Supply chain issues caused by the COVID-19 pandemic, as well as the care needs of patients with COVID-19, have led to shortages of drugs and other products used in cancer care.
The pandemic has exacerbated existing shortages in oncology and created new ones. Contrast dye, fludarabine, and cytarabine are among the products currently in short supply in the United States, and the threat of additional shortages looms large for some health systems.1
“The pharmaceutical supply chain is affected by factors such as disease outbreaks; climatic, economic, and geopolitical events; and the geographic distribution of manufacturers,” explained Vimala Raghavendran, head of the US Pharmacopeia Pharmaceutical Supply Chain Center in Washington, DC.
“Disruptions can lead to drug shortages as well as increases in substandard and counterfeit medicines, putting patients at risk,” she added. “These challenges and vulnerabilities existed before the pandemic, but COVID-19 certainly brought them to the forefront.”
A supply chain disruption is responsible for the shortage of contrast dye that has impacted cancer care.2 The shortage began in April after GE Healthcare experienced a disruption at its manufacturing plant in Shanghai due to a COVID-19 lockdown.3 The disruption at that facility left both iodixanol and iohexol in short supply.
“GE knows where they make the bulk of their supply for the US market, and, at this point, COVID is not a surprise anymore. But they still made no adjustments or preparations in case something happened to that Shanghai manufacturing facility,” said Erin Fox, PharmD, senior director of drug information and support services at the University of Utah Health in Salt Lake City.
In an attempt to address the shortage, the US Food and Drug Administration (FDA) allowed for the temporary importation of iomeprol from Bracco Diagnostics.4 However, iomeprol remains in short supply in the US, and the shortages of iodixanol and iohexol are yet to be resolved.1
Shortages Impact CAR-T Field in Particular
In addition to ongoing supply chain issues, the increasing needs for COVID-19 therapies and supportive care drugs have led to shortages that impact oncology.
One such shortage was for tocilizumab, an interleukin-6 receptor antibody used to prevent and treat the cytokine release syndrome that can occur in patients receiving chimeric antigen receptor (CAR) T-cell therapy.
The FDA granted tocilizumab emergency use authorization to treat severely ill COVID-19 patients in 2021. This move put pressure on supply and resulted in a shortage, but that shortage has since been resolved.1
Multiple chemotherapy agents remain in short supply, however, including cytarabine, dacarbazine, and fludarabine.1 The fludarabine shortage is impacting the CAR-T field as well because fludarabine is commonly used as a lymphodepleting agent before CAR T-cell therapy.
“The fludarabine shortage is currently still ongoing, and although we’ve not needed to switch to alternatives yet for patients, we’ve continued to closely communicate with the pharmacists,” said Yi Lin, MD, PhD, associate professor of medicine and leader of the CAR T-cell therapy program at the Mayo Clinic in Rochester, Minnesota.
“The situation with supply is that we might be okay through the end of this month, but we won’t know until next week if we get next month’s supply,” she said. “It’s very much a moving target, with constant need for adjustment.”
Although many drug shortages involve generic sterile injectables, some newer reagents needed for therapies such as CAR-T cells are also experiencing supply chain pressure.
“The whole CAR-T field is also impacted by other shortages like GMP [Good Manufacturing Practice]-grade retroviral vectors that are needed to make the CAR construct,” Dr Lin explained. “It’s impacting the current care for approved therapy that’s available to patients, and it’s slowing down the preclinical investigations and trials that can bring potentially useful treatment into practice.”