, 2016 U.S. App. LEXIS 9012 (9th Cir. May 17, 2016), demonstrates, that ain’t necessarily so.  We discussed the Monster case a couple of days after Labor Day in 2013, when Monster survived an attack on its preemptive preemption position.  Here it is just a couple of days after Memorial Day in 2016, and the Ninth Circuit has ended the case on grounds of Younger abstention and the Anti-Injunction Act.  That’s a long passage of time.  The judicial process, especially the appellate phase (doubly so in the Ninth Circuit), can take a while. What happened in the interim?

First, please enjoy this reminder of what the Monster case was about.   The San Francisco City Attorney wrote a letter to Monster informing it of an investigation into whether Monster’s marketing of its energy drinks was deceptive and bad in various other ways.  Needless to say, the City Attorney’s beef was really with the federal regulatory regime that already governed what Monster could and could not say about its products.  But San Francisco has been known to try to conduct its own foreign policy, so why should federal regulations stand in the way of its persistent effort to impose a nanny-state on its benighted citizens?   Monster filed a preemptive declaratory judgment action in C.D. Cal. (good idea to drag the San Francisco City Attorney down to SoCal), seeking to shut down the investigation because it was preempted by federal law.  Then the San Francisco City Attorney filed a complaint in San Francisco Superior Court, which Monster removed to federal court on grounds of federal question (preemption again), which the federal court remanded after rejecting the preemption argument. For those of you keeping score at home, that means there was a federal case in Dodger-land and a state case in Giant-land.

The San Francisco (honestly, by this point we are tired of writing the city name out in full, but Boranian warned us that we’d be jeered if we abbreviated the city’s name in any way) City Attorney, as is the case with all Bay Area denizens forced to contemplate anything south of Big Sur, must have seen the C.D. Cal. case as a vast annoyance.  That was certainly the idea behind Monster’s maneuver.  Not surprisingly, then, the City Attorney filed a motion to dismiss the declaratory judgment action in C.D. Cal., arguing that the preemption argument stood no chance. The federal court denied that motion to dismiss.  That is the ruling we applauded back in September 2013.Continue Reading San Francisco vs. The Monster (aka Federal Regulation)

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On May 18, the FDA extended the comment period for its proposed generic drug labeling rule until April 2017 – that is, until after the next presidential election.  We believe that, for all practical purposes, this means that the proposed rule is dead.  Here’s why we think that.

As we have maintained from the beginning, the statute, which requires generic labeling to be the “same” as innovator labeling, simply does not support the FDA proposal to allow CBE labeling changes that would result in generic labeling that is not the “same.”  The FDA can do a lot of things, but it can’t do that – the opposite of what its organic statute specifically requires.  The generic drug industry knows this, too, and from day one has vowed an administrative challenge to any rule that violates statutorily-mandated sameness.

As we have also maintained almost from the beginning, the FDA’s proposed rule has been driven by the desire of the political FDA leadership (who broke the rules regarding impartial communication with outside groups) to overturn the generic preemption decisions, PLIVA v. Mensing, 131 S. Ct. 2567 (2011), and Mutual Pharmaceutical Co. v. Bartlett, 133 S. Ct. 2466 (2013).  They are doing this as affirmative political payback to satisfy the plaintiffs’ trial bar, for whom they broke the aforesaid rules.  The plaintiffs’ trial bar have, of course, been major political supporters of the current administration, and as long as they tell the FDA’s political leadership to jump, during this administration the response will be “how high.”Continue Reading Stick a Fork in It – FDA Anti-Generic Drug Preemption Proposal Postponed Until After the Presidential Election

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Another guest post today, this one by Reed Smith’s Matt Jacobson and Kevin Madagan on the draft guidance document released earlier this week by the FDA. With the 3D printing of medical devices at the forefront of the burgeoning additive manufacturing revolution − and inevitably to become the target, eventually, of product liability litigation – anything the FDA does to move the ball forward (or not) is of great interest.

As always, our guest blogger deserves all the credit (and any blame) for what follows. Take it away Matt.

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The blog is not a stranger to 3D printing, the cooler and slang term for the additive manufacturing process. See here, here, here, and here.

The U.S. Food and Drug Administration (FDA) is not a stranger to 3D printing either. It has already approved more than 80 medical devices and one prescription drug that are produced by 3D printing techniques. It also held a public workshop to obtain information and input about 3D printing issues on October 8 and 9, 2014. FDA brought together technical 3D printing expertise from various industries and sectors to help the agency develop an evaluation process for future submissions of medical devices resulting from additive manufacturing techniques. After the workshop, FDA was silent on 3D printing, well that is, until last Tuesday, when it released a draft guidance for Technical Considerations for Additive Manufactured Devices.

Although the FDA workshop was almost a year-and-a-half ago, it was not for nothing, as the draft guidance is based on the feedback from the workshop. According to FDA, the draft guidance is a “leap-frog” guidance to share FDA’s “initial thoughts regarding technologies that are likely to be of public health importance early in product development.” While the draft guidance is not meant to be a comprehensive document to address all regulatory requirements, it highlights the technical considerations and recommendations for design, manufacturing, and testing of medical devices that include at least one fabrication step using additive manufacturing.

FDA is careful to warn that the guidance does not apply to any devices that use bioprinting − incorporating biological, cellular, or tissue-based products into the additive manufacturing process.Continue Reading Guest Post – Highlights of FDA Draft Guidance on 3D Printing

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Bexis’ Book

FDA-regulated products now account for an estimated one-fifth of overall economic activity in the U.S. They have also been the focus of a litigation explosion. This timely guide covers all aspects of litigation involving drugs, medical devices, vaccines and other FDA-regulated prescription products.
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