Recently, a plant in India failed an FDA inspection, which led to critical shortages in carboplatin and cisplatin stateside. The FDA halted production at the plant due to issues with the purity and sterility of the injectable drugs. These drugs are critical in the care of pediatric and other cancers.

The issue of shortages of chemotherapy has become ever-more burdensome in recent years. The implications for patient care are broad, with solutions requiring a revamp of current regulation and oversight. 

 

Agents in short supply

 

On September 12, 2023, the Biden Administration formally warned of shortages of 15 important chemotherapy drugs due to manufacturing and supply chain issues.

The White House. Strengthening the supply chain for cancer drugs. September 23, 2023.

 

Below is a list of implicated drugs:

US Food and Drug Administration. Current and Resolved Drug Shortages and Discontinuations Reported to FDA.

 

• Methotrexate injection/methotrexate sodium tablet; used to treat solid tumors, leukemia, and lymphoma

• Carboplatin injection; used to treat ovarian cancer

• Cisplatin injection; used to treat ovarian, bladder, and testicular carcinoma

• Azacitidine injection; used to treat myelodysplastic syndromes and different types of leukemia 

• Capecitabine tablet; used to treat breast and colorectal cancer

• Cytarabine injection; used to treat various types of leukemia

 

Why is this happening?

 

The FDA attributes drug shortages to three root causes.

US Food and Drug Administration. Drug Shortages: Root Causes and Potential Solutions. 2019. Updated February 21, 2020.

 

1. A lack of incentive to produce less-profitable drugs like generics. Sometimes, the cost of producing a generic drug is higher than the reimbursement cost.

2. The market fails to recognize or reward manufacturers with mature quality management systems. These systems have a patient and performance focus, and leverage technology, statistical process control, and planning activities to ensure a reliable supply of the drugs manufactured. Purchasers have little information on the status of the facilities making the drugs they buy.

3. Logistical and regulatory barriers. Impediments of this nature make it difficult to recover following a disruption in supply. Specifically, if a new manufacturer wants to enter the market and fill a gap left by a shortage, there is plenty of FDA red tape.

There is also a dearth of information on the origin, quality, and supply reliability in the pharmaceutical industry.

“Hurdles of pharmaceutical production and steep entry costs deter potential new entrants,” stated the author of the JAMA Oncology editorial. “The result has been a supply chain for generic oncology drugs susceptible to disruptions when an essential manufacturer shuts down due to quality issues, as has occurred with the most recent shortages.” 

 

Potential repercussions

 

The effects of chemo drug shortages include rationing of care and delayed care by hospitals. Doses can be reduced, thus rendering treatments less effective. Patient outcomes are worsened by shortages.

 

What can be done?

 

On a macroscopic level, the government could offset low reimbursement rates for generic chemo drugs by entering into purchasing agreements for high-quality products. CMS could further motivate hospitals to choose reliable vendors (ie, members of the FDA’s QMM program). The government could also establish multistakeholder oversight committees to offer continuous dialogue with the FDA regarding drug shortages and production. The US government could expand its stockpile efforts.

Pharmaceutical companies can increase transparency regarding shortages. Currently, Pfizer offers a web tool that updates the public about its facilities and products. This tool could serve as a model for other pharma and biotech companies.

On a more granular level, providers should be proactive and transparent about shortages with their patients.

 

Here are some important highlights:

• Oncologists should reprioritize the nonessential use of antineoplastic agents in limited supply. If an alternative is available of comparable efficacy and safety, then the agent in shortage should not be ordered.

• Intervals of administration between cycles can be lengthened per nationally recognized guidelines.

• Doses can be reduced per nationally recognized guidelines.

• The agent in shortage can be limited or omitted in recurrent agent-resistant cancers.

• Oncologists should consider curbsiding colleagues to review disease site-specific options and alternatives.

• Providers can minimize the waste of agents in short supply by optimizing vial size, employing dose rounding, and using multiuse vials.

• Patients who are distressed by drug shortages should be referred to counselors trained in treating people with cancer.

ASCO also promotes the equitable provision of resources. “Institutions should establish a working multidisciplinary utilization committee to monitor drug shortages, provide and communicate internal policies on utilization, and act as an independent arbiter to promote equitable use of drugs in short supply,” they conclude.