DEA Crackdown on Opiate Production Produces Shortages

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https://www.healio.com/hematology-oncology/practice-management/news/print/hemonc-today/%7Bae9614d6-5bcc-4fb2-bd4b-b0b54f998aca%7D/urgent-action-necessary-to-address-opioid-drug-shortage

The frequency of drug shortages in the United States is rapidly increasing.

Shortages of opioid drugs — such as injectable hydromorphone, morphine, fentanyl and methadone — have placed a particularly heavy burden on EDs, ambulatory surgery centers and hospitals. This issue has escalated since HHS declared the opioid epidemic a public health emergency last year.

American Society of Health-System Pharmacists (ASHP) surveyed its members in April to assess the effects of the acute shortage of injectable opioids. Nearly all (98.4%) of the 343 respondents reported experiencing severe or moderate shortages of morphine, hydromorphone and fentanyl, and more than two-thirds of respondents indicated those shortages affected daily operations and patient care.

Multiple causes

Drug shortages typically are caused by many factors, including difficulty acquiring raw materials, manufacturing problems, regulatory issues, business decisions and other disturbances within the supply chain.

Occasionally, natural disasters significantly impair production. Hurricane Maria — a Category 5 storm that caused catastrophic damage across the northeastern Caribbean last year — is considered the worst natural disaster to hit Puerto Rico, which produces more pharmaceuticals by dollar value for the nation than any of the individual 50 U.S. states or any foreign country.

The volume of opioids allowed to come to market in the United States increased dramatically for years. After the subsequent opioid epidemic ensued, the Drug Enforcement Administration (DEA) set forth policies to ensure production of what is required for legitimate use while guarding against overproduction of harmful substances.

The DEA proposed to cuts to opioid production is 25% in 2016, followed by cuts of an additional 20% in 2017 and another 20% in 2018.

Quotas are intended to ensure adequate and uninterrupted supply for legitimate medical need for more than 250 schedule I and II controlled substances annually. However, this drastic change in production threatens the availability of opioids — a mainstay treatment of cancer-related pain — for terminally ill patients across the country.

The bipartisan Opioid Quota Reform Act of 2018 now directs the DEA to consider additional factors of opioid diversion, abuse, overdose deaths and impact on public health when establishing opioid production quotas.

The act also requires the DEA — if it approves any increase in quotas — to explain why the public health benefits of the increase outweigh the potential harmful consequences.

The bill focuses on helping the DEA to address the oversupply of opioids that contributed to the addiction crisis, but it also may enable the agency to respond more swiftly to shortages.

Pfizer, the largest provider of injectable prefilled opioid syringes, added a Hospira facility in McPherson, Kansas, to focus on production of these products. However, the FDA found significant violations at that plant, citing particulates floating in the liquid medications and loss of control in the manufacturing process. Thus, the plant had to halt production last year.

Manufacturers are required to give the FDA 6 months’ advanced notice when they plan to stop producing a single-source, medically necessary drug. Given that “medically necessary” is not statutorily defined, the enforcement of ample notification to prepare for implication of the shortage is loose at best. Further, the FDA does not investigate drug shortages that are expected to be temporary and self-limiting due to limited resources and the transient nature of temporary shortages, even though these can have a significant impact on providers and hospitals.

Even for medically necessary drugs, the FDA’s authority to resolve a product shortage is limited. The FDA cannot demand a company to produce a drug and has no authority over manufacturer business decisions.

Hospital response

Hospitals are managing the shortages by switching to oral opioids, restricting injection opioid use, prioritizing patients according to clinical need, and converting to nonopioid medications.

In the ASHP survey, nearly three-quarters of respondents indicated they were forced to convert patients to oral opioid medications, and more than half implemented restriction protocols on injectable opioids or prioritized patients based on clinical need.

The most common strategies institutions have used to mitigate the shortage include purchasing vial sizes or concentrations not normally stocked, removing injectable opioids from dispensing cabinets or other decentralized locations, and repackaging injectable opioids from larger vials or syringes. Most hospitals (89%) reported increased costs associated with implementing such strategies.

Pharmacists are working longer hours to find alternatives, and nurses are asked to administer second-choice drugs or deliver standard drugs differently, raising the risk for mistakes.

The Institute for Safe Medication Practices (ISMP) reported several such cases. In one, the provider reported that a patient received five times the appropriate amount of morphine because the smaller-dose vial was out of stock. In another, a patient was mistakenly given too much sufentanil — about 10 times more powerful than fentanyl, which was the opioid of choice.

As a result, some hospitals are opting to administer less potent medications like acetaminophen, which may compromise adequate analgesia.

Strategies for clinicians

Clinicians can follow several strategies to manage the opioid shortage.

They include:

  • Switch therapy to a clinically appropriate oral or enteral opioid whenever possible. The institution’s pharmacy and therapeutics committee should establish uniform conversion tools;
  • Consider nonpharmacologic treatments;
  • Engage anesthesia experts and palliative medicine to develop guidance and formulate strategies for dealing with shortages;
  • Ensure the electronic health record displays opioid options that match the products in stock;
  • Reserve injectable opioids for specific indications and limit the placement to hospital locations in greatest need for these products;
  • Optimize the quantities of injectable opioids kept in automated dispensing cabinets after checking usage patterns at specific locations;
  • Explore options for purchasing product from other wholesalers or manufacturers;
  • Limit waste by considering the doses commonly given on patient care units, and supply those units with appropriately sized syringes or vials;
  • Repackage opioids from large vials into syringes, being careful to assign beyond-use dates as dictated by USP 797; and
  • Review drug records, order sets and treatment protocols for necessary changes.

Collaborative efforts

A coalition of professional medical groups — the American Hospital Association, ASCO, American Society of Anesthesiologists, ASHP and ISMP — sent a letter to the DEA in February requesting an adjustment to the aggregate production quotas set forth for certain opioids to mitigate ongoing drug shortages. The letter also addresses how shortages of injectable opioids may threaten patient care and increase risk for potentially life-threatening medication errors.

In April, the DEA announced it would reallocate Pfizer’s quota allotment to three DEA-registered manufacturers of FDA-approved injectable products; however, it is important to note the DEA cannot control the quantity or speed by which manufacturers produce these products.

The FDA Safety and Innovation Act and the agency’s Strategic Plan for Preventing and Mitigating Drug Shortages established a task force intended to better prevent and forecast shortages. If notified of a potential production disruption, the FDA can determine if other manufacturers are willing and able to increase production, expedite inspections and reviews of submissions, exercise temporary enforcement discretion for new sources of medically necessary drugs, work with the manufacturer to ensure adequate investigation into the root cause of the shortage, and review possible risk-mitigation measures for remaining inventory.

Manufacturers are not required to disclose the problem causing the interruption to the FDA, or to provide a timeline for resolution. However, it is reasonable to think having this information would allow the FDA to implement risk-mitigation strategies quicker. Given that it is difficult to find a manufacturer willing to increase or begin production of a drug in shortage, the FDA could consider establishing an incentive to encourage manufacturers to produce these drugs.

On July 12, FDA Commissioner Scott Gottlieb, MD, announced plans for the formation of a new drug shortages task force. This group will be asked to:

  • Broaden requirements for manufacturer notification of potential shortages;
  • Encourage companies — possibly with financial incentives — to produce drugs vulnerable to shortages with robust manufacturing processes that ensure consistently available quality products; and
  • Institute shortage-prevention mechanisms, such as expanding the FDA’s authority to require applicants of certain drugs to conduct a risk assessment to identify vulnerability in their drug supply that could cause a shortage and establish risk-mitigation plans to address those weaknesses proactively.

The FDA, DEA, HHS, CDC, Congress, industry leaders and health care professionals should make concerted efforts to tackle the drug shortage crisis through a collaborative approach.

Although the initiatives outlined above may improve the shortage crisis over many years, we must move urgently to improve patient care and ensure all patients have access to critically needed medications. In order to do this, adequate funding also must be made available to these agencies to combat such a crisis.

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