Does Canada Manage Them Better?

With the number of US drug shortages being one of the highest seen over the past 10 years, the American Medical Association (AMA) has adopted policies aimed at mitigating them, and researchers offer their understanding of what’s driving these challenging events.

Patients with cancer are among those hit particularly hard by these shortages, with 25 chemotherapies undergoing active shortages as of September 30, 2024, according to a report from the American Society of Health-System Pharmacists (ASHP). That analysis showed that while the number of active shortages across all drug categories was less than the all-time high of 323 in late 2023, that 277 drug shortages were still occurring in the United States as of the second quarter of last year. The chemotherapy drug class ranked 4th in total shortages in the ASHP analysis, behind central nervous system drugs, antimicrobials, and hormone agents, respectively.

The AMA’s new wide-ranging policies have the goal of addressing a lack of teamwork and transparency throughout the US drug supply chain in addition to other challenges related to the shortages.

The policies will “bolster drug manufacturing through the use of incentives such as prioritized regulatory review, reduction of user fees, and direct grant opportunities for manufacturers seeking to invest in manufacturing processes,” according to a statement from the AMA. Additional provisions call for solutions such as a rating system for drug manufacturers’ shortage prevention efforts and legislative support for “more reasonable and sustainable payment rates for prescription drugs.”

Further bringing attention to this persistent problem in the United States were the findings of a study recently published in JAMA. It found that compared with drug supply chain issues occurring in Canada, those occurring in the United States were 40% more likely to result in meaningful shortages.

Due to built-in payer conflicts, reporting gaps, and the complexity of the US drug supply chain, stateside stakeholders may face greater challenges in some respects vs their Canadian counterparts, according to the new research. But the United States is not alone in having difficulties responding to drug shortages, as Canada’s efforts to address drug shortages also leave room for improvement, the paper says.

More Teamwork and Transparency Needed

To help manufacturers of critical generic drugs recoup their investments in capacity and quality, ASHP policy recommendations suggest long-term, guaranteed volume contracts. For the short term, the ASHP recommended enacting meaningful penalties for registered facilities that fail to provide mandatory information about their manufacturing processes, supply chains, and risk management plans to the US Food and Drug Administration (FDA).

As of March 2023, more than half of registered facilities had not done so, according to a May 9, 2023 letter from Kimberlee Trzeciak, now FDA Deputy Commissioner for Policy, Legislation, and International Affairs, to Cathy McMorris Rodgers, chair of the US House of Representatives Committee on Energy and Commerce.

As the above paragraphs imply, American stakeholders face significant hurdles in battling drug shortages.

Canada vs the United States

“Although identification of specific policies and strategies that worked in Canada is beyond the scope of this study, the lower risk of drug shortages in Canada suggests that this would be an informative exercise for US policymakers as they consider lessons from other countries in their response to drug shortages,” wrote the authors of the new JAMA study.

Lead author Mina Tadrous, PharmD, PhD, assistant professor with the Leslie Dan Faculty of Pharmacy at the University of Toronto in Toronto, Ontario, Canada, and colleagues analyzed drugs with issue reports for the same formulation occurring in both countries within 180 days of each other between January 2017 and September 2021. Due to differences in data availability, the analysis excluded radiopharmaceuticals and antibodies, Tadrous said they represent a small portion of cancer drug purchases.

Among 104 total issue reports for all drug categories, antineoplastic/immunomodulating drugs ranked 4th with 12, tied with digestive and metabolic drugs and behind neurologic (20), cardiovascular (13), and systemic anti-infective drugs (14), respectively. Although the report did not name individual drugs, major oncologic drug categories that experienced shortages during the study included platinum-based products and older chemotherapies, Tadrous said.

Commercial and Clinical Realities

Oncology drugs check many of the boxes that can make them both clinically indispensable and shortage-prone. Most oncology drugs tend to be older, intravenously administered, generic, and made by few manufacturers, explained Tadrous. Cancer drugs save lives, he added, and many have few effective or safer alternatives. Therefore, Tadrous said that, vs the thousands of other drugs available, oncology drugs tend to “percolate to the top” of shortage lists that prioritize drugs of concern.

Although the study did not establish causality, he said, Canada’s potential advantages in preventing shortages include a highly integrated healthcare system that “allows more of the stakeholders to sit easily at one table.”

Unlike ad hoc task forces, the Multi-Stakeholder Steering Committee on Drug Shortages (MSSC), a standing task force assembled in 2012, meets regularly to discuss drug shortages at the national level. Under Canada’s single-payer system, the MSSC and other standing task forces can include provincial and territorial public payers, which, unlike America’s Medicare program, pay for drugs directly. Additional task force members can include hospital administrators, wholesalers, regulators, and clinical groups, who communicate constantly to monitor shortages and work with federal regulators to ensure equivalent access to medications throughout each province or territory.

When appropriate, Tadrous added, a standing task force can engage manufacturer advocacy groups and manufacturers to find solutions such as bringing in foreign stocks of drugs or developing shortage mitigation strategies. Accordingly, he said, Canada’s task forces have “developed this ability to nimbly respond to things as they start seeing signals through the supply chain reports.”

Similar efforts are happening in the United States, said Tadrous. “In the United States, it’s a bit more challenging sometimes [because] you see vying for options as different healthcare systems compete against each other.”

US healthcare payers include both federal and state governmental bodies, as well as providers of employer-sponsored coverage. “If you think about all the different employers, insurance companies, and groups that they work with to provide coverage,” said paper Co-author Joshua W. Devine, PharmD, PhD, assistant professor, Master of Public Health Program in the Department of Public Health at Des Moines University in Des Moines, Iowa, “we have many more stakeholders and payers because of the way the healthcare system is designed.”

The US healthcare system also includes many more pharmacies, hospitals, and providers, said Devine. “That complexity can make it a challenge when drugs are in short supply — how do you allocate those limited supplies? Providers, healthcare systems, patients, and others are competing to get access to treatment in a scenario where supply is more constrained than it would be under ideal circumstances.”

Additionally, supply chain issue reporting differs between the United States and Canada. US reports funnel through both the FDA’s mandatory site and a voluntary ASHP website. These systems lack standardized language for reporting underlying reasons, and nearly one in four US reports analyzed listed no reason.

Conversely, Canada’s mandatory single-payer system yielded 10 times more reports. “We get a lot of false positives,” Tadrous said. “But it does offer the opportunity to have an early signal system.”

However, he added, even Canadian manufacturers’ reported reasons commonly provide vague catchalls such as “business decision.” Understanding the factors behind such decisions could help planners better forecast how long a shortage will last, said Tadrous.

Stockpile strategies also differ between the United States and Canada. Whereas Health Canada has stockpiled drugs likely to be affected by supply chain strains like those that occurred during the COVID-19 pandemic, the US Strategic National Stockpile aims to address acute events such as terrorism and disasters. Under a new rule (89 FR 68989) for fiscal year 2025, however, the US Centers for Medicare & Medicaid Services has authorized new payments to smaller, independent hospitals that voluntarily establish and maintain a 6-month buffer stock of at least 1 of 86 essential medicines.

“We believe there’s a big opportunity in both countries to improve how reporting systems work, to allow better analyses and system readiness, and to respond a little better and understand what’s actually happening,” said Tadrous.

Devine added that while their group has begun examining the factors that are working for Canada, “ongoing study will be vital as we implement new policies aimed at strengthening the resiliency of the drug supply chain in both countries, especially for generic sterile injectable drugs.”

The US-Canadian study was funded by the US Agency for Healthcare Research and Quality. Tadrous has received personal fees from Health Canada. Devine reported no relevant financial relationships.

John Jesitus is a Denver-based freelance medical writer and editor.