At times, we have given a glimpse into the sausage making that goes into our production of posts on recent interesting cases and developments.  Part of the process involves standing searches for “published” (including by the electronic services) decisions from trial courts and appellate courts.  Sometimes, the trial court decisions are unpublished but interesting, and the appellate decisions are published but not too interesting.  When we saw the Sixth Circuit decision in Agee v. Alphatec Spine, Inc., — Fed. Appx. –, 2018 WL 1020078 (6th Cir. Feb. 22, 2018), on one of our standing searches, it was not interesting enough to merit a post.  A short per curiam decision noted how awful plaintiffs’ complaint was and how they had waived their position on preemption by mixing up express preemption with the implied preemption raised by the defendant’s motion to dismiss.  We were feeling sleuthy, however, so we tracked down the district court’s decision from a year ago.  It has a nice discussion of Buckman, and will now be published, so we are going to discuss it.

Agee v. Alphatec Spine, Inc., No. 1:15-cv-750, 2017 WL 5706002 (S.D. Ohio. Mar. 27, 2017), reads like the sort of case brought when the plaintiffs are looking for someone on whom to pin liability in the absence of a claim against the most logical defendant.  The plaintiffs claimed that a surgeon used defendant’s product in connect with unnecessary spinal surgeries without proper informed consent, but the surgeon fled the country with criminal charges pending.  So, the plaintiffs asserted various product liability claims against the manufacturers of the product, PureGen.  Usually, we would state clearly what type of product is at issue, but neither decision really says, other than to say the defendants are medical device companies and the product was used to stimulate bone growth.  We did a little looking and saw that PureGen is an “osteoprogenitor cell allograft” derived from donated adult stem cells.  We also saw that there was some history with FDA over whether this was a biologic, requiring approval of a Biologics License Application, or a device that might go through the 510(k) pathway.  In any event, plaintiffs seemed to claim defendants should be liable for their injuries—it was unclear that there were any physical injuries—solely because PureGen “had never been approved by FDA for use in the spine.”  Defendants moved to dismiss.

We will skip over the TwIqbal part of this—although there are nice statements and the interesting fact that some of the plaintiffs were suing in the same court with contrary allegations about another product—and the some of the details of Ohio law to get to the Buckman part.  After reiterating the Buckman standard and the cases explaining that a court is to look at the asserted claims to see if a violation of the FDCA is a critical element, the court did just that, providing something of a roadmap on what is preempted under Buckman.  The claim for defective manufacturing alleged that the failure to obtain FDA approval made the product produce injury.  (That is not close to a manufacturing defect claim under Ohio law, which has codified the claim under ORC 2307.74.)  The design defect claim was identical (and similarly off-target from ORC 2307.75).  The warning defect claim was also predicated on lack of approval of the product, but not even that the warning misrepresented the regulatory status.  The misrepresentation claim was predicated on a representation to plaintiffs and their doctors that the product was approved or concealing from them that it was not.  A similar claim for nonconformance with representation (under ORC 2307.77) was slightly less clear, in that it referenced “representations made by defendants concerning the product and/or with applicable federal requirements.”

The court’s analysis of these claims was clear and quotable:

Each of the above-quoted claims is clearly dependent upon the FDCA to a degree that the claims would not exist but for the statute. It may or may not be the case that the promotion and distribution of PureGen for use in the surgeries references in the complaint was in violation of the FDCA and relevant FDA regulations.  However, if that is the case, it is the sole responsibility and privilege of the federal government, and not private plaintiffs, to bring a suit to enforce those violations.

Well-reasoned. And dispositive.  And now affirmed on appeal.

Having worked in the federal government, we are familiar with how important Department of Justice Guidance Policy memoranda can be.  They set priorities, outline criteria for acceptable guilty pleas and sentencing factors, and can make a huge difference in terms of who gets indicted or sued for what, when, and under which circumstances.  These DOJ guidances are seldom secret.  They can make quite a splash and set in motion a series of CLE conferences, complete with client glad-handing, Statements of the Obvious, and rubber chicken lunches. 


Now that we work on drug and device law, we are familiar with how important Food and Drug Administration Guidances can be.  They can address all sorts of things, such as off-label communications, social media, 510(k) submissions, cybersecurity, and 3D printing, just to name a few.  They, too, inevitably prompt a series of CLE circuses.  We have also become familiar with the propensity for plaintiff lawyers to hire FDA ‘experts’ who skillfully turn to the jury at just the right moment, break out in a wise and world-weary grin, and spin a tale of how the corporate malefactor broke the law.  It is, frankly, a mystery to us why some judges permit these travelling pseudoexperts to instruct the jury on the law,  and it is even worse when the experts’ legal opinions are not close to being legally sound.  For example, think of cases where an expert pretend-ruefully lays out a company’s purported violation of some FDA guidance (a violation, by the way, that the FDA itself has not decried), that is not even an actual violation of law.  What we have in such cases is a faux negligence per se theory – call it negligence per say so.


We’re now more than a month past Christmas, but the federal government seems to be handing out swell presents to the drug and device defense bar.  We wrote earlier this week about the Pharmaceutical Information Exchange Act, which is pending in the House of Representatives and which would introduce a rare note of sanity into the controversy over off-label communications.  A couple of weeks ago we praised the FDA’s decision to postpone implementation of its execrable “intended use” rule.  Today, we have the good fortune to report on the DOJ’s January 25, 2018 announcement that “Guidance documents cannot create binding requirements that do not already exist by statute or regulation.”  This remarkably refreshing policy flows from the Attorney General’s November 16, 2017 Guidance Policy, which stated that government guidances, which are not subject to the notice-and-comment rulemaking process, cannot bind the public.  The Attorney General in November 2017 was talking about DOJ guidances, but last week’s announcement makes clear that the same principles “should guide Department litigators in determining the legal relevance of other agencies’ guidance documents in affirmative civil enforcement.”  Thus, going forward, DOJ “litigators may not use noncompliance with guidance documents as a basis for proving violations of applicable law” in civil enforcement cases.  To the extent that guidances offer a useful paraphrase from existing statutes or regulations, they might be relevant.  To the extent that a defendant read a specific guidance, that fact could conceivably establish knowledge of a legal mandate that can be traced to a statute or regulation.  But the government cannot “treat a party’s noncompliance with an agency guidance document as presumptively or conclusively establishing that the party violated the applicable statute or regulation.”


At first blush, this new guidance will have immediate and profound effects on actions brought by the government against health care companies under the False Claims Act.  Too many of those actions are premised on no actual false statement and no actual violation of a statute or regulation.  Instead, these FCA cases have been permitted to go forward and exercise their in terrorem effect based on some vague violation of vague FDA guidances.  Even if not vague, an FDA guidance has no real legal effect.  The DOJ’s recognition of what guidances are and, more importantly, what they are not, should have the effect of cabining FCA actions in some reasonable and predictable fashion.  (If you think we are leaping to an unwarranted conclusion about what looks to us like the government’s concern about overreaching FCA cases, consider the fact that on January 10, 2018 – shortly before the policy guidance that inspired this post – the government published another policy memorandum, and that memorandum set out the factors that government attorneys should take into account in deciding whether the government should dismiss unmeritorious qui tam lawsuits.  QED.)  Since January 25, some defendants in qui tam cases have already filed motions based on the new DOJ policy.  If you represent a qui tam defendant, and if the complaint cites an alleged violation of an FDA policy, you might want to file a motion.  


What about civil cases brought by private plaintiffs?  The DOJ closed its January 25 announcement of the new policy by stating that “it is not intended to, does not, and may not be relied upon to, create any rights, substantive or procedural, enforceable at law by any party in any matter civil or criminal.”  That is all fine and good and is a typical  of careful draftsmanship.  But why wouldn’t the DOJ announcement strengthen an argument that we have already made (here, for example) that FDA guidances are only what they say they are – guidances – and are not laws or regulations?  Such guidances  have no legal effect on defendants, certainly do not establish negligence per se, and should not be in the bag of tricks of some plaintiff FDA expert who seeks to invade the province of both jury and judge.  Maybe a court will not consider the DOJ’s guidance to be binding, but wouldn’t it be fine if the court at least took the guidance as a worthy source of … guidance?    




As we demonstrated in a post back in 2013, FDA compliance evidence generally − and the fact of a medical device’s clearance as “substantially equivalent” in safety and effectiveness to a predicate device under §510k of the Medical Device Amendments (now 21 U.S.C. §360c(f)(1)(A)) specifically – had for decades been admissible evidence in product liability litigation involving FDA-regulated drugs and devices.  In 2013 we found a half dozen §510k cases directly on point. Block v. Woo Young Medical Co., 937 F. Supp.2d 1028, 1047 (D. Minn. 2013); Placencia v. I-Flow Corp., 2012 WL 5877624, at *6 (D. Ariz. Nov. 20, 2012); Musgrave v. Breg, Inc., 2011 WL 4620767 (S.D. Ohio Oct. 3, 2011); Pritchett v. I-Flow Corp., 2012 WL 1340384, at *5 (D. Colo. Apr. 18, 2012); Miller v. Stryker Instruments, 2012 WL 1718825, at *9 (D. Ariz. Mar. 29, 2012); In re Guidant Corp. Implantable Defibrillators Products Liability Litigation, 2007 WL 1964337, at *7 (D. Minn. June 29, 2007); Corrigan v. Methodist Hospital, 874 F. Supp. 657, 658 (E.D. Pa. 1995); Strum v. Depuy Orthopaedics, Inc., 2013 WL 3184765, at *1 (Ill. Cir. March 8, 2013).

Then, in the Mesh litigation, rulings began to change the law on the premise that, because the United States Supreme Court in Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996), had held that §510k clearance was not preemptive – that is, not entitling a defendant to judgment as a matter of law – it was not even relevant in product liability litigation.  This argument turned on taking a phrase from Lohr out of context:  “[T]he 510(k) process is focused on equivalence, not safety” (id. at 493) and applying it in the evidence context.  As we had pointed out, so doing was contrary to the Supreme Court’s Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341 (2001), decision holding that §510(k) clearance was intended “to ensure . . . that medical devices are reasonably safe and effective.” Id. at 349-50.  Our more recent blogposts have pointed out:  (1) that the FDA now considers §510k clearance to involve considerations of safety and effectiveness, and that (for a variety of reasons) the continued viability of Lohr itself is open to question.

Nonetheless, defendants in mesh litigation have largely been deprived of well-established FDA compliance evidence, and based on the capacious abuse of discretion standard applicable to evidentiary decisions at trial, such rulings have been upheld on appeal. See Eghnayem v. Boston Scientific Corp., 873 F.3d 1304, 1317-18 (11th Cir. 2017) (discussed here); In re C.R. Bard, Inc., MDL. No. 2187, Pelvic Repair Systems Products Liability Litigation, 810 F.3d 913, 921-22 (4th Cir. 2016) (discussed here) (“Cisson”); but see Winebarger v. Boston Scientific Corp., 2015 WL 5567578, at *7 (W.D.N.C. Sept. 22, 2015) (rejecting MDL rulings and admitting §510k clearance evidence in mesh case).

Yesterday, however another MDL judge considered the admissibility of §510k evidence, and held it admissible, flatly rejecting the Mesh decisions.  See In re Bard IVC Filters Products Liability Litigation, 2018 WL 582542 (D. Ariz. Jan. 29, 2018).  In IVC Filters, Judge David Campbell allowed the defendant’s “FDA defense,” ruling that the jury should be allowed to hear about §510k devices’ FDA pedigree.  Id. at *2.  Such evidence was doubly relevant under relevant state law:

  • “Georgia courts have adopted a risk-utility analysis for design defect claims. . . . One of the many factors a jury may consider in its reasonableness determination is the manufacturer’s compliance with federal regulations.” Id. at *2 (citation omitted).
  • “The evidence is also relevant to Plaintiff’s punitive damages claim. Under Georgia law, . . . [c]ompliance with federal regulations is not sufficient to preclude an award of punitive damages, but it is probative.” Id.

Coincidentally, Cisson also purported to interpret Georgia law, but reached a diametrically opposite conclusion.

IVC Filters rejected the false equivalence between preemption and relevance, and Mesh courts’ misapplication of Lohr:

Plaintiffs note, correctly, that the 510(k) process focuses on device equivalence, not device safety.  [Lohr citation omitted]  But this does not render evidence of the 510(k) process irrelevant to the reasonableness of [defendant’s] conduct.  The FDA grants 510(k) clearance only where the device “is as safe and effective as a [predicate device] and does not raise different questions of safety and efficacy than the predicate device.” Safe Medical Devices Act of 1990, Pub. L. No. 101-629, § 12(a)(1)(A)(ii).  The 510(k) process may not speak directly to the applicable standard of care . . ., but it does have probative value in the determination of this action.

Id. at *2 (citation omitted).  See also Id. at *3 n.2 (a preemption decision does “not address[] any evidentiary issue” and even as to preemption “the 510(k) process can in some circumstances preempt state law claims”) (citations omitted).

The excuses given for exclusion in Cisson, the jury giving clearance undue weight and a possible “mini-trial” regarding compliance, could “be adequately addressed without excluding relevant evidence to the detriment of Defendants.”  Id. at *3.  Reasonable “time limits” for each side’s evidence would prevent FDA issues from devolving into any “mini-trial.”  Id. at *4.  On the merits:

Both sides, through appropriate expert testimony or other admissible evidence, will be permitted to tell the jury about the role of the FDA in its oversight of medical device manufacturers, the regulatory clearance process for devices such as IVC filters, and [defendant’s] participation in the 510(k) process and its compliance (or lack thereof) with that process.

Id.  “[A]ny potential confusion” did not require exclusion, but only “a limiting instruction regarding the nature of the 510(k) process.”  Id. Indeed, IVC Filters correctly observed that the issue of jury confusion more likely cuts the other way – in favor of admission of FDA evidence:

[T]he absence of any evidence regarding the 510(k) process would run the risk of confusing the jury as well.  Many of the relevant events in this case occurred in the context of FDA 510(k) review, and much of the evidence is best understood in that context. Attempting to remove any references to the FDA from the trial would risk creating a misleading, incomplete, and confusing picture for the jury.

Id.  “[I]f the evidence was half-baked, containing some references to the FDA but not explaining what role the FDA played with respect to the [IVC] filters, the jury would be left to speculate about the FDA’s involvement and conclusions.”  Id.

Until IVC Filters, we had feared that a single mass tort, under a discretionary standard of review and with the unwillingness of appellate courts to require MDL do-overs, could tilt the evidentiary playing field towards what IVC Filters cogently described as “a misleading, incomplete, and confusing picture for the jury” that excluded §510k clearance evidence that previously been admissible almost as a matter of course.  Now our side has a clearly articulated and compelling opposing view to argue.

Perhaps you have heard that elections have consequences. That is true not only for high-profile issues that hog the headlines on CNN and Fox News, but it is also true for drug and device litigation regulation. Such drug and device regulation can be just as important, if not considerably more important, than whatever current political claptrap is getting all the bandwidth.  Drug and device availability and innovation actually affects people’s lives regularly and profoundly. Despite the typical claims of plaintiff lawyers at trial, the FDA is not a paper tiger.  The FDA’s actions and attitudes have a huge impact on the industry.  Those attitudes and actions can oscillate with election results. For example, in 2016, the FDA issued 15 warning letters to drug and device manufacturers regarding alleged false or misleading advertising. 2017 saw only three such warning letters and one untitled letter.  Change is in the air.  We did not see any coverage this weekend of the FDA’s January 12, 2018 statement “on FDA decision to seek additional time to reassess rule that would have changed longstanding practices for how the agency determined the ‘intended use’ of medical products.”  Take a look at the FDA’s announcement here:  If you are a completist, here is the full proposal of delay from the Federal Register:  Whatever else you might think about the Trump vs. Obama administrations, this rethink is an example of the new FDA leadership doing the right thing.

The background is a bit byzantine.  In the waning days of the Obama administration, on January 9, 2017, the FDA issued a Final Rule on “Clarification of When Products Made or Derived from Tobacco are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding ‘Intended Uses.’” That “clarification” was both a trick and a double-cross.  The tobacco features were a distraction from the FDA’s desperate attempt to save its constitutionally-suspect enterprise of clamping down on communications about off-label use of drugs or devices.  As we have described several times before, the FDA’s power to punish off-label promotion rests on a regulatory two-step, whereby off-label promotions are said to prove an indicated use not included in the label and, thus, not accompanied by adequate directions for use – making the product misbranded. Got that? The regulations supporting this tortured logic have been around since the 1950s, but a recent series of court decisions invoking the First Amendment called into question the FDA’s interpretation of “intended use” and its efforts to shut down truthful medical-science communications about potential benefits from off-label use.  In a 2015 proposed rule, the FDA proposed striking the language from the regulations permitting the FDA to consider a manufacturer’s mere knowledge of actual use as evidence of intended use. Good news, right? We thought so.  But not so fast. The FDA’s January 9, 2017 proposal reversed course, retained knowledge of off-label use as evidence of intended use, clarified that any relevant source of evidence, whether circumstantial or direct could demonstrate intended use, and ultimately invoked the dreaded “totality of the evidence” standard.  A constitutionally frail regulatory regime looked like it was about to become even worse – even more vague, over broad, and chilling.

We bemoaned this ugly turn of events, as did many other legal commentators.  Not to take undue credit, but we suspect that the eruption of the legal blogosphere on this issue had a beneficial result.  The incoming Trump administration placed a brief hold on new regulations, and then delayed the “intended use” regulation to March 19, 2018 so that comments could be received and considered.  Did comments pour in?  Yes they did.  Fifteen comments came in.  Two addressed the tobacco issues.  (That portion of the regulation will go forward.)  Thirteen criticized the new broadening of the types of evidence that could be considered in determining intended use.  One of those comments was written by PhRMA.  We summarized that excellent, persuasive comment here.  Read as a whole (or, if you prefer, the totality of the circumstances), the comments made a strong case that the proposed final rule violated the First Amendment, was so vague as to implicate due process, interfered with the practice of medicine, departed from existing statutes, cases, regulations, and past practices, and would have negative health implications.  You all spoke up, and the FDA listened. The bottom line is that the FDA is now proposing to “delay until further notice” the portions of the final rule amending the FDA’s existing regulations describing the types of evidence that may be considered in determining a medical product’s intended uses.  The FDA will receive comments on this proposal through February 5, 2018.  If you haven’t spoken up on this very important issue, speak up now.  How many times in your life and career can you take a position that actually makes a difference, and that both saves lives and free speech?

We sometimes spend time on this blog grousing.  Not this time.  Well done, FDA. Well done, all of you who contributed to the debate.

A (relatively) long time ago in a state not so far away, the Michigan Legislature enacted the Michigan Product Liability Act.  It contained a provision providing the manufacturers of FDA-approved drugs with immunity from product liability absent the application of two narrow exceptions.  A challenge to the constitutionality of the provision soon followed and the Michigan Supreme Court, in Taylor v. Smithkline Beecham Corp., 658 N.W.2d 127 (Mich. 2003), basically said the legislature can enact a law like that and the immunity on drug manufacturers was as broad as it seemed.  (This guest post provides a nice history.)  Other decisions followed, like Garcia v. Wyeth-Ayerst Labs., 385 F.3d 961 (6th Cir. 2004), and Desiano v. Warner-Lambert & Co., 467 F.3d 85, 98 (2d Cir. 2006), aff’d by equally divided court, 552 U.S. 440 (2008), coming down on opposite sides of the issue of whether the first exception—the defendant “before the event that allegedly caused the injury . . . intentionally withholds from or misrepresents to [FDA] information concerning the drug that is required to be submitted” under the FDCA that would have prevented original or continued approval—runs into Buckman preemption.  What also followed was that Michiganders who wanted to sue over alleged drug started to go elsewhere.  (Not to galaxies several parsecs—a unit of distance, not time—away, but just to other states.)  They did so because they hoped that the immunity in § 600.2946(5) would not follow them.

We have called this phenomenon the Michigan diaspora, and, while the dispersal of the Michigan litigation tourists is merely temporary, their cases do keep popping up in some likely spots.  Just last month, we discussed how West Virginia state courts have applied Michigan law to the claims of Michiganders hoping to find more plaintiff-friendly law.  We have also discussed how the claims of Michiganians claiming gynecomastia from Risperdal have fared in the Philadelphia Court of Common Pleas, a jurisdiction that has seen plenty of action in that particular litigation.  We praised the court’s application of the Michigan statute to bar the claims.  The plaintiffs in that case appealed to the Superior Court of Pennsylvania, which has reversed more than a few defense rulings we have liked.  Instead In re Risperdal Litig., __ A.3d __, 2017 WL 5712521 (Pa. Super. Nov. 28, 2017), respected the force of the Michigan Legislature’s clear enactment and affirmed.

On appeal, the plaintiffs agreed that Michigan law applied, but argued that the statute provided no protection where the use was off-label.  When the plaintiffs (actually all but one of them) were prescribed the drug it had been approved but did not yet have an indication for use in juveniles, which they were at the time.  The statute, however, hinged on whether “the drug was approved for safety and efficacy,” not whether the particular indication had been approved.  Federal courts had followed “the plain language of the statute” and found off-label use was irrelevant to the application of immunity as long as the drug was approved.  2017 WL 5712521, **5-6.  “Thus, we conclude that as long s a drug has received approval, and its label is compliant with FDA regulations, the MPLA applies to bar any product liability claim, despite the drug’s indicated uses.” Id. at *6.

Next, plaintiffs argued that they had enough evidence to raise a genuine issue as to the statutory exception based on a fraud on the FDA.  Defendants claimed that any attempt to meet the exception would be preempted because the FDA had never found such a fraud.  The Superior Court did not take the opportunity to add to either side of the preemption ledger because plaintiffs did not have the evidence they needed anyway. Id. at *7.  The statute did not just require any fraud on FDA, but a withholding of information such that its proper submission would have meant “the drug would not have been approved” or FDA “would have withdrawn approval for the drug.”  Plaintiffs argued that their evidence of purported fraud was relevant to the approval of the additional indication for juvenile use, but they never contended that the drug would not have been approved or would have been withdrawn.  “[T]he proof of fraud a plaintiff is required to present in order to receive the benefit of the fraud exception must relate to the initial FDA approval.” Id. at *8.  Given that FDA had denied a citizen’s petition in 2014 that requested the drug be withdrawn, it was clear that any purported fraud related to the application to add the juvenile use indication almost a decade earlier was insufficient to trigger the exception. Id. We all know Yoda famously said “Do or do not.  There is no try.”  Here, plaintiffs tried and tried again, but they did not get around the statutory immunity despite their sojourn to Pennsylvania.


This guest post is by Reed Smith‘s Matthew Jacobson.  It discusses the FDA’s recent guidance on the hot topic of 3D printing as a manufacturing practice for regulated drugs and medical devices, but not biologics (at least not yet).  As always with our guest posts the author is 100% responsible for the content.


A lot has happened over the past 19 months, some good, some bad, and some just unbelievable. To name a few, and without sounding like a remake of We Didn’t’ Start the Fire, a total solar eclipse, a new human organ was discovered, Brexit, another royal engagement, the Patriots had the largest comeback in Super Bowl history, fourteen top-level people have “left” the presidential administration (not counting the entire Obama administration), Tim Tam’s became available in the U.S., and Bexis and I wrote the most comprehensive law review article to date on the product liability implications of 3D printing.

And as we prepare to head into 2018, the U.S. Food and Drug Administration (FDA) gave us another headline releasing its guidance for Technical Considerations for Additive Manufactured Medical Devices and issuing a statement from FDA Commissioner Scott Gottlieb M.D. on a “new era of 3D printing of medical products.”  For those daily readers, you may remember that we first reported on the guidance when it was in its draft form in May 2016—19 months ago. In that time, FDA has been evaluating comments and feedback provided by entities in the 3D printing industry. The final guidance is, as you may expect, substantively similar to its draft form. As we see it, that is good news, that the new administration’s approach on 3D printing of medical devices is the same as the old—which is rare these days.

The FDA Commissioner says the agency has reviewed more than 100 medical devices and one drug that are currently on the market, which are being manufactured by 3D printers.  He goes on to say that the “FDA is now preparing for a significant wave of new technologies” and that the FDA is “working to provide a more comprehensive regulatory pathway that keeps pace with those advances, and helps facilitate efficient access to safe and effective innovations that are based on these technologies.”  That regulatory framework will need to adjust how “existing laws and regulations that govern device manufacturing [apply] to non-traditional manufacturers like medical facilities and academic institutions that create 3D-printed personalized devices for specific patients they are treating”—in other words, point of treatment device fabrication.  The FDA is also researching the technology itself, has its own 3D printing labs and is providing opportunities for “innovative approaches to pharmaceutical product design or manufacturing, including additive manufacturing of pharmaceuticals.”  In fact, according to the statement “[m]ore than a dozen pharmaceutical manufacturers have formally or informally been in contact with [the FDA’s Center for Drug Evaluation and Research] regarding the use of 3D printing to manufacture drugs.”

The guidance, according to the FDA, is intended to provide FDA’s thoughts on 3D printing and is meant to evolve as the technology grows.  As was its draft version, it is still split up into two categories of considerations: 1) design and manufacturing and 2) device testing.  Both sections overlap in substance, and the device testing section in particular provides strong, detailed recommendations for what a device manufacturer should include in a premarket submission for a device that uses additive manufacturing as a manufacturing technique.

Some noteworthy additions to the draft guidance (we are not repeating what we said then) that us non-technical folks noticed in the latest guidance are:

    • The final guidance adds that patient-matched devices (devices that are based on or “matched” to a specific patient’s anatomy, usually based on medical imaging data) are especially vulnerable to file conversion errors because “anatomic curves are typically geometrically or mathematically complex, which can create difficulties when calculating conversions.”
    • The guidance also adds a section on cybersecurity and privacy related to protecting personally identifiable information and protected health information, which can be an issue for patient-matched devices.
    • Establishing control limits to make sure that a product meets all predetermined requirements when it is “printed.”
    • Pointing out that use of workflow that automates one or more software steps should be considered.
    • Adding to the “Material Controls” section materials of animal origin and composite materials

For the most part it appears the guidance’s changes, some of which we noted above, focused on the different types of 3D printers that are available and each printer’s unique characteristics, which may vary from brand to brand and with the type of material used. The guidance also seems to focus more on providing examples rather than trying to be all inclusive, which will allow for the technology to develop, without the need for the guidance to be updated.

We have been waiting a while for this final guidance to be released. Unfortunately, we may have to wait even longer for the FDA to release a guidance on the truly novel medical devices, which are 3D printed with biomaterials, such as stem-cells.  Dr. Gottlieb says that the FDA “envision[s] that burn patients in the near future will be treated with their own new skin cells that are 3D printed directly onto their burn wounds” and “the potential for this same technology to eventually be used to develop replacement organs.”  However, based on the timing of the FDA’s past communications with 3D printing, it may be longer than 19 months this time. Who knows, by then we may be dealing with the FDA’s position on 3D printing under the Rock’s presidency.

This post is from the non-Reed Smith side of the blog.

Do as I say, not as I do. A crutch used by parents worldwide to justify their own bad habits while trying to ensure their children don’t repeat them. Technically, it’s being a hypocrite. Sure, parents should strive to set an example through behavior. But frankly, sometimes we’ll settle for hypocritical. Well, a federal court in Massachusetts just said the same applies to the FDA. We’ll explain.

A group of plaintiffs brought a putative class action against a group of pharmaceutical companies alleging that their prescription eye drops were intentionally designed to dispense more liquid than the human eye is capable of absorbing. Gustavesen v. Alcon Laboratories, Inc., — F. Supp.3d –, 2017 WL 4374384, at *1 (D. Mass. Sep. 29, 2017). Plaintiffs allege that therefore, medication is wasted and they are required to more frequently re-fill their prescriptions than is necessary to the financial benefit of the defendants. Id. Plaintiffs sought recovery under various states consumer protection statutes as well as for unjust enrichment and “money had and received.” Id. at *2. Defendants filed a motion to dismiss alleging multiple reasons why plaintiffs’ claims fail as a matter of law. The court opted not to consider anything beyond preemption finding that that precluded all of the alleged claims.

To begin its analysis, the court did a nice walkthrough of what it calls the Supreme Court’s trilogy of impossibility preemption decisions. First, of course, is Wyeth v. Levine, where the Court said failure to warn claims are not preempted because of a manufacturer’s ability to make certain labeling changes without prior approval of the FDA, unless there is clear evidence that the FDA would have rejected the change. Id. at *4. Next up was Pliva v. Mensing. A generic drug is required to have the same labeling as the brand-name version. Therefore, a generic drug manufacturer does not have the same ability to change its label as the brand manufacturer. Id. at *5. And, finally came Mutual Pharmaceutical v. Bartlett. Here the Supreme Court said that plaintiff’s design defect claim was preempted because any attempt by the manufacturer to change the design of the drug would have resulted in a new, unapproved drug that the manufacturer would have been prohibited from marketing. Id. Moreover, the court rejected plaintiff’s claim that defendant could have simply stopped selling the drug – defendant is not required to “cease acting altogether to avoid liability.” Id. Put the three cases together and you have the following framework. If FDA regulations allow a manufacturer to make a change without prior approval, no preemption unless clear evidence change would have been rejected. If “a party cannot satisfy a state law without first obtaining the discretionary approval of a federal agency, the state law is preempted.” Id. at *5.

Against that legal backdrop plaintiff’s argued that they had 2 theories of liability that were not preempted. First, they alleged that defendants could have changed the eye dropper tip to deliver a smaller drop and that this would have been prohibited by the FDA. Id. at *7. There are 3 categories of changes for approved drugs – major, moderate, and minor. Moderate changes are the type of labeling change discussed in Wyeth that do not need pre-approval. Major changes on the other hand must be submitted to the FDA before the drug is distributed. Id. To determine whether something is a major change, the court looked to FDA regulations and FDA guidances interpreting those regulations. In this case, that would include a guidance that for sterile products, like eye drops, any change to the container closure system is a major change. Id. The opinion goes more in depth on these regulations – but the conclusion is what is important. Plaintiff’s proposed design change would be a major change that would require prior FDA approval – therefore, the claim is preempted.

Now we come to the “do as I say” part. In response to defendants’ argument that the design change suggested by plaintiffs would be a major change, plaintiffs cited to three occasions where they claim the FDA allowed a container change without prior approval. As to 2 of the events, the documents relied on by plaintiffs don’t support their position. Id. at *9. As to the third:

At most, this is evidence of the FDA’s failure to follow strictly its own guidance. It does not cast doubt on the plain language of the 2004 Guidance deeming all changes to the size or shape of a sterile product’s container to be major changes requiring preapproval.

Id. Also:

[P]laintiffs cite no law indicating that particular actions by an agency—as opposed to the agency’s official position—are relevant to interpreting a regulation. In fact, the Supreme Court has rejected invitations to apply the standards an agency follows in practice rather than the standards it officially promulgates.

Id. In sum, do as the FDA says, not as it does. The regulations and official guidances control over individualized instances where the FDA chose not to apply them. The court can’t be guided by internal decision-making processes in one-off situations.

Having found that a post-approval change of the eye drop container would have been a major change and therefore claims premised on that preempted, the court examined whether plaintiff could sustain a claim for a “pre-approval” design change. Meaning, could/should defendants have design the dropper tips differently before seeking FDA approval. This question was decided in defendants’ favor by the Sixth Circuit in Yates v. Ortho-McNeil-Janssen Pharm, Inc., 808 F.3d 281 (6th Cir. 2015) (see post here). After examining some other district court authority cited by plaintiffs, the court in this case decided Yates was more consistent with Mensing and Bartlett.

Going back to the trilogy – if a manufacturer can’t satisfy its state law duties without FDA permission, the claim is preempted. Well, it’s not possible for a manufacturer to market a re-designed drug because that drug “would require its own NDA to be marketed in interstate commerce.” Id. at *11. So, arguing that the defendant should have changed the design pre-approval runs straight into the same impossibility preemption as a post-approval design change. Moreover, arguing that the defendant should never have sold the product is virtually the same thing as arguing that it should have stopped selling the product – the theory rejected in Bartlett.

A nice preemption decision, especially the use of Mensing and Bartlett outside the generic realm.

Implied Preemption.  Off-label promotion. TwIqbal.  They make up a core of our posts, yet we never seem to tire of them.  Maybe our readers, especially interlopers from the other side of the v., tire of reading about them, but we can often find a wrinkle in a case that merits our huzzahs or inspires a rant.  Today’s case falls into the praiseworthy category, as the court dismissed a complaint predicated on violations of the FDCA in spite of sympathetic allegations that might have carried the day with some other courts. Markland v. Insys Therapeutics, Inc., — F. Supp. 3d –, 2017 WL 4102300 (M.D. Fla. Sept. 15, 2017), involved the alleged death of a patient as a result of respiratory distress from the defendant’s sublingual spray prescription painkiller drug, which she had started the day before.  Rather than offer the typical product liability claims under Florida law, perhaps because the labeling had extensive warnings on respiratory distress, plaintiff asserted only a claim for negligent marketing.  Calling it “negligent marketing” does not really identify what duty was allegedly breached, whether state law recognizes a claim for such a breach, and such a claim would be preempted.  The allegedly actionable conduct in Markland was promoting the drug for off-label use, like the chronic back pain of plaintiff’s decedent, as opposed to the approved indication for breakthrough pain with cancer.  While we do not know the merits, there were many allegations about off-label promotion, which seem to tie to the conduct at issue in well-publicized federal and state investigations.

Defendants moved to dismiss on various grounds, the most relevant of which (for our purposes) were that there was no claim under Florida law for this conduct and it would be impliedly preempted under Buckman anyway.  These had been hot topics recently in some Florida state and federal cases we have discussed, like Mink (here and here) and Wolicki-Gables, but those dealt with PMA devices and the additional issue of express preemption.  Here, with a prescription drug marketed under an NDA approval, there is no express preemption to navigate, but the plaintiff still had to walk a narrow path to state a claim that would not be impliedly preempted.  As we have said before, we think the appropriate order of analysis here would be the determine if there was a cognizable state law claim asserted and then determine if it was preempted, but the Markland court did not separate out its analysis.  It also did not weigh in on whether the allegations here were of truthful off-label promotion that might implicate First Amendment protection.  Instead, it assumed that the off-label promotion alleged violated the FDCA’s prohibition on misbranding.  2017 WL 4102300, *6 & n.4.

The court could take this approach because the plaintiff’s claim was so squarely focused on alleged violations of the FDCA.  Since Buckman, plaintiffs tend to be a bit cagier in making it look like their claims were not predicated on violations of the FDCA or fraud on the FDA.  The Markland plaintiff, however, labeled the defendant’s alleged conduct as violating the FDCA, “federal law,” and “requirements imposed by the FDA regarding the condition that this drug should be utilized to treat cancer patients with breakthrough cancer pain.” Id. at *9.  “Hence, [the claim], while framed in the language of negligence, appears to derive from [defendant’s] alleged off-label promotion of [the drug]” and “the very concepts of off-label use and off-label marketing are born out of the FDCA.” Id.   This was well phrased, as was the later statement that “it is only because of the existence of the FDCA’s restrictions on off-label marketing that Mr. Markland claims [defendant’s] actions were improper or otherwise violated a duty.” Id.

This is the recipe for implied preemption under Buckman.  It also means there is no negligence claim under Florida law, “which bars plaintiffs from using state negligence actions to seek recovery for FDCA violations.” Id. at 10 (citing negligence per se cases).  Of course, Buckman recognized that the FDCA does not provide for a private right of action, and preempts claims with FDCA violations as “critical element[s],” which should prevent such piggybacking.  So, plaintiff’s case was done and could not be revived by amending the complaint.  In other words, there was no need for a second and third strike before judgment could be entered.  This was so despite the Court’s expression of compassion:

The Court does not question for a moment the grievous nature of Carolyn Markland’s death, nor the deep sadness Mr. Markland must face on a daily basis as a result of his wife’s untimely passing. Nonetheless, the Court must act within the bounds of the law.

Id. at *11.  This a good lesson, especially for courts sitting in diversity, that the law should not be expanded to allow for recovery by sympathetic who cannot make their case under accepted tort theories.


Back in 2013, Ramirez v. Medtronic Inc., 961 F. Supp.2d 977 (D. Ariz. 2013), made it to #9 on our worst cases of the year list – which is pretty good (actually, pretty bad) for a trial court decision.  Purporting to apply Stengel v. Medtronic Inc., 704 F.3d 1224, 1228-31 (9th Cir. 2013) (en banc) – an even worse case (#2 on the same list) – Ramirez held, basically, that allegations of off-label use/promotion eliminated preemption altogether, even for Class III pre-market approved products.

When the device is not being used in the manner the FDA pre-approved and the manufacturer is actually promoting such use, there is no law or policy basis on which to pre-empt the application of state law designed to provide that protection.

Id. at 991.

Fortunately, Ramirez has proven to be an outlier, with numerous decisions, several even in the same District of Arizona, considering and rejecting Ramirez’s meat axe approach to preemption.  See Angeles v. Medtronic, Inc., 863 N.W.2d 404, 413 (Minn. App. 2015) (“Ramirez has been rejected by most federal district courts that have reviewed this issue”); Coleman v. Medtronic, Inc., 167 Cal. Rptr.3d 300, 314 (App. 2014) (“[w]e find the approach taken in Ramirez unpersuasive”), app. dismissed & opinion ordered published, 331 P.3d 178 (Cal. 2014); McCormick v. Medtronic, Inc., 101 A.3d 467, 486 n.13 (Md. App. 2014) (“Ramirez has been almost universally rejected”); Shuker v. Smith & Nephew PLC, 211 F. Supp.3d 695, 701 n.5 (E.D. Pa. 2016) (“this Court considered but declined to follow” Ramirez); Jones v. Medtronic, 89 F. Supp.3d 1035, 1051 (D. Ariz. 2015) (“this Court joins the majority of courts in rejecting Ramirez”); Thorn v. Medtronic Sofamor Danek, USA, Inc., 81 F. Supp.3d 619, 627 (W.D. Mich. 2015) (Ramirez “has been rejected by numerous district courts”); Wright v. Medtronic, Inc., 81 F. Supp.3d 600, 610-11 (W.D. Mich. 2015) (same as Thorn); Byrnes v. Small, 60 F. Supp.3d 1289, 1299 (M.D. Fla. 2015) (“the Court disagrees with the reasoning in Ramirez”); Shuker v. Smith & Nephew PLC, 2015 WL 1475368, at *10 (E.D. Pa. March 31, 2015) (“the Ramirez decision has been widely criticized by other district courts reviewing allegations of off-label promotion of PMA-approved devices”); Arvizu v. Medtronic Inc., 41 F. Supp.3d 783, 790. Ariz. 2014) (“the Court finds the reasoning of [decisions rejecting Ramirez] to be more persuasive”); Martin v. Medtronic, Inc., 32 F.Supp.3d 1026, 1036 (D. Ariz. 2014) (“join[ing] the majority of other courts which have rejected Ramirez to the extent that it holds that the preemption analysis does not apply to claims based on off-label promotion”); Beavers-Gabriel v. Medtronic, Inc., 15 F.Supp.3d 1021, 1035 (D. Haw. 2014) (“however, Ramirez has been rejected − for good reason − by numerous courts”); Schouest v. Medtronic, Inc., 13 F. Supp.3d 692, 700 (S.D. Tex. 2014) (Ramirez “read Riegel too narrowly”); Scovil v. Medtronic, Inc., 995 F.Supp.2d 1082, 1096, n.12 (D. Ariz. 2014) (“respectfully disagree[ing] with [the] ruling in Ramirez”); Arthur v. Medtronic, Inc., 2014 WL 3894365, at *5 (E.D. Mo. Aug. 11, 2014) (Ramirez’s “reasoning has been rejected by several courts”); Brady v. Medtronic, Inc., 2014 WL 1377830, at *4 (S.D. Fla. April 8, 2014) (applying “the traditional preemption analysis to [plaintiff’s] off-label marketing claims” contrary to Ramirez); Houston v. Medtronic, Inc., 2014 WL 1364455, at *5 (C.D. Cal. April 2, 2014) (“the Ramirez holding is not consistent with the text of §360k(a), the scope of federal requirements imposed on Class III devices, or Ninth Circuit precedent”); Stephens v. Teva Pharmaceuticals, U.S.A., Inc., 2013 WL 12149265, at *4 (N.D. Ala. Oct. 31, 2013) (Ramirez is “inapposite” and “of no assistance” to plaintiff).

Now the FDA has jumped into the fray, and its view of preemption and allegations of off-label use is no more favorable to Ramirez – and to plaintiffs trying to oust preemption of PMA devices – than these judicial decisions.  The sharpest-eyed of our readers may have noticed the two citations above to relatively recent district court opinions in a case called Shuker.  It so happens that Shuker is currently on appeal, and following oral argument, the Third Circuit Court of Appeals invited the FDA to provide its views on the preemption question.  Last week, the FDA did so.  You can find a copy of the FDA’s amicus brief in Shuker here.

Apparently, in Shuker the plaintiffs allege that the defendant was somehow responsible for Mr. Shuker’s surgeon creating a hybrid hip prosthesis construct that included some components of a Class III PMA system and others belonging to a Class II system cleared under the FDA’s “substantial equivalence” (“§510k”) process.  FDA amicus br. at 3-4.  This hybrid construct was an off-label use.  Id. at 4.  Exactly how the individual Class III and Class II component used in the construct are alleged to have contributed to the plaintiffs’ injuries appears totally unclear, but we do know that the Class III component was later recalled.  Id.

That causes the plaintiffs a big problem. On the one hand, they would love to smear the defendant with the recall, and wave it around like a bloody shirt.  On the other hand, the Class III component – because it was PMA approved – brings the powerful preemption defense into play.  So plaintiffs invoked off-label use to try to have their cake and eat it too.

The FDA did not agree.

Rather, the agency advised that “[t]he district court correctly held that §360k(a) applies to a component of a premarket-approved device even when the component is put to an unapproved use.”  Id. at 6.  First, the FDA clarified the status of device “components” under the FDCA::

The component of the premarket-approved device is itself a “device” under the FDCA, and FDA’s approval imposes device-specific requirements with respect to that component.  The manufacturer generally may not deviate from those requirements without prior approval from FDA, regardless of the uses to which the component may be put by third parties.  Because the component is subject to device-specific federal requirements, §360k(a) expressly preempts any state requirements “with respect to” the component that are “different from, or in addition to,” those device-specific federal requirements.

Id. (emphasis added).  Thus, all components of a pre-market approved device system are themselves PMA devices for preemption purposes, and that status doesn’t change because of off-label use.

With respect to other components, if they are “not subject to device-specific federal requirements,” then they are “outside the scope of §360k(a),” and claims limited to them “are not expressly preempted.”  Id.  To the extent those components are §510k cleared, they “generally” (but apparently not necessarily always) not entitled to preemption.  Id. at 7.

The fact that off-label use (which the FDA calls “unapproved use” in its letter) is possible for a device does not allow – let alone allow the common law to require – a manufacturer of a PMA device to change its design or labeling (read: warnings) or manufacturing processes without prior FDA approval:

As a general matter, the device-specific requirements that attach to a medical device through premarket approval apply even when the device is put to an unapproved use.  Once a device receives premarket approval, the FDCA generally prohibits the manufacturer from making, without FDA permission, changes that would affect the safety or effectiveness of the device. . . .  Those requirements apply irrespective of the use to which the device is ultimately put.  The possibility that a physician may choose to use a device for an unapproved purpose − something the FDCA contemplates, see 21 U.S.C. §396 − does not authorize a manufacturer to vary the design, the manufacture, or (with limited exceptions) the labeling of the device in anticipation of that use.  Such variation would violate federal law.

Id. (emphasis added).  Thus, the general rule that alterations that significantly affect a device’s “safety or effectiveness” require FDA preapproval exists “irrespective” of off-label use.

The FDA observed that “most” courts recognize that PMA imposes “requirements” – and therefore preemption – on medical devices “even when the device is put to an unapproved [off-label] use.”  Id. at 7-8 (citations omitted).  The agency also recognized something this Blog has repeatedly pointed out, that Riegel v. Medtronic, Inc., 552 U.S. 312 (2008), the case in which the United States Supreme Court recognized broad PMA preemption, itself involved an off-label use.  FDA amicus br. at 8 (“Riegel itself involved an off-label use of the device in question”).  The FDA advised that, “[s]imply put, once a device receives premarket approval, it remains subject to federal requirements for purposes of §360k(a) regardless of how it is used.”  Id.

Nor did it matter that the off-label use was only of a “component” rather than of an entire device system. The PMA “requirements” applicable to that component as a “device” “apply equally when third parties put the [component] to an unapproved use with components of another device” even if the other device is §510(k) cleared. Id.

Defendants generally may not deviate from the requirements imposed through premarket approval regardless of how the liner is used.  Claims touching on those requirements therefore implicate §360k(a) even when a component of an approved device is put to the type of unapproved use here at issue.


Preemption of such claims is not only the law, but is good policy:

The conclusion that §360k(a) applies in this context also makes sense as a matter of policy.  Congress entrusted FDA with determining which device designs should be approved for marketing, as well as how approved devices should be labeled to provide medical professionals with appropriate safety information.  Section 360k(a) acknowledges FDA’s judgment in this respect and prevents States from pursuing competing judgments that would impose different or additional requirements on approved devices.  That provision also protects manufacturers that have complied with detailed federal requirements from being subjected to liability under state law for doing what federal law required.  Manufacturers must generally adhere to the specifications established through premarket approval, even if healthcare practitioners subsequently exercise their judgment and employ the device for an unapproved use.

Id. at 9 (emphasis added).  The FDA recognized the precedent cited at the beginning of this post – those cases criticizing Ramirez – as being “consistent” with the Agency’s preemption analysis.  Id.

Thus, the FDA advised that plaintiffs can’t go after the recalled PMA component, but are limited to claims concerning the non-PMA components of the construct only.  Id. at 10 (“§360k(a) requires a court to parse a plaintiff’s claims to determine whether the state-law requirements that underlie them are indeed directed at the premarket-approved component”).  “[A] component that did not receive premarket approval and is not otherwise subject to device-specific federal requirements” is not subject to express preemption under §360k(a).  The FDA “t[oo]k[] no position” on whether such claims were actually alleged, although they conceivably could be.  Id. at 12.

As for implied preemption, the FDA noted that “defendants did not raise implied preemption in their dispositive motions below, nor . . . in their original appellate briefing.” FDA amicus br. at 13.  Assuming that implied preemption was nonetheless at issue, the Agency confirmed:

[T]he existence of an express-preemption provision such as §360k(a) does not ordinarily alter the normal operation of implied-preemption principles.  Accordingly, state-law medical-device claims that are not expressly preempted remain subject to challenge on implied preemption grounds

Id. (citing Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341, 352 (2001)).

The FDA then briefly explored what many courts (but not the FDA) have called the “narrow gap” between express and implied preemption in PMA cases.  Implied preemption impacts two types of claims that are not expressly preempted:  (1) “parallel” claims; and (2) claims concerning “generally applicable federal requirements that do not trigger the operation of §360(k).”  FDA amicus br. at 14.  Purportedly parallel claims are preempted when they “have features that intrude impermissibly on the operation or enforcement of the FDCA, as where they represent an attempt to enforce the federal scheme, rather than asserting independent state-law requirements.”  Id.  As for “generally applicable” claims, “on a case-by-case basis,” “divergent state requirements may stand as an obstacle to the operation or objectives of the federal scheme and may be impliedly preempted on that basis.”  Id.  The FDA did not get any more specific than that as to implied preemption, noting instead that failure to report claims had been dismissed as inadequately pleaded, and therefore avoiding that issue.  Id. at 14 n.7.

What takeaways can we, as defense counsel, extract from the FDA’s filing? How about these:

  • Ramirez was wrongly decided. Off-label use does not affect the applicability of preemption at all. FDA amicus br. at 6-9.
  • PMA preemption applies to PMA components – period.  Id. at 7-10.
  • “[T]he FDCA generally prohibits the manufacturer from making, without FDA permission, changes that would affect the safety or effectiveness of the device.”  Id. at 7. That should help with Mensing/Bartlett preemption.
  • Implied preemption operates independently of express preemption, so that manufacturers of devices not subject express preemption under §360k(a) can still assert implied preemption “on a case-by-case basis.”  Id. at 14.  Also good for Mensing/Bartlett, particularly in the device context.
  • Ostensibly “parallel” claims are preempted where they “intrude impermissibly on the operation or enforcement of the FDCA.”  Id.  The FDA likes Buckman.
  • No state generally bans off-label promotion, only the FDCA, so “promotion” based claims involving off-label use are likely to be impliedly preempted.  In fact, we just saw another one of these the other day.  See Markland v. Insys Therapeutics, Inc., 2017 WL 4102300, at *9 (M.D. Fla. Sept. 15, 2017).
  • The FDA twice carefully qualified its discussion of §510(k) devices, recognizing that express preemption could exist where such a device was “otherwise subject to device-specific federal requirements.”  FDA Amicus br. at 6, 12. Good for limiting Lohr “on a case-by-case” basis.

We were recently asked the question, “are failure to contraindicate claims preempted?”  Our immediate response was, “How could they not be”?  However, it’s not helpful to answer a question with a question, and as with all things preemption, matters are not as simple as they might seem.  Therefore, we thought we’d explore this issue in more depth.

We discussed failure to contraindicate claims several times in the run-up to Wyeth v. Levine, 555 U.S. 555 (2009).  We believed – and still do – that Levine was tried to the jury on a claim that the defendant should have contraindicated the particular use of the drug involved in that case.  It didn’t ultimately turn out that way.  Rather, in Levine, the Supreme Court went through contortions specifically to avoid having to decide a “failure to contraindicate” claim:

[Plaintiff] also offered evidence that the [FDA-approved use] should be contraindicated and that [the drug] should never be administered [that way]. Perhaps for this reason, the dissent incorrectly assumes that the state-law duty at issue is the duty to contraindicate. . . .  But, as the Vermont Supreme Court explained, the jury verdict . . . did not mandate a particular replacement warning, nor did it require contraindicating [the use]. . . .  We therefore need not decide whether a state rule proscribing [the FDA-approved use] would be pre-empted.

555 U.S. at 564-65. Heck, even the plaintiffs’ counsel in Levine conceded that a failure-to-contraindicate “would be preempted” where the FDA “concluded that it should not be” contraindicated.  Levine argument transcript at 32-33; see id. at 39-40.

Levine thus did not allow failure to contraindicate claims – rather it changed the facts of the case to avoid doing that, while still reaching an anti-preemption result.  Pretty obviously, the anti-preemption justices in Levine could not muster a majority that would permit state tort law claims that sought to ban FDA-approved uses.  Compare the result in Levine to the extensive preemption recognized in Riegel v. Medtronic, Inc., 552 U.S. 312 (2008), where the Court did recognize the presence of a contraindicated use.  Id. at 320 (device used in a patient’s “heavily calcified” arteries; “the device’s labeling stated that use was contraindicated for patients with diffuse or calcified stenosis”).  Among Riegel’s preemption holdings was that the plaintiff’s warning claims were preempted.  Id. at 329 (holding “the MDA would pre-empt a jury determination that the FDA-approved labeling for [the device] violated a state common-law requirement for additional warnings”).

The regulatory background for a contraindication is much more stringent than for warnings and other types of labeling. The FDA’s strict prerequisites for contraindications are at 21 C.F.R. §201.57(d). That regulation requires:  (1) a contraindication must relate to a “known hazard” and (2) due to that hazard “the risk of use clearly outweighs any possible benefit.”

Further reflecting that stringency, while the FDA’s changes-being-effected (“CBE”) regulation used to include “contraindications” broadly as something subject to unilateral modification, that’s no longer so.  As discussed in excruciating detail below, the FDA amended the relevant regulation in 2006, and now most contraindications in fact are subject to an express exception in the CBE regulation that requires prior FDA approval.  Thus, the CBE regulation should no longer an obstacle to finding failure to contraindicate claims preempted.  For almost every prescription drug that hasn’t gone generic, arguing that failure to contraindicate claims aren’t preempted on the basis of the CBE regulation is simply bogus, since that regulation is inapplicable.

A failure to contraindicate claim is inherently in conflict with FDA regulatory authority, since it would allow liability based on the defendant’s failure to contraindicate a use that the FDA had looked at and said was okay. Once the FDA says “you can do X,” that regulatory result is in absolute conflict with a state-law cause of action predicated on a theory that “you can’t do X.”  This kind of state-law infringement on FDA powers has been preempted under the FDCA for over 100 years.  See McDermott v. Wisconsin, 228 U.S. 115, 137 (1913) (finding conflict preemption where state law “forb[ade] all labels other than the one it prescribed,” including the FDA-approved label).

So this direct conflict is one preemption argument that applies against a failure to contraindicate claim.  The FDA approves/clears drugs and medical devices for each “intended use.”  21 C.F.R. §§201.128, 801.4804.1.  A failure to contraindicate claim seeks to prohibit an FDA-allowed intended use.  Thus, such claims are really a species of  “stop selling” claim of the sort that the Supreme Court held were impliedly preempted in Mutual Pharmaceutical Co. v. Bartlett, 133 S.Ct. 2466 (2013):

The Court of Appeals reasoned that [defendant] could escape the impossibility of complying with both its federal- and state-law duties by “choos[ing] not to make [sulindac] at all.” We reject this “stop-selling” rationale as incompatible with our pre-emption jurisprudence. Our pre-emption cases presume that an actor seeking to satisfy both his federal- and state-law obligations is not required to cease acting altogether in order to avoid liability.  Indeed, if the option of ceasing to act defeated a claim of impossibility, impossibility pre-emption would be all but meaningless.

Id. at 2477 (citations and quotation marks omitted).  Courts have recognized that disguised stop-selling claims are likewise preempted under Bartlett.  Thus, as we discussed here, in Yates v. Ortho-McNeil Pharmaceuticals, Inc., 808 F.3d 281, 300 (6th Cir. 2015); Utts v. Bristol-Myers Squibb Co., ___ F. Supp.3d ___, 2016 WL 7429449, at *11 (S.D.N.Y. Dec. 23, 2016); and Brazil v. Janssen Research & Development LLC, 196 F. Supp.3d 1351, 1364 (N.D. Ga. 2016), never-start selling claims based on allegations that the defendant should never have submitted the product to the FDA were all held preempted as “stop-selling” claims.

Failure to contraindicate allegations satisfy our rule of thumb for identifying disguised stop-selling claims.  We look at the learned intermediary rule and causation.  Would the claim in question allow the plaintiff to argue that the actions of the “learned intermediary” – the prescribing physician/treating surgeon – are irrelevant to a causation determination because the physician should never have been allowed to prescribe/use the product on the plaintiff in the first place?  If yes, then the claim is a disguised, and preempted, stop-selling claim.  The fraud-on-the-FDA claims in Buckman, the stop-selling claims in Bartlett, the Yates claims that a different design should have been submitted to the FDA in the first place all share this characteristic, as do failure to contraindicate claims.

This is our preferred route to preemption of failure-to-contraindicate claims.  There is simply an inherent conflict between the FDA’s regulatory authority to decide what products/”intended uses” are able to be marketed in the United States and state-law claims that would allow liability for failure to contraindicate a use that the FDA has approved.

There is also a more technical preemption argument – alluded to earlier, when we mentioned the CBE regulation − at least with respect to prescription drugs and biologicals.  As discussed in Levine, 555 U.S. at 568-72, PLIVA, Inc. v. Mensing, 564 U.S. 604, 614-15 (2011), and by us here, the key to implied preemption is what we call the “independence principle.”  As concisely stated in Mensing:

[W]hen a party cannot satisfy its state duties without the Federal Government’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party cannot independently satisfy those state duties for pre-emption purposes.

564 U.S. at 623-24. The branded manufacturer in Levine, but not the generic manufacturer in Mensing, could have revised aspects of its label independently – however temporarily − by using the the FDA’s“changes-being-effected” (“CBE”) process.  Back when plaintiffs in Mensing and Levine alleged that labels should be modified, “[t]he CBE process permit[ted] drug manufacturers to ‘add or strengthen a contraindication, warning, [or] precaution.’”  Mensing, at 614 (citing 21 C.F.R. §314.70(c)(6)(iii)(A) (2006)).

However, neither Levine (2000 injury) nor Mensing (2001 & 2002 injuries) interpreted the current version of the FDA’s CBE regulation.  Effective June 30, 2006 – that regulation was amended by the Physician Labeling Rule (“PLR”) so that 21 C.F.R. §314.70(c)(6)(iii) now reads:

Changes in the labeling, except for changes to the information required in §201.57(a) of this chapter (which must be made pursuant to paragraph (b)(2)(v)(C) of this section), to accomplish any of the following:

FDA, “Requirements on Content and Format of Labeling for Human Prescription Drug & Biological Products, 71 Fed. Reg. 3922, 3997 (Jan. 26, 2006) (reflecting amended language) (emphasis added).  See id. at 3922 (stating effective date).  Exactly this language is in the current version of 21 C.F.R. §314.70(c)(6)(iii) in the United States Code.

That means that the broad applicability of the CBE regulation to “contraindications” alluded to in Mensing and Levine no longer exists.

Since the mid-2006 PLR revision, there has been an express exception to the CBE rule for “changes to information required in” 21 C.F.R. §201.57(a), which is the regulation that requires inclusion of a “Highlights” section to prescription drug labeling.  No “Highlights” section even existed under the format for prescription drug labeling that governed the period of time at issue in Levine or Mensing.

Changes to Highlights information thus cannot be made unilaterally under the CBE regulation.  Rather 21 C.F.R. §314.70(b)(2)(v)(C) applies.  That section concerns “major changes” for which “[a] supplement must be submitted” to the FDA.  Id. §§314.70(b), 314.70(b)(1).  As one might expect, all drug “contraindications” must be included in the Highlights section:

Highlights of prescribing information.  The following information must appear in all prescription drug labeling: . . . (9) Contraindications.  A concise statement of each of the product’s contraindications. . . .

21 C.F.R. §201.57(a)(9) (emphasis added).  Highlights must now be included for any prescription drug approved by the FDA after June 30, 2001.  See 21 C.F.R. §201.56(c) (setting out staggered compliance schedule, completed in 2013, for drugs approved between that date and June 30, 2006, when all new drug applications must contain labeling highlights).

Thus, while the old CBE regulation, considered by the Supreme Court in Levine and Mensing, included “contraindications” generally as types of warnings that could be modified/strengthened unilaterally, now contraindications (and anything else that must be included in PLR Highlights) may not be unilaterally added to the labeling for any drug approved after June 30, 2001.  The Highlights need not present all “Warnings” and “Precautions” contained in the labeling − only a “concise summary of the most clinically significant” safety concerns is required.  21 C.F.R. §201.57(a)(10).  Contraindications, however, are different.  Section 201.57(a)(9) mandates that “each” contraindication be included in the Highlights section for drug labeling.  CFR § 201.57(c)(6).

The FDA discussed the Highlights section and the CBE process further in a 2013 guidance document:

Changes to Highlights through a CBE supplement:  With minor exceptions, changes to Highlights require a prior approval supplement (§§314.70 and 601.12).  If the labeling is already approved in the PLR format and the proposed change(s) qualify for a CBE supplement under §§314.70(c) and 601.12(f), a prior approval supplement is not needed as long as the change does not warrant inclusion in Highlights (e.g., addition of an adverse reaction to the ADVERSE REACTIONS section in the FPI).  If, in the opinion of the applicant, the new information warrants inclusion in Highlights or will be listed under Recent Major Changes in Highlights (i.e., a change to the BOXED WARNING, CONTRAINDICATIONS, OR WARNINGS AND PRECAUTIONS sections), the applicant should notify the appropriate review division about the proposed change to the labeling.  The review division may permit changes to Highlights through a CBE supplement after consideration of the new information.

FDA, Guidance for Industry, Labeling for Human Prescription Drug & Biological Products − Implementing the PLR Content & Format Requirements, 2013 WL 10904638, at *21 (Feb. 2013) (emphasis added).

Putting all this regulatory material together in more easily comprehensible form, the upshot is that failure to contraindicate claims should now be preempted by reason of impossibility under the Mensing/Bartlett “independence principle” for any prescription drug (or biological) approved by the FDA since mid-2001.  Since all contraindications must be included in Highlights, and all changes to Highlights require prior FDA review and approval – either through a Prior Approval Supplement (“PAS”) or, as noted in the above FDA PLR Guidance, through a CBE supplement “after” FDA has consider the new information and permitted the change through a CBE supplement – contraindications can no longer be changed unilaterally via the CBE process.

So far, Highlights haven’t received a lot of attention in preemption cases.  We recently discussed the first case we found on this point, Blackburn v. Shire US, Inc., 2017 WL 1833524 (N.D. Ala. May 8, 2017), which did not involve any allegations concerning contraindications. Blackburn held:

[I]n almost all instances, any change to the Highlights section of an approved drug’s label requires FDA approval. Again, in circumstances such as these, a private party’s claim is only preempted if the drug manufacturer was not able to act independently under federal law to do what state law requires.  That is, preemption exists “when a party cannot satisfy its state duties without the Federal Government’s special permission and assistance.”  [Mensing], 564 U.S. at 623-24.  Such assistance “is dependent on the exercise of judgment by a federal agency,” and as such “that party cannot independently satisfy those state duties for preemption purposes.”  Id. at 624.  Accordingly, when sufficient newly acquired information exists in order to support a label change under the CBE process, as has been plausibly pled here, the claim is not preempted.

However, the same cannot be said with respect to Plaintiff’s assertion that a change to the Highlights section would be permitted here.  Where a private party seeks a label change which requires FDA approval, such as a change to the Highlights section, impossibility preemption exists. . . .  The “impossibility” inquiry turns on a private party’s ability to act independently.  It is of no consequence that the FDA may have allowed a change to the Highlights section of [the drug].  Because Defendants could not have independently changed the Highlights section of [the drug] in order to conform to state law, any argument that begins with the theory that Defendants could (or should) have changed the Highlights section of [the drug’s] label ends in preemption.

Id. at *5-6 (emphasis added).  The court rejected the plaintiff’s attempt to avoid preemption of changes to Highlights by arguing that the defendant could have “sought expedited FDA approval of the Highlights section change or asked the FDA to waive such an approval requirement by submitting a written waiver request to the FDA.” Id. at *6.  The availability of these options doesn’t matter for preemption purposes, since neither allows the defendant to make a change to its label independently, which is what is necessary to avoid preemption under Levine, Mensing, and Bartlett.

Finally, turning away from legal issues, contraindications also work differently in medical practice, where physicians often view them as outright bans.  E.g.Rader v. Smithkline Beecham Corp., 2017 WL 524925, at *5 (Pa. C.P. Feb. 7, 2017) (prescriber testified “if it’s contraindicated, we wouldn’t prescribe it under any circumstances”).  For a physician to proceed in the face of a labeled contraindication invites malpractice claims, perhaps even punitive damages, if anything goes wrong.  Contraindications thus tend to replace, rather than supplement, the usual physician balancing of risks and benefits.

Were juries allowed to impose contraindications that do not meet the FDA’s strict standards, patients and physicians would be deprived of drug and device uses in situations where, from the agency’s perspective, risk does not outweigh benefit.  The dynamics of mass tort litigation only exacerbate matters as a jury-imposed contraindication-based verdict in one state becomes precedent seeking the same effective ban nationwide – particularly as the FDA does not allow product labeling to vary by state.  Thus, particularly pro-plaintiff juries in certain locales would impose Gresham’s Law – with bad common-law decisions driving out what the FDA and the medical profession otherwise view as proper medical practice.  Patients who would benefit from tort-contraindicated uses lose those benefits, even where data reviewed by the FDA show benefits exceeding harm.  That would be the practical effect of allowing plaintiffs to bring, and common-law juries to decide, failure to contraindicate claims.

Thus, not only are failure to contraindicate claims preempted under the rationales discussed above, but as a matter of public policy, such claims should not be recognized in the first place.