INTRODUCTION

 

Congress, in order to reduce the black market in illegal drugs, should begin taking incremental steps toward making drugs less of a criminal justice responsibility and more of a public health responsibility.¹

--Former Baltimore Mayor Kurt L. Schmoke

 

Has the time arrived for the incremental steps that Mayor Schmoke envisioned more than 30 years ago? One does not need to look any further than marijuana, which has been a tightly controlled substance in the U.S. for more than 85 years but is rapidly gaining acceptance as a medical product and a permissible intoxicant.^2,3 It is likely that many pharmacists are supportive of this regulatory movement and may even have “experimented” with this Schedule I drug while in school. But what about something like cocaine? “That won’t happen,” you say? Then you should be aware that Oregon passed a law in 2020 that reduced the penalty for the unauthorized possession of less than two grams of cocaine to the payment of a small fine.⁴

 

Other states, municipalities, and countries have also begun taking steps towards loosening or eliminating penalties for prohibited recreational substances, in some cases including other drugs currently listed in Schedule I of the Controlled Substances Act (CSA). Is this the start of a new national trend leading to a relaxation of restrictions on previously controlled substance and perhaps even to someday permit retail sales? Will the future of drug control start to look more like the 1890s than the 1990s?

 

This continuing education activity will review national and international regulation of controlled substances and some changes that governments are enacting or considering to loosen their control. Do these events indicate that society’s view of controlled substances and use disorders—and pharmacy’s role—are evolving?

 

Pause and Ponder: Will biennial controlled substance inventories and the familiar red “C” go the way of manual typewriters and become relics of a bygone era?

 

REGULATION OF CONTROLLED SUBSTANCES

 

Historical Perspective

In the 19^th Century, what we now call controlled substances were readily available in retail locations. In the 1890s, the Sears and Roebuck catalog (that’s the 19^th Century Amazon for our younger readers) offered a syringe and a small amount of cocaine for purchase for $1.50⁵ (equivalent to about $50 today). Individuals could also order the tonic, Wine of Coca, a mixture of coca-leaf extract and Bordeaux wine, which was promoted as “a genuine rich wine ... well known throughout Europe for its strengthening and nourishing qualities” at retail for 95 cents.⁵ In addition to cocaine, consumers could also openly purchase morphine and heroin from catalogs, apothecaries, and physicians. ⁵

 

The popularity of cocaine-infused beverages, tonics, and powders grew in the late 1800s, and were generally held to have therapeutic value for a variety of conditions, including headache and fatigue, constipation, nausea, asthma, and impotence.⁶ Most pharmacy personnel are probably aware that a pharmacist in Atlanta, John Pemberton, took advantage of prohibition being enacted in parts of Georgia and replaced the wine in Wine of Coca with a sugary syrup and added a kola-nut extract containing caffeine in 1886.⁷ He named the concoction Coca-Cola and described it as a temperance drink.⁷

 

Although frequently denied by the company, Coca-Cola contained a small amount of cocaine (and likely the precursor, ecgonine) and became one of the world’s most popular tonic/beverage sold at retail, often at pharmacy soda fountains.^6,8 Early in the 20^th Century, public opinion about cocaine began to turn negative and the company (by then owned by another pharmacist, Asa Candler), tried to remove cocaine from the beverage but it would not become completely cocaine-free until 1929 when newer extraction methods were developed.⁶

 

Recently, the well-known billionaire, Elon Musk, jokingly(?) tweeted “Next I’m buying Coca-Cola to put the cocaine back in.”⁸ Current legislative changes discussed below suggest that this notion is not so far-fetched.

 

During the early part of the 20^th Century, there were no federal agencies that regulated medical and pharmacy practice, and physicians could freely prescribe cocaine and morphine as treatment for pain.⁹ Drug abuse became increasingly common and emerged as a significant social and public health issue, and a less permissive attitude towards drugs began to take hold.⁹

 

The first federal law to ban the non-medical use of a substance was the Smoking Opium Exclusion Act in 1909; it prohibited the possession, importation, and use of opium for smoking, although it could continue to be used medically.¹⁰ A more significant step was the passage of the Harrison Narcotic Tax Act in 1914 which regulated “narcotics” (defined as opiates and cocaine) by imposing a special tax upon anyone who produced, imported, manufactured, sold, dispensed, distributed, or compounded these substances.¹¹ Note that the act was an economic regulation to comply with treaty obligations and did not directly prohibit the use nor sale of opiates and cocaine.¹

 

The Harrison Act required physicians and pharmacists who prescribed or dispensed “narcotics” to be registered and pay a fee of $1 to $24 per year^11,12 (equivalent to $29 to $700 today). The act mandated special order forms and record keeping whenever narcotic drugs were sold. They could only be provided from packages bearing a government stamp.¹²

 

By using the federal government’s taxing power to restrict the use of opiates to professional practices, the Harrison Act effectively created the first class of prescription drugs.¹¹ (The Food Drug and Cosmetic Act in 1938 formally established prescription-only drugs and the 1951 Durham-Humphrey Act [sponsored by two pharmacist-legislators] gave the U.S. Food and Drug Administration (FDA) authority to designate which drugs would require prescriptions.¹³)

 

After 1919, oversight by the Treasury Department expanded to define the scope of professional practice.¹¹ Previously, physicians interpreted terms in the act such as “legitimate medical purposes,” “professional practice,” and “prescribed in good faith” to mean that they could provide narcotics to ease the suffering of withdrawal in addicts who were regarded as having a disease.¹² However, the Treasury Department interpreted the Harrison Act to mean that any prescription for an addict for the purpose of relieving the trauma of addiction was illegal, and the Courts supported this position.¹² Consequently, the only source available for an addict to obtain narcotics was through illegal means.¹²

 

The law also established the first federal narcotics agents, although their enforcement powers were limited. The Federal Bureau of Narcotics (FBN) was established in 1930 and was given the authority to enforce the Harrison Act and other anti-drug laws and later also oversaw the Marijuana Tax Act (see below).¹⁴ President Herbert Hoover appointed Harry J. Anslinger to be Commissioner of Narcotics, a position he would hold under four U.S. presidents for more than three decades. He became the face of the government’s hardline approach to eradicate drug abuse.¹⁴

 

Later, the 18^th Amendment of the Constitution and the Volstead Act banned the manufacture, transportation, or sale of alcohol in 1919.^10,15 (By this time, many states had already banned the sale of alcohol.) Prohibition was overturned by the 21^st Amendment in 1933.

 

By 1930, 30 states had also prohibited the use of marijuana, beginning with California in 1913 and Utah in 1914.¹⁶ (Ironically, California became the first state to approve the medical use of marijuana 83 years later.) In 1937, Congress passed the Marihuana Tax Act which was modeled after the Harrison Act.⁵⁵ The law didn’t specifically criminalize the use or possession of marijuana, but it required practitioners register and pay a tax, and imposed a fine of up to $2000 (about $40,000 today) and five years in prison for non-payment.^10,17 There is a widely held feeling that the push for stricter control of marijuana was fueled by non-health concerns. Those concerns included

• commercial interests
• anti-immigrant and racial bias
• exaggerated fear about violence and crime
• hysteria about the drug’s alleged contribution to moral decay, and
• pressure from the Federal Bureau of Narcotics

All of these factors played major roles in the push for stricter control of marijuana.^17,18 Such feelings persist today and are part of the effort towards deregulation. The Act was ruled unconstitutional in 1969 in a suit brought by Harvard psychology professor and psychedelic guru, Timothy Leary.¹⁹

 

Today, drugs subject to abuse are regulated by the Controlled Substances Act (CSA), signed into law by then-President Richard Nixon in 1970, which, among other things, established the now-familiar five schedules. This will be discussed further below.

 

REGULATION OF RECREATIONAL DRUGS – INTERNATIONAL

 

The United States is a party to three United Nations (U.N.) drug control treaties²⁰:

• the 1961 Single Convention on Narcotic Drugs
• the 1971 Convention on Psychotropic Substances, and
• the 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

These are designed to establish effective control over international and domestic trafficking in opiates, coca leaf, cocaine, marijuana, stimulants, depressants, and hallucinogens by limiting the international production and trade of psychotropic substances and their chemical precursors.^9,20 The treaties also establish international mechanisms to monitor treaty adherence.²⁰ More than 95% of U.N. Member States are participants in these international treaties.²⁰ Under the CSA, treaty obligations may require the U.S. Attorney General to control or reschedule a substance if existing limits in the U.S. are less stringent than those required by a treaty.⁹

 

Despite these international agreements, more than two dozen countries have moved toward some form of decriminalization of recreational drugs.²¹ The SIDEBAR differentiates decriminalization and legalization.

 

SIDEBAR: Decriminalization and Legalization

Decriminalization is not the same as legalization.

 

When a drug is legalized, it may be restricted but there is no punishment for possession or use. Typically, regulations may exist regarding where and how the legal drug can be produced, sold, and consumed. Criminal or civil penalties may apply if production, sale, or consumption take place outside of regulations (think alcohol).

 

When a drug is decriminalized, possession and use are still “illegal” but, there are no criminal penalties (e.g., incarceration) for use or possession. Instead, there may be civil penalties (e.g., fines, or mandated treatment or educational programs), and usually, possession limits. In addition, use or possession do not lead to a criminal record that might affect employment, housing, or travel opportunities if a substance is decriminalized. Selling or manufacturing drugs would normally still carry criminal penalties.²²

 

 

Most people will bring up the Dutch city of Amsterdam when discussing lax drug policies. Indeed, people 18 years of age or older can purchase marijuana and other “soft” drugs (magic mushrooms, Salvia, Peyote cactus) legally and openly in coffee shops and other establishments in The Netherlands. .²³ Smoking tobacco products are also tolerated in public places except near schools or playgrounds.

 

Dutch drug policy rests on two principles.²³ (Note that Dutch policy applies nation-wide, but most people think of Amsterdam when this topic arises.) One is the fundamental belief that all human beings may decide about matters relating to their own health and includes acceptance of euthanasia for terminally ill patients. The other is that concealing socially negative phenomena does not cause those practices to disappear and instead makes them far more difficult to influence and control.

 

The Dutch divide drugs into two groups, soft and hard drugs, based on their human health impact. Hard drugs such as cocaine, LSD, morphine, and heroin are forbidden in the Netherlands. Soft drugs are tolerated but strict laws limit quantities, conditions of sale, and use. For example, driving under the influence of a soft drug is treated similarly to driving under the influence of alcohol. Large scale growing, processing, and trading in marijuana is forbidden, but Dutch courts bestow milder penalties than in most other countries.²³

 

Another frequently cited model is Portugal. On July 1, 2001, Portugal became the first country in the world to decriminalize all drugs, including methamphetamine and heroin, removing the distinction between soft and hard drugs.^24,25 Possession is decriminalized for personal use within certain limits, depending on the drug.²⁴ Generally, the limits are based on a hypothetical 10-day supply for an average individual.²⁵ Drug use became an administratively sanctionable misdemeanor under the responsibility of the Ministry of Health, rather than involving law enforcement.²⁵ The intent of the law was to focus police resources on those who profit from the drug trade, rather than their victims, while also providing a public health approach to drug users.²⁴

 

Individuals caught possessing drugs for personal use in Portugal are sent to a commission composed of health experts and a legal expert.²⁶ The commission evaluates the person’s drug use and, if necessary, will refer them to voluntary treatment. (While most treatment is voluntary, in some cases, the commission can choose to issue a fine or mandate some form of therapy.) Additionally, the country expanded access to treatment and harm reduction services like needle exchanges.²⁶

 

However, selling drugs is still illegal. Portuguese law considers it a crime if someone produces, buys, or transports an illicit drug that is above the legal amount for personal use.²⁴ For example, possession of more than 5 grams of hashish could potentially lead to arrest and prosecution for drug trafficking. A conviction for drug trafficking in Portugal can be subject to between one and five years in prison.²⁴

 

Beginning January 31, 2023, drug users 18 years of age and older in British Columbia, Canada who possess up to 2.5 grams of illegal drugs for personal use will not be arrested, charged, nor have their drugs confiscated.²⁷ Drugs include heroin, fentanyl, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy). While those substances will remain illegal, police will offer users information on available health and social services. The province said it asked for the change in its request to the Canadian government for the drug laws exemption in order "to remove the shame that often prevents people from reaching out for life-saving help."²⁷

 

Canada’s intent is to use the province as a potential model for similar changes elsewhere in the country as part of a multi-faceted health-based strategy to end Canada’s drug overdose crisis, which reached record highs during the COVID-19 pandemic. The program has some exemptions; it will not apply to drug use on primary and secondary school grounds, child-care facilities, airports, or to members of Canada's military. The pilot program is set to run until January 31, 2026.²⁷

 

On the other hand, some countries have very harsh drug laws. In Malaysia, you can be fined, jailed, or deported for having drugs in your possession and those who sell drugs can be punished with death.²⁸ Execution is also the penalty for some drug crimes in China, Vietnam, and The Philippines. In Dubai, you can be imprisoned for possession of many prescription drugs that are legal in other parts of the world and failing a drug test can be grounds for incarceration even if the individual is not in possession of any drugs.²⁸ In Russia, even Americans in possession of vape cartridges containing hashish oil can be subject to arrest and detention, as WNBA star Brittney Griner discovered.²⁹

 

U.S. RECREATIONAL DRUG REGULATION

 

Controlled Substances Act

As noted above, in the early 1900s, drugs could be purchased at retail outlets with few, if any, limitations. Strong restrictions emerged later in the 20^th Century. In the 1960s, attention was being paid to a medical approach to preventing and treating drug abuse along with a powerful emphasis on law enforcement.⁹ By 1969, newly elected President Richard Nixon made reducing drug abuse, especially heroin abuse, one of his top priorities.⁹ Nixon feared that drugs were undermining the integrity of America’s youth and was convinced that abuse and addiction gave rise to crime, the biggest issue in his 1968 campaign.³⁰ Nixon sensed a need to restore control to a broken system and declared a “war on drugs.” Dismissing the current laws as “inadequate and outdated,” he called for a single, modern law to confine drug use to legitimate medical purposes.³⁰

 

One weapon in the war was the enactment of the CSA.⁹ The CSA was part (Title II) of an omnibus bill (a proposed law covering a number of diverse or unrelated topics) called the Comprehensive Drug Abuse Prevention and Control Act of 1970. The new legislation offered a more systematic approach to regulation of abused drugs and provided additional law enforcement resources.⁹

 

Congress, in enacting the CSA, dealt with two competing interests related to drug regulation.³¹ They recognized that while improper use of controlled substances can be detrimental to Americans' health and general welfare, many of these substances have a useful and legitimate medical purpose and are necessary to maintain health and well-being. The Act simultaneously aims to protect the public from the dangers of controlled substances while also ensuring access for legitimate purposes.³¹ To achieve both goals, the statute created two complementary legal schemes. One provision required individuals and entities working with controlled substances to register with the government, report certain information to regulators, and have a responsibility to prevent diversion and misuse of controlled substances.³¹ The act also contained provisions to prevent trafficking in controlled substances by establishing penalties for the production, distribution, and possession of controlled substances outside the legitimate scope of the registration structure.³¹ CSA policies that were intended to curtail illegitimate use of these drugs included prescription refill limitations, security standards, recordkeeping requirements, order forms, production quotas, and the registration of importers and exporters of controlled substances.^11,30 The new law was, however, not exclusively punitive; it eliminated mandatory minimum sentences for drug crimes.³⁰

 

Moreover, Title I of the comprehensive act had more of a public health focus.³⁰ It provided authority and funding to permit the Department of Health, Education, and Welfare to deliver prevention and treatment efforts through community mental health centers and public health service hospitals. It authorized the National Institute of Mental Health to increase substance abuse research and training.³⁰ It also protected subjects’ privacy rights under the care of approved researchers.

 

Over the next few decades, public concern over drug abuse increased and Congress responded by enacting policies that created a harsher system of drug control and served as a basis of the ensuing “War on Drugs.” ³⁰ Congress repeatedly amended the law to address the heightened concern, and it became more punitive and criminally focused and less directed towards rehabilitation and improved treatment.³⁰

 

A new Federal Agency, the Drug Enforcement Administration (DEA), was created in 1973 to enforce the new law. This was done in part to coordinate federal and state enforcement activities and to reduce inter-agency rivalries.^9,30 After the CSA was enacted, there were nearly 500,000 importers, exporters, manufacturers, distributors, and practitioners covered by the law, making the DEA the largest administrative agency in the U.S.¹¹

 

Scheduling

The centerpiece of the CSA, as pharmacists are aware, was the creation of a scheduling system that provided a means for assigning regulated substances into one of five categories based upon the drug’s medical risks, therapeutic use, and potential for abuse and dependence.^9,31 The classification system also establishes the obligations and penalties of the law.³¹ The most restrictive category is Schedule I which is comprised of drugs with high potential for abuse, but no accepted medical use.³² The placement of a drug in a schedule is fluid, and drugs can be moved to a different schedule, either up or down, added to the controlled substances list, or deleted.³⁰ Any individual, not just regulatory officials or health care providers, can request that the DEA add, remove, or change a drug’s scheduling.⁹

 

In determining into which schedule a drug or other substance should be placed, or whether a substance should be re-scheduled or decontrolled, certain factors must be considered. The DEA is required to seek a scientific and medical evaluation of the substance from the Department of Health and Human Services  to apply what is known as the eight-factor test when determining scheduling.³² These factors are

(1) Its actual or relative potential for abuse
(2) Scientific evidence of its pharmacological effect, if known
(3) The state of current scientific knowledge regarding the drug or other substance
(4) Its history and current pattern of abuse
(5) The scope, duration, and significance of abuse
(6) What, if any, risk there is to the public health
(7) Its psychic or physiological dependence liability
(8) Whether the substance is an immediate precursor of a substance already controlled

 

These criteria help to stratify the seriousness of the public health concern among the controlled substances. Will new regulatory strategies remove these distinctions?

 

PAUSE AND PONDER: Do the “C” schedules serve a purpose?

 

DECRIMINALIZATION – STATE AND LOCAL ACTIONS

 

While the general trend at the federal level for the past five decades has been a toughening of the restrictions on abused drugs, especially opioids, one exception is marijuana. States have led the way by actively relaxing restrictions on marijuana, first by legalizing medical use and later permitting limited non-medical use.

 

The medical use of marijuana has been legalized in 37 states plus the District of Columbia (D.C.), Puerto Rico, Guam, the Northern Mariana Islands, and the U.S. Virgin Islands.³³ The medical marijuana movement began in California in 1996, but it wasn’t until 2012 that Colorado and Washington became the first two states to decriminalize the non-medical use of marijuana (for people 21 years of age or older).³³ (California voters had rejected a proposition in 2010.) In the 2022 election, two additional states, Maryland and Missouri, approved the recreational use of marijuana. bringing the total up to 21 (plus D.C.) although similar proposals were rejected in Arkansas, North Dakota, and South Dakota.³³

 

Beyond Marijuana

 

More recently, states and municipalities have gone beyond marijuana and have decriminalized other controlled substances. In May 2019, Denver, Colorado became the first governmental entity in the U.S. to decriminalize a (non-Cannabis) Schedule I drug, the psychedelic ingredient from mushrooms, psilocybin.³⁴ The proposal was placed on the municipal ballot after garnering almost 9500 petition signatures and was supported by 50.5% of voters in the election.³⁴ Denver was also the first major U.S. city to legalize the possession of small amounts of marijuana in 2005.³⁴

 

The new ordinance states that the “enforcement of any laws imposing criminal penalties for the personal use and personal possession of psilocybin mushrooms... shall be the lowest law enforcement priority in the City and County of Denver.” It mandates that “no department... shall use any city funds or resources to assist in the enforcement of laws imposing criminal penalties for the personal use and personal possession of psilocybin mushrooms by adults.”³⁵ Adult is defined as an individual 21 years of age or older.

 

One advocacy group (Decriminalize Denver) noted its support for the ordinance by stating that “Humans have used these mushrooms for thousands of years for healing, rites of passage, spiritual insight, strengthening community, and raising consciousness.” Decriminalize Denver has argued that “One arrest is too many for something with such low and manageable risks for most people, relative to its potential benefits.”³⁴ In contrast, opponents have warned that “Denver is quickly becoming the illicit drug capital of the world” and that the long-term health effects of these drugs are unknown.³⁴

 

Other municipalities have followed the same path as Denver. Oakland and Santa Cruz, California also decriminalized psilocybin in 2019 and 2020, respectively. In both cases, their respective City Councils took the action rather than mounting a referendum.^36,37 The Santa Cruz ordinance is very similar to what was enacted in Denver preventing resources from being used to investigate and arrest people 21 years of age and older solely for the personal use and possession of “entheogenic plants and fungi”³⁷ (a psychoactive, hallucinogenic substance or preparation especially when derived from plants or fungi and used in religious, spiritual, or ritualistic contexts³⁸). Community testimony from people sharing mental health struggles and treatment likely contributed to the Council’s decision. Santa Cruz later extended its policy and banned enforcement actions against individuals using peyote and other mescaline-containing cacti. Oakland also decriminalized mescaline cacti, ayahuasca and ibogaine.³⁹ The City Council in Ann Arbor, Michigan also unanimously approved mushroom decriminalization in 2020.⁴⁰

 

Voters in Washington D.C. also approved similar measures in 2020, termed the Entheogenic Plant and Fungus Policy Act, which would decriminalize natural psychedelics including magic mushrooms, ayahuasca, and mescaline, and makes arrests for their possession or use the lowest priority for DC police. Due to D.C.’s unique status, implementation of the act was delayed for Congressional review and approval. D.C. received approval in 2021 but not before one member of Congress threatened to derail the process.⁴¹

 

In late 2021, Seattle became the largest city (to date) to decriminalize Schedule I psychedelic drugs.^39,42 The City Council unanimously passed a resolution that “the investigation, arrest, and prosecution of anyone engaging in entheogen-related activities should be among The City of Seattle’s lowest enforcement priorities.” Its City Council asked the city’s police department to codify that practice as departmental policy.³⁹ The resolution was limited to natural substances, notably psilocybin and ayahuasca, and later peyote; it excluded synthetic materials such as LSD.^39,42 In support of its approval, the resolution noted both the therapeutic potential of psychedelics and protection of indigenous peoples who use these compounds for cultural and spiritual practices.⁴² More than 100 additional cities are moving to decriminalize psychedelic mushrooms.⁴³

 

States are also supporting decriminalization measures and Oregon is at the forefront of these activities. In the 2020 election, voters in the state passed two companion referenda that significantly changed the state’s drug policy. Measure 109 approved the use of a psychedelic mushroom for medical use by authorizing the Oregon Health Authority to create a program to permit licensed service providers to administer psilocybin-producing mushroom and fungi products to individuals 21 years of age or older.⁴⁴ The new law will allow anyone age 21 or older who passes a screening procedure to access the services for “personal development."⁴⁵ A client does not need to be diagnosed with or have any particular medical condition to receive psilocybin. Clients would complete a preparatory session and then attend a session at a psilocybin service center where they would receive and consume the psilocybin product under the supervision of the service facilitator.⁴⁴

 

Unlike the cities that decriminalized psychedelic drugs for personal use, the Oregon measure took a medical approach with the purpose of improving the physical, mental, and social well-being of people in the state and reducing the prevalence of mental illness conditions among adults who have not been helped by more mainstream therapies.^44,46 The measure restricts psilocybin sales to licensed service providers and does not permit sales directly to users. Individual counties can opt out of the program.⁴⁶

 

In the 2022 election, Colorado became the second state to approve psychedelics.⁴⁷ The proposition legalizes regulated access to natural medicines for people 21 years of age or older, including plants or fungi that impact an individual's mental health and provides civil and criminal immunity for providers and users.⁴⁷

 

Pharmacy staff should note that there is a growing interest in the potential therapeutic applications of psychedelic drugs to help many psychiatric disorders and these may become FDA-approved pharmaceutical products.⁴⁸

 

While several municipalities and states have authorized the decriminalization of mushrooms and other psychedelics and justified their actions due to their healing and spiritual value, there have been other movements to expand decriminalization beyond those with potential medical benefits.

 

In the same election that decriminalized mushrooms, voters in Oregon approved another measure (110) to become the first state to lighten penalties for possession of both large and small amounts of a wide assortment of scheduled substances.⁴

 

Under the new law, the penalty for possession of larger amounts of controlled substances was reduced from a felony offense to a Class A misdemeanor punishable by up to 364 days of imprisonment and a fine of up to $6,250. For possession of smaller amounts of controlled substances, the measure reduced the penalty from a criminal misdemeanor to a new, Class E violation, which is punishable by a $100 fine. In lieu of a fine, a person charged with a violation may instead complete a health assessment at an Addiction Recovery Center.⁴

 

The threshold differentiating large from small amount are defined for different substances. For cocaine, the Class E violation applies to unauthorized possession of less than two grams. For oxycodone, it is unauthorized possession of fewer than 40 pills, tablets, or capsules. Someone in possession of less than 1 gram heroin would be subject to the new Class E penalty.⁴ The new measure also removes penalty enhancements for possession of small amounts of controlled substances where the individual previously had a felony conviction or multiple previous convictions for possession.^4,45

 

The new program is loosely based on Portugal’s model, described above, but was modified in accordance with recommendations from Oregon’s recovery community.²⁶ Oregon’s approach will focus on diversion and harm reduction for people who use drugs while retaining punitive approaches for drug trafficking. A goal of the new program is to improve Oregon’s ranking as one of the worst states at providing treatment for addiction.²⁶ In 2016 and 2017, Oregon ranked first in the country for analgesic drug misuse, second in the U.S. for methamphetamine misuse, and fourth for cocaine and alcohol misuse while ranking 48th in access to treatment.²⁶ In all, almost 10% of the state’s population had a substance use disorder.

 

The state is expanding its addiction recovery centers and anyone will be able to access them whether or not they have received a citation.²⁶ The funding for expanded services will come from a higher than anticipated yield from marijuana taxes, which has exceeded $100 million per year.²⁶

 

Oregon’s program has produced mixed results. In the first year after decriminalization took place, police issued approximately 2000 citations, but, despite the waiver of the fine if a person calls the hotline for a health assessment and counseling, only 92 of those ticketed called the hotline and only 19 of them requested resources for services.⁵⁰ Almost half of people receiving a citation failed to make a court appearance. State health officials reported 473 opioid overdose deaths in the first 8 months of 2021, surpassing the total for all of 2020, and nearly 200 deaths more than the state saw in 2019.⁵⁰ The state also reported that visits to emergency rooms and urgent care centers for opioid overdose have been increasing. The Oregon Health Authority cites an upturn in fentanyl abuse and a pandemic-related downturn in reporting in 2020 as possible reasons for the disappointing results. In addition, Oregon’s inpatient facilities, detox clinics and recovery-focused nonprofits were adversely affected by issues related to COVID-19 including workforce shortages; there is uncertainty whether providers can adequately expand to meet increased needs.⁵¹

 

Pause and Ponder: Is there a role for pharmacists in improving outcomes?

 

However, it has also been suggested that the more lenient rules take away the threat of jail time that some individuals need to encourage them to get into recovery while fewer low-level offenders will be forced into court-ordered behavioral health services.⁵¹ Portugal takes a more robust approach than Oregon, having “dissuasion commissions” that pressure anyone caught using drugs, including marijuana, to seek treatment. Tools include fines, prohibiting drug users from visiting certain venues or from traveling abroad, seizure of personal property, community work, and having to periodically report to health services or other facilities.⁵⁰

 

California, Maine, and New Jersey, among others, have also been considering enacting decriminalization measures.^52,53 A bill pending approval in California would decriminalize most psychedelics. The bill would allow people aged 21 and older to possess psilocybin, DMT, ibogaine, mescaline, LSD, and MDMA for personal use and “social sharing.”⁵² The bill advanced to the final step of Assembly approval when the sponsor removed ketamine from the list of substances due to concerns over date rape. The bill prohibits sharing drugs with anyone under 21 years of age or possessing them on school grounds. It would also allow personal cultivation of mushrooms. Proponents touted the benefits to individuals who would be aided by the use of psychedelics to treat trauma including military veterans. Opponents argued that social sharing could result in more overdoses from contaminated products and give drug dealers a built-in defense.⁵²

 

PROS AND CONS

 

Why have states and municipalities chosen to decriminalize drugs? Although a detailed discussion of the benefits and detriments of lax drug policies is beyond the scope of this activity, it is worth briefly examining some of the arguments that have driven the move towards decriminalization. Table 1 describes the pros and cons frequently used to support the various arguments.

 

 

Table 1. Pros and Cons re: Decriminalization of Recreational Drugs^{1,16,54,55,56,57}

 

Justifications for decriminalization

Justifications for continuing prohibition of recreational drugs

·       A sense that the “War on Drugs” is expensive, harmful to society, and not working ·       The suggestion that a medical model will be more effective ·       Decriminalization will reduce profits for drug traffickers ·       More than half of people in prison have untreated substance use disorders and o   Imprisonment actually leads to increased illicit drug and medication misuse following a period of incarceration with a much higher risk of drug overdose upon release o   Relapse to drug use in someone with an untreated opioid use disorder can be fatal due to loss of opioid tolerance that may have occurred while the person was behind bars o   A criminal conviction or a record of imprisonment can significantly hamper a person’s employment prospects and other opportunities

·       Risk of endorsing or encouraging risky behaviors ·       Decriminalization would drive down the cost of drugs, making them more accessible ·       Few non-violent users are actually imprisoned ·       A black market will still exist for users under the permitted statutory age ·       The current treatment infrastructure is inadequate to accommodate the anticipated increased demand ·       The threat of incarceration is an incentive to seek treatment ·       If restrictions are abandoned, other social costs will increase

 

As a proponent for decriminalization, Mayor Schmoke proposed that the abuse of drugs should be “dealt with as a moral and medical problem than as a criminal problem ... a problem for the surgeon general, not the attorney general.”¹ The number of people incarcerated for drug-law violations in state and federal prisons in the United States increased 12-fold between 1980 and 2018. Yet there is no statistically significant relationship between state drug imprisonment rates and three markers of state drug problems: self-reported drug use, drug overdose deaths, and drug arrests.⁵⁷

 

Pause and Ponder: Should recreational drugs be regulated like alcohol?

 

Many advocates recommend an approach similar to the policy in Portugal and treat illicit drug use the way most states regulate alcohol and marijuana, by making it legal for stores to sell such drugs to adults.⁵⁷ In Portugal, which has led the way towards decriminalization, the use of cocaine among young adults (15-34) is 0.3% compared with 2.1% in the European Union (EU) countries.⁵⁸ Amphetamine and MDMA use are also lower. The overall overdose death rate in Portugal is five times lower than in the EU (which has a lower rate than in the U.S.).⁵⁸ HIV infection rates among IV drug users have also dropped.⁵⁸

 

Where Will This Lead?

Are the localities decriminalizing recreational drug use an anomaly or do they represent the tip of the iceberg for liberalization of personal drug use? The movement could follow the path taken by marijuana.

 

States have pursued a pattern of first decriminalizing and/or allowing medical use of marijuana before finally proposing legalization.^16,59 States used their experiences with the intermediate steps as a means to anticipate the expected effects of total legalization.¹⁶ The liberalized marijuana policies in medical marijuana states exposed the public to more open marijuana use and may have changed attitudes towards the drug, along with a sense that prohibition is too costly.⁵⁹

 

Efforts are ongoing to legalize marijuana at the federal level. Congress is currently considering the Marijuana Opportunity Reinvestment and Expungement (MORE) Act. It would remove marijuana from the list of scheduled substances under the Controlled Substances Act and eliminate criminal penalties for an individual who manufactures, distributes, or possesses marijuana.³ It would also establish a process to expunge convictions and conduct sentencing review hearings for individuals previously convicted of federal cannabis offenses. It would establish and fund a grant program to provide resources to administer services for individuals adversely impacted by the War on Drugs, including job training, legal aid, reentry services, and health education programs and would levy a 5% tax on the sale of cannabis products.³

 

Will legalizing marijuana serve as a model for other C-I drugs to follow? Indeed, a bipartisan bill was recently introduced in the U.S. Senate calling on the DEA to reclassify breakthrough therapies such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) as Schedule II drugs.⁶⁰

 

SUMMARY AND CONCLUDING COMMENTS

 

The pendulum of drug control may be swinging closer to the more lenient approach that existed 100 years ago. In a decade, the U.S. moved from no state permitting recreational use of marijuana to almost half of the states doing so, along with decriminalization being debated at the federal level. Will additional recreational drugs follow the same path? Several municipalities and a few states have already made significant strides in that direction. In particular, Oregon and the nation of Portugal have established programs making controlled substances a medical and public health issue rather than a law enforcement issue, although with mixed results. Will the distinction between “hard” and “soft” drugs disappear in the U.S., as more states adopt measures aimed at decriminalizing drugs?

 

If so, there will be many questions about how pharmacy may be affected. Will drugs for which there is some evidence for medical applications like cannabinoids and psychedelics such as psylocibin, find their way to the pharmacy shelf? If Oregon’s medical model for psychedelics is followed by other states, will it enable new opportunities for pharmacists? Will cocaine and heroin once again be available as OTC products in pharmacies?

 

It is important for pharmacy staff to stay abreast of regulatory changes in their own states and nationally. They should become part of the conversation about the direction such regulations should take.

 

 

 

Download CE Activity

INTRODUCTION

“The skyrocketing cost of insulin has become a crisis in the US. Some people are dying because they can't afford the life-saving drug.” Columnist Rachel Gillett.¹

 

Diabetes is a rapidly growing global health problem with enormous health, social, and economic consequences.^1-3 This chronic metabolic disorder is characterized by prolonged hyperglycemia due to inadequate pancreatic production or utilization of the hormone insulin.³ Approximately 6.5% of the global population (almost 300 million people) suffer from diabetes.² In the U.S., the Centers for Disease Control and Prevention (CDC) estimates that 10.5% of the population (34 million people) have diabetes and that the prevalence rises to 26.8% among those aged 65 years or older.⁴ Direct medical costs and lost productivity attributable to diabetes was estimated to be $327 billion in 2017, making it the most expensive chronic disease in the nation.^5,6

 

Complications from diabetes are a serious public health concern. Diabetes is a principal cause of retinopathy, kidney failure, heart attacks and stroke, lower limb amputation, and ketoacidosis which can be fatal.³ Individuals with diabetes are twice as likely to have heart disease or stroke than those without diabetes.⁵ A total of 16 million emergency department (ED) visits were reported with diabetes as a listed diagnosis among adults aged 18 years or older in 2016.⁴

 

Management of diabetes is critical to preventing complications and high health care costs from the disease. However, many patients do not adequately manage their diabetes, in part due to high treatment costs. This continuing education activity will discuss some of the reasons behind the high costs of treating the disease and the impact that high prices have on patients. It will also review regulatory and public health efforts to reign in the rising costs of insulin.

 

INSULIN

 

Diabetes can be managed, and its consequences avoided or delayed with diet, physical activity, tobacco avoidance, and regular screening and treatment for complications.^3,5 Medication, of course, is also a key to management. Prescribers use many different classes of oral medications to manage diabetes,⁷ but the emphasis in this activity will be on insulin. Insulin is the mainstay of therapy for individuals with type 1 diabetes, and many patients with type 2 diabetes also benefit from insulin therapy.⁸ Prior to the discovery of insulin in 1921, diabetes was difficult to manage. The primary treatment consisted of highly restrictive diets, which compromised the immune system and stunted growth, and often led to death by starvation.⁹

 

In 1921, Frederick Banting, a Toronto surgeon without laboratory training, medical student Charles Best, physiologist John Macleod, and biochemist James Collip successfully isolated and purified insulin from a dog’s pancreas and showed that it would normalize blood glucose levels when administered to diabetic animals.¹⁰ Later, insulin was extracted in larger amounts from cattle and was first given to a 14-year-old dying diabetic patient who developed an allergic reaction. After the Canadian researchers purified it further, they gave a second dose to the patient 12 days later; the patient showed dramatic improvement as his blood glucose dropped to near normal levels with no obvious adverse effects.¹⁰ This observation spurred widespread use of insulin in patients with diabetes. Banting and Macleod were jointly awarded the 1923 Nobel Prize in Physiology or Medicine in recognition of their life-saving discovery (The committee did not recognize Best, the lowly med student, for his contribution).¹⁰ Banting, Collip, and Best were also awarded patents on insulin and the method used to make it in 1923. They all sold their patents to the University of Toronto for $1 each.¹⁰ Banting famously said, “Insulin does not belong to me, it belongs to the world,” proclaiming his desire that everyone who needed it should have access to it.¹⁰

 

Researchers at the university tried to manufacture insulin for distribution but realized they could not meet the demands of the North American market.¹¹ The university licensed the technology to Eli Lilly which possessed the expertise to produce large batches of insulin. Under the arrangement, Lilly was allowed to apply for U.S. patents on any improvements to the manufacturing process.¹¹ The university also established licensing agreements to produce insulin with other companies, including Nordisk and Novo which laid the foundation for the future domination of the insulin market by a few companies.¹¹ When the animal-based insulin patents began to expire, researchers developed new technologies. They bioengineered human insulin in 1982 and then analog insulin (insulin which has been genetically modified to improve its pharmacokinetic profile) and created new therapies and continued patent protection.¹¹ Today, approximately 7.4 million Americans use insulin, including roughly 1.4 million people who use it to treat type 1 diabetes.⁹

 

Pharmacists and technicians are aware that patients with type 1 and type 2 diabetes use a combination of short-acting, rapid-acting, intermediate-acting, and long-acting insulins to control their glucose levels. Today, the insulin analogs are widely prescribed and are the standard of care for people with type 1 diabetes and also a component of care for people with type 2 diabetes; the analogs are generally more expensive than other, older types of insulin.⁹

 

Even though diabetes is treatable and has been for more than a century, it remains the 7^th leading cause of death in the U.S., accounting for 87,647 fatalities in 2019.^5,9 Despite the availability of this century-old treatment, many patients undertreat their diabetes, contributing to complications and high mortality from the disease. Results from an international survey of patients with type 1 diabetes found that approximately 25% of patients in the U.S. had rationed insulin in the previous year.¹² Why would patients show such low adherence to a proven, lifesaving medication?

 

One reason is cost. High-list prices, health plan structures, and high out-of-pocket costs make it difficult for many diabetic patients to adhere to their medications, especially insulin. Some patients maintain that they spend an estimated 50% of their monthly income on insulin and diabetes products.¹¹ Studies have found that approximately one of every four survey respondents in the U.S. report underuse of their insulin at least once within the previous year due to high cost.^12,13 This is the highest rate of insulin rationing of any high-income country in the world.¹⁴ An international survey found that only 6.5% of respondents from high income countries excluding the U.S. reported rationing in the previous year, compared with roughly 25% in the U.S.¹⁴ In addition to rationing insulin, 33.5% of individuals from the U.S. reported rationing of blood glucose testing supplies.¹⁴

 

The financial burden is, not unexpectedly, especially acute for economically disadvantaged individuals who have a higher rate of diabetes. Rates of diabetes are higher among people living in impoverished regions of the U.S., such as Appalachia and the Mississippi Delta, and also among those who are eligible for Medicare and Medicaid.⁹ Adults with less than a high school education are also more likely to be diagnosed with diabetes than those with at least a high school diploma.⁹ Similarly, minority communities are also disproportionally affected by this disease, with Native Americans, Hispanics, Black Americans, and Asian Americans representing more than 45% of those diagnosed with the disease, despite these groups making up 39% of the U.S. population.⁹ Cost-related rationing of insulin was the leading cause of hospital admissions for diabetic ketoacidosis among inner-city minority patients.¹⁴ Approximately 24% of adults with diabetes earning below the poverty level use insulin, either alone or in combination with oral medications.¹⁵

 

An online survey performed by the American Diabetes Association in 2018 also found that a quarter of respondents reported that the cost of insulin had affected their purchase or use of insulin during the previous year. The percentage was even higher for dependent child insulin users (34%).¹⁶ More than 20% of users admitted missing doses monthly or even weekly. They also had to choose between buying insulin or other health-related purchases such as physician visits (32%), health insurance (26%), or other medications (36%). Many also had to choose between purchasing insulin or other essential items such as utilities (30%), housing (27%), transportation (32%), as well as non-essential purchases like vacations (41%) and entertainment (43%).¹⁶ Patients have also made employment decisions based on the availability of adequate health insurance to cover the cost of their insulin.¹¹ Patients also claim that they have been forced to make unhealthy food choices that can worsen the disease, purchasing cheaper alternatives due to spending on insulin.¹¹ The excessive costs also caused 23% of individuals to change to a less expensive insulin type or brand, while many skipped filling at least one insulin prescription.¹⁶

 

Moreover, surveys have found that insulin users for whom cost affected their purchase or use of insulin experience adverse health effects at higher rates than those for whom cost was not an issue. When cost was a factor, 72% of individuals experienced episodes of poor blood glucose control during the previous three months (compared with 42% in users who were not affected by the cost), and 80% had their most recent A1C level measured at 7.5 or higher (59% when cost was not a factor).¹⁶ Patients have also claimed that they have intentionally allowed themselves to reach a state of diabetic ketoacidosis so that they would receive insulin in an ED instead of purchasing it.¹¹

 

Not unexpectedly, 73% of individuals dealing with price increases also experience negative emotions (e.g., stress or anxiety), more than twice the rate of those not facing a price increase (31%).¹⁶ There have even been reports of deaths in patients with type 1 diabetes due to a lack of affordable insulin.^14,17 The underutilization of insulin due to concerns over cost not only produces serious avoidable short- and long-term health consequences, but also raises overall costs for the U.S. health care system.^9,15 It is remarkable that this has occurred with a medication whose discoverers refused to profit from it.

 

PAUSE AND PONDER: How would you start a conversation about economic stress with a patient who appears to be underusing insulin?

 

ARE COSTS REALLY THAT HIGH?

 

There is a public perception that the cost of prescription drugs is out of control; indeed, Americans pay an average of three times as much as patients in the U.K. for the world’s top 20 medications.¹⁸ But is insulin, in the words of Representative Tom Reed (R., N.Y.), “the poster child of this broken marketplace”?¹⁸

 

Insulin in the U.S. is more expensive than anywhere else in the world. The average manufacturer price of insulin is more than four times higher in the U.S. than it is in the next most expensive country (Chile) and more than 10 times the average cost in the 32 developed countries surveyed.¹⁹ In 2018, spending on insulin in the U.S. was $28 billion, compared with $484 million in Canada.²⁰ The average American insulin user spends almost five times as much annually than their Canadian counterparts. The average cost per unit of insulin in the United States increased by 10.3% between 2016 and 2019 compared with an increase of only 0.01% in Canada during the same time period.²⁰ By comparison, in 1923, two years after the introduction of insulin therapy, the U.S. had the lowest global price of insulin.²¹ As recently as the 1960s, vials of insulin were available in the U.S. for 84¢, equivalent to $7.36 in today’s dollars.¹⁸

 

The list price of insulin per milliliter in the United States increased, on average, 2.9% annually between 1991-2001, 9.5% per year from 2002 and 2012, 20.7% annually between 2012 and 2016, with a smaller increase from 2016 to 2018.⁶ Analog insulins have seen the largest price increase, rising more than 1000% since the 1990s.^14,17 The average annual per capita cost of insulin now approaches $6,000.⁶ (Note that the average yearly social security benefit in the U.S. is $18,458.)

 

The cost of insulin contributes an estimated $48 billion to the direct costs of treating diabetes (before accounting for any rebates or discounts) which represents 20% of the total spending.⁶ If current trends continue, the cost of insulin could reach $121.2 billion by 2024, or $12,446 annually for each patient receiving insulin.⁶

 

WHY?

The reasons for the enormous increase in the retail price of insulin are complex and varied. It has been argued that one of the common justifications for the high price tag on prescription drugs, research and development costs, is not applicable to insulin.¹⁷ Insulin is not a new drug and even the most commonly used modern analogs are 20 years old or more.¹⁷ In addition, over the past 60 years, the increase in the cost of insulin exceeds the rate of inflation by nearly 43-fold.¹⁸ If research and development costs are not driving the price increase, what is?

 

Notably, there is little competition in the insulin market. Only three companies, Eli Lilly, Novo Nordisk, and Sanofi, manufacture over 90% of the world’s insulin and investigations have found that they generally raise their prices at the same time.^17,21-23 It should be pointed out, however, that the manufacturing of biologics, compared with small molecules, involves a higher level of engineering and facility requirements. Additional steps are needed to ensure compliance with good manufacturing practices, regulatory requirements and to minimize batch-to-batch variability, all of which would affect production costs.²¹ The scale and optimization of production processes are also important to reduce the overall cost of the finished product which hinders smaller pharmaceutical manufacturers from entering the market.²¹

 

Other factors also contribute to rising insulin prices. An important trend over the past decade is a shift in insulin prescribing from less expensive human insulins to more expensive human insulin analogs.¹⁵ More than 90% of privately insured patients with type 2 diabetes in the U.S. who receive insulin are currently prescribed the more expensive analog version.^17,21

 

Price Setting

Another significant factor affecting the price of insulin is the large number of stakeholders (e.g., manufacturers, wholesalers, pharmacy benefit management services [PBMs], pharmacies, health plans, employers, and the Federal government) involved in the insulin supply chain and price setting, all of whom use varying degrees of negotiating power.^9,15 Multiple transactions occur among these stakeholders during distribution and payment and there is no one agreed-upon price for any insulin formulation.¹⁵

 

Although pharmacy staff are generally aware of the pricing dynamics, a brief review will place the insulin costs into context. Prices, rebates, and fees are negotiated among the stakeholders affecting the ultimate price paid by the patient with diabetes at the point of sale. The true cost of insulin can be difficult to pinpoint because of the complex nature and lack of transparency in the financial agreements among the stakeholders.^11,24

 

Manufacturers set a list price for their product, but the list price is usually not what payers pay nor what the manufacturers receive.^15,24 The manufacturers, generally, receive the net price which is the list price minus fees paid to wholesalers, discounts paid to pharmacies, and rebates paid to PBMs or health plans.¹⁵ While manufacturers control the list price of insulin, a substantial portion of the negotiating power has shifted from manufacturers to PBMs.¹⁵

 

PBMs attempt to lower costs by leveraging formulary coverage. PBMs administer the prescription medication benefit for more than 266 million Americans and 70% of all prescription claims are managed by the top three PBMs.¹⁵ PBMs have the power to provide exclusive formulary coverage and use this discretion to give them substantial clout in negotiations with manufacturers.¹⁵ Insulin manufacturers compete fiercely, attempting to gain favorable formulary placement and maximize market share and revenue for their products.^9,15 They use rebates as one bargaining chip.^9,15

 

These interactions give PBMs little incentive to discourage manufacturers from increasing their list prices since rebates, discounts, and fees PBMs negotiate are typically based on a percentage of a drug’s list price.⁹ There is an advantage for manufacturers to raise the list prices to provide bigger incentives (discounts) for the participants in the supply chain.¹¹ In other words, PBMs benefit when there is a larger “spread” between the list price and the real price paid by the health plan, so both the PBMs and manufacturer gain from higher list prices.^9,11,15 Since payers ultimately pay the “real” (discounted) price and not the list price, inflating the benchmark price does not increase the cost to the PBMs.¹¹

 

A Senate investigation found instances in which insulin manufacturers were apparently discouraged from setting lower list prices for their products, which would likely lower out-of-pocket costs for patients, due to concerns that PBMs and health plans would react negatively.⁹ Although it might be expected that rebates would reduce patient costs at the point-of-sale, they may be used instead by the employer or the health plan to reduce insurance premiums.¹¹ Significantly, insulin list prices have tended to rise more rapidly than the net price due to increasing rebates and discounts negotiated between stakeholders. In some cases, rebates and discounts may approach half of the insulin list price.^15,25 This suggests that participants in the distribution system are largely responsible for the increase in insulin costs.²⁵ It has been estimated that proceeds from insulin sales flowing to insulin manufacturers and insurers have decreased over time, while PBMs, pharmacies, and wholesalers have substantially increased their share of the funds.²⁵

 

Many participants in the pricing system benefit from the arrangement, but one essential participant who does not is the patient who needs insulin and is paying the artificially inflated list price. In particular, patients with high deductible insurances, Medicare recipients in the “donut hole,” patients subject to co-insurance, and especially patients without health insurance are in jeopardy.^11,24 Over the past decade there has been a shift away from traditional health plans, which provided broad coverage, to high-deductible health plans, and the deductibles themselves have risen; even plans available under the Affordable Care Act can have high deductibles depending on the “tier.” ¹¹ Thus, it would seem that decisions made from negotiations between stakeholders that affect formulary choice may not be based on the patient’s best financial or medical interest.¹⁵

 

Recently, the Federal Trade Commission (FTC) voted unanimously to conduct an in-depth probe of PBMs since, according to one commission member, “(f)or most Americans, pharmacy middlemen control what medicine you get, how you get it, when you get it, and how much you pay for it. Yet PBM practices are cloaked in secrecy, opacity, and almost impenetrable complexity.”²⁶

 

Patent Issues

Not only do a few companies dominate the market, they also maintain significant patent protection that limits incursion of competitive alternatives into the market. Currently, there are no patents on human insulin and most patents on first generation insulin analogs have also expired.²¹ Manufacturers have made improvements with new formulations providing more reliable control of diabetes and more convenience for users. However, the newer formulations prolong the patent life and provide up to 37 years of market protection.¹⁷ Companies also engage in what is known as “patent evergreening,” where they continually apply for renewed patents for their drugs after making incremental (in some cases, insignificant) changes to their medications.^17,18,23,27

 

For example, the long-acting insulin product insulin glargine (Lantus) was first patented in 1994 and was due to expire in 2015. Sanofi filed 74 patents for newer versions of the drug that can provide protection until 2031.^11,17,18 Sanofi maintains that the newer patents “are related to new and unique inventions” although there is evidence suggesting that the improvements are mostly minimal.¹⁸ Sanofi also points out that while the list price for its insulin has increased, the actual price paid by consumers is lower than it was in 2006, due to the nature of the market.¹⁸ In addition to modifying the insulin product, manufacturers have also filed and received patents for insulin delivery devices which effectively extends the patent life of the delivered insulin.^18,21

 

Patent disputes can influence cost in many ways. The threat of a lawsuit alleging patent infringement would discourage other manufacturers from developing competing products even if the suit is without merit.¹⁷ Even if the suit is litigated and found to be without merit, large litigation costs and marketing delays would occur.²² In 2014, Sanofi filed a suit against Lilly alleging a violation of its patent on insulin glargine. The companies reached a deal under which Lilly agreed to delay the launch of its product until 2016 and pay royalties to Sanofi.²⁸

 

Even more disturbing is the strategy of “pay-for-delay” patent dispute in which a competing manufacturer acknowledges the original patent and agrees to defer marketing its product for a specified period of time.^17,22 In return, the competing manufacturer receives a payment from the patent holder, a legal means for a manufacturer to pay a competitor not to enter the market.²² When Merck filed a new drug application for its rival to insulin glargine, Sanofi filed a suit claiming that Merck violated 10 of its patents, including ones for the drug and its insulin delivery device.²⁸ After the suit was filed, Merck announced it would no longer pursue its interest in the drug, possibly reaching a deal to receive payments from the suing company.²²

 

Biosimilars

Patents are not the only barrier to the introduction of alternatives to brand-name insulin. Insulin is a therapeutic biologic (not a chemically synthesized small molecule/drug) and the FDA treats alternative biologic products as biosimilars and not as generics; this leads to a more cumbersome and expensive regulatory approval process.^17,23 The FDA defines biosimilars as “a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the FDA.” ²⁹ Production and approval of biosimilars costs nearly as much as a new drug and requires similar testing and regulatory approval.^22,23 The development of a biosimilar takes five to nine years and costs at least $100 million,³⁰ leaving little financial incentive to develop cheaper options. The first insulin biosimilar, Basaglar, was introduced in the U.S. in December 2016, almost two years after the first biosimilar was approved in Europe, and requires that a prescriber supplies a new prescription.¹⁷ A second biosimilar (Admelog) was approved in 2018.¹⁷

 

In 2021, the FDA approved Semglee (insulin glargine-yfgn) as the first interchangeable insulin biosimilar.²⁹ The “interchangeable” designation means that it can be substituted for Lantus (insulin glargine, approved in 2000) without the intervention of a prescriber, similar to pharmacist-initiated generic drug substitution for small molecules.^27,29

 

PAUSE AND PONDER: What factors would you consider before substituting an interchangeable insulin? Would cost be one?

 

CAN ANYTHING BE DONE TO CONTAIN INSULIN COSTS?

 

The soaring cost of insulin has caught the attention of legislators, healthcare advocates, and the public.

Rising drug prices are a concern to the public at large. More than half of respondents in a March 2022 poll by the Kaiser Family Foundation agreed that limiting how much drug companies can increase the price of prescription drugs each year to the rate of inflation should be a “top priority” for Congress.³¹ A majority of respondents also say placing a limit on out-of-pocket costs for seniors (52%) and, specifically, capping out-of-pocket costs for insulin at $35 a month (53%) should be top priorities for Congress in the coming months.³¹ Several different approaches to reigning in costs involving multiple stakeholders have been proposed.

 

Congressional Actions

The most far-reaching proposal is the Build Back Better Act (BBBA) which was passed by the U.S. House of Representatives on November 19, 2021, but stalled in the Senate. This is a broad and complex 2,135-page bill with many provisions that would commit $2.2 trillion to a long list of health, social, and environmental proposals.³² The BBBA includes several provisions that would lower prescription drug costs for people with Medicare and private insurance and reduce drug spending by the federal government and private payers.^32,33

 

The key proposals dealing with drug costs, if eventually passed, would include³³

• Allowing the Federal Government to negotiate prices for some high-cost drugs covered under Medicare Part B and Part D
• Requiring rebates to limit annual increases in drug prices in Medicare and private insurance for drugs whose prices rise faster than the inflation rate
• Cap out-of-pocket spending for Medicare Part D enrollees by instituting a hard cap of $2,000 in 2024
• Eliminate cost sharing for adult vaccines covered under Medicare Part D
• Limit cost sharing for insulin for individuals with Medicare and private insurance. Currently, Part D and private insurance plans vary in terms of the insulin products they cover and what enrollees pay for insulin products. Under the BBBA, participating plans would cover insulin products at a monthly copayment of $35. Participating plans would not have to cover all insulin products at the $35 monthly copayment but would include one of each dosage form (vial, pen) and insulin type (rapid-acting, short-acting, intermediate-acting, and long-acting).

 

Since the large BBBA endeavor has not progressed in Congress, the House of Representatives passed a scaled back version (Affordable Insulin Now Act) in March of 2022 that specifically addressed insulin costs.³⁴ The bill would cap cost-sharing under the Medicare prescription drug benefit for a month's supply of covered insulin products at $35 and cap private health insurance cost sharing for selected insulin products at $35 or 25% of a plan's negotiated price (after any price concessions). The cap would become effective in 2023. At the time this activity was prepared, the effort was awaiting Senate action. A modified bipartisan Senate bill with a $35 co-pay cap has been introduced.

 

The industry trade group, the Pharmaceutical Research and Manufacturers of America (PhRMA), does not favor the act, calling the proposed law heavy-handed and flawed. PhRMA’s position is that it would make the “broken insurance system worse and throw sand in the gears of medical progress” and “doesn’t address perverse incentives in the system that are leading to higher costs for patients.”³⁵

 

Biosimilars

The previously discussed biosimilars also aim to encourage more affordable insulin substitutes.²³ Before 2010, the U.S. lacked a regulatory pathway for the development of biosimilar medications.^15,36 In 2010, the Biologics Price Competition and Innovation Act (BPCIA) was signed into law as part of the Affordable Care Act. This new law created an FDA approval pathway for biosimilar and interchangeable biologic products while preserving incentives for the development of new medications.^36,37 Typically, biosimilars marketed in the U.S. have launched with initial list prices 15% to 35% lower than comparable list prices of the original reference products.²⁹ The BPCIA provides two separate pathways for a biological product to compete with a reference product: either as a biosimilar or as an interchangeable. Interchangeable products are subject to more stringent requirements.^23,36

 

To be considered a biosimilar, the route of administration, dosage form, and strength must be the same as the reference product.^36,38 The sponsor must show that it is “highly similar” to the reference product and that no clinically meaningful differences between the biosimilar and the reference product exist in terms of safety, purity, and potency of the product.³⁸ Only minor differences in clinically inactive components are permitted in biosimilar products.³⁰

 

The biosimilar must also possess the same mechanism of action as the reference product for the condition it is intended to treat, and the manufacturing conditions and facilities must meet standards to ensure safety, purity, and potency.^36,38 To be interchangeable, the manufacturer must demonstrate two things^36,38:

• That the product produces the same clinical result as the reference product in patients.
• If it is to be used more than once in a given individual, any safety risks or diminished efficacy from switching between the reference substance and the biosimilar is no greater than the risks from using the reference product alone.

 

Pharmacists should take note of an important difference between biosimilars and generics. Generics (small molecules) only need to demonstrate bioequivalence, while biosimilars need to demonstrate therapeutic equivalence.³⁶ The equivalence must be based on data derived from animal studies, clinical studies, and analytics that show a similarity to the reference product.³⁶ As noted above, meeting the biosimilar criteria requires much more time and expense than substantiating generic equivalency. Pharmacists also need to appreciate that even if a product is defined as “interchangeable,” it is not possible to create identical versions of reference biologic medicines due to their complexity.³⁰

 

The BPCIA also has market exclusivity provisions that address manufacturers’ concerns.³⁶ Applicants for biosimilar products cannot submit an application until four years after the date on which the reference product was first licensed. Further, the FDA cannot approve the biosimilar or interchangeable until 12 years after the date on which the reference product was first licensed. In addition, the applicant must provide the manufacturer of the reference product with notice of intent 180 days before marketing the product. The first interchangeable product also has market exclusivity for at least a year.³⁶

 

FDA approval of biosimilars, however, is not the only obstacle to marketing insulin substitutes. As noted above, biosimilars must contend with patent evergreening.^17,27 Biosimilars will also not necessarily grab a large market share.²⁷ Lilly, Novo Nordisk and Sanofi have launched their own “authorized generics,” essentially their own drugs repackaged and marketed at discounted prices.²⁷ Lilly and Sanofi produced the first two (Basaglar and Admelog), which provides little in the way of competition; they are priced only about 15% to 20% less than their respective original forms.^17,39

 

More significantly, the complex price setting maneuvering that affects the cost of insulin could also impede cheaper biosimilar acceptance. Since PBMs can make more money from discounts on brand name products, they have more to gain from prioritizing the dominant brands and little incentive to include biosimilars in formularies.^17,27,39 In addition, since pharmacists can substitute interchangeable products, pharmacists have the discretion whether or not to dispense the less expensive formulation.

 

Over the Counter

Pharmacy personnel should recall that when Congress established federal prescription drug regulations in 1951, the types of insulin available at that time, unlike the more recent analogs, did not require a prescription.⁴⁰ Human insulin injection is available over the counter in 49 U.S. states and the District of Columbia and about 15% percent of U.S. patients who buy insulin purchase it over the counter without a prescription.^40,41 This presents a dilemma for patients and clinicians.^40,41 On one hand, this provides an opportunity for patients to obtain insulin without delay, especially in an urgent situation,⁴¹ at a more affordable price (average price of $54.09, compared with $114.40 for prescription short-acting insulins.¹⁹). On the other hand, it could be dangerous for a patient to adequately assess the appropriate dosage and timing for optimal glucose control without training or guidance from a health care provider especially if they are switching between different versions of insulin.⁴⁰ Physicians may not be aware that insulin can still be purchased OTC and may be puzzled by a patient’s sudden change in blood glucose.⁴¹ The FDA maintains that the older insulins were approved for OTC sale because they are less concentrated and did not require medical supervision for safe use.⁴¹

 

State Activities

States have also taken measures to influence insulin cost and use while waiting for federal actions.

In 2019, Colorado became the first state to limit co-pays for patients who use insulin, capping individual prescription at $100 for a 30-day supply ($200 if patients use two types of insulin), although payers have exploited some loopholes.⁴² The law applies to private insurers but not to patients on Medicare. Since then, seven other states (Illinois, Maine, New Mexico, New York, Utah, Washington, West Virginia) have enacted similar measures and five others (Connecticut, Florida, Kentucky, Tennessee, Virginia) are contemplating similar legislation.⁴² In New Mexico, the cap is set at $25.

 

Pharmacy staff are also reminded that, generally, individual state laws govern generic substitution.⁴² Some states have become concerned that biosimilars are not “identical” to the reference product, consequently pharmacy staff should become familiar with their state’s regulations regarding biosimilar substitution.⁴³ At least one U.S. state (Indiana) does not permit OTC sales of insulin due to the safety concerns noted above.^19,41

 

Individuals

Insulin prices have risen to such an extent that patients have taken matters into their own hands. The disparity in price has motivated many Americans to travel to Canada to purchase their insulin where the price may be as little as 1/10 the cost in the U.S.^1,9,44 Governmental policy controls insulin prices in Canada, including price caps and negotiations with manufacturers and often insulin does not require a prescription.⁴⁴

 

PAUSE AND PONDER: How would you advise a patient who is contemplating purchasing insulin from Canada as a cost-saving measure?

 

In another approach to reducing the cost of insulin, biohackers have been attempting to make insulin by converting proinsulin obtained from yeast to insulin with the hope of providing a method for do-it-yourself production that could be shared online.^18,45 If they are successful, anyone, hypothetically, could construct a lab and manufacture open-source insulin in a garage at a lower cost.¹⁸ However, they could still run afoul of FDA regulations and need to conform to Good Manufacturing Practices.^18,45

 

PAUSE AND PONDER: How would you respond to a patient who asks you about OTC or “homemade” insulin?

 

Patients are also filing lawsuits challenging manufacturer’s “schemes” to unlawfully inflate the benchmark prices of rapid- and long-acting insulins.¹¹

 

SUMMARY AND CONCLUDING REMARKS

Insulin maintains a critical place in the treatment of diabetes more than 100 years after the discovery of its beneficial effects, yet the disease is poorly managed in many patients, in part due to the escalating cost of newer forms of the drug. Insulin prices in the U.S. are far higher than in the rest of the world, fueled by a pricing system riddled with disincentives to keep prices low. Patients with no or low-quality health insurance are particularly impacted. Congress and states are examining possible solutions to the problem, notably by placing caps on out-of-pocket spending on insulin.

 

Pharmacy staff, as the point of contact with patients receiving insulin, are ideally situated to help patients who are struggling with adherence to their medication. Patients would benefit from pharmacists who can advise them about the different forms of insulin and delivery devices.⁴⁶ The Endocrine Society recommends that pharmacists learn about lower cost options offered by manufacturers and share their findings with patients and prescribers.²⁴ Pharmacists should also be ready to discuss the pros and cons of OTC insulin products. Pharmacists have also gained an opportunity (and responsibility) to manage costs with the approval of the first interchangeable insulin product.

 

Another helpful role would be to educate patients about available patient assistance programs especially since many patients may be unfamiliar with them or unsure about whether they qualify and how to apply.⁴⁶ This is a function that pharmacy technicians can fulfill. It is also vital that pharmacy staff remain familiar with Congressional and State efforts to lower out-of-pocket costs of insulin described above and some may choose to serve as patient advocates. Finally, if open-source methods of manufacturing insulin prove to be successful, it could potentially introduce opportunities for compounding pharmacies to make insulin at a lower cost.¹⁸ Insulin may never be as affordable as Frederick Banting hoped, but at least encouraging signs suggest that fewer patients will find it necessary to forego their life-saving treatment because of the expense.

As this activity was being prepared for posting, the Senate passed the long-debated Inflation Reduction Act which dealt with climate, taxes, and health care. The relevant features will allow the government to negotiate costs for certain drugs paid for by Medicare (10 in 2026 and 20 in 2029) and will cap out-of-pocket expenses for insulin at $35 per month for Medicare patients but not for private insurers.

 

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