Quality Issues Lead to Shortages of Common Cancer Drugs

As cancer centers continue to face shortages of commonly used oncology drugs, key stakeholders from the FDA, the National Comprehensive Cancer Network, and even members of Congress, are looking for answers as to how the shortages happened and how they can be prevented in the future.

Shortages of cancers drugs, including carboplatin and cisplatin as well as methotrexate, began in early 2023 and it is unclear when those shortages will be resolves. Carboplatin is used to treat patients with ovarian cancer; cisplatin is used to treat advanced ovarian cancer, testicular cancer, and bladder carcinoma. Methotrexate is used to treat leukemia, as well as breast, skin, head and neck, lung and uterine cancer.

A recent survey by NCCN found that 93% of cancer centers have faced shortages of carboplatin and cisplatin. Many indicated that that supplies have reached a critical level. All of the centers surveyed are still able to treat patients who need cisplatin without any delays or claim denials. But for carboplatin, that number drops to only 64% of centers that are able to keep all current carboplatin patients on the regimen. Overall, 16% report treatment delays as a result of needing to re-obtain prior-authorization for modified treatment plans, but none have met with outright denials.

Insta Pharmaceuticals, an India-based company manufacturers the three generic cancer products that are distributed through Accord Healthcare, experienced quality issues at end of last year. Among the findings of an FDA inspection are that Insta’s test procedures and laboratory control mechanisms were not followed and that procedures for quality control were not followed. “There is a cascade of failure in your Quality Unit's lack of oversight on the control and management of GMP documents that are critical in ensuring the drug products manufactured and tested at your site are safe and effective,” the FDA said after its inspection. The agency found that the company had not established procedures for preventing microbiological contamination, that environmental monitoring was deficient and there weren’t adequate procedures to ensure purity and quality.

Also contributing to the shortages is that carboplatin can be a substitute for cisplatin, Erin R. Fox, Pharm.D., associate chief pharmacy officer, Shared Services, University of Utah Health and adjunct professor, University of Utah College of Pharmacy, said in an interview.

“Cisplatin and carboplatin are used for so many different cancers as a backbone of standard of care in many cancers,” she said. “There are a large number of patients that are affected.”

Several manufacturers of carboplatin and cisplatin have indicated there has been an increase demand, according to the American Society of Health System Pharmacists. (Fox’s group at University of Utah develop the ASHP’s drug shortages list.)

Additionally, Fox said another reason for the shortage is that it can be difficult to ramp up supply when needed. “These are hazardous drugs. They’re hard to make and they need a dedicated manufacturing facility.”

Members of both the Senate and the House of Representatives have expressed concerned about the oncology drug shortages. In the House, Debbie Dingell (D-MI) and Tim Walberg (R-MI) in May asked the FDA for a briefing how the agency is working with manufacturers to address the shortages. In the Senate, several members called the FDA to be more transparent about the reason for drug shortages, noting that the agency’s site for shortages doesn’t include a reason for Accord Healthcare’s shortage of carboplatin and cisplatin.

Addressing drug shortages, however, will require collaboration of all stakeholders — the FDA, manufactures, providers, and payers. In the meantime, physicians. In the meantime, because providers don’t know when the shortage will be resolved, they will need to prioritize the use of these drugs based on efficacy, safety, and cost. NCCN, however, has called on the payer community to provide flexible and efficient systems of providing coverage for alternative therapies.

Another good start to eliminating the shortage, Fox said, is that the FDA indicated in late May that is allowing temporary importation of cisplatin from China-based Qilu Pharmaceutical, which will be distributed by Apotex Corp. And according to Reuters, the FDA is looking for new suppliers of methotrexate.