Food and Drug Law

Intellectual Property in Crisis: Does SARS-CoV-2 Warrant Waiving TRIPS?

Daniel Walsh, MJLST Staffer

The SARS-CoV-2 virus (which causes the disease COVID-19) has been a massive challenge to public health causing untold human suffering. Multiple vaccines and biotechnologies have been developed to combat the virus at a record pace, enabled by innovations in biotechnology. These technologies, vaccines in particular, represent the clearest path towards ending the pandemic. Governments have invested heavily in vaccine development. In May 2020 the United States made commitments to purchase, at the time, untested vaccines. These commitments were intended to indemnify the manufacture of vaccines allowing manufacturing to begin before regulatory approval was received from the Food and Drug Administration. The United States was not alone. China and Germany, just to name two, contributed heavily to funding the development of biotechnology in response to the pandemic. It is clear that both private and public institutions contributed heavily to the speed with which biotechnology has been developed in the context of the SARS-CoV-2 pandemic. However, there are criticisms that the public-private partnerships underlying vaccine manufacturing and distribution have been opaque. The contracts between governments and manufacturers are highly secretive, and contain clauses that disadvantage the developing world, for example forbidding the donation of extra vaccine doses.

Advanced biotechnology necessarily implicates intellectual property (IP) protections. Patents are the clearest example of this. Patents protect what is colloquially thought of as inventions or technological innovations. However, other forms of IP also have their place. Computer code, for example, can be subject to copyright protection. A therapy’s brand name might be subject to a trademark. Trade secrets can be used to protect things like clinical trial data needed for regulatory approval. IP involved in the pandemic is not limited to technologies developed directly in response to the emergence of SARS-CoV-2. Moderna, for example, has a variety of patents filed prior to the pandemic that protect its SARS-CoV-2 vaccine. IP necessarily restricts access, however, and in the context of the pandemic this has garnered significant criticism. Critics have argued that IP protections should be suspended or relaxed to expand access to lifesaving biotechnology. The current iteration of this debate is not unique; there is a perennial debate about whether it should be possible to obtain IP which could restrict access to medical therapies. Many nations have exceptions that limit IP rights for things like medical procedures. See, e.g., 35 U.S.C. 287(c).

In response to these concerns the waiver of a variety of IP protections has been proposed at the World Trade Organization (WTO). In October 2020 India and South Africa filed a communication proposing “a waiver from the implementation, application and enforcement of Sections 1, 4, 5, and 7 of Part II of the TRIPS Agreement in relation to prevention, containment or treatment of COVID-19.” The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) sets minimum standards for IP standards, acquisition, and enforcement and creates an intergovernmental dispute resolution process for member states. Charles R. McManis, Intellectual Property and International Mergers and Acquisitions, 66 U. Cin. L. Rev. 1283, 1288 (1998). It is necessary to accede to TRIPS in order to join the WTO, but membership in the WTO has significant benefits, especially for developing nations. “Sections 1, 4, 5, and 7 . . .” relate to the protection of copyrights, industrial designs, patents, and trade secrets respectively. Waiver would permit nation states to provide intellectual property protections “in relation to prevention, containment or treatment of COVID-19” that fall below the minimum standard set by the TRIPs Agreement. At time of writing, 10 nations have cosponsored this proposal.

This proposal has been criticized as unnecessary. There is an argument that patents will not enter effect until after the current crisis is resolved, implying they will have no preclusive effect. However, as previously mentioned, it is a matter of fact that preexisting patents apply to therapies that are being used to treat SARS-CoV-2. Repurposing is common in the field of biotechnology where existing therapies are often repurposed or used as platforms, as is the case with mRNA vaccines. However, it is true that therapies directly developed in response to the pandemic are unlikely to be under patent protection in the near future given lag between filing for and receiving a patent. Others argue that if investors perceive biotech as an area where IP rights are likely to be undermined in the event of an emergency, it will reduce marginal investment in vaccine and biotech therapies. Finally, critics argue that the proposal ignores the existing mechanisms in the TRIPS Agreement that would allow compulsory licensing of therapies that nations feel are unavailable. Supporters of the status quo argue that voluntary licensing agreements can serve the needs of developing nations while preserving the investments in innovation made by larger economies.

The waiver sponsors respond that a wholesale waiver would permit greater flexibility in the face of the crisis, and be a more proportionate response to the scale of the emergency. They also assert that the preexisting compulsory licensing provisions are undermined by lobbying against compulsory licensing by opponents of the waiver, though it is unlikely that this lobbying would cease even if a waiver were passed. The sponsors also argue that the public investment implies that any research products are a public good and should therefore be free to the public.

It is unclear how the current debate on TRIPS will be resolved. The voluntary licensing agreements might end up abrogating the need for a wholesale waiver of IP protections in practice rendering the debate moot. However, the WTO should consider taking up the issue of IP protections in a crisis after the current emergency is over. The current debate is a reflection of a larger underlying disagreement about the terms of the TRIPS Agreement. Further, uncertainty about the status of IP rights in emergencies can dissuade investment in the same way as erosion of IP rights, implying that society may pay the costs of decreased investment without reaping any of the benefits.

 


COVID-19 Vaccination: Pervasive Skepticism and Employer Mandates in the United States

Drew Miller, MJLST Staffer

On December 31, 2019, the COVID-19 pandemic began when the World Health Organization’s (WHO) Chinese office picked up a media statement by the Wuhan Municipal Health Commission regarding cases of “viral pneumonia.” Nearly a year later, despite the protective measures instituted on a global scale to slow the spread, COVID-19 has claimed the lives of nearly 1,500,000 people worldwide) and shows no sign of slowing down. All hope is not lost; scientists and biopharmaceutical companies have worked diligently throughout the crisis, and a large-scale vaccination release seems imminent. However, given the prevalence of anti-vaccination sentiment in the United States, it may be difficult to distribute the vaccine to enough people; employer-mandated vaccines likely offer the best chance for widespread vaccination, but the standards governing such mandates remain unclear.

Anti-Vaccination Sentiment in the US

Whether the vaccine will provide outright immunity or simply partial protection, it will regardless be a critical step toward ending the pandemic. However, vaccines are obviously only effective if people agree to get the shot, and that may prove to be a significant barrier in the United States. Vaccine doubt and anti-vaccination movements continue to grow in popularity for a variety of reasons. Social media’s unique ability to bring together like-minded individuals across the globe inevitably results in the creation of insular groups; anti-vaccine support from celebrities such as Jenny McCarthy and Jim Carrey provide a degree of validation to “regular” people who feel the same way; and general government distrust, which has sharpened considerably under the tumultuous and polarizing Trump presidency, heightens suspicions surrounding FDA testing and approval processes. Finally, as noted by Dr. Paul A. Offit, an infectious disease expert and co-inventor of a vaccine for rotavirus, “Vaccines are a victim of their own success. We have largely eliminated the memory of many diseases.”

Moreover, skepticism regarding the safety and efficacy coronavirus vaccine is not entirely unfounded. The vaccine development process typically takes a decade, whereas this one began under a year ago. A group of researchers at the Johns Hopkins Center for Health Security and the Texas State University anthropology department writes, “If poorly designed and executed, a COVID-19 vaccination campaign in the U.S. could undermine the increasingly tenuous belief in vaccines and the public health authorities that recommend them – especially among people most at risk of COVID-19 impacts.” The results of a poll conducted by Pew Research Center in September indicates the consequences of all these factors: just over half (51%) of U.S. adults definitely or probably would get a COVID-19 vaccine if it were available today—a 21% drop from 72% in May.

Employer-Mandated Vaccines

With skepticism at an all-time high, the responsibility for raising vaccination rates in the U.S. may fall to employers. The U.S. Occupational Safety and Health Administration (OSHA) allows employers to legally impose an influenza vaccine requirement on their workers, but there are several requirements and exceptions that make such a mandate more difficult to impose.

First, employees are entitled under the Americans with Disabilities Act (ADA) to request medical and disability exemptions. This exemption requires proof of an underlying disability or medical condition that renders an employee essentially unable to safely get the vaccine. Second, employees may also claim religious exemptions to avoid an employer-mandated vaccine. However, Title VII of the Civil Rights Act of 1964 states that an employee must have a “sincerely held religious belief” against vaccination. In 2020, the Third Circuit Court of Appeals held that an employee’s “holistic health lifestyle” and personal belief that vaccines are harmful were insufficient to trigger protection under the Civil Rights Act. See Brown v. Children’s Hosp. of Philadelphia, 794 Fed. Appx. 226 (3rd Cir. 2020). The court wrote, “[I]t is not sufficient merely to hold a ‘sincere opposition to vaccination’; rather, the individual must show that the ‘opposition to vaccination is a religious belief.’” Id. (citing Fallon v. Mercy Catholic Med. Ctr. of Southeast Pa., 877 F.3d 487, 490 (3rd Cir. 2017)).

There are two primary standards governing the situations in which employers may legally require vaccinations regardless of religious or medical exemptions. Title VII does not require employers to make “reasonable accommodations” for medical or religious reasons if it would pose an undue hardship, which it defines as “more than de minimis cost” to the operation of the business. The ADA standard is stricter, requiring reasonable accommodation barring undue hardship, which it defines as an “action requiring significant difficulty or expense.”

Finally, because vaccinations are “medical examinations” under the ADA, the COVID-19 vaccine would need to be deemed “job-related, consistent with business necessity or justified by a direct threat, and no broader or more intrusive than necessary.” Although the Equal Employment Opportunity Commission (EEOC), which is responsible for enforcing federal anti-discrimination laws in employment, has labeled COVID-19 as a “direct threat” to the workplace and stated that employers are allowed under the ADA to “bar an employee from physical presence in the workplace if he refuses to have his temperature taken or refuses to answer questions about whether he has COVID-19, has symptoms associated with COVID-19, or has been tested for COVID-19,” it has not yet stated whether employers will have the right to make a vaccine mandatory.

Conclusion

As such, the rights of employers to legally impose COVID-19 vaccination requirements on employees are uncertain and, absent clear direction or regulation, will likely require case-by-case analysis to determine the validity of each exemption and the corresponding hardship to business. Consequently, even if employers do have the legal right, protracted legal battles are the only remedy, and given the pervasive fear of vaccinations in today’s social climate, there are likely to be a great many of them. Meanwhile, the COVID-19 pandemic will continue to ravage the nation.


FDA Approval of a SARS-CoV-2 Vaccine and Surrogate Endpoints

Daniel Walsh, Ph.D, MJLST Staffer

The emergence of the SARS-CoV-2 virus has thrown the world into chaos, taking the lives of more than a million worldwide to date. Infection with SARS-CoV-2 causes the disease COVID-19, which can have severe health consequences even for those that do not succumb. An unprecedented number of vaccines are under development to address this challenge. The goal for any vaccine is sterilizing immunity, which means viral infection is outright prevented. However, a vaccine that provides only partially protective immunity will still be a useful tool in fighting the virus. Either outcome would reduce the ability of the virus to spread, and hopefully reduce the incidence of severe disease in those who catch the virus. An effective vaccine is our best shot at ending the pandemic quickly.

For any vaccine to become widely available in the United States, it must first gain approval from the Food and Drug Administration (FDA). Under normal circumstances a sponsor (drug manufacturer) seeking regulatory approval would submit an Investigational New Drug (IND) application, perform clinical trials to gather data on safety and efficacy, and finally file a Biologics License Application (BLA) if the trials were successful. The FDA will review the clinical trial data and make a determination as to whether the benefits of the therapy outweigh the risks, and if appropriate, approve the BLA. Of course, degree of morbidity and mortality being caused by COVID-19 places regulators in a challenging position. If certain prerequisites are met, the FDA as the authority to approve a vaccine using an Emergency Use Authorization (EUA). As pertaining to safety and efficacy, the statutory requirements for issuing an EUA are lower than normal approval. It should also be noted that an initial approval via EUA does not preclude eventual normal approval.  Full approval of the antiviral drug remdisivir is an example of this occurrence.

In any specific instance, the FDA must conclude that a reason for using the EUA process (in this case SARS-CoV-2):

can cause a serious or life-threatening disease or condition . . . based on the totality of scientific evidence available . . . including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that . . . the product may be effective in diagnosing, treating, or preventing [SARS-CoV-2] . . . the known and potential benefits of the product, when used to diagnose, prevent, or treat [SARS-CoV-2], outweigh the known and potential risks of the product . . . .

21 USC 360bbb-3(c). On its face, this statute does not require the FDA to adhere to the full phased clinical trial protocol in grating an EUA approval. Of course, the FDA is free to ask for more than the bare minimum, and it has wisely done so by issuing a set of guidance documents in June and October. The FDA indicated that, at the minimum, a sponsor would need to supply an “interim analysis of a clinical endpoint from a phase 3 efficacy study;” that the vaccine should demonstrate an efficacy of at least 50% in a placebo controlled trial; that phase 1 and 2 safety data should be provided; and that the phase 3 data “should include a median follow-up duration of at least two months after completion of the full vaccination regimen” (among other requirements) in the October guidance.

It is clear from these requirements that the FDA is still requiring sponsors to undertake phase 1, 2, and 3 trials before FDA will consider issuing an EUA, but that the FDA is not going to wait for the trials to reach long term safety and efficacy endpoints, in an effort to get the public access to a vaccine in a reasonable time frame. The Moderna vaccine trial protocol, for example, has a study period of over two years. The FDA also has a statutory obligation to “efficiently review[] clinical research and take[] appropriate action . . . in a timely manner.” 21 USC § 393(b)(1).

One method of speeding up the FDA’s assessment of efficacy is a surrogate endpoint. Surrogate endpoints allow the FDA to look at an earlier, predictive metric of efficacy in a clinical trial when it would be impractical or unethical to follow the trial to its actual clinical endpoint. For example, we often use blood pressure as a surrogate endpoint when evaluating drugs intended to treat stroke. The FDA draws a distinction between candidate, reasonably likely, and validated surrogate endpoints. The latter two can be used to expedite approval. However, in its June guidance, the FDA noted “[t]here are currently no accepted surrogate endpoints that are reasonably likely to predict clinical benefit of a COVID-19 vaccine . . . .  [and sponsors should therefore] pursue traditional approval via direct evidence of vaccine safety and efficacy . . . .” This makes it unlikely surrogate endpoints will play any role in the initial EUAs or BLAs for any SARS-CoV-2 vaccine.

However, as the science around the virus develops the FDA might adopt a surrogate endpoint as it has for many other infectious diseases. Looking through this list of surrogate endpoints, a trend is clear. For vaccines, the FDA has always used antibodies as a surrogate endpoint. However, the durability of the antibody response to SARS-CoV-2 has been an object of much concern. While this concern is likely somewhat overstated (it is normal for antibody levels to fall after an infection is cleared), there is evidence that T-cells are long lasting after infection with SARS-CoV-1, and likely play an important role in immunity to SARS-CoV-2. It is important to note that T-Cells (which coordinate the immune response and some of which can kill virally infected cells) and B-Cells (which produce antibody proteins) are both fundamental, and interdependent pieces of the immune system. With this in mind, when developing surrogate endpoints for SARS-CoV-2 the FDA should consider whether it is open to a more diverse set of surrogate endpoints in the future, and if so, the FDA should communicate this to sponsors so they can begin to build the infrastructure necessary to collect the data to ensure vaccines can be approved quickly.

 


Can the Legal System Help Combat COVID-19

Amanda Jackson, MJLST Staffer

As the novel coronavirus, COVID-19, continues its global rampage, the United States has been hard hit.  Now third with respect to number of new cases, there is little evidence to show that the case count will decrease any time soon.  If Italy provides any indication of what is to come, the United States is only going to be hit harder by the life-threatening virus.  Both federal government and local governments have taken drastic measures to combat the spread of COVID-19, including state-wide shelter-in-place orders, closing schools and universities, banning dining in at bars and restaurants, and moving non-essential businesses to work-from-home models.

As the confirmed cases continue to rise, so does uncertainty and uneasiness among the nation and the world as a whole.  What will fix this crisis?  How long will these measures be in place?  How many more people will get sick and potentially pass away from the virus?  What will happen to the economy?  Will my loved ones be okay?  The questions never seem to end.  Luckily, however, there are some answers as to how different laws, administrative agencies, and regulations in place in the United States can aid in the fight against the quickly spreading coronavirus.

First, the Defense Production Act (DPA) can alleviate shortages in medical equipment.  As concern about the novel virus itself grows, concern for the availability of necessary supplies and equipment also seems to grow at record speeds.  A lack of masks and other personal protective equipment for healthcare workers, a shortage in ventilators and beds for sick patients, and even a need for healthcare workers and hospital space are becoming more prevalent as the COVID-19 crisis continues.   The DPA, a Korean War-era law, enables the federal government to require private companies to provide for the needs of national defense.  The DPA may not be able to satisfy the need for healthcare workers and hospital space, but it can allow the federal government to direct manufacturers to produce the desperately needed medical equipment for healthcare workers and patients.  However, the President must invoke the DPA in order for it to make a difference, and as of right now, the DPA has not been invoked to aid in the fight against coronavirus.  Although some companies have increased or altered production to help restock the necessary equipment, it remains unclear whether that alone, without invoking the DPA, will be enough to meet the needs of the United States in the coming weeks.  Even so, the DPA provides a robust option to fulfill the needs of the nation in the fight against the pandemic.

Second, the Federal Drug Administration’s (FDA) and the National Institute of Health’s (NIH) ability to fast track vaccines and therapeutic drugs can speed up development of a COVID-19 vaccine or therapy.  Called an Emergency Use Authorization (EUA), the FDA is able to authorize emergency use of an unapproved product or an unapproved use of an approved product under a declaration of a public health, domestic, or military emergency, or a material threat.  The evidence required for approval of an EUA is that the product “may be effective” to treat, diagnose, or prevent the conditions associated with the declaration.  This is a lower standard than the “effectiveness” standard used for typical FDA approvals, a process that takes on average twelve years to go from a new drug in a laboratory to a drug on a pharmacy shelf.  In determining whether to approve the EUA, the Commissioner has to determine that the known and potential benefits of the product outweigh the risks associated with the product, while also considering the threat prompting the emergency declaration.  Fortunately, the FDA has already issued multiple EUAs with respect to the novel coronavirus, such as for tests to detect COVID-19.  The FDA has also instituted flexible measures outside of EUAs that enable states to take a more prominent role than typically allowed.  For example, the FDA is now allowing states to approve COVID-19 tests without requiring FDA approval or an EUA.  Moreover, NIH is also fast-tracking development of a coronavirus vaccine, with a Phase I clinical trial of the vaccine candidate having already begun.

Third, declarations of major disaster areas will open up emergency funds to help states and local governments respond to an outbreak.  Major disaster area declarations are often requested when a disaster exceeds the response capabilities of state and local governments under extremely severe circumstances.  Major disaster area declarations enable a wide range of federal assistance for both individuals and public infrastructure.  With respect to coronavirus, the President has already declared New York and other hard-hit states as major disaster areas, the first time in United States history that a major disaster has been declared for a public health threat.  The declaration enables the federal government to pay for a majority of the states’ costs and mobilize the Federal Emergency Management Agency (FEMA) to deploy assistance in the state, among other methods of assistance.

Fourth, shelter-in-place orders by local governments may reduce the spread of the virus.  Shelter-in-place orders mandate that residents stay in their homes, except for essential trips (e.g., to the grocery store or a pharmacy).  Many shelter-in-place orders also force all non-essential businesses to close.  These orders are generally constitutional under a state’s police power.  At least eight states and many cities have issued shelter-in-place orders as a means to flatten the curve and reduce the impact of coronavirus on society and the healthcare system.  Some law enforcement officials appear to be taking the orders very seriously, breaking up parties in violation of the shelter-in-place rules or stating that the orders will be “strictly enforced.”

Moreover, there are multiple bills working their way through the federal government that will hopefully provide some more answers and relief for the American people.  Although those options are only a few of the tools in the government’s toolbox, if used properly, they can help the nation combat COVID-19.


Foodborne Illness Law: E. coli, Salmonella, and More

Katherine Nixon, MJLST Staffer

Sometime in the fall of 2018, I walked into Chipotle hoping for a nice savory burrito bowl. The best burrito bowl—at least in my opinion—is made up of the following: brown rice, chicken, cheese, lettuce, hot salsa, sour cream, and guacamole. One ingredient missing can throw off the whole experience. Well, I walked into Chipotle only to find a printed sign on the glass in front of the various ingredients. Let’s be honest, that never means anything good. The sign notified customers that Chipotle would not currently be offering romaine lettuce due to an E. coli outbreak. At first, all I could think was “Noooo, not my beloved burrito bowl. What will it be like without the crunchy lettuce?”

In looking past my immediate concern over the negative effect that a lettuceless burrito bowl would have on my taste buds, I was ultimately thankful I had not eaten the romaine lettuce. Big picture things. It was discovered that the romaine lettuce came from a farm in Santa Barbara County, California. It was distributed through many avenues and not just to food establishments like Chipotle. Unfortunately, people became very sick. According to the Center for Disease Control and Prevention (CDC), 62 people were infected from 16 states and the District of Columbia. Further, 25 people were hospitalized and 2 people developed a form of kidney failure. This ended up being a big deal. That particular outbreak began in October 2018 and wasn’t declared over until January 9, 2019.

Believe it or not, E. coli outbreaks occur with some frequency. A massive outbreak that began in September 2019 was just declared over by the CDC on January 15, 2020. Again, the source of that outbreak was romaine lettuce. Other outbreaks in 2019 came from ground bison, flour, and ground beef. Aside from E. coli, there are other types of outbreaks as well. For instance, in 2019, there were several Salmonella outbreaks related to food items such as papayas and frozen raw tuna. Many people fell sick.

At this point, you might be wondering—what does this all have to do with law? It turns out there is a whole body of law generally referred to as “foodborne illness law.” I know—you definitely don’t learn about that in your normal law school curriculum. Yet, the name is somewhat self-explanatory. As succinctly put by the Public Health Law Center at Mitchell Hamline School of Law, “[A] person who is injured as a result of a foodborne illness may bring a civil cause of action against another by claiming that the other individual is legally liable for the harm caused by the foodborne illness.” Sometimes, there is even strict liability.

Overall, this type of law can be highly technical and usually involves the help of experts. It also can be quite difficult. Including the difficulty that often comes in discovering the source of a certain outbreak as well as the manufacturer of that source. It can be like piecing a giant puzzle together. However, once the pieces start to fit together, it all begins to make sense. If you have a science background, especially biology, this may be an area of law for you to consider. Next time you are at a family gathering and Uncle Eddy asks what you want to do, tell him you want to specialize in foodborne illness law. That will surely grab his attention.

 

 


Treating Depression with Ketamine? How The Investment Was Made

Hunter Moss, MJLST Staffer

Depression is a serious mental disorder that afflicts millions of Americans each year. One in three of these individuals struggles to find a treatment method that alleviates their condition, and are aptly said to suffer from treatment-resistant depression. In the most severe cases, treating depression can be a life or death decision—depression is the leading cause of over 41,000 suicides every year. For those dealing with depression, every day is a struggle to persevere and try to regain a sense of normalcy.

A new therapy for treatment-resistant depression was approved by the Food and Drug Administration (FDA) earlier this week, one that could help those that have been unable to find relief elsewhere. The unexpected source of the therapy is esketamine. If the name of this drug sounds familiar, it is because the name is based on, and molecularly similar to, the street drug named ketamine. While originally synthesized in the 1960’s as an anesthetic and first used widely in the Vietnam War, ketamine is now known as a party drug, providing the user with mild hallucinations and a sense of euphoria. Due to its dangerous side-effects and potential for abuse, ketamine was placed on the Schedule III of the United States Controlled Substance Act in August of 1999.

In the early 1990’s, researchers at Yale University first recognized the potential for ketamine to treat the symptoms of depression. Since then, scientists sought to confirm the viability of ketamine as a treatment option for individuals who did not experience relief from other treatment methods. A 2012 study out of Baylor College of Medicine proved just that: 85% of patients with severe depression reported the treatment to be effective. Unlike selective serotonin reuptake inhibitors (SSRIs), which are most commonly prescribed to treat depression and can take weeks to build in a patient’s system before becoming effective, ketamine can provide nearly immediate relief with its full effect being felt in as little as two days.

With the science firmly in place, the next hurdle advocates of ketamine faced was of perception—in the eyes of the FDA and the public alike. Radical clinics began to emerge across the country to provide patients suffering from treatment-resistant depression with a safe, heavily-monitored environment to undergo care. Because ketamine had yet to be recognized as a potential aid for depression by the FDA, clinic physicians would often have to prescribe the drug under the guise of using it as an anesthetic. The “don’t ask, don’t tell” approach to a new treatment for a severe mental disorder created some inevitable quandaries for both doctors and patients, who would be unable to receive insurance coverage for a non-FDA approved treatment program.

While the medical community was well aware of the healing potential of ketamine, pharmaceutical companies were reluctant to make the investment. The average price-tag of a clinical trial for the FDA is $19m. There is certainly a market for the drug with countless Americans suffering from depression. The issue holding pharmaceutical companies back is related to patent law. In order to receive a patent, the proposed invention must be novel—and considering that ketamine has been around for nearly sixty years, that would be an impossible claim to make. Without patent protection, the multi-million dollar investment is bad economics for big pharma, even if the trials could provide relief for millions of Americans.

So why did Janssen Pharmaceuticals, the developer of a treatment method for depression based on ketamine, make the investment and receive FDA approval for its new drug Sprovato? The answer is because Sprovato is esketamine, a sufficiently different molecule from ketamine to be patentable. Certain molecules can be left-handed and have right-handed doppelgangers. While it is beyond the scope of this blog piece (and the ability of its author) to explain the difference between the two, esketamine is the left-handed version of ketamine’s right hand. The deviation between the molecules is a significant enough difference to pass the novelty requirement necessitated by the U.S. Patent and Trademark Office (USPTO). While there is some debate as to whether esketamine is as effective as its counterpart, esketamine passed the FDA’s clinical trials and, for the most part, has been received as a viable alternative to ketamine treatment. This development could help legitimize the countless ketamine clinics that have emerged across the United States over the last few years, yielding a promising new alternative for those struggling with severe depression. At the same time, the story of ketamine raises questions about the roles of several actors in the health care system, specifically pharmaceutical companies, the FDA and the USPTO, in delaying the introduction of life saving medication in order to adhere their respective financial and regulatory requirements.


Health Supplements: The “Wild West” of FDA Regulations

Gabe Branco, MJLST Staffer 

At some point, we all have taken a multivitamin and/or some type of dietary supplement. They are hard to miss in most stores such as Target or Wal-Mart.  The bright colored packaging and unfulfilling promises of “losing weight quickly” without dieting or “building muscle” without working out catches everybody’s attention. Most people assume that these products, ironically labeled “health” or “dietary” supplements, must be safe to ingest due to placing them in the same category as a “drug,” or because they deem the supplement to be “natural.” However, the reason people are mistaken is because the Food and Drug Administration (“FDA”) chooses to differentiate “health” products from “drugs.”

Under the FDA’s current regulatory scheme, “health” supplements are treated more like special foods than drugs. Drugs are considered unsafe until proven safe through clinical trials. These trials must be done on all drugs, even those that are sold without a required prescription. The trials must show that the drug is both safe and effective for the specified use. Once the drug is approved, manufacturers are subject to carefully monitored conditions and packaging requirements. The packaging requirement includes conditions the drug has been proven to treat, known side effects, contraindications, and unsafe interactions with other drugs. After the drug has been manufactured and released to the public for consumption, the FDA follows up on any adverse effects consumers and their doctors report, along with any adverse effects reported by the manufacturer.

“Dietary” supplements, on the other hand, are seen as safe until proven unsafe, a stark contrast to their drug counterpart. The Dietary Supplement Health and Education Act (DSHEA) defines “dietary” supplements as a category of food. As such, “dietary” supplements do not undergo the rigorous pre-manufacturing and post-manufacturing approval and monitoring process that drugs do. DSHEA prohibits supplements from containing anything that may have “a significant or unreasonable risk of illness or injury” when the supplement is used as directed on the label, or with regular use if there are no directions. While the regulation makes clear these supplements should not significantly or unreasonably expose the public to increased risk of harm, DSHEA fails to enforce the regulation with any preventative measures.

DSHEA effectively allows manufacturers to print any statement they wish on “dietary” supplement labels, so long as it is followed by the phrase “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This practice is troublesome because the statement may suggest or claim outright that the “dietary” supplement treats symptoms or results in an outlandish outcome if taken. Even with the FDA warning, consumers would have little to no reason to assume that supplements placed on shelves everywhere could contain none of the listed ingredients or unknown ingredients that can cause adverse health effects.

The FDA has the authority to stop any production of “dietary” supplement if it is shown there is an increased risk of harm to the public. However, this only occurs after the release of the supplement and subsequent adverse effects impact consumers. Due to the lack of pre-manufacturing testing requirements, many “dietary” supplements contain germs, pesticides, or toxic heavy metals that may adversely impact consumers. In addition, many “dietary” supplements either do not contain what is listed on the label, contain more or less of what is listed on the label, or even contain ingredients not listed on the label. This issue could also stem from parties other than the manufacturers and sellers. Without any regulations pre-manufacturing, many suppliers of ingredients may mix or substitute the ingredients sold to manufacturers with less expensive or tainted filler ingredients.

These issues become problematic when an ingredient the FDA would deem a “drug” finds its way into a “dietary supplement.” Many male enhancers or muscle building “dietary” supplements have been found to contain substances much like Viagra or Cialis, which are regulated as “drugs.” In addition, certain weight loss supplements have been found to contain sibutraimine, which has been banned in the United States. All of these supplements were recalled by the FDA in a reactionary manner. However, in most instances a “dietary” supplement may contain a drug that has little to no known effects. Having little to no known effects makes it more difficult to detect if a “dietary” supplement indeed contains a drug, and if it then must undergo the more rigorous FDA drug requirements. By providing manufacturers and sellers a pathway to produce categorical “drugs” and distribute them to the public without undergoing the rigorous FDA drug testing processes, DSHEA potentially does more deregulation than regulation.

FDA regulations concerning “dietary” supplements should be as stringent as regulations governing drugs. The simplest solution would be to implement the same pre-manufacturing and post-manufacturing procedures that are required of “drug” manufacturers into the “dietary” supplement realm. Doing so would fulfill DSHEA’s requirement that the “dietary” supplements do not cause a significant or unreasonable increase in risk of injury or illness. Additionally, this would allow the FDA to regulate “drugs” to its fullest potential.


Impact of China’s Generics Push on Innovator Drug Companies

Sherrie Holdman, MJLST Staffer

With a population of 1.42 billion, China presents a large market for both innovator manufacturer and generic drug companies.  Currently, about 95% of marketed drugs are sold by generics. However, many patients in China opt to use more expensive, imported, brand-name drugs.  In an effort to address this problem, China’s State Council has announced its “Opinions Concerning Reforms of Policies to Improve the Supply and Utilization of Generics” to encourage the people of China to use generic drugs early this year.  As a regulatory document, the Opinion shed light on the future direction of China’s generic market.

The Opinion identifies three important suggestions to guide implementation. The first suggestion is to promote research and development of generic drugs in China.  The Opinion proposes a drug list to be compiled that identifies drugs for which generic counterparts don’t exist yet. The Opinion also encourages the government to develop key technologies in manufacturing generics.  The second suggestion aims to improve the quality and efficacy of generic drugs. Generics will only be approved if their quality and efficacy are equivalent to the original drugs.  To facilitate this goal, the State Council proposes speeding up the conformity assessment of quality and efficacy of generic drugs and improving the quality management of generic drugs.  The third suggestion is to provide policy incentives for generics development, including implementation of a tax policy for generic manufacturers. Under this policy, a generic manufacturer, once designated as a “high technology enterprise,” will have a preferential tax rate of 15%, compared to the 25% rate for other companies.  In order to be a “high technology enterprise,” the generic manufacturer will need to meet certain qualifications. Meanwhile, the Opinion encourages patentees to voluntarily grant compulsory licenses to Chinese generic manufacturers when there is “a serious threat to the public health.”  However, despite its long existence in Chinese patent law and regulation, the compulsory licenses are historically rare in practice, partly because of the difficulty in defining what constitutes a “serious threat to the public health.”    

In order to balance the interests of innovator and generic drug companies, the Opinion provides recommendations for strengthening the enforcement of intellectual property rights.  For example, the Opinion proposes establishing an “early warning patent system” to prevent generic manufacturers from infringing on valid patents and thus mitigating the risk of infringement.  Moreover, the State Council proposed to enhance accessibility of innovative drugs, especially imported oncology drugs, by applying no tariffs on imported new drugs. A five-year patent extension for new drugs was also proposed to enhance the intellectual property protection of innovator drugs.

Following the announcements promulgated in the Opinion, on April 25, 2018, China Food and Drug Administration (CFDA) released its “Public Comment Draft of Pharmaceutical Data Exclusivity Implementing Rules (provisional).” The Draft proposes that “innovative new drugs” will enjoy six years of data protection and “innovative therapeutic biologics” will enjoy 12 years of data protection.  By proposing data protection for new drugs, China encourages multinational corporations to include China in international multicenter clinical trials and to concurrently apply for market introduction in China.  Even if the new drug is introduced to China at a later time, the drug will still be entitled to a data protection period (e.g., from one to five years). The public comment period for the Draft was closed on May 31, 2018 and the final rule is expected soon.  

Facing China’s generics push, innovator drug makers can strengthen their IP strategy in numerous ways.  For example, companies should disclose information about the patents in the drug list in a timely manner, making the public and government aware of the patents.  Further, companies should also establish a multi-directional scheme for IP rights protection including not only patent, but also knowhow, trade secret, design, trademark and copyright.