Antitrust was our favorite course in law school.  That law school was located in the south side of Chicago, city of big shoulders and bigger minds (Posner, Easterbrook, et al.) who weren’t shy about subjecting antitrust law to flinty-eyed analysis.  It was exciting.  It was logical.  It focused on real world results.  Earlier Chicago School antitrust pioneers included Aaron Director, Ronald Coase, and Robert Bork.  You have probably heard of that last fellow.  His nomination to SCOTUS descended into a partisan circus resulting in his rejection, which was due as much to his beard and his lip-smacking over the SCOTUS case inventory “intellectual feast” as to his actual qualifications for the office.  His nomination also resulted in a new verb used for clobbering SCOTUS nominees: to “Bork” someone, especially someone who has a substantial written record.

 

We would hate to be Borked.

 

Applied correctly (i.e., Chicago-ly), antitrust law looks at how things really work and what really makes sense.  It is, in short, quite different from drug and device product liability law, where the realities of science, medical practice, and warnings are submerged in fanciful morality tales.  So it is with some exhilaration that we take this brief summer vacation away from Fosamax, Bausch, and the latest insane talc verdict to consider an antitrust case, Washington County Heath Care Auth., Inc. v. Baxter Int’l Inc., 2018 U.S. Dist. LEXIS 112064 (N.D. Ill. July 5, 2018).  That case is of interest to us because it turns on the real world realities of regulation and recalls.  Spoiler alert:  FDA regulation is extensive and voluntary recalls are not easy. (Nobody on the blog had anything to do with the case.  The opinions herein are wholly/only ours, not the parties’ or their lawyers’.)  

 

In Washington County Health Care Authority, the plaintiffs claimed that  the two largest producers of intravenous saline products violated the Sherman Antitrust Act by colluding to increase prices by initiating a series of bogus voluntary recalls that depleted the saline inventories of health care facilities throughout the nation.  The defendants filed a motion to dismiss, arguing that this theory is implausible.  They cited Twombly.  We on this blog often cite Twombly, but now we are reminded that Twombly was an antitrust case.  The defendants won their motion to dismiss, because the plaintiff’s theory that the defendants maneuvered their way into voluntary recalls was implausible.   Substitute the word “nutty” for “implausible” and you’d be a little closer to the truth.

 

Why was the plaintiffs’ theory nutty?  At different times, the two defendants issued voluntary recalls of IV saline due to leaks and the presence of particulate matter.  So, as an initial matter, you’ve got to believe that manufacturers would intentionally make up a story that their products were defective.  Who does that?  (As a DDL defense hack, we feel the Washington County Health Care Authority case pulling us through the looking-glass.  We’re used to hearing plaintiffs gripe that our clients should have recalled their products.  Can you spell damned-if-you-do-damned-if-you-don’t?) Further, to make out an antitrust case, there must be evidence that the two manufacturers agreed on this plan.  Was there any actual evidence of this agreement?  There was not.  The plaintiffs identified “parallel behaviors,” but those behaviors “are no more probative of an agreement than of independent self interested conduct.”  Moreover, the behaviors weren’t all that parallel. First, the timing was not quite consistent.  Second, one manufacturer recalled eight times as much product as the other.  Why would one conspirator confer such a benefit on its rival? 

 

There is another problem with the antitrust complaint.  Agreement or no agreement, the complaint contained no allegations suggesting that the reasons the manufacturers provided for the recalls were false.  The complaint did not say there weren’t leaks or there weren’t particulates.  Rather, the complaint characterized the defects as “inconsequential” or “technical,” thus permitting the defendants to engage in the recalls “without significant business or reputational risks.”  That contention is facially implausible, but it is also undercut by the FDA’s classification of the recalls as Class I or II, which are the two most serious recall designations.  A Class I recall occurs when “there is a reasonable probability that the use of, or exposure to, a volatile product will cause serious and adverse health consequences or death.”  21 C.F.R. § 7.3(m)(1).  A Class II recall “is a situation in which use of or exposure to, a violative product may cause temporary or medically reversible adverse health consequences or where  the probability of serious health consequences is remote.”  No rational manufacturer would willingly walk into those categories.  

 

Even more basically, and no matter what category is implicated, voluntary recalls “impose high upfront costs and invite FDA scrutiny of the very instrument of the unlawful agreement.”  FDA considers a removal of a product from the market to be a voluntary recall if it “regards the product as involving a violation that is subject to legal action e.g., seizure.” 21 C.F.R. § 7.46(a).  Thus, the court concluded that a complaint “premised on a theory that the defendants intentionally manufactured a public health crisis by orchestrating  bogus product recalls that would, despite the public health crisis and rigorous regulatory oversight of product recalls, escape the FDA’s attention, lacks facial plausibility.”   And then there is a consideration of the practicalities of recalls.  “Product recalls are expensive and draw attention from regulators, especially in the pharmaceutical industry.”  The recalling company must submit a detailed recall strategy for evaluation by the FDA, must actually implement recall notifications, and must vigilantly monitor the recall and provide periodic updates to the FDA (tracking the number of purchasers notified of the recall and their responses, among other things).  21 C.F.R. § 7.42; 21 C.F.R. § 7.53. None of that is cheap or easy. 

 

Finally, it is hard to say that the non-agreement to cook up an expensive, self-inflicted reputational wound succeeded in raising prices.  The complaint acknowledged that in response to the saline solution shortage, the FDA permitted saline to be imported from foreign manufacturers – “another fact that illustrates the implausibility of the plaintiffs’ theory that the defendants colluded in a manner that convinced their regulator to allow imports from foreign competitors.” 

 

Hurray for the Windy City, where smart professors and smart judges are happy to blow away frail antitrust fables.  Now if only those winds could also clear the terrain of silly drug and device cases.   

 

Researchers at Temple University here in Philly recently published a scientific article, “Learning Impairments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes Biosynthesis: Role of the cdk5 Kinase Pathway,” in the scientific journal Molecular Neurobiology.  That sounds pretty dense, but what the article concludes is that the generic drug zileuton (branded name Zyflo) has been shown – in a transgenic mouse study – to reduce both physical evidence of Alzheimer’s disease, and its mental symptoms.  To wit:

[A]ged tau transgenic mice were randomized to receive zileuton . . . starting at 12 months of age for 16 weeks and then assessed in their functional and pathological phenotype.  Compared with baseline, we observed that untreated tau mice had a worsening of their memory and spatial learning.  By contrast, tau mice treated with zileuton had a reversal of these deficits and behaved in an undistinguishable manner from wild-type mice.

“Learning Impairments” Article, at Abstract (emphasis added).  In lay terms, it might just successfully treat (we hesitate to throw the “c” word around) Alzheimer’s disease.

Nothing else works very well at treating Alzheimer’s disease.

Zileuton/Zyflo has been on the market since 1996, indicated for treatment of asthma, and is thus available for generic production under Hatch-Waxman.

Since this drug has already been FDA approved, it may also be used off-label, right now, to treat Alzheimer’s patients under the therapeutic rationale explained in the “Learning Impairments” article.  With the drug’s basic safety profile already established by FDA approval and twenty-something years of clinical use, the primary issue in any such off-label use is effectiveness – does it actually benefit Alzheimer’s patients – rather than safety.

Let’s assume, for the moment, that zileuton/Zyflo actually has therapeutic value for treating Alzheimer’s in humans.  This is a drug that can be produced generically, so who is going to finance the Phase III human studies necessary to provide the “substantial evidence” that the FDA requires for a label change adding a new indication?  If any generic manufacturer can take a “free ride” on studies sponsored – at great expense – by someone else, then there is not much incentive for anyone to spend that money.  Thus, this extremely consequential new indication may become a regulatory orphan.  Of course, if the drug shows sufficient promise, other sources of funding could become available – third party payers who pay for the medical needs of Alzheimer’s patients, or even the research fund that is supported by the recently issued Alzheimer’s semipostal stamp.

If this off-label use is truly beneficial, then it would (in the absence of any better treatment option) likely become the medical standard of care despite being off-label.  Eventually, the FDA would be forced to engage in some ad hoc, retrospective approach in order to reconcile the label with clinical practice.  That’s how the FDA finally resolved the regulatory conundrum of so-called “pedicle screws,” where regulation fell behind clinical practice – a retrospective study supported the safety and effectiveness of off-label spinal use, but only after manufacturers endured a decade of meritless product liability litigation.  See 63 Fed. Reg. 40025-41 (FDA Jul. 27, 1998).

While further studies are being performed, however, what happens to scientific communication?  This could be (or it could not be – too early to tell for sure) an historic breakthrough in treatment of Alzheimer’s.  If it is, does the FDA continue to prohibit any manufacturer of zileuton/Zyflo from informing the medical community of information on the effectiveness of the off-label treatment, such as optimal dosage and administration practices?  We’ve frequently decried the unconstitutionality of such speaker- and topic-based restrictions on manufacturer scientific communications under the First Amendment.  However, for the most part the FDA’s refusal to conform to current First Amendment norms has flown under the public’s radar, allowing the agency to get away with dilatoriness, and the rest of the government to monetize the FDA’s unconstitutional stance with through “false” claims litigation that isn’t really about falsity.

Alzheimer’s, however, is the elephant in the room.  Without some sort of effective treatment, our health care system cannot indefinitely support the cost of palliative Alzheimer’s care.  Almost everybody knows somebody suffering from dementia, or else someone suffering through the heartbreak of caring for someone with dementia.  The FDA will run into a political and medical buzz saw if its retrograde attitude towards truthful off-label promotion gets in the way of making information about an effective (we hope) treatment for Alzheimer’s available to the public.

And now – but probably not coincidentally – it looks like the FDA is finally getting off the regulatory schneid.  A couple of days ago, the agency issued a “statement” from the commissioner about what was billed as a “new effort” “to advance medical product communications to support drug competition and value-based health care.”  The big news in the statement is rather buried in regulatory-speak, but it is legitimate big news:

Additionally, it’s our [FDA’s] belief that giving companies clear guidelines for providing payors with truthful and non-misleading information about unapproved products and unapproved uses of approved or cleared products will help facilitate communications that can allow payors to provide coverage for these new products and new uses more quickly after FDA approval or clearance.  And our hope is that these communications can also help companies and payors establish pricing structures that benefit patients as well as health plans.

(Emphasis added).  That’s a reference to (among other things) off-label use.  Specifically, the FDA is now approving “truthful and non-misleading” off-label promotion when directed to an audience of third party payors.

The details of this regulatory retreat from Moscow are found in the FDA’s new final guidance, “Drug and Device Manufacturer Communications With Payors, Formulary Committees, & Similar Entities − Questions & Answers, available here.  That’s another mouthful, so we’ll call it the “Off-Label Promotion (OLP) Guidance,” since that’s really what it is.

The FDA is now allowing those who market prescription drugs and medical devices (see id. at 16 explaining the identical treatment of all classes of medical devices) to provide information about off-label uses of these products to “payors, formulary committees, or other similar entities with knowledge and expertise in the area of health care economic analysis.”  OLP Guidance at 1 (footnote omitted)

This audience includes public and private sector payors, formulary committees (e.g., pharmacy and therapeutics committees), drug information centers, technology assessment committees, pharmacy benefit managers, third party administrators, and other multidisciplinary entities that, on behalf of health care organizations, review scientific and/or technology assessments to make drug or device selection or acquisition, formulary management, and/or coverage and reimbursement decisions on a population basis.

OLP Guidance at 5 (footnotes omitted).

That’s the who.

The “what” is just about everything.  The kind of information that regulated drug and device manufacturers can now provide to third-party payors about off-label uses is defined as:

“any analysis (including the clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis) that identifies, measures, or describes the economic consequences, which may be based on the separate or aggregated clinical consequences of the represented health outcomes, of the use of a drug.  Such analysis may be comparative to the use of another drug, to another health care intervention, or to no intervention. . . .  [Off-label promotion] may include comparative analyses of the economic consequences of a drug’s clinical outcomes to alternative options (including the use of another drug) or to no intervention.

[The information] can be presented in a variety of ways that can include, but are not limited to, an evidence dossier, a reprint of a publication from a peer-reviewed journal, a software package comprising a model with a user manual, a budget-impact model, a slide presentation, or a payor brochure.

OLP Guidance at 4-5.

The “when” varies a bit depending on whether what kind of off-label use is at issue.  The FDA has drawn what we believe to be a new distinction between “material differences” from the labeling that “relate[] to an approved indication” and so-called “unapproved indications.”  Id. at 7.  In our experience, the FDA has always considered any variance from labeling limitations to be off-label use.  But now, as to approved indications, “material differences from the FDA-approved labeling (e.g., new or increased risks, different dosing/use regimens, different endpoints, more-limited/targeted patient populations)” are treated differently, and somewhat less stringently.  Id. at 6.  A presentation “should include an accurate overview of the design of the economic analysis, including a statement of the study objectives.”  Id. at 11 (going into considerable detail).

As to promotion of uses involving such “material differences” from labeling, a basis in “competent and reliable scientific evidence” is sufficient.  Id. at 10.  In determining the sufficiency of the scientific basis, the FDA will be deferring to “existing current good research practices for substantiation developed by authoritative bodies.”  Id.  The prior FDA requirements of “substantial evidence” is nowhere mentioned.  It appears to be gone as a restriction on off-label promotion under the OLP Guidance.  Promotion of “material differences” must include a “conspicuous and prominent statement describing” those differences.  Id. at 14.

However, off-label promotion “regarding unapproved products and unapproved uses of approved/cleared products” is also now allowed by the FDA.  Id. at 18-20.  As to this type of what might be considered “true” off-label uses, distribution of the following information to third-party payers is now OK with the FDA:

  • “Product information (e.g., drug class, device description and features).”
  • “Information about the indication(s) sought, such as information from the clinical study protocol(s) about endpoint(s) being studied and the patient population under investigation (e.g., number of subjects enrolled, subject enrollment criteria, subject demographics).”
  • “Anticipated timeline for possible FDA approval/clearance/licensure of the product or of the new use.”
  • “Product pricing information.”
  • “Patient utilization projections (e.g., epidemiological data projection on incidence and prevalence).”
  • “Product-related programs or services (e.g., patient support programs).”
  • “Factual presentations of results from studies, including clinical studies of drugs or devices or bench tests that describe device performance (i.e., no characterizations or conclusions should be made regarding the safety or effectiveness of the unapproved product or the unapproved use).”

Id. at 18-19.

This kind of off-label promotion should be accompanied by a variety of disclaimers and other information to ensure that the off-label nature of the uses involved is understood:

  • “A clear statement that the product or use is not approved/cleared/licensed, and that the safety or effectiveness of the product or use has not been established.”
  • “Information related to the stage of product development” and “whether a marketing application for the product or new use has been submitted to FDA or when such a submission is planned.”
  • “[M]aterial aspects of study design and methodology and . . . material limitations related to the study design, methodology, and results. Firms should also ensure that results are not selectively presented.”
  • “A prominent statement disclosing the indication(s) for which FDA has approved, cleared, or licensed the product and a copy of the most current FDA-required labeling.”

Id. at 19.  Significantly, there is no prerequisite that an FDA application for marketing be either pending or contemplated, although if this is the case, it should be disclosed.

As to off-label promotion of these so-called “unapproved uses” (and also drugs and devices that have not yet received any FDA regulatory OK), the FDA tries to salvage what it can of the justifications it used to advance in opposition to our side’s First Amendment arguments about truthful off-label promotion:

FDA believes that the categories of information . . . are, on the one hand, broad enough to encompass the information that payors may need to make informed coverage and reimbursement decisions and, on the other hand, limited enough to maintain appropriate incentives for firms to conduct robust studies to evaluate the safety and efficacy of unapproved products and unapproved uses of approved/cleared/licensed medical products. . . .  FDA believes that the risk that payors will be misled is relatively low.  Payors are a sophisticated audience with established procedures to carefully consider the full range of relevant evidence about new uses of medical products.

OLP Guidance 21-22.

Finally, the OLP Guidance reminds us that “[f]irms’ communications to other audiences about unapproved products or unapproved uses of approved/cleared/licensed products could raise additional or different considerations and are beyond the scope of this guidance.” Id. at 22.

In conclusion, let’s look at that last point a bit. The OLP Guidance punches another huge hole in the FDA’s previous attempts to ban regulated entities from distributing truthful information about off-label uses to anybody.  As discussed at some length in Greater New Orleans Broadcasting Ass’n, Inc. v. United States, 527 U.S. 173, 192-94 (1999), the number and nature of exceptions to a speech prohibition adversely affect both the prohibition’s rationality and its ability to advance the governmental interest that motivates it.  We fail to see how any constitutionally valid distinction can exist between providing the identical information, with identical disclaimers and limitations, to one “sophisticated” audience (third-party payors) while prohibiting that information’s distribution to another “sophisticated” audience – that being medical doctors that directly prescribe these drugs and devices.

And that’s just within the rubric of commercial speech.  Greater New Orleans also cautioned, “decisions that select among speakers conveying virtually identical messages are in serious tension with the principles undergirding the First Amendment.”  Id. at 194.  We now have Sorrell v. IMS Health, Inc., 564 U.S. 552 (2011), for the proposition that, with respect to pharmaceutical detailing, we’re not just dealing with commercial speech.

Thus, we believe that, as a practical matter, the OLP Guidance effectively dooms any First Amendment defensibility of an FDA ban on the same truthful information being distributed, in the same fashion, to the rest of the medical community beyond third-party payors.  Conversely, to those regulated entities that seek to inform physicians of truthful scientific information about their products, we believe that the OLP Guidance can serve as a roadmap to success in an Amarin Pharma, Inc. v. FDA, 119 F. Supp.3d 196 (S.D.N.Y. 2015), situation by establishing that off-label promotion is “truthful,” “not misleading,” and therefore protected against governmental enforcement activity.  After all, just as third-party payers are sophisticated professionals interested in possible effective treatments for Alzheimer’s disease, so are the doctors directly involved in treating Alzheimer’s patients.

Prescription drug manufacturers are not insurers of injuries sustained while taking their products. Even in the most plaintiff-friendly jurisdictions, there needs to be some fault—whether framed in negligence, strict liability, or something else—and causation between the fault and the injury. It is surely not easy to stomach for someone who sustains such an injury while taking a drug, but sometimes there is no fault even if there is a significant injury related to the use of the drug. If the drug’s manufacturer warned about the risk of plaintiff’s ultimate injury consistent with the available evidence, which it examined and shared with FDA appropriately in connection with approval and after approval, and the prescribing physician(s) gave due consideration to the risk in treating the patient, then the manufacturer did what it was supposed to do and the patient might suppress the urge to sue someone. Often, of course, such patients become plaintiffs and courts are faced with deciding summary judgment in cases with a real injury, related in some way to the use of the drug, but no real claim against the manufacturer. In those situations, the courts often get it wrong and allow some claim to get past summary judgment. Nelson v. Biogen Idec, No. 12-7317 (JMV) (MF), 2018 WL 1960441 (D.N.J. Apr. 25, 2018), got it right. Joe Blute and Yalonda Howze of Mintz Levin, who defended the case and told us about it, deserve some credit for that.

The facts of Nelson do not exactly scream failure to warn, even with the severity of the injury claimed by the plaintiff, who received Tysabri, a prescription medication for his multiple sclerosis. He claimed to have developed progressive multifocal leukoencephalopathy (“PML”), a condition about which the drug’s labeling contained black box warning, multiple other warnings in physician labeling, and warnings in a medication guide that the drug’s Risk Evaluation and Management Strategy (“REMS”) program required the patient acknowledge when receiving the drug through infusion provided by a healthcare provider. With such extensive warnings also comes the expected developed record of interacting with FDA about PML, which we will attempt to summarize. The medication was approved in 2004, but withdrawn because of PML cases the next year. PML results from exposure to the JC virus, which is prevalent in humans but only causes PML in vulnerable patients. Before seeking to bring the drug back to market, the manufacturer conducted FDA-requested research on testing for the JC virus. After taking an advisory committee recommendation, FDA re-approved the drug in 2006 with a slew of robust warnings on PML and a REMS program that essentially documented understanding and/or acceptance of the PML risk at each step of the prescribing chain every time the patient received the drug. The label was updated in August 2008, November 2009, and July 2010 to provide more information on the PML risk. Meanwhile, the manufacturer worked to develop a better assay to detect exposure to the JC virus. After years of research and interaction with FDA, in 2012, a new assay was approved and the label was amended to reference it.

Meanwhile, plaintiff was prescribed the drug for his MS in April 2008 after being advised of the PML risk. Plaintiff moved and continued on the drug when prescribed by two other physicians, each of whom also warned him of the risk of PML. Plaintiff was negative for the JC virus in 2009, but started demonstrating signs of PML in 2010, which was confirmed later that year by brain biopsy. Plaintiff sued and was on the fifth version of his complaint when the court considered summary judgment on plaintiff’s remaining claim for failure to warn under the New Jersey Product Liability Act (along with a Daubert motion that was denied as moot).

The court started its analysis with a discussion of three prior decisions on similar claims with the same drug. We will skip that, partly because we have discussed these cases before.  Because this was under the NJPLA, the first issue was whether the “super-presumption” of the adequacy of the PML warnings would apply given plaintiff’s argument about post-approval compliance. The presumption did not look to be dispositive, as the court noted that the substance of the warnings to both the prescribing physicians and the patient were clear, strong, and effective. Yet, the court found that there was no evidence of “manipulation of the post-market regulatory process,” the basis of the so-called “McDarby exception,” noting the interaction between the manufacturer and FDA on an assay that could be used to detect the JC virus in connection with the use of the drug. (The court also assumed without deciding that the McDarby exception could apply.) In the face of this presumption, plaintiff relied on proposed expert testimony that only indirectly addressed the adequacy of warnings. His expert claimed a better assay could have been developed and approved in time to affect the various physicians’ decision to prescribe the drug to plaintiff. Even if his testimony were admissible and if he took the next step of connecting a new assay to the content of the drug’s label—which he did not and could not as a non-physician—there were still obvious issues with relying on this testimony to establish an inadequate label and proximate cause for failure to warn, including that the prescribing physicians were aware of the PML risk and discussed it with the plaintiff on multiple occasions. Put it all together and there was no evidence to carry a failure to warn claim, with or without a presumption of adequacy

As a bit of overkill, the court went ahead and considered the manufacturer’s preemption defense, which argued that the proposed changes to the drug’s label would have been impossible to make during the relevant time. The prior decisions that we elided above also found impossibility preemption, but they were not decided in the Third Circuit after the Fosamax decision tried to make the application of Levine’s once-novel “clear evidence” standard just a question for juries. Even acknowledging the high standard and the decision in Fosamax (albeit with a recurring, and surely unintentional, misspelling), the court still found “There is clear evidence that FDA would not have approved an earlier change to the Tysabri label or have approved the JC Virus assay.” FDA specifically rejected similar proposals twice in 2010, before approving the assay and corresponding labeling change in 2012 after additional research had been committed. That was pretty clear evidence of impossibility back when plaintiff was taking the drug.

So, the manufacturer won summary judgment thrice over. The co-developer also won because it had no ability to change the label, a useful nugget as innovator liability and other theories to impose liability on other defendants continue to get raised when the logical defendant is not liable. In Nelson, no defendant was liable to an injury that, while unfortunate and serious, was warned of about as thoroughly as is possible with a prescription drug. We would prefer such a case never to have been brought or to have been dismissed for failure to state a claim, but summary judgment is still the right result.

 

This guest post is from Reed Smith‘s Matt Jacobson, who is keeping us up to date with the FDA’s initiatives concerning pharmacogenomics and personalized medicine.  It is 100% his work, as Matt deserves all the credit (and any blame).

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This blog, or at least Bexis and this guest blogger, try to be on the forefront of products liability implications of new technologies. See, e.g., here, here, and here.  So when the FDA issued two guidances on next generation DNA sequencing, we thought we would let you know since this new technology plays an important role in genetic-based personalized medicine, and in turn, prescription medical product liability litigation.

Now for some background.

The Human Genome Project is said to be, at least according to the National Human Genome Research Institute, “one of the great feats of exploration in history.” It was a large collaborative project that mapped out the sequence of essentially the entire human genome.  And, a little less known fact, in addition to the human genome, it mapped out the genomes of brewers’ yeast, the roundworm, and the fruit fly, among other things.  While the project was a huge accomplishment, it was slow—taking over a decade to complete in 2003—and expensive, costing billions of dollars.

Next generation sequencing or “NGS” is a newer technology that allows researchers to sequence DNA quicker and cheaper. Using NGS, an entire human genome can be sequenced within a single day.   This is remarkably faster than the Sanger sequencing technology that was used in the Human Genome Project.   Because NGS is capable of quickly identifying a person’s genome and much cheaper (on average under $1000), it can help physicians and researchers find genetic variants, which will help them personalize medicine to treat an individual’s condition.

Although in genome research NGS has mostly superseded the conventional Sanger sequencing, the U.S. Food and Drug Administration (“FDA”) had yet to issue any final guidances on the new technology. That was until recently.  And the FDA did not release just one guidance, it released two.  Both of which had been published in draft forms previously and submitted for comments.  The joint purpose of the guidances is to streamline the regulatory process for NGS tests.

FDA’s press release said that it released the final guidances “to drive the efficient development of a novel technology that scans a person’s DNA to diagnose genetic diseases, which are usually hereditary, and guide medical treatments.”  The FDA went on to say that “[t]he guidances provide recommendations for designing, developing, and validating tests that use the technology, called next generation sequencing (NGS), and will play an important role in the continued advancement of individualized, genetic-based medicine.”

The first guidance is entitled “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics.”  In the guidance, the FDA states that NGS can help speed up the clinical use of “a variety of diagnostic purposes, including risk prediction, diagnosis, and treatment selection for a disease or condition.”  It provides FDA’s thoughts on whether a publically accessible genetic database “is a source of valid scientific evidence that could support the clinical validity of genetic and genomic-based tests in a premarket submission, regardless of the type of technology for the test.”  The short answer is yes, as long as the database conforms to the FDA’s recommendations.  Those recommendations are split into four categories:  1) database procedures and operations, 2) data quality, 3) variant evaluation and assertions, and 4) professional training and conflicts of interest.  For example, the FDA provides the following assistance as to what a genetic database should contain:

  • the database’s information regarding data sources and standard operating procedures should be publically available
  • clear guidelines on how genetic information is aggregated, curated, and evaluated
  • processes in place related to backing up and preserving the data
  • compliance with all federal laws and regulations, including the Health Insurance Portability and Accountability Act, the Genetic Information Nondiscrimination Act, the Privacy Act, and the Federal Policy for the Protection of Human Subjects
  • privacy protection security measures
  • commonly accepted nomenclature and formats are used
  • metadata should detail numerous types of useful information to assure that linking specific genetic variants to diseases or conditions are accurate
  • each variant evaluation should be performed by at least two qualified and trained professionals to lessen the risk that any single assertion could be incorrectly made
  • types of evidence used for evaluating variants, and their corresponding strengths, should be defined and combined in a protocol

Assuming a database follows the FDA’s recommendations, the FDA then plans to implement a recognition process on a voluntary basis. The FDA hopes that this will help streamline premarket review of genetic and genomic-based tests, including NGS.

The second guidance issued by the FDA is entitled “Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS)–Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases.” This guidance describes FDA’s intent to “create a flexible and adaptive regulatory approach to the oversight” of NGS.  It is directed particularly towards “germline diseases”—a fancy way of denoting medical conditions caused by mutations in the DNA of either egg or sperm cells that result in the genetic error being present in every cell of a offspring’s body.

The NGS guidance is based in part on comments that the FDA received at four of its public workshops held in 2015. FDA states that “[t]his guidance document provides recommendations for designing, developing, and validating NGS-based tests intended to aid clinicians in the diagnosis of symptomatic individuals with suspected germline diseases.”  The FDA also lists numerous categories to which the guidance does not apply.  The FDA spends considerable effort outlining the proper regulatory pathway for a NGS based test.  It then turns to providing recommendations for designing, developing, and validating NGS tests used to diagnose individuals with suspected genetic diseases.  It describes what the FDA will look for in premarket submissions in order to guide those submitting such applications for NGS-based tests.

Personalized medicine is the next frontier. NGS will help speed up the process and the guidances from FDA may help speed up the regulatory part of it.  Certainly, the FDA realizes that its approach to reviewing these innovations needs to keep up with the rapid evolution of the technology.  As FDA commissioner Dr. Scott Gottlieb said about the guidances, “they provide a modern and flexible framework to generate data needed to support the FDA’s review of NGS-based tests.”  That does sound promising.

Now if you made it this far and are wondering how this applies to products liability, Bexis and I recently gave a presentation on pharmacogenomics or how genes affect a person’s response to drugs.  NGS tests will only help advance pharmacogenomics.  You can register and watch the presentation here and I promise will be more entertaining than this post.

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:  https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592358.htm.  If you are a completist, here is the full proposal of delay from the Federal Register:  https://www.federalregister.gov/documents/2018/01/16/2018-00555/clarification-of-when-products-made-or-derived-from-tobacco-are-regulated-as-drugs-devices-or.  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.

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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.