Drug and Medical Supply Shortages Impacting Patient Safety at ‘Alarming Rate’

By Pat Anson, PNN Editor

Over half of U.S. hospitals are reporting shortages of drugs and supplies used in anesthesia, pain management and emergency care, according to a new survey by a nonprofit healthcare organization. Nearly nine of out of ten (86%) respondents said they were rationing or restricting the use of medications in short supply.

The survey of nearly 200 hospital administrators, pharmacists and supply chain managers was conducted by the Emergency Care Research Institute (ECRI) in July.

“Their responses suggested that providing safe and appropriate drugs, supplies, and equipment has become extremely challenging and led to numerous instances of unsafe practices, compromised care, and potentially harmful errors. Many of the respondents clearly communicated their struggles to address shortages which are occurring at an alarming rate,” the ECRI report said.

Respondents reported shortages of over 20 drugs, single-use supplies, or medical equipment. The shortages primarily affect surgery and anesthetics (74%), emergency care (64%), pain management (52%), cardiology (45%), hematology and oncology (44%), infectious diseases (39%), and obstetrics and gynecology (37%).

“While medication and supply shortages have been widely reported across healthcare, we now know with certainty that these shortages are causing preventable harm and have the potential to cause even more if they are not addressed soon,” Marcus Schabacker, MD, president and CEO of ECRI, said in a statement.

“There are strategies hospitals can use to reduce the impact of shortages, but they are a deviation from standard practice and resource-intensive -- two characteristics that themselves can increase the likelihood of preventable harm.”

Many hospitals (42%) are stretching supplies by using medications after their expiration date, reusing single-use devices, or using drugs for purposes outside of their specific labeling. Nearly a quarter of respondents (24%) said they knew of at least one medical error related to a drug, supply or device shortage.

Specific examples of how shortages have impacted patient care include:

• Interruption or delays in chemotherapy

• Use of more opioid analgesia due to lidocaine shortages

• Incorrect medication instructions given to patients

• Postponement or cancellation of surgeries 

To address shortages of masks, gowns and other personal protective equipment, many hospitals have turned to non-traditional sources that supplied products with “alarmingly poor performance,” according to ECRI.

For example, tests on KN95 masks obtained from nontraditional suppliers found that up to 70% did not filter particulates the way manufacturers claimed. And tests on disposable gowns revealed that over half failed to meet even minimum standards for protection.

“The extent to which medication, supply, and equipment shortages are negatively impacting patient care is inexcusable,” said Rita Jew, PharmD, president of the Institute for Safe Medication Practices, an ECRI affiliate. “While pharmacies and hospitals can triage shortages short-term, we need long-term, nationally coordinated solutions to solve the persistent shortages we’ve witnessed repeatedly over the last several years.”

Supply Interruptions

Many respondents also expressed concern about drug shortages worsening after a Pfizer plant in North Carolina was heavily damaged in July by a tornado. The Rocky Mount plant was a leading supplier of sterile injectable drugs used in surgery, pain management and emergency care. Pfizer recently resumed production at the plant, but doesn’t expect full operations to be restored until later in the year.     

“While manufacturing has resumed, it is important to note that some medicines may not be back in full supply until next year,” the company said in a statement.

The American Society of Health-System Pharmacists (ASHP) recently expanded its shortage list for injectable morphine to include morphine vials made by Pfizer. The company said the vials are on back order and could not estimate a release date. The lack of supply is having a snowball effect on other drug manufacturers, who say they’re running out of injectable morphine and hydromorphone due to increased demand.

The ASHP recommends that providers use “extreme caution” when switching morphine concentrations or interchanging them with other injectable opioids because patients could react to them differently.

Limited supplies of morphine, hydromorphone and other injectable opioids were being reported long before the tornado damaged Pfizer’s plant or the pandemic disrupted the global supply chain. Despite that, the Drug Enforcement Administration has aggressively cut the supply of many opioids, reducing production quotas for hydromorphone by 71% and morphine by 65% from their peaks in 2016.       

GRAPHIC COURTESY OF MONTY GODDARD

The Food and Drug Administration put injectable morphine and hydromorphone on its drug shortage list in 2017, the year after DEA started cutting the opioid supply.  In recent months, the ASHP added oxycodone and hydrocodone tablets to its drug shortage list, but their limited supply has not yet been acknowledged by the FDA.

A recent federal lawsuit accused the DEA of “incompetence” in its handling of the nation’s drug supply, specifically the production quotas the agency sets for amphetamines used in ADHD medication.

Drug makers are required to report shortages and supply interruptions to the FDA. Doctors, pharmacies and consumers can also report them by email to the FDA at drugshortages@fda.hhs.gov. To report a drug shortage to the ASHP, click here.

Why Cheap Generic Drugs Are Harder to Find

By Dr. Geoffrey Joyce, University of Southern California

Past public ire over high drug prices has recently taken a back seat to a more insidious problem – no drugs at any price.

Patients and their providers increasingly face limited or nonexistent supplies of drugs, many of which treat essential conditions such as cancer, heart disease and bacterial infections. The American Society of Health System Pharmacists now lists over 300 active shortages, primarily of decades-old generic drugs no longer protected by patents.

While this is not a new problem, the number of drugs in short supply has increased in recent years, and the average shortage is lasting longer, with more than 15 critical drug products in short supply for over a decade. Current shortages include widely known drugs such as the antibiotic amoxicillin; the heart medicine digoxin; the anesthetic lidocaine; and the medicine albuterol, which is critical for treating asthma and other diseases affecting the lungs and airways.

What’s going on?

I’m a health economist who has studied the pharmaceutical industry for the past 15 years. I believe the drug shortage problem illustrates a major shortcoming of capitalism. While costly brand-name drugs often yield high profits to manufacturers, there’s relatively little money to be made in supplying the market with low-cost generics, no matter how vital they may be to patients’ health.

The shortage includes chemotherapy drugs, antibiotics, medications to treat ADHD and other critical drugs. Some patients are able to get their drugs, while others are not, and in some cases patients are getting ‘rationed care.’

Brand Name Drugs More Profitable

The problem boils down to the nature of the pharmaceutical industry and how differently the markets for brand and generic drugs operate. Perhaps the clearest indication of this is the fact that prices of brand drugs in the U.S. are among the highest in the developed world, while generic drug prices are among the lowest.

When a drugmaker develops a new pill, cream or solution, the government grants the company an exclusive patent for up to 20 years, although most patents are filed before clinical testing, and thus the effective patent life is closer to eight to 12 years. Nonetheless, patents allow the drugmakers to cover the cost of research and development and earn a profit without the threat of competition from a rival making an identical product.

But once the patent expires, the drug becomes generic and any company is allowed to manufacture it. Since generic manufacturers are essentially producing the same product, profits are determined by their ability to manufacture the drug at the lowest marginal cost. This often results in low profit margins and can lead to cost-cutting measures that can compromise quality and threaten supply.

Outsourced Production Creates Supply Risks

One of the consequences of generics’ meager margins is that drug companies outsource production to lower-cost countries.

As of mid-2019, 72% of the manufacturing facilities making active ingredients for drugs sold in the U.S. were located overseas, with India and China alone making up nearly half of that.

While overseas manufacturers often enjoy significant cost advantages over U.S. facilities, such as easy access to raw materials and lower labor costs, outsourcing production at such a scale raises a slew of issues that can hurt the supply. Foreign factories are more difficult for the Food and Drug Administration to inspect, tend to have more production problems and are far more likely than domestic factories to be shut down once a problem is discovered.

In testimony to a House subcommittee, Janet Woodcock, the FDA’s principal deputy commissioner, acknowledged that the agency has little information on which Chinese facilities are producing raw ingredients, how much they are producing, or where the ingredients they are producing are being distributed worldwide.

The COVID-19 pandemic underscored the country’s reliance on foreign suppliers – and the risks this poses to U.S. consumers.

India is the world’s largest producer of generic drugs but imports 70% of its raw materials from China. About one-third of factories in China shut down during the pandemic. To ensure domestic supplies, the Indian government restricted the export of medications, disrupting the global supply chain.

This led to shortages of drugs to treat COVID-19, such as for respiratory failure and sedation, as well as for a wide range of other conditions, like drugs to treat chemotherapy, heart disease and bacterial infections.

Low Profits Hurt Quality

Manufacturing drugs to consistently high-quality standards requires constant testing and evaluation. A company that sells a new, expensive, branded drug has a strong profit motive to keep quality and production high. That’s often not the case for generic drug manufacturers, and this can result in shortages.

In 2008, an adulterated version of the blood-thinning drug Heparin was recalled worldwide after being linked to 350 adverse events and 150 deaths in the U.S. alone.

In 2013, the Department of Justice fined the U.S. subsidiary of Ranbaxy Laboratories, India’s largest generic drug manufacturer, US$500 million after it pleaded guilty to civil and criminal charges related to drug safety and falsifying safety data. In response, the FDA banned products made at four of the company’s manufacturing facilities in India from entering the U.S., including generic versions of gabapentin, which treats epilepsy and nerve pain, and the antibiotic ciprofloxacin.

And while there may be multiple companies selling the same generic drug in the U.S., there may be only a single manufacturer supplying the basic ingredients. Thus, any hiccup in production or shutdown due to quality issues can affect the entire market.

A recent analysis found that approximately 40% of generic drugs sold in the U.S. have just one manufacturer, and the share of markets supplied by just one or two manufacturers has increased over time.

Repatriating the Drug Supply

It is hard to quantify the impact of drug shortages on population health. However, a recent survey of U.S. hospitals, pharmacists and other health care providers found that drug shortages led to increased medication errors, delayed administration of lifesaving therapies, inferior outcomes and patient deaths.

What can be done? One option is to simply find ways to produce more generic drugs in the U.S.

California passed a law in 2020 to do just that by allowing the state to contract with domestic manufactures to produce its own generic prescription drugs. In March 2023, California selected a Utah company to begin producing low-cost insulin for California patients.

Whether this approach is feasible on a broader scale is uncertain, but, in my view, it’s a good first attempt to repatriate America’s drug supply.

Geoffrey Joyce, PhD, is director of Health Policy at the USC Schaeffer Center, an associate professor and chair of the Department of Pharmaceutical and Health Economics at the USC School of Pharmacy, and research associate at the National Bureau of Economic Research.

Prior to his position at USC, Dr. Joyce was a Senior Economist at the RAND Corporation and currently co-directs UCLA's post-doctoral program in Health Services Research.

This article originally appeared in The Conversation and is republished with permission.

Tight Rx Opioid Supply Causing Shortages of Oxycodone and Hydrocodone

By Pat Anson, PNN Editor

At least three U.S. drug companies have reported shortages of oxycodone, the latest sign that efforts to limit the supply of opioid pain medication have gone too far and are harming patients.

On March 17, the American Society of Health-System Pharmacists (ASHP) added immediate release oxycodone to its nationwide list of drug shortages, with shortages of 5, 15, 20 and 30 mg tablets being reported by Amneal, Camber and Rhodes Pharmaceuticals. Other drug companies still have oxycodone tablets of various doses available, according to ASHP.

Amneal and Rhodes did not provide a reason for their shortages, while Camber told ASHP it was “awaiting DEA quota approval for active ingredient,” which presumably is oxycodone. All three companies, which specialize in making generic drugs, said the tablets were on back order.

“We have been following up on some reports of these shortages and have recently added immediate-release oxycodone tablets to our shortage database,” said Michael Ganio, PharmD, Senior Director of Pharmacy Practice and Quality at ASHP.

In addition to the oxycodone shortage, Ganio told PNN there were anecdotal reports of hydrocodone medications being in short supply.

“We have not heard back from all manufacturers of hydrocodone/acetaminophen products, but some have reported availability while others have reported some package sizes are not currently available,” Ganio said in an email. “We don’t have state-by-state data, so unfortunately I cannot offer any insight on specific (pharmacy) chains or states. However, it’s common with shortages that manufacturers with product available will limit sales to existing purchasers. That can mean products may not be available depending on previous purchase history from those pharmacies.”

(Update: On May 26, the ASHP added hydrocodone/acetaminophen tablets made by several generic drugmakers to its list of shortages.)

The ASHP’s list of shortages usually mirrors the drug shortage list maintained by the Food and Drug Administration, but the federal agency does not currently list either oxycodone or hydrocodone tablets as being in short supply.

‘It’s Gotten Worse’ 

Pain patients have complained for years about pharmacists being unable to fill their opioid prescriptions, usually claiming they were “out of stock” or awaiting a delayed shipment. But the problem seems to have become more widespread in recent months.

“I've gone through shortage just this month for oxycodone yet again. I've also had shortage for morphine in the past,” said Michelle Farrell, who lives in Arizona. “My normal pharmacy said it was due to restrictions in place by the manufacturer this month. They were limiting the distributor and on down the (supply) chain.” 

After several days delay, Farrell was able to get her oxycodone prescription filled at another pharmacy.

A woman in Orange County, California said her CVS pharmacy was out of oxycodone for months.

“I have gone 4 months (fills) of an alternative medication because 10 mg oxycodone 10-325 has been completely out of stock at my home CVS store, as well as stores within a 20 mile radius. Yesterday was the first time my pharmacy could fill my prescription. Thank god. It is destabilizing having to be forced off your stable medical regimen,” she said in an email.

A woman in Melbourne, Florida recently told PNN she had to visit several pharmacies to get a prescription filled for hydrocodone. She needs pain medication for spondylarthritis and fibromyalgia. 

"I called CVS about picking up my medicine and I was told there is no hydrocodone available anywhere, it's with the manufacturer and had been out a month. Their pharmacist said he has no idea when they will be available again," said Kristina, who asked that we not use her last name. 

“I called a different CVS and she said the same thing, it's a national shortage, had been for about 3 weeks…. I was told there were 3 pills of 5mg hydrocodone within a 20-mile radius of (area code) 32926.”

CVS did not respond to a request for comment. Neither did the Florida Department of Health or the Florida Board of Pharmacy.

Kristina was eventually able to get her prescription filled, but only after her doctor got around the problem by increasing her dosage to 7.5 mg tablets of hydrocodone, which were available. Ironically, the manufacturer of those tablets was Amneal, one of the companies now reporting shortages of oxycodone.

What can a patient do when faced with a shortage? The ASHP recommends sharing as much information as possible with pharmacists about their medical history.

“The pharmacist can typically talk to the prescriber to find an alternative based on what products are available. However, if the medication is a Schedule II controlled substance, transferring prescriptions between pharmacies is not allowed. If another pharmacy has a product available, the prescriber will have to send a new prescription for the medication,” said Ganio.

“All of this sets up a challenging dynamic of doing double work, especially when pharmacies are experiencing some staffing shortages. We know that drug shortages can be frustrating for patients, and they can also impact care, which is why ASHP is working to push for transparency and resiliency in the system to avoid these situations in the future.”

Likely Reasons for Shortages

There are several possible reasons for the shortages. One is ongoing problems in the drug supply chain caused by the COVID-19 pandemic. The U.S. still relies heavily on foreign sources for many drugs and their active ingredients, a situation a U.S. Senate report this week called an “unacceptable national security risk.”   

Another reason is aggressive cuts in the opioid supply by the Drug Enforcement Administration. Since their peak in 2013, DEA production quotas for drug manufacturers have fallen by 65% for oxycodone and 73% for hydrocodone. The DEA says it’s tightening the supply to prevent diversion, even though its own estimates show that less than 1% of prescription opioids are used by someone they are not intended for.  

Third, the DEA and the Department of Justice have been aggressive in going after doctors who prescribe opioids in high doses, which made many physicians leery of going to prison or paying steep fines, which one doctor likened to extortion. Rather than risk their livelihoods and freedom, some doctors stopped prescribing opioids. 

The fourth likely reason for the shortages is opioid litigation. As The New York Times explained in a recent article, three large drug distributors reached a $21 billion settlement with 46 states last summer, requiring them to impose strict limits on the pharmacies they do business with. Pharmacies are capped in the amount of opioids and other controlled substances they can dispense in any given month, regardless of patient needs. A unusually large order for opioids could result in a pharmacy getting red-flagged and the order cancelled.  

‘Pendulum Swung Too Far’

The end result of all these efforts is that opioid prescribing in the U.S. has fallen by nearly 50 percent, even as drug deaths continued to climb to record levels, fueled primarily by street drugs made with illicit fentanyl. 

“It seems like the pendulum has swung too far in the other direction, where people deserving and people needing controlled substances are unable to access them,” said Colin Banas, MD, Chief Medical Officer for DrFirst, a healthcare technology consultant.  

A recent survey of 400 patients by DrFirst found that one in four (27%) had run out of medication while waiting for their prescription to be renewed. Many had to contact their pharmacy or doctor more than once to get their prescription renewed. 

Banas is concerned that DEA plans to reimpose “guardrails” on prescribing that were suspended during the pandemic will undermine telehealth and make it even harder to get controlled substances. The DEA’s proposed rules, which many consider confusing, will require patients to have an in-person meeting with a provider before being prescribed a Schedule II controlled substance like oxycodone. 

“If I need to see a pain specialist and I’m in a very rural area, and the closest doctor is 90 miles away… there’s some very legitimate concern where we might be cutting those patients off by requiring the in-person visit,” Banas told PNN. 

One of the twisted ironies of the oxycodone shortage is that 30 mg tablets that are so difficult to get from a U.S. pharmacy are widely available on the black market — but they are counterfeit. Known on the street as M-30s or Mexican Oxy, the blue pills look just like the real thing, but are made with a potentially lethal dose of illicit fentanyl. Some Mexican pharmacies are selling them to unsuspecting U.S. tourists who can’t get them at home.

Another Drug Shortage Caused by Covid-19 Has Me Worried

By Victoria Reed, PNN Columnist

I recently read a news article about the Food and Drug Administration issuing an emergency use authorization for Actemra (tocilizumab) for the treatment of hospitalized covid-19 patients. The medication was originally developed as a treatment for rheumatoid arthritis (RA), one of the chronic pain conditions I live with.  

Actemra is a biologic drug that calms down overactive immune systems by blocking the interleukin-6 (IL-6) receptor. Persistent dysregulated expression of the IL-6 receptor is involved in the pathogenesis of RA and other chronic inflammatory and autoimmune diseases. It is believed that this over-activation of the IL-6 receptor is also responsible for the so-called “cytokine storm” that causes severe illness and death in covid-19 patients.

The symptoms of RA are pain, fatigue and swelling in the lining of the joints and other parts of the body, including the heart, lungs and eyes. This inflammation can lead to disability, joint destruction and cause serious damage to the lungs and heart.

I have had long-term success controlling my RA symptoms with Actemra and have been getting the drug by IV infusion monthly for about 8 years. Prior to that, I didn’t have good control with other biologic meds such as Enbrel and Orencia.

When I read that news story, I was initially only mildly concerned about Actemra becoming unavailable. Nevertheless, I contacted my doctor for confirmation that I was still on track for my upcoming monthly infusion. However, she did not and could not confirm that the medication would be available to me. Why?

Actemra has now been hijacked by doctors treating covid-19 patients, and this has created a major shortage. I have been informed that its availability for RA patients is uncertain for the foreseeable future. This is really very upsetting!

Covid-19 patients are using up resources in hospitals across the country. The overwhelming needs of these severely ill patients are causing other patients who need surgery or have treatable illnesses to die from a lack of available resources. Hospitals in hard-hit areas are short on everything -- staff, meds, beds and time. As a result, many chronic pain patients like me are being denied the treatments that we rely on to have functional lives. I must say that this seems patently unfair.

What’s even more disconcerting is that Genentech, Actemra’s manufacturer, can’t say when the shortage will end and expects “additional intermittent periods of stockouts (lack of supply) in the months ahead, especially if the pandemic continues at the current pace.”

RA and lupus patients saw this happen earlier in the pandemic when word got out that Plaquenil (hydroxychloroquine) might help treat covid-19. That medication also became scarce and was inaccessible to patients with autoimmune conditions for a while.  

One thing for sure is we are all very tired of the covid virus and its variants. I understand that doctors and scientists are desperate to find things that work, and they want to save lives. But I rely on Actemra to help relieve my pain and fatigue and keep damaging inflammation down. It is the mainstay of my treatment.  

Due to the Actemra shortage, I may have to consider other medications that might not work as well or just wait out the shortage and hope my disease activity doesn’t become unbearable.  

If the pandemic continues, many more people are going to lose their lives from covid infections. However, all patients deserve an equal chance at receiving the care they need, including chronic pain patients. The pain community is already suffering from opioid hysteria and many of us have to fight to stay on these pain medications. We shouldn’t have to fight for our other meds too! 

RA is a serious, systemic and often misunderstood condition that can shorten a lifespan by many years if not treated aggressively and with the proper medications.  Patients sometimes go through many trials of medications before finding one that relieves symptoms and arrests disease activity.  

I truly hope this shortage is short-lived -- for myself and others like me -- who rely on Actemra to remain functional and productive.  

Victoria Reed lives in Cleveland, Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis.