There’s a conversation oncologists describe as one of the hardest in medicine, and it’s not about delivering a grim diagnosis.

“There’s nothing more anguishing than looking at a patient and telling them that we know how to treat their cancer, and that the treatment is quite cheap — but we don’t have enough of it,” said Andrew G. Shuman, MD, a head and neck cancer surgeon and professor at the University of Michigan Medical School, Ann Arbor, Michigan.

That conversation is now taking place at cancer centers across the US, nearly 3 months into a critical shortage of ifosfamide, a decades-old chemotherapy drug that remains an important component of several potentially curative and salvage chemotherapy regimens, particularly for sarcomas and testicular cancers.

The FDA first added ifosfamide to its drug shortage database on June 12, 2026, after hospital order fill rates reportedly plummeted by nearly two thirds, leaving some major cancer centers with only a few weeks of inventory on hand. The drug is currently still listed in shortage, with the FDA estimating supply problems could persist through September or October and the European Medicines Agency projecting the issues will continue into 2027.

“When we look on the shelf and don’t have enough to get us much past Labor Day, those dates don’t make us feel particularly reassured,” said Shuman, also chief of the clinical ethics service for Michigan Bioethics.

With ifosfamide in limited supply, some hospitals have been turning to drug-conservation strategies to reduce waste, such as rounding down doses or splitting vials, and, in some cases, making more consequential decisions about who gets the drug and who doesn’t.

“We’re in this impossible position of being asked to do bedside rationing, which is every physician’s worst nightmare,” said Jacob B. Reibel, MD, MSCE, a medical oncologist at Dartmouth Cancer Center in Lebanon, New Hampshire.

This, Shuman said, is “absolutely what we and pretty much every major hospital around the country have been forced to do in certain circumstances.”

While cancer centers have faced intermittent cancer drug shortages for decades, the

latest shortage provides a stark reminder of the 2023 crisis, which severely affected chemotherapy backbones cisplatin and carboplatin and forced cancer centers to employ rationing strategies. The 2023 shortage also brought growing recognition of the structural vulnerabilities in the US supply chain for essential low-cost generic drugs as well as calls for action and change.

Three years later, oncologists are still confronting major shortages of essential chemotherapy drugs, which include cisplatin and carboplatin. Why has the US remained so vulnerable to drug shortages — and why have structural fixes continued to stall?

A Shortage That Fits the Profile

While chemotherapy shortages remain a persistent problem, the American Society of Health-System Pharmacists has singled out the new ifosfamide shortage as “particularly severe” in a recent tracking report. Hospitals and clinics purchasing through Premier, one of three dominant group purchasing organizations (GPOs) negotiating drug contracts, received just 38% of their ifosfamide orders, the company told The New York Times in late June.

The ifosfamide shortage fits a pattern. It’s an injectable drug, as are 60% of drugs in shortage in 2026; its US supply ran overwhelmingly through a single foreign manufacturer, as did nearly half of the drugs in shortage this year; and production collapsed following manufacturing problems, one of the most common causes of drug shortages. The FDA had issued a warning letter to the ifosfamide manufacturer, Simtra BioPharma Solutions, back in March 2026, after an unannounced September 2025 inspection documented recurrent microbial contamination at the manufacturing facility, Simtra Deutschland GmbH, in Germany.

Given the frequency of drug shortages, mitigation and response efforts now consume the equivalent of about 2.5 full-time positions at the University of Michigan. That is “an astronomical amount of resources for what should be a preventable problem,” Shuman said.

After the 2023 platinum crisis, Reibel and colleagues analyzed the short-term impact the shortage had on patients with advanced solid tumors. At the peak of the shortage, the researchers reported a 15% absolute reduction in platinum prescribing, though did not find a difference in mortality before vs during the shortage.

The lack of mortality difference in the short-term may reflect the availability of effective alternatives, Reibel hypothesized; however, the substitutions may have still come at a cost, as many options were more expensive and potentially associated with more toxicities.

For ifosfamide, finding adequate substitutes is a challenge. The choice that remains is “whether to delay treatment or to try some other regimen which is just inferior to what the standard of care would be,” Reibel said.

More broadly, he said, “we may get to that point where we just don’t have the treatments that we know to be effective.”

A Market Designed to Fail

The question is why the market for these drugs is so poorly equipped to prevent shortages.

In a functioning market, scarcity raises prices, new suppliers enter, and equilibrium returns. However, the market for generic sterile injectables can’t do this, said Marta E. Wosińska, PhD, senior fellow in the Center on Health Policy at the Brookings Institution, Washington, DC.

In a 2025 analysis, Wosińska and Rena Conti, PhD, identified several interlocking problems. Medicare pays the same price for a generic regardless of manufacturer, so investments in reliability go unrewarded. GPO contracts can lock in prices without guaranteeing volume, while hospitals may switch suppliers for relatively small savings. The result is little incentive for manufacturers to maintain backup facilities or large inventories. Among generic sterile injectables approved from 2000 through 2011, Wosińska noted that just over 1% referenced more than one facility capable of producing the finished drug compared with nearly 20% of branded sterile injectables.

The problems aren’t new. An FDA-led task force published a 2019 report that identified many of the same economic and structural vulnerabilities behind drug shortages but addressing them requires changes the FDA cannot make alone.

Nobody fully bears the cost of maintaining resilience against drug shortages, which means “the only one carrying the bag here is the patient,” Wosińska said.

Pharmaceutical wholesalers face similar pressures. Wholesalers typically hold less than 1 month of inventory across product lines, despite handling drugs whose shelf lives run years, said Prashant Yadav, PhD, senior fellow for global health at the Council on Foreign Relations in Washington, DC, and a longtime scholar of healthcare supply chains.

“No wholesale chief financial officer will allow the supply person to hold a lot of inventory,” Yadav said, because analysts track wholesalers’ inventory turnover, and a slowdown can be viewed negatively by investors, which could affect stock prices.

Inspection timing abroad adds another layer of fragility, he said. When manufacturing problems are found at an overseas facility, production can slow or stop during remediation. For a drug made on one line, stopping the line stops the national supply.

Reforms Stall. Is There a Fix?

In 2018, health systems tried to address persistent drug supply chain issues in a real way by launching the nonprofit generic drug manufacturer, Civica.

The aim of Civica was to prevent chronic drug shortages in the US and help lower the cost of essential medications. The nonprofit offered fixed-price and fixed-quantity contracts with 6 months of buffer inventory.

Despite Civica’s large reach — supplying over 1400 hospitals — fewer than 10% of generic sterile injectable sales flow through it, underscoring how difficult it is to shift purchasing incentives toward supply reliability for generics.

The 2023 platinum crisis created a new moment to usher in drug supply chain reforms. While the FDA allowed more regulatory flexibility, including temporarily importing drugs or supplies from manufacturers registered with trusted foreign regulators, deeper structural repairs stalled.

More recently, in May 2024, leaders of the Senate Finance Committee released bipartisan draft legislation to create a Medicare program incentivizing hospitals and GPOs to prioritize supply reliability alongside price in their purchasing contracts. Portions of the draft would have reduced or waived Medicaid inflation rebates for certain generic drugs at risk for shortage. The proposal faced opposition from hospital groups, and the draft never became law.

“There was this incredible inconsistency,” Wosińska said, describing institutions that decried shortages publicly while lobbying against provisions that threatened their discounts.

The administration’s recent announcement about imposing tariffs on imported generic drugs could also create new supply risks. The tariffs, which are now 0%, would rise to 100% in August 2028 and 200% the following year, although implementation details remain unclear.

While tariffs can encourage manufacturers to move production of brand-name drugs to the US, research suggests the same strategy may not work for low-margin generic drugs. In fact, a 2025 analysis from Wosińska found that tariffs could have the opposite effect: Because manufacturers may have limited ability to pass higher costs on to US buyers, tariffs could squeeze already-thin margins, prompting manufacturers to cut costs or exit the US market altogether.

The policy also may not target the vulnerabilities driving shortages, Yadav noted. Finished sterile injectables reaching the US come largely from India, while China is primarily upstream in raw ingredients; the current ifosfamide shortage, meanwhile, stems from manufacturing problems in Germany.

Smaller-scale domestic efforts to address drug shortages are emerging. Mark Cuban’s Cost Plus Drug Company opened a fill-and-finish facility in Dallas to produce sterile injectables, including carboplatin and methotrexate. While the facility can help bridge some critical supply gaps, its scope may be limited. Expanding beyond sterile injectables, for instance, can be challenging, given the $358,247 cost of submitting an abbreviated new drug application to the FDA, a fee Cuban recently told Healthcare Brew “kills the economics” for companies like his.

The fundamental problem is rooted in the payment system, said Yadav. Manufacturers would need to be paid more for maintaining redundant production capacity, backup suppliers, or buffer inventory. If government contracts included even a modest premium for demonstrated supply reliability, “everybody on the manufacturing and wholesaling side will start getting their act together.”

Ultimately, the ifosfamide shortage reflects the same structural failures that have left the US vulnerable to recurring shortages of essential drugs.

“It’s a tragedy, but it’s one that we could have anticipated a decade ago,” Shuman said. “Absolutely predictable. Also, absolutely preventable.”

Will oncologists continue to face these chronic drug shortages, waiting for the next crisis to hit?

“I hope we don’t,” Reibel said. “I’m worried that we will.”

Wosińska reported previously serving as an economic advisor to the US Senate Committee on Finance, providing expert guidance on drug pricing. Yadav, Shuman, and Reibel reported having no relevant financial relationships.