Pharmaceuticals

Tribal Sovereign Immunity May Shield Pharmaceutical Patent Owner from PTAB Inter Partes Review

Brenden Hoffman, MJLST Staffer

 

The Eleventh Amendment to the United States Constitution provides for State Sovereign Immunity, stating: “The Judicial power of the United States shall not be construed to extend to any suit in law or equity, commenced or prosecuted against one of the United States by Citizens of another State, or by Citizens or Subjects of any Foreign State.”   Earlier this year, the Patent Trial and Appeals Board dismissed three Inter Partes Review proceedings against the University of Florida, based on their claim of State Sovereign Immunity. See Covidien LP v. University of Florida Research Foundation Inc., Case Nos. IPR 2016-01274; -01275, and -01276 (PTAB January 25, 2017).

Early last month, the pharmaceutical company Allergan announced that it had transferred its patent rights for the blockbuster drug Restasis to the Saint Regis Mohawk Tribe. Restasis is Allergan’s second most profitable drug (Botox is the first), netting $336.4 million in the second quarter of 2017.  Under this agreement, this tribe was paid $13.75 Million initially and will receive $15 Million in annual royalties for every year that the patents remain valid. Bob Bailey, Allergan’s Executive VP and Chief Legal Officer, indicated that they were approached by the St. Regis tribe and believe that tribal sovereign immunity should shield the patents from pending IPRs, stating “The Saint Regis Mohawk Tribe and its counsel approached Allergan with a sophisticated opportunity to strengthen the defense of our RESTASIS® intellectual property in the upcoming inter partes review proceedings before the Patent Trial and Appeal Board… Allergan evaluated this approach closely, with expert counsel in patent and sovereign immunity law. This included a thorough review of recent case law such as Covidien LP v. University of Florida Research Foundation Inc. and Neochord, Inc. v. University of Maryland, in which the PTAB dismissed IPR proceedings against the universities based upon their claims of sovereign immunity.”

IPRs are highly controversial.  The United States Supreme Court recently granted cert. in Oil States Energy Services, LLC v. Greene’s Energy Group, LLC  to determine “whether inter partes review, an adversarial process used by the Patent and Trademark Office (PTO) to analyze the validity of existing patents, violates the Constitution by extinguishing private property rights through a non-Article III forum without a jury.” Until this issue is resolved, IPRs will continue to be by companies such as Allergan seeking to protect their patent rights.  Over the past few years, hedge fund manager Kyle Bass made headlines as a “reverse troll,” by filing IPRs against pharmaceutical companies while simultaneously shorting their stocks. Bailey has stated that “the IPR process has been a thorn in our side…We get a call from reverse trolls on a regular basis. Now we have an alternative.” This move has been well regarded by many critical of IPRs, including an October 9, 2017 post on ipwatchdog.com titled “Native Americans Set to Save the Patent System.”  In addition, the St. Regis Mohawk tribe has indicated that these types of arrangements can help the tribe generate much-needed capital for housing, education, healthcare and welfare, without requiring the tribe to give up any land or money.

However, this arrangement between Allergan and the St. Regis Mohawk tribe has attracted strong criticism from others.  Mylan Pharmaceuticals, a party in the IPR proceedings challenging multiple Allergan patents on Restasis, has called this transfer a “sham” and made comparisons to racketeering cases with lending fraud.  “Allergan Pulls a Fast One” on the Science Translational Medicine Blog states, “‘The validity of your patents is subject to review, unless you pay off some Indian tribe’ does not seem like a good way to run an intellectual property system,” this is a “slimy legal trick,” and “this deal smells.” He suggests that “legal loopholes” like this sully the whole pharmaceutical industry look bad and that this will force Congress to take action.  

In fact, U.S. Senator Claire McCaskill, the top-ranking Democrat on the Homeland Security and Governmental Affairs Committee, has already written a letter to the Pharmaceutical Research and Manufacturers of America urging  them to review “whether the recent actions Allergan has taken are consistent with the mission of your organization.”  She believes that “This is one of the most brazen and absurd loopholes I’ve ever seen, and it should be illegal…PhRMA can and should play a role in telling its members that this action isn’t appropriate, and I hope they do that.”  On October 5, 2017, McCaskill introduced a bill to the Senate “To abrogate the sovereign immunity of Indian tribes as a defense in inter partes review of patents.”


Recalling History with The FDA’s Safety Alerts

MJLST Guest Blogger, Tommy Tobin

[Editor’s Note: MJLST is pleased to welcome back Tommy Tobin for another series on Food and FDA law. This is #1 of 3 in April. You can find his earlier posts here.]

The FDA’s Safety Alerts for Human Medical Products provide insight on how the agency is protecting the American consumer. For example, through the agency’s online list of alerts, consumers are warned against using suppositories that claim that they can cure cancer. Such alerts harken back to the agency’s origins at the turn of the twentieth century.

While Dr. Harvey Washington Wiley is not a household name to most Americans today, his legacy is felt each day in our households. Dr. Wiley spent decades calling for increased protections for consumer safety. His “Poison Squad” experiments pitted healthy young volunteers against food additives to determine the effects on health. With the passage of federal legislation in 1906, the organization that was to become the FDA was on its way to its modern-day role.

One of Wiley’s remarkably prescient articles was his 1914 co-authored piece “Swindled Getting Slim,” which he wrote after leaving government service. Even at that time, Dr. Wiley found that “the whole list of obesity-cures would strain credulity to the breaking point.” Rallying against fakes, frauds, and fad diets, the piece warned the public about purveyors of weight-loss remedies that presented “simple old-time frauds under new names and new auspices, with marvelous scientific explanations of how they do the work.”

One of the products that Dr. Wiley had in his cross-hairs was the titular “Get Slim.” In his article, Wiley wrote that “Pink lemonade costs five cents a glass at the circus, but when you buy it in the form of ‘Get Slim,’ $1 is the price of a ‘twelve days’ dose.’” Not only was “Get Slim” expensive, it was also dangerous. A 1916 issue of Good Housekeeping updated readers about the story:

In the January, 1914 Good Housekeeping was published an article by Dr. Wiley and Anne Lewis Pierce entitled “Swindled Getting Slim.” In it the true character of several so-called obesity-cures was made plain, among them “Get Slim,” manufactured by Jean Downs, of New York City. The demand for “Get Slim” rapidly fell off, and the manufacturer, convinced that Good Housekeeping had caused it by calling her “cure” a fake, brought suit for $50,000. After various delays…the case was brought to trial…December 15th, 1915. Two days were spent in taking testimony, Jean Downs telling how she made the stuff and several chemists and biologists testifying that, if made as she said she made it, it was more dangerous than Dr. Wiley had said. In his charge to the jury Justice Lehman said that a magazine was within its rights in criticizing a preparation offered to the public and that unless they thought the publication of the article was inspired by malice they must find in favor of the defendant. The jury so found. Thus endeth “Get Slim.”

One of the ways the modern-day FDA carries on the work of Dr. Wiley is to warn the public against dangers lurking in their household products. For example, the FDA has issued numerous Safety Alerts against products with undisclosed drug ingredients—including several weight loss products—in recent years.

“Pink Bikini” and “Shorts on the Beach” were capsules marketed by Texas-based Lucy’s Weight Loss System. These weight loss products were the subject of a nationwide recall in 2016 when the FDA found that their ingredients included several active, undisclosed pharmaceutical ingredients. These included Sibutramine, an appetite suppressant withdrawn from the American market years earlier because it created cardiovascular risks, and Phenolphthalein, a known carcinogen which also had been disallowed due to serious health concerns. In its safety alert, the FDA noted that the offending pills should “not be consumed.”

In 2014 alone, the FDA noted over 35 public notices and recalls for products with undeclared drug ingredients. This is in addition to warnings and recalls related to consumer dangers with bacterial contaminations, glass particles, and other issues with dozens of nutritional, drug, and medical device products.

To date this year, the FDA has warned the public that certain injectable products labeled “latex free” contained latex, which could be life-threatening for those with allergies. In addition, the FDA issued a Safety Alert for certain male sexual enhancement supplements, including one with the name XtraHRD, for containing active drug ingredients. Without proper identification, consumers may take such products without knowing they contained drugs.  As such, consumers are advised not to take these capsules and to return any in their possession to the company for a refund. In considering the danger to the public, the Safety Alert noted “Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. [Erectile dysfunction] is a common problem in men with these conditions, and consumers may seek these types of products to enhance sexual performance.”

Public health and safety is at the core of the FDA’s mission. The FDA’s modern-day efforts toward this mission honor its roots as well as the work of Dr. Wiley and others.


Industry Giants Praise FDA Draft Guidance on Companion Diagnostics

Na An, MJLST Article Editor

In July 2016, the US Food and Drug Administration (FDA) published a draft guidance document titled “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product.”  The new draft guidance aims to serve as a “practical guide” and assist sponsors of drugs and in vitro diagnostics (IVD) in developing these two products simultaneously.  So far, FDA has received six public comments on the draft guide which are mostly positive, with Illumina calling the document “worth the wait,” and Genentech claiming it “crucial for the advancement of personalized medicine.”

A companion diagnostic includes a medical device, in this case an in vitro device, which provides safety and efficacy information of a corresponding drug or biological product.  It is a critical component of precision medicine, the cornerstone of which is the ability to identify and measure biomarkers indicative of the patient’s response to a particular therapy.  Approximately, a quarter of new drugs approved over the past two years were a drug-IVD companion.  However, the codevelopment process is complicated by the fact that these two products may be developed on different schedules, subject to different regulatory requirements, and reviewed by different center at the FDA.  The long-awaited draft guidance was in the works for more than a decade and intended to help sponsors and the FDA reviewers navigate these challenges.

In this draft guidance, FDA reiterates its general policy that IVD devices should receive marketing approval contemporaneously with the authorization of the corresponding therapeutic product.  FDA states that “the availability of an IVD with ‘market-ready’ analytical performance characteristics . . . is highly recommended at the time of initiation of clinical trials intended to support approval of the therapeutic product.”  FDA also recommends: “Using an analytically validated test is important to protect clinical trial subjects, to be able to interpret trial results when a prototype test is used, and to help to define acceptable performance characteristics for the development of the candidate IVD companion diagnostic.”  The new draft guidance provides much more information about the technical and scientific aspects of the development process.  For example, the draft guidance details the use of IVD prototype tests for the purpose of testing the drug early in the development, considerations for planning and executing a therapeutic product clinical trial that also includes the investigation of an IVD companion diagnostic, the use of a prospective-retrospective study approach, the use of training and validation sample sets, and the use of a master file for the therapeutic product to provide data in support of the IVD companion diagnostic marketing application.

The draft guidance has received high marks from industry giants. Illumina said the draft “has been a long time coming, eagerly anticipated, but worth the wait.”  Yet, the gene sequencing giant also seeks more clarity from FDA on risk assessments and expectations for analytical validation prior to investigational IVD use in trials.  “There is an opportunity here for FDA to add clarity on this important decision making process. We suggest this discussion on significant risk versus nonsignificant risk determinations be expanded and put into an appendix with examples. This is a unique opportunity for FDA to help sponsors get this process right,” Illumina says.  On a similarly positive note, Genentech called the draft “crucial for the advancement of personalized medicine,” and supplementary to two previous guidance documents on next generation sequencing.  In addition, Genentech notes that the scope of this IVD and drug co-development draft guidance “is limited, and therefore it does not address the requirements for development of complementary diagnostics or the challenges of co-development using high-throughput technologies such as Next-Generation Sequencing (NGS) based test panels, which are an increasingly attractive tool for both developers and providers.”  AstraZeneca, on the other hand, seeks more clarity on guidance on complementary diagnostics and clarifying between “patient enrichment” and “patient selection” and the resulting considerations on determination of significant risk uses of investigational devices.

We eagerly wait for FDA’s view of these comments and impacts of the guidance on the codevelopment of a drug-IVD companion.


Let’s Talk: The Cold & Flu Season & Personalized Medicine

Allison Kvien, MJLST Managing Editor

As we approach cold and flu season, it is time we all start thinking about properly taking care of ourselves. Many individual factors have been linked to your heath. A Newsweek article reported that people who get less than 5 hours of sleep a night are 4.5 times as likely to become ill. According to The L.A. Times, an elevated heart rate could mean that a cold is on the way. Finally, an article from Harvard found a link between your popularity and how early in the season you become ill (yes, really—and I guess this explains why I haven’t gotten the flu since I was a kid). While this is all helpful information, it represents only a few factors that contribute to a person’s overall health. Over the years, the practice of medicine has become more accepting of the concept that “one size does not fit all” and that patients may need more personalized medicine.

One interesting development in personalized medicine was ten years ago, in 2005, when FDA approved the first race-specific drug, BiDil. As Dorothy E. Roberts explained in her MJLST article, BiDil, is “a combination drug that relaxes the blood vessels, [and] was authorized to treat heart failure in self-identified black patients.” Many scholars and citizens alike have found the approval of BiDil controversial, for a variety of reasons, legal, political, ethical, and otherwise. It may be, however, simply one more step on the path to personalization of medicine for patients. As Roberts reported, “BiDil increased survival by an astonishing 43 percent. Hospitalizations were reduced by 39 percent.” Roberts’s opinion, however, was that BiDil should have been approved for all heart failure patients, regardless of race because there was no underlying genetic difference in African Americans that the drug relied on for its positive results. The economic results of the BiDil drug may prevent others from going developing race-specific drugs for a while, though; BiDil has been described as a “flop.”

Cold season medicine is normally pretty generic. Think: Airborne, Sudafed, Advil, and cough drops, my favorite of which are the less-than-pleasant tasting Fisherman’s Friends that completely numb your throat—seriously, try them. I think the concept of personalized cold and flu medicine is particularly interesting because our current cold season medicine is normally over-the-counter and generalized. Can you imagine a future where you pick up a cold medicine tailored specifically to your genetic background? Well, it may already be happening. Just two years ago, FDA approved personalized flu vaccines for three groups: the elderly, children, and those with allergies. These personalized vaccines may allow some groups of our population to receive them when they wouldn’t otherwise be able to, or to at least receive them more safely. Specifically for flu vaccines, anyway, this step in personalization may not also reflect increased overall effectiveness in preventing illness. But let’s not give you an excuse to not get your flu vaccine. Go get that flu shot that was made just for you!


The “Patent Dance” for Now: Rehearing Denied in Amgen v. Sandoz

Jeff Simon, MJLST Staffer

On July 21, 2015, the Federal Circuit’s decision in Amgen v. Sandoz established that a biosimilar applicant does not have to follow the patent dispute resolution procedures set forth by the Biologics Price Competition and Innovation Act. The BPCIA’s “patent dance,” located at 42 U.S.C. § 262(l)(2)(a), sets forth procedures requiring biosimilar applicants to disclose the biosimilar application and information describing the methods and procedures of its production to the sponsor of the reference biologic drug. The Federal Circuit’s fractured decision denied the compulsory nature of the “patent dance,” while still holding that biosimilar applicants are required to provide the biologic drug sponsor 180 days advanced notice of the first commercial marketing of its biosimilar product in accordance § 262(l)(2)(a).

Considering that the decision of the court was split by favoring the biosimilar applicants regarding the issue of the “patent dance” while favoring the biologic sponsor when it came to market disclosure, the decision was far from a satisfying result for either party as neither party came out as the clear victor. As such, both Amgen and Sandoz filed petitions for an en banc rehearing on August 20, 2015. Amgen’s petition for review once again contended that the language of § 262(I)(2)(a) as stated by congress, specifically the use of the word “shall,” indicates that the “patent dance’s” procedures are mandatory. Sandoz contended among other things that the 180-day provision necessarily increases the exclusivity period from 12 years to 12 and a half years and further that the court incorrectly asserted that notice was mandatory and enforceable. Both parties submitted amicus curiae briefs in agreement that, as a matter of first impression, it was appropriate for an en banc rehearing.

However, despite a fractured panel deciding a matter of first impression, Federal Circuit denied a rehearing in decision on October 16, 2015. The decision came as surprise to many of those associated with the biologic drug industry, especially considering the novelty and discord upon the issues. Considering the fact that both parties sought a rehearing, the court may have decided that the issue was undeserving of the court’s continued interest and resources. Both parties may file petitions for certiorari.

In regards to the future implications of the decision, it’s important to note that many of the high revenue pioneer biologic drugs are set to have their US patents expire within the next few years. This expected “patent cliff’ is certain to drive momentum within the biosimilar market. This wave of biosimilar applications is sure to have large implications upon the BPCIA, and particularly whether the “patent dance” is optional. All considered, the issues presented in Amgen may be approaching a level of importance that draws the attention of SCOTUS. It’s possible that a grant of certiorari may be in order to settle the debate on the BPCIA’s “patent dance” and market disclosure requirements, particularly considering the economic ramification of the anticipated biologics’ patent cliff.


Inter Partes Review: A Questionable Item in the Generic’s Tool Kit

Will Orlady, MJLST Lead Articles Editor

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman). Since then, pioneer pharmaceutical manufacturers and their generic counterparts have resolved patent disputes in federal district court under the Hatch-Waxman patent dispute framework. This framework is admittedly complex. But it forces interested parties to engage with Hatch-Waxman, mandating compliance with congressionally determined policy decisions regarding pharmaceutical exclusivity. Hatch-Waxman’s patent dispute framework was part of the larger bill, crafted to balance the interests of pioneer and generic drug manufacturers. Congress enacted the law to address two (apparently competing) goals: (1) to encourage innovation in pharmaceutical research and development and (2) to help generic drugs reach the market more quickly. The tension between these goals merits further discussion.

Before Hatch-Waxman, concerns grew that drug prices were too high and that access to certain treatments was too limited. Thus, there was both need and substantial demand for cheaper, generic drugs. On the other hand, pioneer drug manufacturers complained of inadequate market exclusivity following FDA’s New Drug Application (NDA) process. Put simply, pioneer companies spent (and continue to spend to this day) approximately $1 Billion brining a new drug to market. On top of the money, pioneer manufactures potentially spend several years of their drugs’ valuable patent terms going through the NDA process. Thus, pioneer companies noted that recouping R&D and regulatory expenses was not feasible given the “short” market exclusivity period.

Hatch-Waxman was a carefully wrought legislative compromise. It granted pioneers a patent term extension based on the length of FDA’s regulatory review, non-patent market exclusivity provisions, a mechanism for increasing the public notice of patents and patent challenges, and an automatic injunction forbidding FDA approval of a generic drug in certain circumstances. The generic manufacturers got, among other things, the Abbreviated New Drug Application (ANDA), making the regulatory process for generic drugs less onerous. To be sure, Hatch-Waxman is not without its critics, and its nuances are immense. But it is important to remember that the act represents a careful Congressional balancing of industry and public interests. Hatch-Waxman’s patent dispute resolution mechanism squarely fits within this compromise.

Enter the America Invents Act (AIA) of 2011. Of note, the AIA revised certain post-grant opposition procedures. Specifically, the law expanded the importance of inter partes review (IPR). IPR is a process by which a third party may have a patent reexamined by the patent office to verify that the office validly issued the patent. Since the AIA’s enactment, IPR has become immensely popular. Why is this? IPR offers a potential alternative to district court litigation. It provides advantageous invalidation standards—e.g. the “broadest reasonable interpretation” during claim construction. Further, IPR allows patent challenges with relatively limited discovery, cutting both the time and cost of district court patent litigation. Finally, IPR petitioners have been enormously successful in invalidating many of the patents challenged to date.

Needless to say, IPR frightens patentees holding rights to valuable patents. Can you see where I’m going here? Are particular Congressional mandates and policy determinations on a collision course?

The post-AIA surge of IPR proceedings has pioneer pharmaceutical manufacturers worried—rightly so. Generic manufacturers are already petitioning the U.S. Patent and Trademark Office (PTO) for IPR of patents protecting various pharmaceutical and biologic products. Given the aforementioned advantages of IPR, this shouldn’t come as a surprise, but that is not to say that it is not remarkable. Generic manufacturers could be leveraging the advantages of IPR to force pioneer drug manufacturers to settle patent disputes out of district court. Or, of more consequence, they could be using IPR to skirt the patent dispute frameworks required by Hatch-Waxman and the BPCIA (for biologics).

Indeed, if pioneer pharmaceutical manufacturers hold patents allowing for market exclusivity, the patents should be validly issued. It is, however, simultaneously important to remember that Congress has treated drug and biologic patents differently since, at the very least, 1984. Pharmaceutical patents are remarkable in at least three key ways. First, patents on commercially successful drugs are extraordinarily valuable. Congress (at least ostensibly) allows this because of the enormous regulatory barriers to entry. In other words, it’s a trade. FDA imposes supra-burdensome regulatory costs to ensure new drugs are safe and effective. Consequently, Congress allows pioneer drug manufacturers to unilaterally exploit the market to recoup losses, and make money. Second, pharmaceutical patents read on particles of matter that are harnessed to treat disease and save lives. This creates a unique demand. And third, pharmaceutical patents read on products which require sensational development costs, including the time and money required for regulatory approval.

Does this mean pharmaceutical patents should be treated differently, or made exempt from IPR? The answer is not so simple. But legislators, scholars, and practitioners should consider whether IPR is having unintended consequences within the pharmaceutical industry. Just as a quick example: Did Congress truly intend for the AIA’s IPR to be a way around Hatch-Waxman or the BPCIA? And even if it did, does it make sense to put enormously valuable patents at the mercy of an overburdened administrative agency? As I said, the answers don’t come readily. It’s a policy debate that needs to happen. Until it does, I think it unwise to abandon previously established Congressional compromises—i.e. Hatch-Waxman—for a hasty change to our patent system.


A Story to Warm Your Iron-Rich Hemoglobin

Becky Huting, MJLST Articles Editor

While recently home in Chicago on spring break, I offered to make my dad a spinach-packed smoothie. My dad (a good sport) agreed, but asked me to make it light on the spinach as he understood men at his age (60) should be taking it easy on the iron intake. I had heard this principle before, and knew that men’s and women’s vitamin supplements were different in part due to the additional iron needs of women. My dad was right about one thing: he needs a lot less iron than me. His recommended dietary allowance for iron is 8 mg/day whereas mine is a lofty 18 mg/day. In actuality, men rarely suffer from iron deficiency so supplements are usually unnecessary, and in fact too much iron can indeed be harmful. There are possible links with excessive iron consumption to diabetes as well as neurodegenerative disease.

But where his concerns are unfounded are in the nutritional numbers. One cup of uncooked spinach contains only .8 mg of iron. That is only one-tenth of his daily iron needs. Three ounces of ground beef containing 15% fat contains 2.2 mg of iron. What about his daily serving of canned, drained clams, you ask? Fine, you have me there: if my father actually consumed such item, he’d have gone over at 23.8 mg of iron. It is very hard though for a human to overdose on iron from food, because an adult body has systems in place to regulate the amount of iron it absorbs. In short, my dad need not be concerned about spinach in his smoothie, except for reasons of palatability.

So given the different nutritional needs of men, women, and also children, what entity is telling consumers whether a vitamin is for them by way of labels? The Food and Drug Administration (FDA) relinquished that duty back in October of 1994, when the Dietary Supplement Health and Education Act (DSHEA) was passed. This law created a new regulatory framework for the safety and labeling of dietary supplement that places the responsibility on the product manufacturers rather than the FDA. The DSHEA was a response to lobbying by health food companies to vote down several bills that would have had the effect of increasing the FDA’s powers over supplement labeling. Celebrities even got involved. In one commercial, Mel Gibson portrayed a citizen being raided and arrested by FDA agents for possessing a bottle of Vitamin C.

This mentality that too much government oversight is a bad thing is a popular ideal. After all, it’s only a vitamin. Perhaps a label signifying use by pregnant and nursing moms is enough, but consider the 60-year-old guy grabbing this supplement in haste. He is now getting 27 mg iron per day from the vitamin alone, perfect for a pregnant woman, but over 3X his nutritional needs. Are a few words on a label enough to signify safety to a consumer? Certainly there is an argument that too much information will lead to a cluttered, confused label. So where do you come down, bring the FDA back in or leave it to the companies? And do you feel like a green smoothie? I promise you the banana masks the spinach flavor.


Scientific Responsibility: Why Lawyers are Imperative in Scientifically Informed Neuro-ethics

Thomas Hale-Kupiec, MJLST Staff Member

In Volume 11, Issue 1 of the Minnesota Journal of Law, Science, & Technology, Eagleman, et al. conclude that “the neuroscientific community should continue to develop rehabilitative strategies so that the legal community can take advantage of those strategies for a rational, customized approach” in Why Neuroscience Matters for Rational Drug Policy. Though perhaps this assertion is valid in the context of Drug Addiction, I believe it is necessary to limit this assertion to solely rehabilitative drug addiction studies; to allow a further extension of this conclusion would be sociologically detrimental. I postulate that beyond ideas of who we define as a “Neuroscientist,” legal experts need to be at the forefront of this debate in order to better define and formulate ideas of “rehabilitation.”

In a related reflection entitled ‘Smart Drugs’: Do they work? Are they ethical? Will they be legal?, researcher Stephen Rose poses a number of ethical and neurological impacts of mind enhancing substances. The author posits an interesting question: what is “normal” for a brain? If someone undergoes pharmacological manipulation, what should the standard be for “abnormal?” For instance, Rose poses that some substances could be used for patients with Down Syndrome to allow for cognitive enhancement. Is this a valid designation as “abnormal?” Inexorably linked to this issue would be Autism Spectrum Disorder — where on the spectrum does a cognitive “abnormality” manifest? Further, how do we define potentially less visible disorders such as “anxiety?” With this spectrum of diseases and mental health conditions, variety of measured “abnormalities,” and varying pharmacological treatment effectiveness, I think we need to be mindful that neuroscientific constructions are often blurry, but always need to be conceptualized within the paradigm of ethics.

More than ever, the question of “what is abnormal” and “what mandates treatment” needs to be addressed in pharmaceutical policy. For instance, federally designated controlled substances like marijuana may be effective at treating anxiety and other medical conditions. Should the legal community allow for Eagleman’s assertion to snowball? Imagine an increasing number of states embrace evidence that the active ingredients in marijuana could treat certain medical conditions? Should the scientific community solely argue the validity of these findings? Legal professionals, bioethicists, and regulators need to be included in these questions. It is not that the data driven outcomes need to be pursued; rather, that a level of ethics and sociological morals need to be layered above these decisions.


Country of Origin Labeling for Food and Pharmaceutical Products

by Daniel Schueppert, UMN Law Student, MJLST Staff

The USDA has recently lifted restrictions on the practice of shipping US Chicken to China for processing, for an eventual return to the US. Under the present regulations, chicken originating from US farms can be shipped to China for processing, then shipped back to the US for sale. This chicken need not include Country of Origin Labeling (COOL) to indicate that it has been processed in China. This change comes in the wake of a years of food safety scares relating to China’s food supply. Although the Food Safety Inspection Service (FSIS) has completed audits of the China’s “poultry processing inspection system” and certified some of the Chinese processing plants and procedures, American consumers have retained some reservations about the safety of chicken processed in China. As it stands, this system leaves consumers in the position of not knowing which country their chicken products have been processed because the Chinese operations are considered a comparable food component to what results from US processing.

This recent action by the USDA clearly raises questions concerning the United States’ food safety, and perhaps security. A sophisticated consumer may nevertheless be able avoid chicken products known to be processed in China, but absent COOL disclosures this may be a difficult task and arguably involve some guess work. This is not necessarily the case with generic pharmaceuticals, an area in which there are substantial parallels to the chicken debate. Some of the concerns raised relating to the quality and safety of chicken processed in China also bring to light the COOL requirements for other consumables like pharmaceuticals. Import screening and labeling for pharmaceuticals, and particularly off patent generics, is a convoluted area of regulatory law where Federal agencies to not always agree. Currently many of the various components of just one pharmaceutical drug are manufactured all over the world and come from a variety of sources. Manufacturing in India, China, and Eastern Europe account for a large part of the market.

The FDA’s main measure on determining the quality of components in generic drugs is a fuzzy spectrum concerning the “bioavailability” of certain chemicals but this measure does not necessarily take account of inert components or varying quality or quantities of active ingredients. Much like chicken, a consumer or regulatory agency would be hard pressed to find a problem with these products until a quality control issue develops and American consumers are put at risk. COOL labeling regarding Chicken and Drugs are developing issues without a clear regulatory action in sight. Stay tuned to the Minnesota Journal of Law, Science & Technology for further updates.


United States v. Caronia After-The-Fact: What Was All That Fuss About, Again?

by Ashley Zborowsky, UMN Law Student, MJLST Notes & Comments Editor

Thumbnail-Ashley-Zborowsky.jpgIn a split decision on December 3, 2012, the Second Circuit issued its long-awaited opinion in U.S. v. Caronia–a case concerning off-label promotion and commercial free speech. The 2011 U.S. Supreme Court holding in Sorrell v. IMS Health acknowledging off-label promotion to be “per se” protected under the First Amendment marked a significant shift in this area of law. Previously, the Food and Drug Administration (FDA) was able to recover billions of dollars in penalties from manufacturers engaged in off-label promotion, or the act of promoting regulated products for uses other than those approved by the agency. Despite other challenges on constitutional grounds, the FDA has been successful at defending its current practice–that is, until recently.

After Sorrell, it was unclear how the Second Circuit would apply this precedent in Caronia. For a robust discussion of the holding in Sorrell and alternate regulatory pathways to mitigate the effects of constitutional challenges to FDA authority, see Rethinking Off-Label Regulation in the Wake of Sorrell v. IMS Health: Can State Involvement Compensate for Waning FDA Authority to Curb Commercial Free Speech? Much to the agency’s chagrin, the Second Circuit found that truthful, non-misleading off-label speech is in fact protected by the First Amendment and therefore cannot be prosecuted under the Federal Food, Drug and Cosmetics Act (FDCA). Although the circuit court opinion is not binding outside of its jurisdiction and is only one early example of how Sorrell will be interpreted by lower courts, the Caronia decision signals potentially diminishing regulatory authority in this realm.

To be sure, the gradual constitutional erosion of its authority to police purported FDCA violations is a viable cause for concern–but is it imminent? Though analysts predicted a more panicked response on behalf of the agency, the FDA has apparently decided not to petition the U.S. Supreme Court for certiorari, stating that the agency “does not believe. . . the Caronia decision will significantly affect [ its] enforcement” of off-label promotion. Because of its limited precedential value and the fact that both Sorrell and Caronia only recognize speech that is truthful and non-misleading as protected, the Second Circuit decision may have very little practical effect. In fact just last month in a related case out of the Ninth Circuit, U.S. v. Harkonen, the court chose to ignore Caronia altogether–asserting that the First Amendment does not protect “fraudulent speech.”

While off-label promotion itself cannot form the basis of an FDCA violation under Caronia, it may still be introduced as evidence of criminal misbranding. As such, it seems that the Caronia uproar could have all been for naught. The FDA’s reaction (or lack thereof) to the Second Circuit’s holding indicates that this is likely true. If nothing else, however, Caronia will surely increase the number of constitutional challenges to FDA enforcement activity, forcing the agency to reexamine its priorities. Thus, while Caronia has the potential for wide-ranging implications down the line, industry stakeholders will just have to wait and see. Although Caronia has done little to alter the regulatory landscape presently, it may only be a matter of time before a circuit split begins to evolve.