A cancer diagnosis is already devastating. It’s even more gut-wrenching when your doctor tells you that a drug shortage has disrupted your treatment regimen—that your hospital can’t get its hands on the very drugs that can save your life. Many cancer patients are now facing this grim reality as hospitals nationwide weather what is “likely the worst chemotherapy drug shortage crisis that the U.S. has ever seen,” says Amanda Nickles Fader, a gynecologic oncologist at Johns Hopkins Medicine.
Researchers estimate that the average drug shortage (including the current one) impacts half a million patients, Fader says. Fifteen crucial drugs—the kind that can render cancers curable—have been out of stock in hospitals for months. Doctors have had to ration their dwindling supplies, scrimp on dosages and swap out prescriptions with inferior alternatives. Fader says she has heard of at least one cancer patient who frantically requested transfer to a different treatment center out of state to access care but failed to get it simply because other locations also lacked the medications that the patient so desperately needed.
Oncology drugs aren’t the only therapies in short supply. According to a survey of 1,123 pharmacists conducted by the American Society of Health-System Pharmacists, anti-inflammatory drugs, antimicrobials, hormonal medications and oral liquid medicines are also hard to come by. At the height of the drug shortage in June and July, 309 drugs were running low—the highest number in nearly a decade. A few manufacturers have since promised to restock certain critical drugs in the next few months. The Biden administration recently announced efforts to address the drug shortages: the Food and Drug Administration is working with U.S. generic drug manufacturers and has authorized at least one non-U.S. manufacturer to import stock into the country from China. But Fader says many hospitals across the U.S. are still feeling the pinch.
The scarcity of oncology drugs is particularly dire because these medications can so directly mean the difference between life and death. The most affected treatments include the platinum-based injectable drugs carboplatin and cisplatin, which are used to treat breast cancer, gynecologic cancers, testicular cancer, head and neck cancers and bladder cancer. In a survey of 27 cancer care sites conducted in May, 93 percent reported a carboplatin shortage, and 70 percent reported a cisplatin shortage.
A Vulnerable Industry
The health care industry is no stranger to drug shortfalls. They have come and gone over the decades, but they’re getting more acute each time, Fader says. “We are seeing a persistence and worsening in the number of drugs that are in simultaneous shortage,” she adds.
Many of the affected drugs are generics—medications whose patent and exclusivity have expired, meaning any company can legally manufacture them. But there is little incentive to do so. Competition is tight: there are only a handful of distributors that buy these drugs, and they have a lot of negotiating power, so they can angle for the lowest price from a single supplier. The market can only accommodate a few competing manufacturers.
Generic drugs are often priced so low that manufacturers have to operate on slim profit margins. To break even, these companies run at near-maximum output levels. On top of that, they may be tempted to cut corners and roll back quality control just to reduce costs. There are often only a few or even a single manufacturer of a given generic drug, so when one of them shutters, that is enough to throw off the entire supply chain.
That’s what happened in the case of platinum-based drugs. A plant owned by Intas Pharmaceuticals in northwestern India voluntarily suspended generics manufacturing last December after the FDA found Intas was knowingly violating quality assurance standards. A surprise FDA inspection revealed the extent of Intas’s questionable practices: the supplier altered records, skimped on testing raw ingredients and flouted lab control protocols. It even destroyed evidence of its wrongdoing—by dousing documents with acid and chucking shredded slips at the bottom of a stairwell and in the back of a truck.
In an e-mailed statement to Scientific American, Intas’s U.S. subsidiary Accord Healthcare said that its parent company is working with the FDA to release its preexisting but limited inventory for U.S. distribution and to restart its manufacturing of U.S.-bound critical medicines under independent oversight.
To mitigate the generics shortage, the FDA temporarily authorized Chinese company Qilu Pharmaceutical to import nonapproved cisplatin from China into the U.S. and Canadian company Apotex to act as the drug’s U.S. distributor. The agency also relaxed part of its import alert to Intas to allow some of the manufacturer’s products that are in shortage, including platinum chemotherapy injectables, to enter the U.S.
Several nonprofit organizations have also stepped up to help fill the gap. The Society of Gynecologic Oncology, of which Fader is president-elect, worked with the National Comprehensive Cancer Network (NCCN) to issue alternative-drug guidelines for cancer care and persuade insurers to cover workaround treatments for the drugs that are running short. In addition, the advocacy group Angels for Change helps patients source drugs that are in short supply.
If the unprofitable generic market structure is a house of cards, then the Intas manufacturing problems were a destabilizing breeze—and by no means the last. These no-brand drugs, some of which cost less per vial than a cup of coffee, suffer from gaping market vulnerabilities that require nothing less than an industry overhaul. And government intervention is necessary, experts say. “When it comes to the economics [of generics], it really requires legislative action,” says Alyssa Schatz, NCCN’s senior director of policy and advocacy.
Solving the Shortages
One obvious solution is to boost manufacturing. This could take the form of artificially jacking up demand for generics—enough to sustain multiple manufacturers in the industry. For instance, the government could purchase excess capacity by paying for more drugs than the market needs.
The idea of overpurchasing isn’t new—the military used it to acquire F-35 fighter jets from at least two major contractors in order to sustain more than one business, says Andrew Mulcahy, a senior policy researcher at the nonprofit research group RAND Corporation. The same approach could be applied to generic drugs and would probably be a lot cheaper to execute, Mulcahy says.
A more drastic fix would be for the government to take over drug production, either by acting as a direct manufacturer or by partnering with private companies. As an example of the latter, in March California contracted the nonprofit company Civica to manufacture insulin for the state. Civica champions a new business model that aims to stabilize the demand and supply of generics: it secures bulk orders from participating medical centers at a fixed price, thereby building enough demand to enable contract suppliers and its own manufacturing arm to stay afloat. These take-it-or-leave-it prices could be higher than what a truly open market might produce. But a steady supply of generics might be worth the greater expense.
After all, race-to-the-bottom pricing for generics is the root cause of their throttled supply chain, experts say. While low prices may seem like a good thing for patients, they can’t be so low that manufacturers have no incentive to stick around. “There’s going to be a delicate balance,” says Brooke Bernhardt, chief pharmaceutical officer at St. Jude Children’s Research Hospital.
Several potential policy changes could also increase the medical system’s agility in responding to future shortages. Congress is currently deliberating on a proposed Drug Shortage Prevention Act that would authorize the FDA to require manufacturers to report anticipated shortages ahead of time. Fader and Schatz also advocate for expanding the scope of the FDA’s list of essential medicines so that the agency can prioritize strengthening the supply chain of these drugs, both in the event of a shortage and over the long term.
All these strategies face the slippery-slope issue of narrowing down which generics to prioritize, however. There are always more drugs that could count as essential, so what’s the optimal number? “Is it these 10 drugs? It is these 20 drugs?” Bernhardt asks. “Where do we draw the line?”
One thing is clear: more information and transparency wouldn’t hurt. Given the U.S. government’s reactive approach to drug shortages, extra clarity on what is driving the scarcities would help. For starters, the FDA could require manufacturers to disclose the reasons why their offerings are running low, Mulcahy says—not just which drugs are in short supply. Providing these details could help tease out the nuances between the situations involving various drugs and allow for government officials to justify taking action on individual generics.
“We’re still kind of playing catchup in terms of understanding what the problem is,” Mulcahy says.