Spike in drug shortages raises alarm

Pharmaceutical drug shortages increased more than five-fold from 2008 to 2014, according to a study published in Academic Emergency Medicine. In fact in 2007, FDA listed 154 drugs that were either in short supply or no longer available. In April 2016, that number had grown to more than 300 drugs in short supply.

AlkireThe shortage has significantly impacted the U.S. healthcare industry, most notably in emergency departments, pressuring hospitals to pay at least $230 million more a year than they ordinarily would to find alternative treatments, says Michael Alkire, chief operating officer for Charlotte, North Carolina-based Premier, a national alliance of hospitals and healthcare providers.

The recent spike in drug shortages is multifactorial, and includes a lack of competition, quality issues, manufacturing delays, and increased FDA oversight and inspection of the manufacturing process.

Alkire points out that the generic drug market, in particular, has experienced shortages since 2008. That year, contaminated heparin manufactured in China led to the deaths of 81 U.S. patients and more stringent FDA quality inspections. As a result, some active pharmaceutical ingredient (API) and generic drug manufacturers went out of business, causing product and raw material shortages.

Since then, FDA's backlog of generic drug application approvals has multiplied from 1,500 generic drugs to about 4,000 applications. Some are for drugs that could compete with those that have experienced shortages and price spikes. "With a wait time of 42 months to bring a new generic drug to market, there is a high barrier to entry that greatly inhibits competition," Alkire says.

Next: Broken supply chains

Broken supply chains

These issues, combined with an increase in generic manufacturer consolidation, have led to many examples of only one or two U.S. companies being responsible for the entire country's supply of certain drugs. "If there's a disruption in production among these manufacturers, shortages occur," Alkire says.

Sterile injectable drugs are also susceptible to shortages, because few production lines are capable of producing a certain drug. In fact, a given line might be responsible for half of the U.S. production of a particular drug.

JensenIn recent years, several key facilities experienced manufacturing problems when they failed to assure product sterility. Consequently, temporary shutdowns turned into market-wide shortages, says Capt. Valerie Jensen, RPh, associate director, Drug Shortage Staff, FDA, Silver Spring, Maryland. A common scenario is a line shutting down to address serious manufacturing quality failures, but the loss is too steep for other production lines already operating at full capacity to make up.

In addition, sometimes delays happen when suppliers don’t have the raw pharmaceutical ingredients or components needed to manufacture drugs, or shortages of other components (e.g., stoppers, vials, or containers) used to make the product occur.

Kristy Hawley, MPH, scholar, George Washington University School of Medicine and Health Sciences Office for Clinical Practice Innovation, Washington, D.C., adds that there is an inherent market failure, which is evidenced by companies that stop producing products that appear to be in high demand (e.g., normal saline). Low reimbursement rates from Medicare Part B have been cited as one of the reasons for this market failure, she says.

Don Hall, MPH, a Managed Healthcare Executive editorial advisor and principal, Delta Sigma LLC, Littleton, Colorado, adds that for health plan executives, much of the problem with drug shortages generally relates to generic drugs for which pharmaceutical companies get lower reimbursement. “It is putting pressure on health plans to pay more for the generics or pay for the brand name,” says Hall, a former health plan executive. “This is particularly acute for some oncology and cardiology drugs.”

Next: Most common shortages

Most common shortages

Drug shortages have a daily impact on clinicians, health systems, payers, and patients-with the biggest impact being felt in the emergency department.

HawleyDrug shortages for medications impacting emergency care have risen dramatically by more than 400% between 2008 and 2014, as reported in the Academic Emergency Medicine study. Nearly half of the drugs in short supply were used for high-acuity or life-threatening conditions. For a minority of products (32 drugs over 13 years), no substitute was available. As a result, some patients in emergency departments did not receive first-line treatments for their conditions, says Hawley, a coauthor of the study.

According to the study, infectious disease, analgesia, and toxicology were the most common categories of emergency medicine drugs that experienced shortages between 2008 and 2014. Within these categories, the most common drugs in short supply were acyclovir injections (infectious diseases), hydromorphones (analgesia), and antivenin polyvalent injections (toxicology).

Toxicology shortages are of particular concern when substitutes aren't available, because patients face serious risks. "Having appropriate pain control is a major concern for critically ill and surgical patients who rely on these medications for comfort and to relieve psychological stress," Hawley says. "Pain and associated stress can deleteriously affect wound healing."

When injectable drugs are scarce, hospitalized patients' care can be severely impacted. "Often an alternative is available, but it can take time and significant education to use a different medicine when the drug of choice is not available," says Erin R. Fox, PharmD, director, Drug Information Service, University of Utah Health Care, Salt Lake City.

For example, when a preferred antibiotic is unavailable, doctors and pharmacists have to work together to choose another antibiotic that will work for a specific patient. Sometimes this means using a more expensive antibiotic or one that covers more infections than necessary, which could possibly lead to resistance.

Also in short supply are prefilled syringes of emergency medications. "These medicines are needed in emergencies and are used by first responders or in code carts," says Fox, a coauthor of the Academic Emergency Medicine study. "The same medicines are still available in vials, but they aren't packaged and ready to use for an emergency."

Other drugs in short supply include antimicrobials, chemotherapy drugs, cardiovascular drugs, drugs used to treat central nervous system disorders, and anesthetics used for surgery patients, Alkire says.

Next: Top areas of concern

Top areas of concern

Drug shortages are particularly harmful in emergency care settings where providers must rapidly treat ill and injured patients. The effects of drug shortages have had significant impacts on hospitals, because shortages have resulted in:

• Delays or cancellations of necessary medical procedures;

• Added risk of patient care errors and adverse events; and

• Increased costs for providers when substituting more expensive therapeutic alternatives.

When a drug shortage occurs, hospital labor costs increase. One study, published in the American Journal of Health-System Pharmacy, estimated that the labor costs to manage shortages at hospitals exceeds $216 million annually.

Rucco"It takes a tremendous amount of time to bring an alternative product into a hospital and make sure it will be safe to use," Fox says. Pharmacists and technicians spend hours switching stocking locations, changing electronic medical records, and entering new products into the many different pharmacy automation databases.

Shortages also lead to price spikes, with some manufacturers capitalizing on a lack of competition by hiking their prices by 400% or more. What’s more, sometimes hospitals have been forced to purchase sufficient quantities of drug substitutions to meet their needs when they are notified of a potential shortage, often at inflated costs, which increases costs for patients, says Dana Rucco, BS, MS, RPh, director of pharmacy services, Long Island Jewish Medical Center, of Northwell Health System, Great Neck, New York.

Next: Patient care in jeopardy

Patient care in jeopardy

Substitutions exist for most medications, but they may not be as effective, may have more side effects, or providers may not have as much experience prescribing them. This could potentially lead to increases in medication errors, such as issues with drug dosing or interactions.

In the Academic Emergency Medicine study, among the 32 drugs in short supply that had no substitute were antidotes that reverse the effects of drug overdose (i.e., therapeutic or recreational drugs) and treatments for exposure to toxic substances. Rabies immune globulin was the longest affected medication in the infectious disease category. While relatively rare, patients are at serious risk if the drug is unavailable, Hawley says.

Shortages of other injectables such as naloxone are also problematic because no substitute exists for opioid intoxication without switching the method of delivery, such as an intranasal preparation used by first responders on drug abusers, which is more expensive than the sterile injectable form that most physicians use.

If a vaccine is in short supply, it may result in a missed opportunity to immunize someone. "The patient may not come back for the immunization once stock is available," Fox says. "When a critical medicine such as a chemotherapy drug faces a shortage, in some cases the alternative can result in poor outcomes, even though physicians expect the alternative to have the same outcome."

Karen Appold is a medical writer in Lehigh Valley, Pennsylvania.