Mild Traumatic Brain Injury and the Pupillary Light Reflex

According to a recent review study of Pubmed Central/National Library of Medicine databases, the pupillary light reflex provides an optimal opportunity to investigate mild traumatic brain injury (mTBI).

Based on the findings of the review, the pupillary system may provide a noninvasive “window” to mTBI, in terms of documenting its existence and the often-accompanying symptom of photosensitivity. When an individual experiences mTBI, visual dysfunction may occur, and the pupillary light reflex may be affected. Pupils are routinely assessed for abnormal size and responsivity to determine the neural integrity of the visual system. Investigating pupillary light reflex in the mTBI population, researchers found that pupillary response was significantly delayed, slowed, and reduced, symmetrically, with a smaller baseline diameter. These findings may indicate dysfunction of the pupillary pathway.

Several objective biomarkers for the presence of mTBI and photosensitivity provide further insight into neurological dysfunction. In mTBI, photosensitivity may be due to dysfunction in the baseline neural sensor. Photosensitivity as a perceptual phenomenon can be confirmed through objective, noninvasive, rapid, vision-based, pupillary biomarkers.

Pupillary light reflex in mTBI may be investigated with pupillometers to assess subtle abnormalities in pupil size as well as pupillary responses. The resulting information can provide diagnostic or prognostic indicators relating to the extent of the injury, and neurophysiological linkages. Pupillometers offer precise and extensive pupillary testing for the mTBI population, especially those individuals who experience photosensitivity. The major drawback is cost. Development of a more inexpensive hand-held pupillometer would help with diagnosis of mTBI and improve patient care.

With such instrumentation, pupillary light reflex could be used to investigate the possibility of a very early, acute-stage mTBI/concussion in emergency rooms, in the workplace, and even on the sideline of sports games. Such information can be relevant to a worker’s compensation determinations, social security disability determinations, and return-to-play/work/learn standards for both adults and children.

This post was written by Bruce H. Stern of STARK & STARK., COPYRIGHT © 2017
For more Biotech legal analysis, go to The National Law Review 

Trump Administration Limits Affordable Care Act’s Contraceptive Coverage Mandate

On Friday October 6, 2017, the Trump administration released two interim final rules expanding the exemptions allowed under the Patient Protection and Affordable Care Act’s (the “ACA’s”) contraceptive coverage mandate. Under the ACA, employer group health plans generally are required to cover contraceptives, sterilization, and related patient education and counseling, with exemptions provided for religious houses of worship. The exemption was expanded by the Department of Health and Human Services (HHS) as a result of the Supreme Court’s decision in Burwell v. Hobby Lobby 34 S. Ct. 2751 (2014), which held health plans of closely held for-profit corporations are not required to cover contraceptives if doing so would contradict the owner’s religious beliefs under the Religious Freedom Restoration Act.

The interim final rules, released by the Treasury Department, Department of Labor (DOL), and HHS, are effective immediately and provide exemptions from the contraceptive coverage mandate to many employers with “sincerely held religious beliefs” or “sincerely held moral convictions”. The interim final rules limit the exemption for “sincerely held moral convictions” to houses of worship, tax-exempt entities, and closely held for-profit corporations, but permit publicly traded for-profit entities to use the exemption for “sincerely held religious beliefs.” According to the Trump administration, the United States has had a long history of providing protections in the regulation of health care for individuals and entities with objections based on religious beliefs or moral convictions. To take advantage of the new exemption, eligible employers must notify employees that they will no longer provide contraceptive coverage but need not inform the federal government. The Employee Retirement Income Security Act of 1974, as amended (ERISA) requires that a Summary of Material Modification (SMM) is provided within 60 days of a “material reduction” in covered services or benefits provided under a group health plan. A material reduction includes the elimination of benefits payable under a group health plan. According to an Obama administration report released last year, 55 million women have gained access to no-cost birth control as a result of the contraceptive coverage mandate. It is not clear how many entities may claim the exemptions, but HHS has predicted about 200 entities (affecting 120,000 women) may do so based on the number of entities that filed lawsuits.  Written comments on the interim final rules are due December 5, 2017.

This post was written by Cassandra Labbees of Epstein Becker & Green, P.C. All rights reserved., ©2017
For more legal analysis go to The National Law Review

Cannabis Prop 65 Liability: Lessons Learned from the Dietary Supplement Industry

The cannabis industry appears to be next on the liability “hit list” under California’s notorious Proposition 65 statute. In June 2017, more than 700 Prop 65 notices were served on California cannabis businesses. Companies in this emerging market should start mitigating risk under Prop 65 now. Fortunately, lessons can be learned from the dietary supplement industry’s expensive Prop 65 battles over the past decade.

California’s Prop 65, also known as the Safe Drinking Water and Toxic Enforcement Act, requires a warning on all products that contain chemicals known to cause cancer or reproductive harm, even in amounts a fraction of what is deemed safe by federal standards. Prop 65 has caused havoc within the dietary supplement and herbal product markets over the past decade, led by a cottage industry of “bounty hunter” attorneys who have weaponized the statute, ostensibly in the public interest but in reality as a lucrative for-profit business. These bounty hunters are now turning their attention to cannabis. Though amendments to the statute were adopted in 2016 for the purpose of reducing this abuse, Prop 65 litigation will continue and cannabis companies must stay vigilant.

Many businesses faced with the necessity of using a Prop 65 warning have no concern with the impact that a warning may have on sales or with consumer confidence in the product. After all, who would look twice at a Prop 65 warning on motor oil or insect repellent? Like the dietary supplement industry before them, however, many cannabis businesses will resist including a warning that the product contains a chemical known to cause cancer or reproductive harm. Many cannabis products rely on the consumers’ belief that the product is harmless and even therapeutic. For many, this will be an important business decision that may give rise to expensive mistakes − a decision should be made with an understanding of the basis for Prop 65 liability and exposure.

What Is Prop 65 and What Does It Require?

Prop 65 was passed by California voters in 1986 after an aggressive lobbying campaign by environmental and public health activists. The stated purpose of Prop 65 was to improve public health. The general consensus, however, is that Prop 65 has placed an undue burden on California businesses while achieving no significant impact on public health over the past 30 years.

As noted above, Prop 65 requires a warning on all products that contain chemicals known to cause cancer or reproductive harm. There are more than 900 such chemicals listed, and marijuana smoke has been included on the list since 2009.

For a warning to be acceptable under Prop 65, it must (1) clearly make known that the chemical involved is known to cause cancer and/or birth defects and/or other reproductive harm and (2) be given in such a way that it will effectively reach the person before he or she is exposed. The warnings must be “clear and reasonable,” meaning that the warning may not be diluted by other language. Various means of communicating the warning are allowed, including product-specific warnings on a posted sign or shelf, warnings on the product label or electronic warnings for internet purchases.

Important Exemptions

There are several important exemptions to Prop 65 that make a warning unnecessary. Businesses with nine or fewer employees are exempt from the statute. There also is an exemption involving chemicals that occur naturally in food. Lead, for example, will be considered naturally occurring only if it “is a natural constituent of a food” and is not added as a result of human activity such as pollution or poor manufacturing processes. The burden is on the company to prove the exemption, however, which is typically time-consuming and expensive.

Another important exemption is provided by “safe harbor” exposure levels for many chemicals on the Prop 65 list, below which no warning is required. The listed chemicals include additives or ingredients in pesticides, food, drugs and common household products. Most food contains at least some level of one or more of these substances. Prop 65 safe-harbor levels, however, are in many cases around 1,000 times lower than levels set by the Food and Drug Administration (FDA), Environmental Protection Agency (EPA) and World Health Organization (WHO). The exposure levels established by Prop 65 are often lower than what occurs naturally in fruits, vegetables, grains and even drinking water.

For example, the Prop 65 limit for lead is 0.5 mcg / day, which is below the amount of lead naturally found in many fruits, vegetables and herbs grown in non-contaminated soil. By comparison, the FDA allows 75 mcg / day and the European Union allows 250 mcg / day for lead. The European Food Safety Authority estimates the average adult consumes around 50 micrograms per day, which is 100 times the Prop 65 limit. It is nearly impossible to manufacture herbal products, including cannabis, without trace amounts of lead. Therefore, despite the “naturally occurring” exemption, discussed above, it can be dangerous to simply assume that an herbal product, including cannabis, complies with safe-harbor levels.

Only about 300 of the more than 900 Prop 65 chemicals have specific safe-harbor levels. For those chemicals without a safe-harbor limit, the burden will be on the cannabis business to establish that the subject chemical is within a safe range. This typically requires expensive testing, the results of which may be open to multiple interpretations as to whether a warning is required.

Determining the Exposure Level

Determination of the “exposure level” also is an important consideration. Prop 65 focuses on the level of a chemical to which the consumer is actually exposed. Although a product may have a very low amount of a chemical on the Prop 65 schedule that is below the safe-harbor level, liability under the statute may nevertheless be triggered based on the recommended serving size. It is advisable for companies to work with a laboratory that specializes in Prop 65 testing to determine the cumulative exposure level in order to verify the recommended serving size.

Enforcement of Prop 65

Prop 65 is enforced through litigation brought by the government or by private attorneys that “act in the public interest.” It is the threat of these private lawsuits that causes such consternation among those targeted with Prop 65 liability. After a 60-day notice period, the attorney may file a civil suit against the offending company. Typically, the plaintiff will demand that the defendant provide warnings compliant with Prop 65, pay a penalty, and either recall products already sold or attempt to provide health hazard warnings to those who purchased the products.

Though purportedly brought in the public interest, it is the collection of penalties and attorneys’ fees that in reality drives this litigation. Prop 65 allows individuals who bring suit to recover 25 percent of the penalties awarded, which by statute is calculated at $2,500 per violation per day. Amendments made to Prop 65 in 2016 allow for certain voluntary actions by the defendant – reformulation of the product, for example – in lieu of penalties. The threat of paying the plaintiff’s attorney’s fees makes litigating Prop 65 cases potentially very expensive. The attorney is incentivized to drag out the litigation, and the longer the case goes on, the more difficult it becomes to resolve because of the mounting fees.

This framework has created a cottage industry of Prop 65 “bounty hunter” lawyers who affiliate with “public interest” organizations that bring these cases for profit. According to the California Attorney General, 760 settlements were reported in 2016 with total settlement payments of more than $30 million. Attorneys’ fees accounted for 72 percent of that amount. The 2016 amendments to the statute have attempted to address these abuses to some extent by requiring a showing that the public benefits derived from the settlement are “significant” and by requiring contemporaneous record keeping for fees and costs sought to be recovered. Prop 65 litigation nevertheless continues to burden many industries in California, now including the cannabis industry. For Prop 65 liability, prevention is certainly less costly than a cure.

 

This post was written by Ian A. Stewart of Wilson Elser © 2017

For more legal analysis go to The National Law Review

Worried About Fake News? You Should Really Worry About Fake Drugs

While the concept of “fake news” continues to trigger Twitter followers and grab headlines, the trade in counterfeit drugs is a worldwide problem of significant scale.  This article discusses the problem and talks about some things trademark owners are doing to address the public safety issues posed by fake drugs.

The Problem.

Trademark counterfeiting?  Most think of fake Rolex watches sold on city street corners or faux designer purses sold in suburban kitchens.  While knock-off luxury goods may seem harmless, the economic harm inflicted on legitimate businesses—and the workers they employ—is enormous.  The Federal Bureau of Investigation estimates that the dollar value of counterfeit goods sold in the U.S. at $200-250 billion annually.  Many of North Carolina’s leading industries, including tobacco, furniture, apparel and pharmaceuticals, are among the most frequent targets of trademark counterfeiting. Also, according to Interpol, trademark counterfeiting often provides for a source of income and reliable import channel for those with other nefarious purposes, such as illegal drug or human trafficking and potentially even terror activities.

In addition to these very negative economic consequences, there is a particular level of harm associated with certain kinds of trademark counterfeiting.  Counterfeit goods aren’t subject to the same regulatory standards and safety inspections as items produced by legitimate manufacturers. So, in areas of manufacture where quality control is important, counterfeit products fall short.  Consider, for example, the potential harm that could be caused by substandard, bogus automobile tires or airplane parts.

Counterfeit pharmaceutical drugs are clearly an area where public safety concerns are paramount.  Counterfeit medicines have been found in all areas of the globe, including the highly regulated U.S. market, and extend to medicines, vaccines, testing and diagnostic equipment, and other medical devices.  Both branded and generic pharmaceutical products can be falsified.  And sales are not just limited to the black market—such products make their way to hospitals and pharmacies, often through internet sales trade channels.

Lifestyle or “popular” drugs are often counterfeited, and there have been recent increases in cosmetic, weight loss and opioid drugs.  However, such drugs are not limited to such trends—counterfeit malaria vaccines, cholesterol medications and cancer treatments can also be found in the U.S.  The World Health Organization (WHO) estimates that an average of up to 10% of medicines are counterfeit, and in developing countries, that percentage is considerably higher.

The Center for Medicine in the Public Interest estimates the annual worldwide dollar value of counterfeit pharmaceuticals at $200 billion annually and rising. Sadly, the damage is far greater than lost sales. WHO estimates that approximately 200,000 people die each year as the result of ineffective counterfeit anti-malarial drugs.

Counterfeit medicines also may cause adverse affects or allergic reactions, and they may not effectively treat the ailment for which prescribed.  They may promote drug resistant disease strains or contain no active ingredient, the wrong active ingredient, or the incorrect strength (too much or too little) or dosage of the intended ingredient.  According to a WHO investigation, approximately 1/3 of such drugs contain no effective ingredient.  Given the lack of inspection of counterfeit manufacturing facilities, such products are often produced under non-sterile circumstances, resulting in bacterial or other contamination.  Clearly, the ways in which counterfeit drugs can cause serious negative patient outcomes are extensive and extreme.

Combating the Problem.

Drug companies, and their attorneys and security departments, take a multi-pronged approach to combating counterfeiting.  Many of these efforts are used to combat counterfeiting generally, but some have been developed with particular focus toward the nuances of the counterfeit pharmaceutical market.

The counterfeiting problem can appear daunting, given an array of unknown manufacturing sources, the breadth of possible sales outlets, and the strong consumer preference for the “cheap but name brand” combination. Successful anti-counterfeiting practices do not generally follow a reactive “Whack-A-Mole” approach, attempting to squelch every low-level advertisement or email blast that comes out. Rather, systematic and strategic prosecution, akin to practices used in the intelligence community, is preferred. Investigations of networks and relationships, rather than merely products and sellers, can help identify high-payoff targets, the disruption of which can have positive effects across several echelons of the counterfeit trade. Focusing limited enforcement resources on valuable choke points which contribute to an ecosystem response can often be the most fruitful and strategic approach.

Counterfeit pharmaceuticals in particular, given their specific methods of typical advertisement and sale, are prone to certain forms of interdiction over others. It is well known that counterfeit pharmaceuticals are advertised heavily on both internet ads and email “spam” messages, all of which attempt to direct a prospective purchaser to a product-ordering website. Attempting to interdict the advertising messages, which are often sent by botnets or third-parties through a referral-affiliate relationship, or to shut down specific websites, is a losing proposition. This is the case because there are hundreds of thousands or more of each, and the costs to re-establish a confiscated website are negligible compared to the significant enforcement costs. However, academic researchers working with industry and enforcement contacts identified several potential chokepoints on which these sorts of pharmaceutical sales pathways rely. See Dharmdasani et al., “Priceless: The Role of Payments in Abuse-advertised Goods,” CCS ’12, October 16–18, 2012, Raleigh, N.C.  One key chokepoint relationship for online transactions is a seller’s host bank, nearly always non-U.S. and non-EU, that is willing to accept abusive credit card transactions related to these unlawful goods from card processors such as Visa and MasterCard.

Pharmaceutical

Nearly all online counterfeit pharmaceutical revenue can flow through these concentrated banking relationships, and researchers discovered that intercepting just one or two of these banking relationships, and seizing related funds, could have ripple effects disrupting thousands of drug transaction websites and referral affiliates. For example, a 2011 study determined that across 95% of spam e-mail for pharmaceuticals and similar goods, only three acquiring bank institutions were used. Id. This research demonstrates a guiding principal of anti-counterfeiting efforts: enforcement is most successful where the “termination cost [to the counterfeiter] is inevitably far higher— in fines, in lost holdback, in time and in opportunity cost—than the cost of the intervention itself [by the rights holder]. … [R]elatively concentrated actions with key . . .  institutions can have outsized impacts.” Id.

Targeted investigations and enforcement are only one aspect of a comprehensive anti-counterfeiting approach. Successful rights holders employ a broad-based strategy, involving secured supply chain management, thorough technology and distribution agreements with market partners, and high-tech security solutions such as secure packaging, microchips, holograms, and the like. The combination of many of these controls can make enforcement actions easier and more productive, and thus reduce the prevalence and success of counterfeit competitors. In addition, it is important to inform consumers and retailers about both the dangers of counterfeits and the value of accessing authentic products. Pharmaceutical companies should engage in advertising to alert the marketplace to the dangers of counterfeit pharmaceuticals and to also assist others in identifying counterfeit drugs – including examination of packaging and medicines for quality, condition, spelling and grammar; and checking manufacturing and expiration dates and batch numbers on both exterior and interior packaging.

The problem of fake drugs is in fact very real news and companies here in North Carolina and around the world are taking steps to defend their brands and protect their customers in the marketplace.

Authentic Vial                Counterfeit Vial

Botox Authentic    Fake Botox Vial

This article originally was published in the August 2017 edition of the Newsletter of the Board of Legal Specialization, a publication of the North Carolina State Bar.

This post was written by Sarah Anne Keefe & Stephen Shaw of Womble Carlyle Sandridge & Rice, PLLC. Copyright © 2017. All Rights Reserved.

Growing Questions About Employee Medical Marijuana Use Leave Employers in a Haze

The intersection of employment and marijuana laws has just gotten cloudier, thanks to a recent decision by the Rhode Island Superior Court interpreting that state’s medical marijuana and discrimination laws. In Callaghan v. Darlington Fabrics Corporation, the court broke with the majority of courts in other states in holding that an employer’s enforcement of its neutral drug testing policy to deny employment to an applicant because she held a medical marijuana card violated the anti-discrimination provisions of the state medical marijuana law.

Background

Plaintiff applied for an internship at Darlington, and during an initial meeting, she signed a statement acknowledging she would be required to take a drug test prior to being hired.  At that meeting, Plaintiff disclosed that she had a medical marijuana card.  Several days later, Plaintiff indicated to Darlington’s human resources representative that she was currently using medical marijuana and that as a result she would test positive on the pre-employment drug test.  Darlington informed Plaintiff that it was unable to hire her because she would fail the drug test and thus could not comply with the company’s drug-free workplace policy.

Plaintiff filed a lawsuit alleging Darlington violated the Hawkins-Slater Act (“the Act”), the state’s medical marijuana law, and the Rhode Island Civil Rights Act (“RICRA”). The Hawkins-Slater Act provides that “[n]o school, employer, or landlord may refuse to enroll, employ, or lease to, or otherwise penalize, a person solely for his or her status as a cardholder.”  After concluding that Act provides for a private right of action, the court held that Darlington’s refusal to hire Plaintiff violated the Act’s prohibition against refusing to employ a cardholder.  Citing another provision that the Act should not be construed to require an employer to accommodate “the medical use of marijuana in any workplace,” Darlington contended that Act does not require employers to accommodate medical marijuana use, and that doing so here would create workplace safety concerns.  The court rejected this argument, concluding:

  • The use of the phrase “in any workplace” suggests that statute does require employers to accommodate medical marijuana use outside the workplace.
  • Darlington’s workplace safety argument ignored the language of the Act, which prohibits “any person to undertake any task under the influence of marijuana, when doing so would constitute negligence or professional malpractice.” In other words, employers can regulate medical marijuana use by prohibiting workers from being under the influence while on duty, rather than refusing to hire medical marijuana users at all.
  • By hiring Plaintiff, Darlington would not be required to make accommodations “as they are defined in the employment discrimination context,” such as restructuring jobs, modifying work schedules, or even modifying the existing drug and alcohol policy (which prohibited the illegal use or possession of drugs on company property, but did not state that a positive drug test would result in the rescission of a job offer or termination of employment).

The court thus granted Plaintiff’s motion for summary judgment on her Hawkins-Slater Act claims.

With respect to Plaintiff’s RICRA claim, the court found that Plaintiff’s status as a medical marijuana cardholder was a signal to Darlington that she could not have obtained the card without a debilitating medical condition that would have caused her to be disabled. Therefore, the Court found that Plaintiff is disabled and that she had stated a claim for disability discrimination under RICRA because Darlington refused to hire her due to her status as a cardholder.  Importantly, the court held that the allegations supported a disparate treatment theory.

Finally, while noting that “Plaintiff’s drug use is legal under Rhode Island law, but illegal under federal law [i.e. the Controlled Substances Act (the CSA”)],” the Court found that the CSA did not preempt the Hawkins-Slater Act or RICRA. According to the court, the CSA’s purpose of “illegal importation, manufacture, distribution and possession and improper use of controlled substances” was quite distant from the “realm of employment and anti-discrimination law.”

Key Takeaways

While this decision likely will be appealed, it certainly adds additional confusion for employers in this unsettled area of the law – particularly those who have and enforce zero-tolerance drug policies. The decision departs from cases in other jurisdictions – such as CaliforniaColoradoMontanaOregon, and Washington – that have held that employers may take adverse action against medical marijuana users.  The laws in those states, however, merely decriminalize marijuana and, unlike the Rhode Island law, do not provide statutory protections in favor of marijuana users.  In those states in which marijuana use may not form the basis for an adverse employment decision, or in which marijuana use must be accommodated, the Callaghan decision may signal a movement to uphold employment protections for medical marijuana users.

While this issue continues to wend its way through the courts in Rhode Island and elsewhere, employers clearly may continue to prohibit the on-duty use of or impairment by marijuana. Employers operating in states that provide employment protections to marijuana users may consider allowing legal, off-duty use, while taking adverse action against those users that come to work under the influence.

Of course, it remains unclear how employers can determine whether an employee is under the influence of marijuana at work. Unlike with alcohol, current drug tests do not indicate whether and to what extent an employee is impaired by marijuana.  Reliance on observations from employees may be problematic, as witnesses may have differing views as to the level of impairment and, in any event, observation alone does not indicate the source of impairment.  Employers choosing to follow this “impairment standard” are advised to obtain as many data points as possible before making an adverse employment decision.

All employers – and particularly federal contractors required to comply with the Drug-Free Workplace Act and those who employ a zero-tolerance policy – should review their drug-testing policy to ensure that it (a) sets clear expectations of employees; (b) provides justifications for the need for drug-testing; (b) expressly allows for adverse action (including termination or refusal to hire) as a consequence of a positive drug test. Additionally, employers enforcing zero-tolerance policies should be prepared for future challenges in those states prohibiting discrimination against and/or requiring accommodation of medical marijuana users.  Those states may require the adjustment or relaxation of a hiring policy to accommodate a medical marijuana user.

The Callaghan decision also serves as a reminder of the intersection of medical marijuana use and disability.  Here, the court allowed a disability discrimination claim to proceed even though Plaintiff never revealed the nature of her underlying disability because cardholder status and disability were so inextricably linked.

Finally, employers should be mindful of their drug policies’ applicability not only to current employees, but to applicants as well. In Callaghan, the court found the employer in violation of state law before the employee was even offered the internship or had taken the drug test.

This post was written byNathaniel M. Glasser and Carol J. Faherty of Epstein Becker & Green, P.C.

New FDA Commissioner Hits the Ground Running

Fresh off his noticeably smooth confirmation, the new Commissioner of Food and Drugs, Dr. Scott Gottlieb, appeared before Congress last Thursday and unveiled his strategic initiatives and priorities for the Trump Food and Drug Administration (“FDA”).  These run the gamut from improving regulatory science and policies to streamlining clinical trials to spurring innovation on behalf of patients.  Two initiatives, in particular, merit closer attention and discussion: combating opioid abuse and addressing drug price increases through more, accelerated generic competition.

Opioid Regulation

In his first post to the FDA Voice blog, Dr. Gottlieb wrote:

As Commissioner, my highest initial priority is to take immediate steps to reduce the scope of the epidemic of opioid addiction. . . .  I believe it is within the scope of FDA’s regulatory tools – and our societal obligations – to take whatever steps we can, under our existing legal authorities, to ensure that exposure to opioids is occurring under only appropriate clinical circumstances, and for appropriate patients.

First among these steps, the Commissioner is establishing an Opioid Policy Steering Committee, comprised of “some of the agency’s most senior career leaders, to explore and develop additional tools or strategies FDA can use to confront this epidemic.”  The strategies under consideration include (1) mandatory education for health care professionals about (i) appropriate prescribing recommendations; (ii) how to identify the risk of abuse in individual patients; and (iii) how to get addicted patients into treatment; and (2) working more closely with provider groups to develop standards for prescribing opioids in different clinical settings, so that “the number of opioid doses that an individual patient can be prescribed is more closely tailored to the medical indication.”

Limiting the availability of prescription pain medication is a dicey proposition, however.  As Dr. Gottlieb acknowledged, certain situations “require a 30-day supply” and, “[i]n those cases, we want to make sure patients have what they need.  But there are plenty of situations where the best prescription is a two- or three-day course of treatment.”  The individualized medical judgments and circumstances that drive opioid prescribing likely mean that no single approach is likely to strike the proper balance between over-prescribing and ensuring sufficient access to adequate pain management.  Interestingly, the variability between opioid prescribers and patients did not stop the Centers for Medicare and Medicaid Services from proposing hard limits on opioid dosing for non-cancer pain or palliative/end-of-life care (i.e., chronic pain) for Medicare Advantage Organizations and Prescription Drug Plan Sponsors.

In fact, pain patients already have struggled under bright-line limitations on opioids.  As we previously reported, the State of Massachusetts enacted a new law in March 2016 that prohibits “a practitioner [from] issu[ing] a prescription for more than a 7-day supply . . . [w]hen issuing a prescription for an opiate to an adult patient for outpatient use for the first time [or] to a minor,” the first such limitation legislatively imposed by any state.”  Mass. Gen. Laws ch. 94C, § 19D (2016).  Massachusetts physicians surveyed following the law’s enactment complained that “the pendulum has swung too far, depriving pain patients of needed relief,” and that “regulations won’t solve the addiction problem . . . .  Instead, they make doctors reluctant to prescribe opioids.”

Broadly targeting opioids as a class of drugs also may cast too wide a net.  A recent article in the journal Substance Abuse reported “[t]he US opioid epidemic has changed profoundly in the last 3 years” in that “[h]eroin and fentanyl have come to dominate an escalating epidemic of lethal opioid overdose, whereas opioids commonly obtained by prescription play a minor role, accounting for no more than 15% of reported deaths in 2015.”  The article urged that the changing etiology of opioid overdose “require[s] substantial recalibration of the US policy response.”

What is clear—and what Dr. Gottlieb seems to recognize—is that opioid abuse and addiction are dynamic issues that differ from prescriber to prescriber and from one patient to another.  Those variables may make a one-size-fits-all”strategy unviable.

Drug Prices

During a budget hearing before the House Committee on Appropriations, Dr. Gottlieb testified that, “while the FDA does not have a direct role in drug pricing, we can take steps to facilitate entry of lower-cost alternatives to the market.”  He identified policy challenges that the last Congress had attempted to address through legislation designed to expedite access to affordable drugs.  Such legislation included the CREATES Act, which we previously analyzed.  The proposed law sought to prevent brand-name drug companies from using FDA safety rules (i.e., Risk Evaluation and Mitigation Strategies (REMS) and requirements thereunder, e.g., Elements to Assure Safe Use (ETASU)) for medicines with higher risk potential to block or delay generic entry.  “FDA has an important role to play in making sure that its statutory and regulatory processes are working as intended,” Gottlieb told Congress, “not being manipulated in ways that FDA and Congress did not intend.”

In response to growing political pressure in Washington to expedite drug reviews, Dr. Gottlieb assured lawmakers that biomarkers, new technologies, and more efficient clinical trial designs would make it possible to shorten the regulatory process.  But accelerated approval of expensive, investigational (albeit life-saving) therapies has raised concerns among health policy experts.

A recent op-ed published by the New England Journal of Medicine (NEJM) cautioned that

accelerated approval can lead to situations in which private payers may choose not to cover a drug because of high cost and lack of evidence of clinical efficacy, thereby thwarting the pathway’s goal of getting potentially important therapies to patients earlier, while major government payers are forced to cover the product, directing substantial tax dollars to drugs not yet shown to have clinical benefit.

The NEJM article’s authors argue that any biopharma company granted an accelerated approval should be subject to certain price restrictions until the confirmatory trials are completed, reasoning that “the price paid by taxpayers should reflect the strength of the available evidence about the drug’s clinical impact.”  Additionally, they proposed that all drugs moving through an accelerated-approval pathway should be subject to formal economic impact analyses after one to two years on the market, possibly funded by an increase in the user fees for manufacturers that use this pathway.

Dr. Gottlieb is also evaluating the generic drug and biosimilar review and approval process.  More specifically, Dr. Gottlieb is looking at measures to  facilitate communication between the industry and FDA, address complex molecules, and to speed up the approval of biosimilar products.

These recommendations are not without some appeal.  Despite seeking to deliver more “bang” for the taxpayer’s “buck,” however, prospectively capping the federal reimbursement for a high-cost drug product still subject to additional clinical trials and/or other R&D may create a financial disincentive to pharmaceutical manufacturers to foot the expense of developing breakthrough drugs to fill an unmet medical need.

Stay Tuned

To deliver on the promises of reducing the incidence of opioid abuse and lowering drug prices, Dr. Gottlieb’s FDA must navigate the competing interests and thorny health policy issues highlighted above.

Jason L. DroriDavid L. Rosen and Judith A. Waltz of Foley & Lardner LLP.

Voluntary Product Registry: Dietary Supplement Update

Leading dietary supplement trade association makes strides in developing product registry.

  • As previously covered, a leading dietary supplement trade association — the Council for Responsible Nutrition (CRN) — has been pursuing the goal of creating a Voluntary Product Registry for Dietary Supplements.  According to CRN, the goal of the registry is to increase transparency and give regulators greater access to information about the composition of supplement products currently on the market.

  • At a recent conference, CRN announced that it had retained the global science safety firm, UL, to develop and administer the product registry.  The current plan is to implement a two-tiered database.  Tier one will permit companies to add basic information about their products at no cost, and the information will be accessibdietary supplementle to any interested party.  Tier two will provide companies with a fee-based opportunity to add more detail about their products, and access will be restricted to specific audiences (e.g., regulatory authorities, retailers).

  • CRN anticipates that the registry will be operational by the end of 2016, and member companies will be required as a condition of membership to input all their product labels into the registry by July 2017.