As Chemotherapy Drug Shortage Continues, Unimaginable Decisions and Lacking Accountability Reign

Over the past 8 months, key chemotherapy drugs that are used to treat a variety of cancers have been in a shortage, greatly impacting patients, treatment providers, and the oncology field overall.

Image credit: Sherry Young - stock.adobe.com

In a recent survey conducted by the National Comprehensive Cancer Network’s (NCCN) Best Practice’s Committee, which features 27 institutions from across the United States, 93% responded that they are currently experiencing a shortage of carboplatin and 70% have a similar shortage of cisplatin.¹

Carboplatin and cisplatin are drugs that have been widely used to treat different types of cancers for decades. These platinum-based regimens have been shown to be very effective when used together or separately. According to the NCCN, an estimated 500,000 new cancer patients every year use these drugs.²

A shortage of carboplatin and cisplatin could have disastrous effects for the many patients who rely on them. Based on accounts from across the country, this is exactly what is happening.

Treatment providers have been recommended to stretch out the time between drug treatments, scrape out tiny drops from vials to create new doses,³ and even prioritize which patients should get treatment first.⁴

Lisa Davis, PharmD, FCCP, BCPS, BCOP, an outpatient oncology pharmacist specialist at the University of Arizona Cancer Center, discussed some of the new realities she and her colleagues have faced since the shortage began. At her center, they have had to change patients’ treatments to less optimal combinations of drugs for their form of cancer, switch patients from oral to intravenous therapies—or intravenous to oral—and change the order of drug therapy sequences.

In some cases, they have had to discontinue drug therapy for patients with incurable cancer to provide the medication to patients whose cancer can still be cured, which can be especially stressful for those with incurable cancer who were responding to the discontinued drug.

“The providers, and particularly the pharmacists, have experienced a lot of stress, tension, and guilt,” Davis said.

This problem is not isolated to carboplatin and cisplatin; there are a dozen other cancer drugs that are currently in shortage,⁵ and through the first quarter of this year, there were 301 active national drug shortages.⁶

“Our inaction in fundamentally solving the cancer-drug shortage problem—which has existed for years but is now as severe as we’ve ever faced—has likely signed a death sentence for Americans,” said Ted Okon, executive director of the Community Oncology Alliance.⁷

The issues that have led to this crisis are myriad and profound, and it can be difficult to pinpoint a specific event that causes any drug shortage. The drug manufacturing industry is a complex and multifaceted system with countless stakeholders involved in the process.

Occasionally, though, one event can be seen as a catalyst that exacerbates the existing problems the pharmaceutical industry faces. In this case, Intas Pharmaceuticals—a factory in western India that at one point produced half of the cisplatin and 20% of carboplatin that is used in the United States—suspended production after the FDA inspected their site in November 2022 and found widespread violations.

The Washington Post reported that inspectors found freshly torn-up documents that were doused with acid, seemingly to prevent potential visitors from seeing failures in quality assurance.⁸

Tinglong Dai, a professor of operations management and business analytics at the John Hopkins Carey Business School,⁹ described the scene at the factory as “a stunning array of violations of good manufacturing practice,” as the inspection highlighted “compromised data integrity and sloppy documentation practices to unreliable testing methods and inadequate measures against microbiological contamination.” Investigators even found a truckload of shredded documents near the facility, according to the report.

Suffice to say, this mass of violations necessitated Intas suspending production,¹⁰ which in turn led to the current shortages of chemotherapy drugs and scrambling from treatment providers to find alternatives and treat patients as effectively as possible. Beyond methods to extend and optimize the remaining supply of chemotherapy drugs a treatment center has, discussing alternative treatments with patients has been an unfortunate but oftentimes necessary next step.

“The challenges when we specifically talk about certain disease sites, the question is ‘What are the options?’” Sarah Hayward, a pharmacy specialist in gynecologic oncology at the Stephenson Cancer Center at Oklahoma University, said in a roundtable discussion about the considerations when prescribing and seeking out alternative drug options.¹¹

“In some of our disease sites, such as gynecologic oncology and lung, the data continues to point where platinum-based therapies in certain situations are with curative-intent. And we don’t have a lot of other options,” Hayward explained.

Despite the lack of options that are as effective as carboplatin and cisplatin—and the lack of alternative options in general—oncology organizations, such as the Society of Gynecologic Oncology,¹² have put out recommendations for acquiring alternatives and treating patients, which Hayward said has been “really fantastic.”

Hayward further explained that it is important to be engaged with other providers treating a variety of disease sites to possibly procure alternative treatments that are not platinum-based due to the reality of working in an institution with a large amount of disease types. Natalie Osagie, a hematology-oncology clinical pharmacy specialist from the Department of Veterans Affairs, elaborated that clinicians need to ensure that a set number of cycles of a particular drug are allocated, because a patient can’t receive 1 dose and not be guaranteed to continue treatment with the same drug weeks later.

Osagie emphasized maintaining communication between treatment centers and drug providers to make sure there is agreement in which drugs are available and which are plentiful enough to prescribe to patients.

The current extraordinary measures that can be seen in clinical sites across the country can make anyone wonder what can be done to fix the current shortage and prevent the next one from occurring at all. Unsurprisingly, the answer is difficult to find.

“In the short term, it is critical to improve supply chain transparency so that hospitals, physicians, and patients can easily identify the source of medicines,” Dai explained. He noted that this would allow stakeholders to make informed purchasing decisions, which will gradually lead to market demand being directed toward a more resilient supply chain.

In terms of long-term solutions to this long-term problem, Dai did not mince words, saying, “It is absolutely essential to do whatever it takes to increase domestic manufacturing capacity for essential medicines.”

He suggested multiple avenues to solidify the supply chain, including near-shoring, which is the practice of sourcing more supply from neighboring countries, and friend-shoring, an initiative to build strong supply chains in countries that share similar ideological beliefs and values.

Ultimately, some entity will have to lead the charge on establishing the necessary reforms and policy changes to rehabilitate the country’s supply chain. Yet, there remains no clear leader with the ability or willingness to undertake key actions, and questions have arisen as to where the responsibility should fall—whether it’s the government, the manufacturers, or otherwise.

In a recent interview, Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said that the FDA does not have the ability to intervene and order companies to produce more of specific drugs or require that certain drugs have diversified supply chains to avoid shortages.¹³

“FDA doesn’t have the authority to order manufacturers what or how much to produce. It is the action of the generic companies that ultimately resolve shortages,” Pazdur explained.

Dai agrees that manufacturers need to take a more active role in production and ensuring resilience, but notes that the FDA has a critical leadership role to embrace in this process. In conjunction with increased resources from the federal government, the FDA can take the opportunity to create a new standard in dealing with drug shortages.

“The FDA's role in addressing and preventing drug shortages is often questioned, but the truth remains: if not the FDA, then who?” Dai said.

To its credit, the FDA has begun to allow imports of cisplatin from drugmaker Qilu Pharmaceutical in China to help increase supply and ease the pressure on the supply chain,¹⁴ and the agency is working with Intas to reopen their regulation-defying plant.

Regardless, the drug shortage persists as a monumental challenge for pharmacists, treatment providers, and patients across the country to overcome. It remains to be seen when and if this shortage will ease, but stakeholders agree that the FDA and drug manufacturers will need to take proactive steps to ensure that a shortage of this magnitude can never happen again.

References

1. NCCN Releases Statement Addressing Ongoing Chemotherapy Shortages; Shares Survey Results Finding More Than 90% of Cancer Centers are Impacted. NCCN. June 7, 2023. Accessed July 18, 2023. https://www.nccn.org/home/news/newsdetails?NewsId=3970

2. Richard Pazdur discusses root causes of cisplatin and carboplatin shortages and what can be done to alleviate it. The Cancer Letter. May 30, 2023. Accessed July 18, 2023. https://cancerletter.com/conversation-with-the-cancer-letter/20230530_1/

3. Noguchi Y. Some cancer drugs are in short supply, putting patients’ care at risk. Here’s why. NPR. June 15, 2023. Accessed July 18, 2023. https://www.npr.org/sections/health-shots/2023/06/15/1181876655/cancer-drugs-cisplatin-carboplatin-shortage4

4. Kekatos M. Cancer drug shortage is forcing doctors to decide which patients get treatment. ABC News. June 2, 2023. Accessed July 18, 2023. https://abcnews.go.com/Health/cancer-drug-shortage-forcing-doctors-decide-patients-treatment/story?id=99753886

5. Current and resolved drug shortages and discontinuations reported to FDA. U.S. Food and Drug Administration. Accessed on July 18, 2023. https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm

6. Murphy T. Cancer centers say US chemotherapy shortage is leading to treatment complications. The Associated Press. June 7, 2023. Accessed July 18, 2023. https://apnews.com/article/cancer-chemotherapy-drug-shortage-6a653e9f0878b4ddf05358fb90911952

7. Schladen M. Cancer drug shortages decried in congressional hearing. Ohio Capital Journal. June 15, 2023. Accessed July 18, 2023. https://ohiocapitaljournal.com/2023/06/15/cancer-drug-shortages-decried-in-congressional-hearing/

8. Gilbert D. How troubles at a factory in India led to a U.S. cancer-drug shortage. The Washington Post. June 27, 2023. Accessed July 18, 2023. https://www.washingtonpost.com/business/2023/06/27/cancer-drug-shortage-generics/

9. Tinglong Dai, PhD. John Hopkins Carey Business School. https://carey.jhu.edu/faculty/faculty-directory/tinglong-dai-phd

10. Gilbert D. How troubles at a factory in India led to a U.S. cancer-drug shortage. The Washington Post. June 27, 2023. Accessed July 18, 2023. https://www.washingtonpost.com/business/2023/06/27/cancer-drug-shortage-generics/

11. Critical Conversations: Navigating drug shortages and empowering oncology pharmacists. Hematology/Oncology Pharmacy Association. June 15, 2023. Accessed July 18, 2023. https://www.hoparx.org/about-us/advocacy-awareness/training/drug-shortages-webinar/

12. SGO Statement: Carboplatin and cisplatin shortages. Society of Gynecology Oncology. April 21, 2023. Accessed July 18, 2023. https://www.sgo.org/news/drugshortage/

13. Richard Pazdur discusses root causes of cisplatin and carboplatin shortages and what can be done to alleviate it. The Cancer Letter. May 30, 2023. Accessed July 18, 2023. https://cancerletter.com/conversation-with-the-cancer-letter/20230530_1/

14. To ease cancer drug shortage, FDA will allow imports from China. NBC News. June 5, 2023. Accessed July 18, 2023. https://www.nbcnews.com/health/cancer/cancer-drug-shortage-fda-will-allow-imports-cisplatin-china-rcna87751