Patient access to cancer drugs can mean the difference between life and death. Persistent shortages threaten patients’ access to the lifesaving and life-sustaining therapies they need. To share insights and advance potential solutions to mitigate such shortages, a virtual summit titled “Mitigating Cancer Drug Shortages” was convened Sept. 26 by the U.S. Pharmacopeial Convention (USP), the American Cancer Society (ACS), and the ACS Cancer Action Network (ACS CAN). The event spotlighted perspectives from manufacturers, regulators, healthcare providers, legislators, academia and patients, and issued a call to action for stakeholders to come together to advance needed reforms.
[Editor’s note: The following is a snapshot of take-aways from the summit. It is not intended as a comprehensive summary or report. To view a recording of the summit, click here.]
Legislation needed to end “crisis”
“We are in a drug shortage crisis,” observed keynote speaker Sen. Gary Peters (D-MI), Chairman of the Senate Homeland Security and Governmental Affairs Committee. “Right now, there are at least 15 cancer drugs in shortage, and hundreds of other essential drug products that are in short supply…. These shortages create serious health and national security concerns,” Peters asserted.
Peters has made combating drug shortages a “top” legislative priority. Earlier this year, he released a report on drug shortages, presided over a related hearing and introduced bipartisan legislation on the issue. Peters also introduced in 2023 the bipartisan “Mapping America’s Pharmaceutical Supply (MAPS) Act,” supported by USP, to create a federal database to map the U.S. medicines supply chain and produce actionable insights to inform needed investments and reforms to address supply chain vulnerabilities. “We must urgently put these solutions in place to ensure that everyone can access the lifesaving medications that they need,” Peters told summit attendees.
Patient perspectives show urgency
Cancer drug shortages “unfortunately…have been going on for quite a long time,” noted patient advocate and 30-year cancer survivor Gwen Darien, Executive Vice President, Patient Advocacy and Engagement, National Patient Advocate Foundation, and member of the USP Board of Trustees. Addressing the summit, Darien emphasized that cancer drug shortages impact hundreds of thousands of patients, and can delay treatment, make it less effective, and impact quality and length of life.
Such shortages “have been endemic in cancer care delivery” and periodically “become worse,” Darien said. “So, we have the same conversation over and over again.” Therefore, “I would ask everybody to come together and really think about how we’re going to solve this problem together...and look at it from not simply the manufacturing lens but also from the human lens, and think about what patients like me, [as well as their] friends and family, face when they’re diagnosed with cancer.”
Shortages hit some harder than others
Past drug shortages provide insights on potential future supply chain issues and can facilitate stakeholder prevention or mitigation efforts. While drug shortages “all have unique stories about what causes them… there are some commonalities,” noted summit participant Vimala Raghavendran, Vice President, Informatics Product Development, USP. For example, Raghavendran said, data show drug shortages are more likely with increased manufacturing complexity, low prices that allow minimal profit margins, and geographic concentration of production. Based on an analysis by USP’s Medicine Supply Map team of 20 of the most essential oncology medicines – including four already in shortage – “there are several essential cancer medications that are vulnerable to future drug shortages,” Raghavendran said.
Looking beyond just cancer drugs, the number of drug shortages is large and increasing, with “359 molecules with an active shortage in the U.S. market currently,” noted summit presenter Michael Kleinrock, Lead Research Director, IQVIA Institute for Human Data Science. That’s up from 168 in 2011, Kleinrock noted. Generics make up the lion’s share of aggregate shortages at 82%, and a majority are sterile injectables at 58%, he said. Looking at cancer drug shortages in particular, 80% of the volume of those shortages is concentrated in just four molecules – including methotrexate, megestrol, carboplatin, and cisplatin – with “inspection driven disruption” the likely primary cause in most cases, Kleinrock suggested.
The impact of such shortages on oncology clinics and their patients can be widespread, touching hundreds of thousands of individuals, affirmed summit presenter Julie Gralow, Executive Vice President and Chief Medical Officer, American Society of Clinical Oncology (ASCO). Based on data from ASCO members’ response to the recent shortages of chemotherapy drugs cisplatin and carboplatin, however, the impact of such shortages can vary considerably in part due to providers’ use of mitigation strategies including delays in treatment, use of lower doses, longer intervals between doses, an altered sequence of drug treatment vis a vis surgical treatment, prioritizing treatment of patients with earlier-stage disease, and substitution of medicines with alternatives, Gralow reported.
“A common theme was that there was a disproportionate impact based on the patient’s location or their socioeconomic status,” Gralow noted. Those with “lower socioeconomic status” had less of an ability to travel to alternate sites farther away to access limited supplies of drugs in shortage, Gralow explained.
Solutions target vulnerabilities
Summit participants suggested various potential, actionable solutions to help mitigate future cancer drug shortages.
- Building “early warning capabilities” using “predictive analytics” to identify and prioritize shortage prevention for vulnerable drugs can facilitate targeted solutions, Raghavendran said. USP recommendations also include establishing a list of “vulnerable medicines” based on predictive analytics; investments in long-term supply contracts for medicines with unsustainably low prices; investments in measures that encourage multiple suppliers for medicines and geographic diversification of manufacturing; and exploration of payment and purchasing models that value and incentivize supply chain resilience and reliability. These and other recommendations are outlined in a recent USP policy position paper.
- “We need more transparency and information that’s tied to these drug shortages,” Gralow opined. A “reliable quality score” for the manufacturing of individual low-cost drugs also could be used to support higher prices that reduce the likelihood of shortages in those cases, Gralow suggested.
- When it comes to underlying causes, “it really is all about the cost” of specific drugs that makes them vulnerable to shortage, said summit participant David Gaugh, Interim President and CEO, Association for Accessible Medicines. When it comes to generic drugs in particular, prices “come down too much,” he said. “We need to really look at … price point.” Referring to generics provider Civica, a non-profit created by hospitals and philanthropies that partners with U.S. health systems to supply drugs determined to be in shortage or at risk of shortage, Gaugh noted that Civica’s business model “does work.” However, Civica functions in a “closed system,” Gaugh said. “It’s wonderful for that closed system, because they do get a higher price point, they do get a longer-term contract, it’s a firm contract.” However, “that’s what doesn’t exist in the open market today and we really need to find a way to move that Civica-type model into the forefront.” (See related blog, titled “Manufacturing Solutions are Essential to Strengthen the Global Medicines Supply Chain”).
- Advanced manufacturing technologies (AMTs) like pharmaceutical continuous manufacturing can enable potential efficiencies to “reduce the cost of production to make the economics of production more favorable,” thus contributing to supply chain resilience and a reduced likelihood of shortages, suggested summit participant Anthony Sardella, Chair of the API Innovation Center, and Senior Research Fellow at the Center for Analytics and Business Insights, Washington University in St. Louis. There are also potential benefits that could be achieved by repurposing existing excess U.S. manufacturing capacity, Sardella indicated. Overall, “incentivizing resiliency as well as quality manufacturing … are going to be very helpful to the industry and the economics of the entire supply chain,” he noted. The non-profit API Innovation Center deploys funding to facilitate commercialization of AMTs including for production of oncolytic drugs, Sardella explained.
- FDA works with manufacturers in a variety of ways to help prevent drug shortages – from pre-market reviews focused on manufacturing quality to providing guidance on risk-management – and to help address shortages when they occur, noted summit participant Jacqueline Corrigan-Curay, Deputy Center Director, Center for Drug Evaluation and Research, at the U.S. FDA. Looking ahead, “actions that we think are important” include “more surveillance inspections,” as well as a “management approach to quality,” and greater adoption of AMT to facilitate supply chain resilience, Corrigan-Curay said. (See related blog, titled “Pharmaceutical Continuous Manufacturing: Regulatory Landscape in the Spotlight at USP Workshop.”)
- “Advancing federal coordination” is needed to address drug shortages, said summit participant Stephen Colvill, Assistant Research Director, Duke-Margolis Center for Health Policy. The center recently issued a white paper on the topic. In the paper, “we propose establishment of a new cross-cutting federal ‘Prevent Drug Shortages’ initiative…that would bring together all the relevant federal agencies that are needed to solve for this problem, include private sector involvement, and then address several policy priorities and gaps in the current approach,” Colvill summarized. “There is a need for a whole-of-government effort to address this problem.”
While it’s clear there is no one-size-fits-all solution to cancer drug shortages, and that a range of policies and actions will be needed to mitigate future shortages and the negative impact they can have on patients and their loved ones, significant strides will require continued stakeholder collaboration, dialogue, innovation and persistence. See our call to collective action to lend your organization’s voice to this important effort. To view a recording of the summit, click here.
Learn more about USP efforts to advance quality-focused solutions for a stronger medicines supply chain.