Life-Threatening Consequences Loom as Cancer Drug Shortages Grip the US
Pictured: Chemotherapy drip/Courtesy, iStock, zlikovec
Across the U.S., there is a shortage of at least 14 cancer drugs, with the situation being particularly critical for two of them: cisplatin and carboplatin. These two platinum-based chemotherapy drugs are used extensively in cancer treatment, leading to heightened concern among doctors, patient groups and industry analysts.
Cisplatin and carboplatin have a cure rate of more than 90% when used in the treatment of testicular cancer, according to NCI. They are also effective in treating various other types of cancer, including bladder, cervical, ovarian, lung, gastric, breast and head and neck cancers.
The World Health Organization has recognized the essential nature of cisplatin and carboplatin in providing fundamental healthcare.
Doctors and experts alike have expressed concern that if the shortages are not promptly resolved, some cancer patients may face life-threatening consequences. Due to shortages of these medications, some hospitals have been compelled to ration their supplies by reducing doses to prolong availability. Additionally, they have had to prioritize patients who would benefit most from the treatment.
In her testimony before Congress on the topic, American Society of Clinical Oncology (ASCO) Chief Medical Officer Julie Gralow said the shortages had reached crisis level.
“Today’s shortages are the worst I have seen in my 30-year career,” Gralow said. “The number of U.S. patients at risk could be as high as 500,000 a year.”
Why Do Drug Shortages Currently Exist?
The current situation is due almost entirely to a range of production problems at a single manufacturing facility in Gujarat, India. In late 2022, Intas Pharmaceuticals was cited by the FDA for 11 specific violations revealed at an inspection between November 22 and December 2, 2022.
Specifically, the FDA accused Intas of a “cascade of failure” related to a lack of oversight on the control and handling of critical production documents. The FDA also criticized the company for lapses in record-keeping, poorly defined procedures and control and issues pertaining to microbial contamination risk and environmental monitoring, among other problems. Finally, the FDA accused Intas of dropping the ball on establishing the “accuracy, sensitivity, specificity, and reproducibility” of its testing methods.
In a statement to Hindu Businessline, company representatives said that after it received FDA observations last year, Intas made the "immediate and voluntary decision to temporarily cease the manufacturing and distribution of products" made there and destined for the U.S.
“Clearly, we need multiple sources of raw materials and ingredients for critical drugs,” Gralow told BioSpace.
Drug Shortages Aren’t New, but Now at Crisis Level
Gralow said that though the current shortage crisis first affected primarily smaller cancer centers, it’s now extended well beyond that group.
“Providers are facing devastating moral dilemmas by being forced to allocate the limited supply of carboplatin and cisplatin to those patients who will experience the most significant benefit—such as those in the curative-intent setting or for patients with an expected long-term survival benefit,” she said.
One analyst said that the pandemic and its after-effects have exacerbated the life-or-death nature of the shortages. Because people were more hesitant to pursue cancer screenings and other predictors of early-stage cancer during the pandemic, today, the influx of late-stage cancer diagnoses is particularly problematic, Julie Ferris, vice president of commercial optimization at Definitive Healthcare, told BioSpace.
Figure 1: Drug availability in 2022. Permission granted to use graph data from Definitive Healthcare; Design: Nicole Bean, BioSpace.
“The chemotherapy shortage shows the harsh realities in the post-COVID era,” she said. “The data shows an uptick in cancer diagnoses coming at later stages.”
Oncologist Kristen Rice emphasized the dire nature of the situation in an op-ed published in STAT News on June 19. “I honestly don’t understand why patients are not rioting in the streets about this,” she said. “The generic cancer drug shortage can be fixed, but only if the private sector and policymakers each pursue ideas to fix it permanently.”
What Can Be Done?
Experts agree that the FDA needs a more robust supply chain in the short term so that when one plant can’t manufacture critical drugs, it doesn’t put people’s lives at risk.
“One thing that can be done quickly is requiring manufacturers to notify FDA if they see an increased demand for any of their products,” Gralow said. “Health systems and providers also need better communication with drug companies, so they can start planning for potential shortages as early as possible.”
She said importing drugs from other countries is another option for an immediate remedy. Indeed, the FDA announced on May 24 that it would begin importing cisplatin from Qilu Pharmaceutical, a Chinese drugmaker, to augment the existing supply.
While it’s a step in the right direction, “this is a very short-term fix,” Gralow said.
In the long term, the shortage problem should be addressed by legislative action, she and others noted. Systemic changes are required to incentivize companies to produce these meds domestically.
“Policymakers need to fix the economic factors that are driving generic manufacturers out of the market and stabilize the market with long-term contracts and guaranteed prices for generic drugs,” Gralow said. “Health plans and facilities should consider paying slightly more for a generic drug when its manufacturer can guarantee the quality of their product and a sustained supply.”
Ferris agreed that both short- and long-term solutions are required.
“The FDA should establish an emergency plan of action for if there is a production issue, so we are not left in a situation where we have to be reactive, but instead have a plan ready to limit disruption,” she said. “Global markets are wonderful but can be unpredictable.”