Briefly, an Intas plant that manufactures carboplatin in India was shut down after a Food and Drug Administration (FDA) inspection revealed several major quality concerns. This led to a shortage of carboplatin, and in turn, a “cascade shortage” of cisplatin, which was used as a substitute platinum chemotherapy drug. Unfortunately, urologists who treat urologic cancers are very familiar with such shortages, as a BCG shortage has been affecting non-muscle invasive bladder cancer patients for several years.
The underlying issues that contribute to both the current cancer drug shortages are not unique. These issues are similar to those that contribute to the BCG shortage and other ongoing generic prescription shortages. In fact, the average generic drug shortage lasts for about 1.5 years. Several legislative and national agency related policy changes have been suggested by experts to abate and prevent such drug shortages.
Potential FDA Solutions
The FDA currently requires drug manufacturers to provide advanced notice to the agency either six months, or as soon as possible, in the event that a disruption in production of a specific drug is anticipated. Despite this guidance, there are currently twelve cancer drugs that are facing a major shortage. Therefore, even with advanced notice, manufacturers are unable to ramp up production efforts to keep up with demand. Part of this issue relates to the lack of incentives to produce generic drugs – given their low cost and lack of patent protection, the profit margins on these drugs are much narrower than brand name drugs. Therefore, drug companies are not incentivized to invest in and divert resources to generic medication production.Increased transparency into generic drug quality assessments and manufacturing capacity will allow the agency, physicians, consumers, and companies themselves better monitor for and anticipate shortages. This will allow the agency to serve as a liaison between different manufacturers in the event that a disruption arises. It is also essential that the FDA fast track approval of new manufacturing facilities as shortages emerge. Modifying expiration dates during times of acute shortage will help avoid wastage of medications in short supply.
Potential Policy Solutions
In response to the current chemotherapy shortage, policymakers have already put forward several bills to both mitigate the current crisis, as well as prevent further issues in the future. H.R. 3810, introduced by Rep. Eschoo (D-CA), is entitled the “Drug Origin Transparency Act of 2023.” The proposed legislation requires drug manufacturers to report supplies of active ingredients to the FDA and on drug labels. H.R. 3008, the “Drug Shortage Prevention Act,” is a bipartisan bill (Rep. Jacobs D-CA, Rep. Mills R-FL) that requires drug sponsors to notify the FDA in the event of an unanticipated spike in demand, such as the cisplatin demand following the initial carboplatin shortage or the rise in demand noted with pediatric analgesics and antibiotics that led to shortages over the winter. The “Ensuring Access to Lifesaving Drugs Act of 2023,” H.R. 3793, was introduced by Rep Slotkin (D-MI) and aims to improve the FDA’s ability to safely, based on sound data, extend the shelf-life dates of drugs that are experiencing shortages.The Pandemic and All Hazards Preparedness Act (PAHPA) will be reauthorized this year, therefore, it is possible that policies introduced as individual bills will be included in the reauthorization package. Additional actions that policymakers can take to prevent future drug shortages are to consider tax incentives or other incentive programs for generic drugmakers to invest in these low-cost medications, and temporary drug importation measures from countries such as India and China, similar to the FDA’s 2022 temporary allowance of baby formula from overseas during a shortage.
Additional Stakeholder Actions
During times of acute drug shortages, pharmaceutical companies have a moral and ethical obligation to prioritize the manufacturing of generic life-saving drugs. Similarly, insurance companies must improve flexibility of coverage during medication shortages, reduce prior authorization requirements, and reduce regulatory burdens for physicians to allow alternative agents to be used during drug shortages.Written by: Ruchika Talwar, MD, Urologic Oncology Fellow, Department of Urology, Vanderbilt University Medical Center, Nashville, TN
References:
- Kimball, S. (2023, June 2). FDA considers temporary cancer drug imports from unapproved companies to ease U.S. shortage. CNBC.
- Nonzee NJ, Luu TH. The Drug Shortage Crisis in the United States: Impact on Cancer Pharmaceutical Safety. Cancer Treat Res. 2019;171:75-92.
- Noguchi, Y. (2023, June 15). Some cancer drugs are in short supply, putting patients’ care at risk. Here’s why. NPR.
- Yong, E. (2023, June 26). The Cancer-Drug Shortage Is a Disaster. The Atlantic.