Key Drivers and Mitigation Strategies of Oncology Drug Shortages 2023 to 2025

Abstract

Drug shortages remain a problem in the United States, jeopardizing patient care. To help inform solutions, this study reviewed recent oncology drug shortages for causes and mitigation strategies. Using the FDA’s Drug Shortage Database, 15 oncology drugs with shortages between 2023 and 2025 were identified. Twelve drugs had shortages lasting >2 years (maximum: >13 y). Searches of PubMed and Google Scholar, online media sources, and FDA documents uncovered 9 main causes: manufacturing quality problems, limited-source dependency, regulatory bottlenecks, global over-reliance, absence of buffer stocks, demand surges, low economic incentives, active pharmaceutical ingredient shortages, and shelf-life constraints. Mitigation strategies involved 4 stakeholders: regulators (expedited regulatory action, importation, expiration extensions), manufacturers (capacity expansion), providers (dose-sparing regimens, therapeutic alternative protocols, allocation prioritization), and purchasers-distributors including GPOs (supply collaboration). Policies to mitigate drug shortages should include new approaches to identify vulnerable markets and involve multiple stakeholders. Factors identified in this study also offer pathways for shortage prevention.

Drug shortages remain a recurring problem in the US health care system, with significant implications on patient care.¹ According to the US Food and Drug Administration (FDA), there were 270 drugs in shortage in March 2025, of which about 8% were chemotherapy agents.² Shortages of oncology drugs are a source of great clinical concern, because they may result in delays in treatment initiation or continuation, medication errors, and use of less effective or less safe therapies, often leading to poorer clinical outcomes.^1,3,4 In addition, oncology drug shortages may place added burden on clinicians and contribute to higher health care costs.³

Oncology drugs shortages can be long-lasting. Between 2009 and 2019, 9 out of the 11 drugs used to treat acute T-cell lymphoblastic leukemia were affected by shortages according to the US Food and Drug Administration FDA.¹ One such shortage—of asparaginase—persisted for nearly 5 years, after a supply disruption in 2016.⁵ Although the causes of shortages may vary, generic sterile injectable solutions, including many chemotherapy agents, are particularly vunlerable.⁶ The FDA attributes more than 60% of shortages to manufacturing quality problems; in 18% of cases, the reasons for the shortage remain unidentified.¹

The FDA collects data from drug manufacturers and maintains a public database of drugs for which the available or projected nationwide supply falls short of the demand.^7,8 The FDA’s Drug Shortage Database supports mitigation efforts, including expediting review of manufacturing changes or temporary importation of unapproved drugs.⁷ However, the database does not document specific mitigation strategies, limiting the ability to assess the effectiveness of individual interventions.⁹

To inform strategies to address oncology drug shortages, this study analyzed the causes and mitigation strategies of oncology drug shortages reported between 2023 and 2025. Given the limitations of FDA-reported data, the analysis incorporated information from peer-reviewed literature, gray literature, and media reports in addition to FDA sources.

METHOD

The FDA Drug Shortage Database was used to identify oncology drugs with recorded shortages as of May 9, 2025.⁸ Because the FDA Drug Shortages Database does not provide retroactive information, we combined this list with data collected through a similar approach on July 01, 2023.⁷ For each drug, the Database was used to collect drug name, active ingredient, manufacturer, shortage start and end dates, reasons for the shortage, and any previous product discontinuations.⁸

The FDA’s Orange Book was used to obtain each drug’s route of administration, license type [NDA (branded drug) or ANDA (generic drug)], and all manufacturers licensed by the FDA to commercialize the drug.¹⁰ There were no biological drugs identified in the sample. The FDA Online Label Repository was used to obtain the drug’s FDA-approved indications.¹¹ The DynaMedex drug database was used to identify if the drug was the treatment of choice or the first-line treatment for at least 1 indication.¹² In addition, FDA warning letters, recalls, and enforcement actions were searched using both the drug name and the associated manufacturer’s name, as some FDA documents (e.g., warning letters) refer only to the manufacturer.¹³

Searches of PubMed and Google Scholar platforms, as well as online media sources, were implemented using combinations of drug names and manufacturer names with the term “shortage.” Searches were limited to English-language sources. Data extraction focused on 2 domains: shortage causes and mitigation strategies. Within each domain, key themes were identified to capture patterns across multiple shortage events. Extracted data was entered into a structured Excel spreadsheet with citations added to each entry. Frequencies of drugs associated with each theme were summarized, and representative examples were selected for illustration.

RESULTS

A total of 15 oncology drugs with recorded shortages between 2023 and 2025 were identified (Table 1). Fourteen drugs were injectables. Drugs were approved for various indications such as leukemia, lymphoma, breast, ovarian, colorectal, and prostate cancers; 7 drugs were the treatment of choice or the first-line treatment for at least one indication. Nine drugs were available exclusively as generics, 5 were multisource products (available in both branded and generic versions), and 1 drug—Lutetium Lu 177 vipivotide tetraxetan—was a branded radiopharmaceutical with no generic.

TABLE 1.

Characteristics of Oncology Drugs in Shortage between 2023 and 2025

Non-Proprietary (Generic) Name	Route(s) of Administration*	Drug Type* †	Main Clinical Indication‡	Manufacturers Reporting Shortage, N(%)§ *	Manufacturers Previously Exiting the Market, N §	Shortage Initial Posting Date §	Shortage Length as of May 09, 2025	Date Resolved as of May 9,2025§
Leucovorin calcium	Injection, oral	Generic only	Reduce toxic effects associated with folic acid antagonists∥	7 (78)	9	January 2012	13 y 4 mo	Current
Amifostine	Injection	Multisource	Reduce kidney failure associated with chemotherapy	1 (50)	2	May 2020	4 y 5 mo	Discontinued in Oct 2024
Floxuridine	Injection	Generic only	Metastatic gastrointestinal adenocarcinoma	1 (50)	2	June 2020	2 y 8 mo	February 2023
Cytarabine	Injection	Generic only	Various types of leukemia∥	4 (57)	3	September 2021	2 y 10 mo	July 2024
Dacarbazine	Injection	Generic only	Metastatic malignant melanoma	3 (75)	2	October 2021	3 y 3 mo	January 2025
Paclitaxel (protein-bound)	Injection	Multisource	Ovarian carcinoma, breast cancer, lung cancer, Kaposi sarcoma∥	2 (67)	0	October 2021	3 y 7 mo	Current
Azacitidine	Injection, oral	Multisource	Myelodysplastic syndromes, various leukemia types∥	9 (100)	0	December 2020	4 y 5 mo	Current
Pentostatin	Injection	Multisource	Hairy cell leukemia∥	1 (50)	1	March 2022	3 y 2 mo	Current
Streptozocin	Injection	Generic only	Metastatic islet cell cancer of the pancreas∥	1 (50)	1	July 2022	2 y 10 mo	Current
Fludarabine phosphate	Injection	Generic only	B-cell chronic lymphocytic leukemia	4 (67)	4	May 2022	1 y 1 mo	April 2024
Capecitabine	Oral	Multisource	Breast and colorectal cancer	6 (46)	1	February 2023	1 y 4 mo	June 2024
Carboplatin	Injection	Generic only	Ovarian carcinoma∥	8 (42)	7	April 2023	2 y 1 mo	Current
Cisplatin	Injection	Generic only	Ovarian, testicular, and bladder carcinoma	6 (100)	2	February 2023	2 y 3 mo	Current
Lutetium Lu 177 vipivotide tetraxetan	Injection	Branded only	Prostate cancer	1 (100)	0	March 2023	7 mo	October 2023
Methotrexate	Injection, oral, subcutaneous	Generic only	Various solid tumors, leukemia and lymphoma	5 (83)	7	March 2023	2 y 2 mo	Current

^*Source: FDA’s Orange Book of Approved Drug Products with Therapeutic Equivalence Evaluations.

^†New drug application—NDA—indicated branded drugs; abbreviated new drug applications—ANDA—indicated generic drugs; multisource drugs had both NDA and ANDA-license products; no biological drugs were identified in the sample.

^‡Source: FDA Online Label Repository.

^§Source: FDA Drug Shortages Database.

^∥Indicates drugs that are the drug of choice or the first line of therapy for at least one indication.

Twelve drugs had been in shortage for more than 2 years. The longest-standing supply disruption among the group was leucovorin calcium, with shortage spanning over 13 years. At the time of the analysis, 8 of the 15 drugs remained in active shortage, whereas 6 drugs had their shortages resolved in the past 2 years. One drug—amifostine—was permanently discontinued from the US market after a shortage lasting over 4 years. Manufacturer market exits were common: 7 drugs had lost 2 or more manufacturers before or during their current shortage episodes. Notably, 9 manufacturers had exited the leucovorin calcium market, and 7 had manufacturers previously discontinued carboplatin and methotrexate production.

Causes of Drug Shortages

Nine key themes emerged as contributors to oncology drug shortages: manufacturing quality issues [good manufacturing practice (GMP) violations], limited source dependency, regulatory bottlenecks, global over-reliance, absence of buffer stocks, demand surges, low economic incentives, active pharmaceutical ingredient (API) shortages, and shelf-life constraints (Table 2).

TABLE 2.

Causes of Shortages Identified Among the Study Drugs

Theme	Definition	No. Drugs Flagged	Drugs Flagged	Examples
Good Manufacturing Practices (GMP) issues	Manufacturing disruptions, plant shutdowns, GMP or sterility violations, capacity limits, contamination events	15	All study drugs	1. Leucovorin calcium: FDA contamination and sterility citations at Bedford, Teva, and Pfizer (2008-2014; 2023-2025) halted output and recalls.14 2. Streptozocin: Mold and sterilization failures at Teva’s Irvine plant prompted a 2021 FDA shutdown, erasing >15% of US supply.15
Single-source risk	Heavy reliance on one (or very few) finish dose or API manufacturers; minimal redundancy	15	All study drugs	1. Amifostine: US dependence on a lone supplier (Clinigen) meant production ceased entirely when Clinigen halted production in 202416 2. Dacarbazine: The market relies on just 3 producers; Teva’s 2021 plant closure instantly erased 15% of US supply, underscoring the thin redundancy.17
Regulatory bottlenecks	FDA import bans, warning-letter holds, delayed approvals, or forced allocation/expiration extensions	9	Leucovorin calcium, Amifostine, Lutetium Lu 177 vipivotide tetraxetan, Methotrexate, Streptozocin, Azacitidine, Pentostatin, Cytarabine, Dacarbazine	1. Azacitidine: FDA 2023 import restrictions on Intas stalled critical suppliers, creating a regulatory choke-point in US supply.18 2. Pentostatin: Sole producer Pfizer halted output in 2022-2023 whereas its API vendor resolved compliance failures, leaving the market without an approved alternative.19
Global over-reliance	Over-dependency on overseas (often single-region) supply chains or off-shored production nodes	7	Amifostine, Floxuridine, Lutetium Lu 177 vipivotide, Methotrexate, Capecitabine, Fludarabine phosphate, Paclitaxel (protein-bound)	1. Floxuridine: After Fresenius exited, supply hinged on Hikma; with only 2 companies—Cerona and Zhejiang Hisun as backups.20 2. Capecitabine: A thin roster of global manufacturers (Accord, Dr Reddy’s, H2-Pharma) and offshore API sourcing meant one supplier’s outage rippled worldwide, leaving no domestic safety net.21,22
No-buffer inventory	Just-in-time inventory / lack of strategic buffer stock that magnifies small disruptions	7	Methotrexate, Carboplatin, Cisplatin, Streptozocin, Fludarabine phosphate, Azacitidine, Pentostatin	1. Carboplatin: Just-in-time practices at Fresenius Kabi and Teva meant zero safety stock; when cisplatin shortages spiked demand, inventories vanished overnight.23 2. Floxuridine: After Fresenius exited, wholesalers kept only thin day-to-day stock; a single Hikma API delay wiped out supply before new batches could ship.20
Demand spikes	Sudden demand spikes driven by label expansions, guideline changes, or shortage-driven substitutions	5	Lutetium-177, Methotrexate, Capecitabine, Carboplatin, Paclitaxel (protein-bound)	1. Lu-177 vipivotide tetraxetan: Post-approval demand (March 2022) overwhelmed the sole Italian plant, and the product’s 5-day shelf-life left no buffer, triggering immediate shortages.24 2. Paclitaxel (protein-bound): Off-label expansion into pancreatic and lung cancer, coupled with limited conservation in the United States, pushed demand beyond production capacity.30
Economic vulnerability	Low generic profitability or unattractive margins that discourage investment in backup capacity	5	Leucovorin, Cisplatin, Fludarabine, Cytarabine, Dacarbazine	1. Leucovorin calcium: Thin generic margins steered firms toward higher-priced levoleucovorin, leaving the cheap version chronically under-funded and easily knocked offline.26 2. Cisplatin: Rock-bottom profitability discouraged backup capacity; when Intas shutdown, no one was willing (or ready) to absorb the cost of ramp-up.27
Raw-material/API gaps	Shortages of active pharmaceutical ingredients or other critical raw materials	5	Floxuridine, Capecitabine, Azacitidine, Pentostatin, Cytarabine	1. Floxuridine: Hikma’s supply dried up when its API source ran short after Fresenius exited in 2019, and no backup vendor entered the market.20 2. Azacitidine: API shortages hit Accord, Viatris, and Wockhardt simultaneously, whereas Cipla/Celgene could not increase production sufficiently to increase supply.28
Shelf-life constraint	Ultra-short shelf-life or complex logistics that preclude stockpiling (e.g., radiopharma)	1	Lutetium Lu 177 vipivotide	1. Lu-177 vipivotide tetraxetan: 5-day post-calibration shelf-life leaves insufficient time for stockpiling; any customs or shipping delay can spoil the dose before it reaches patients.29

Source: Authors’ analysis of FDA documents, medical literature, and online media.

API indicates active pharmaceutical ingredient.

All 15 study drugs were linked to GMP issues, which included FDA citations, contamination events, and sterility failures. For example, mold and sterilization lapses identified during a 2021 FDA inspection prompted the shutdown of Teva’s Irvine, CA manufacturing facility, erasing more than 15% of the US supply of streptozocin and causing widespread shortages.¹⁵ All 15 drugs also exhibited a high degree of supply concentration, with reliance on a single or very limited number of API or finished drug manufacturers. For instance, US supply of amifostine depended solely on Clinigen until the company ceased production in 2024, rendering the drug permanently unavailable in the US market.¹⁶

Regulatory bottlenecks were implicated in shortage among 9 study drugs including delays in approvals, import holds, and expiration extensions slowing the return of products to market. Seven drugs were linked to concentration in a few markets. Foreign manufacturing of both APIs and finished doses in one or a few locations introduced fragility, especially when located in single geographic regions. Although its sole API supplier resolved compliance failures, Pfizer halted production of pentostatin in 2022 to 2023, leaving the market without an approved alternative.¹⁹ Inventory practices also played a role: 7 drugs operated under just-in-time models with minimal buffer stock, leaving no cushion when supply chains were interrupted.

In 5 cases, demand spikes contributed to shortage onset. In 2022, paclitaxel (protein-bound) experienced heightened demand due to off-label use in pancreatic and lung cancers, contributing to depletion of its available stock.²⁵ Economic disincentives, such as low profitability, discouraged reinvestment and were implicated in shortages of 5 drugs, especially older generic drugs such as cisplatin and dacarbazine. Although not identified explicitly, this could be a problem among most generic drug shortages because of the relatively low prices of these drugs. Five drugs also faced raw material or API constraints, including floxuridine in 2023.²⁰ The shelf-life limitation of Lutetium Lu 177 vipivotide tetraxetan stood out as a unique challenge, precluding stockpiling and heightening vulnerability to distribution and transit delays.²⁹

Mitigation Strategies Used to Address Drug Shortages

Eight key mitigation strategies were identified, organized across 4 operational levels: regulatory level (expedited regulatory action, importation, expiration extension), manufacturer level (capacity expansion), provider level (dose-sparing regimens, therapeutic alternative protocols, and allocation prioritization), and procurement-distribution level (supply collaboration) (Table 3).

TABLE 3.

Shortages Mitigation Strategies Identified Among the Study Drugs

Theme	Definition	No. Drugs Flagged	Drugs Flagged	Examples
Regulatory level
Regulatory expedition	Accelerated FDA reviews / manufacturing adjustments	13	Amifostine, Floxuridine, Lutetium Lu 177 vipivotide tetraxetan, Methotrexate, Capecitabine, Carboplatin, Cisplatin, Streptozocin, Fludarabine phosphate, Paclitaxel (protein-bound), Azacitidine, Cytarabine, Dacarbazine	1. Dacarbazine: Amifostine: DA expedited approvals for manufacturing adjustments, extended expiration dates for existing stockpiles, and authorized temporary importation of non-US-approved dacarbazine.17 2. Paclitaxel (protein-bound): Rapid regulatory approvals, shelf-life extensions, and emergency import waivers sped new and existing producers back to market, cushioning the Abraxane shortage.30
Importation	FDA-authorized emergency import of non-US formulations	12	Leucovorin calcium, Methotrexate, Capecitabine, Carboplatin, Cisplatin, Streptozocin, Fludarabine phosphate, Paclitaxel (protein-bound), Azacitidine, Pentostatin, Cytarabine, Dacarbazine	1. Leucovorin calcium: FDA permitted emergency import of European calcium folinate to bridge the domestic gap.14 2. Fludarabine Phosphate: Shortage relief relied on FDA-approved importation of non-US formulations alongside accelerated supplier clearances.31
Expiration extension	FDA-approved shelf-life extensions for existing stockpiles	10	Amifostine, Floxuridine, Lutetium Lu 177 vipivotide tetraxetan, Carboplatin, Cisplatin, Fludarabine phosphate, Paclitaxel (protein-bound), Azacitidine, Cytarabine, Dacarbazine	1. Fludarabine phosphate: FDA granted shelf-life extensions on existing vials, allowing new batches and imports to be produced.31 2. Lutetium Lu 177 vipivotide tetraxetan: FDA-approved extended expiration dates for existing stockpiles.24,32
Manufacturer level
Capacity expansion	Manufacturer restarts, new suppliers enter, or production scale-up	13	Amifostine, Floxuridine, Lutetium Lu 177 vipivotide tetraxetan, Methotrexate, Capecitabine, Carboplatin, Cisplatin, Streptozocin, Fludarabine phosphate, Paclitaxel (protein-bound), Azacitidine, Pentostatin, Cytarabine	1. Methotrexate: Acord Healthcare has restarted production of commonly used agent methotrexate with FDA oversight.33 2. Azacitidine: New producers Dr Reddy’s and Fresenius Kabi increased production, broadening the manufacturing base and easing shortages.28
Provider level
Dose-sparing regimens	Dose rounding / fixed-dose / vial-sharing to stretch inventory	11	Leucovorin calcium, Amifostine, Floxuridine, Methotrexate, Capecitabine, Carboplatin, Cisplatin, Paclitaxel (protein-bound), Azacitidine, Cytarabine, Dacarbazine	1. Methotrexate: Hospitals used ≤10% dose-rounding and cohort dosing to stretch vials, prioritizing pediatric all while preserving therapeutic outcomes.33,34 2. Cisplatin: Fixed-dose protocols limited waste and were reserved for curative-intent cases in line with NCCN guidance.35
Therapeutic alternative protocols	Substitution with an alternative drug or regimen	6	Leucovorin calcium, Methotrexate, Capecitabine, Fludarabine phosphate, Paclitaxel (protein-bound), Dacarbazine	1. Leucovorin calcium: Shortages prompted a switch to the more expensive levoleucovorin, preserving folate rescue without clinical compromise.26,36 2. Paclitaxel (protein-bound): Providers substituted solvent-based paclitaxel or docetaxel to bridge Abraxane gaps, accepting higher toxicity for continued therapy.37
Allocation prioritization	Triage or reserve systems that restrict use to high-priority cases	11	Amifostine, Lutetium Lu 177 vipivotide tetraxetan, Methotrexate, Capecitabine, Carboplatin, Cisplatin, Streptozocin, Fludarabine phosphate, Paclitaxel (protein-bound), Azacitidine, Pentostatin	1. Amifostine: Fixed 500 mg/day regimens reserved solely for high-risk radiotherapy patients, triaging scarce vials to those with greatest clinical need.38 2. Streptozocin: Hospitals and wholesalers rationed supply to pancreatic neuroendocrine-tumor cases, distributing limited stock by historical-demand quotas.39
Procurement and distribution level
Supply collaboration	GPO negotiations, wholesaler coordination, or diversified sourcing partnerships	4	Capecitabine, Carboplatin, Streptozocin, Pentostatin	1. Capecitabine: Hospitals and GPOs coordinated demand-based allocation and vial-sharing, directing limited stock to priority colorectal and breast-cancer patients.40 2.Streptozocin: group purchasing organizations (GPOs) negotiated novel sourcing strategies to stabilize supply chains.39

Source: Authors’ analysis of FDA documents, medical literature, and online media.

API indicates active pharmaceutical ingredient. GPO, group purchasing organization.

At the regulatory level, expedited FDA actions played a central role in shortage mitigation for 13 drugs. These included accelerated FDA reviews of manufacturing changes, emergency regulatory waivers, and streamlined approvals, which enabled earlier batch releases, temporary shelf-life extensions, and re-entry of manufacturers into the market. Emergency importation was authorized for 12 drugs, allowing temporary access to non-US formulations of agents such as leucovorin calcium, capecitabine, and methotrexate. Shelf-life extensions, approved for 10 drugs, allowed continued use of existing inventory while production resumed.

At the manufacturer level, supply was bolstered through increased capacity for 13 drugs. Specific strategies included reactivating dormant facilities, onboarding of new suppliers, and increasing output by existing suppliers. For example, Dr Reddy’s and Fresenius Kabi re-entered the market for azacitidine after a shortage, and Cerona Therapeutics distributed floxuridine for Hikma, when Hikma experienced manufacturing challenges due to a raw material shortage.^28,41

At the provider level, dose-sparing strategies were recorded for 11 drugs. These included vial-sharing, fixed-dose protocols, and dose rounding to stretch available inventory. Such practices were common in pediatric oncology and curative-intent protocols where complete substitution was not feasible. Therapeutic alternative protocols were implemented in 6 cases. Providers often substituted levoleucovorin for leucovorin calcium or used solvent-based taxanes as alternatives to paclitaxel protein-bound, although such substitutions sometimes introduced increased toxicity or higher cost.^36,37 In addition, 11 drugs were subject to allocation frameworks that prioritized treatment for high-risk or high-need patients. For example, hospitals directed the use of amifostine to patients undergoing high-dose radiotherapy and directed streptozocin inventory toward patients with pancreatic neuroendocrine tumors.^38,39

Lastly, collaborative efforts at the procurement-distribution level involving group purchasing organizations (GPOs), manufacturers, and distributors helped direct limited inventory to high-need sites. Four drugs (capecitabine, carboplatin, streptozocin, and pentostatin), benefited from GPO-led supply-sharing networks that distributed inventory based on historical utilization and clinical urgency.^19,39,40,42

DISCUSSION

Drawing from publicly available sources, this study identified causes of shortage and mitigation strategies for 15 oncology drugs experiencing shortages between 2023 and 2025. Two causes—manufacturing quality problems and dependency on limited sources—affected all the drugs in the study. Additional causes identified were regulatory bottlenecks, over-reliance on global sources, absence of buffer stocks, demand surges, economic disincentives, API shortages, and shelf-life constraints.

Most of these factors align with the categories tracked by the FDA and recorded in its Drug Shortage Database: GMP compliance, regulatory delays, shortage of active (API) or inactive ingredients, product discontinuations, shipping delays, and demand increases.⁶ However, shipping delays, which are included in FDA tracking, were not identified in this study.

The findings are also in line with FDA’s list of root causes of shortages: lack of incentives to produce less profitable drugs, failure of the market in recognizing and rewarding better quality manufacturing, and logistical and regulatory challenges that hinder market recovery after a disruption.¹

Notably, several factors identified in this study—dependency on limited sources, over-reliance on global sources, absence of buffer stocks, and shelf-life constraints—are not part of the FDA’s lists. Although these factors may be monitored by the FDA even if they are not listed, they do provide additional insights into the causes underlying recent drug shortages and therefore could help inform new policies and regulatory actions aiming to prevent or mitigate shortages.

For example, new approaches could be introduced to identify markets dependent on limited sources. More than 80% of oncology drugs experiencing shortages had drug manufacturers exiting the market before the shortage.⁷ Previous estimates suggest that more than 1 in every 4 generics markets has undetected upstream supply chain vulnerabilities where a dependency on limited API sources is obscured by a diversification of the supply chain for finished drugs.⁴³

Monitoring market exits and API diversification would help identify vulnerable markets where incentives to facilitate market entry of new manufacturers are needed. Dependency on single global sources or regions should also be monitored, to identify the types of drugs and therapeutic classes that may require incentives to promote greater supply diversification.

Efforts to create buffer stocks also merit attention. In 2025, the Centers for Medicare and Medicaid Services (CMS) finalized a policy to provide payments to help small, independent hospitals establish and maintain a 6-month buffer stock of 86 essential medicines either directly or through contractual arrangements with drug manufacturers and distributors.⁴⁴ The results of CMS’s new policy should be carefully monitored, as this study suggests that creating buffer stocks could help offset supply disruptions and, if successful, the policy could be scaled up to additional drugs or provider types.

This study also reinforces the importance of stakeholder engagement across multiple levels. At the regulatory level, expedited FDA actions, including emergency importation and shelf-life extensions, were central to recovery efforts. Given that manufacturers must seek FDA approval for most production modifications (e.g., switching API suppliers in the case of a shortage), delays in regulatory response can prolong shortage duration.⁴³ Strengthening administrative and regulatory mechanisms may help accelerate the regulatory response and expedite shortage recovery .

At the manufacturer level, capacity extensions were a critical mitigation tool. International examples, such as Austria’s 2024 investment in Sandoz to increase the domestic production capacity of penicillin, demonstrate how public-sector incentives can address chronic vulnerabilities in essential drug supply.⁴⁵ Similar models—such as grants or low-interest loans—could be applied to oncology drugs at high risk of shortage.

Providers also played a key role in mitigating the clinical impact of drug shortages through strategies such as dose-sparing regimens, therapeutic alternative protocols, and allocation prioritization.⁴⁶ Facilitating timely information-sharing with oncology providers—including updates on shortage status, available alternatives, and prioritization frameworks—could accelerate and harmonize responses.

The role of group purchasing organizations (GPOs) and distributors is increasingly relevant. GPOs are intermediaries through which most hospitals procure pharmaceuticals, devices, and other medical supplies. The industry is highly concentrated with 4 GPOs representing about 90% of the US market.⁴⁷ GPO’s business practices can contribute to drug shortages. GPOs may allow manufacturers to become the sole supplier of a drug in exchange for fees, essentially creating a dependency in limited sources even when multiple manufacturers are available. GPOs typically use proprietary algorithms to allocate inventory according to their contracts with hospitals and pharmacies,⁴⁸ which can exacerbate shortages in areas or facilities with higher demand or in rural hospitals that have low volume. Expanding models of coordinated supply-sharing networks like the ones identified in this study may improve equity and resilience, particularly when combined with safeguards against overdependence on individual manufacturers.

This study had several limitations. First, the review of FDA documents, medical literature, and media sources implemented in this study did not follow systematic review protocols. Second, the factors contributing to or mitigating shortages among the study drugs may not have been recorded in publicly available sources. Together, these limitations suggest that the study may not have captured all the factors and mitigating strategies linked to shortages among the study drugs. Yet, given the general scarcity of information on causes and mitigation strategies of drug shortages, this study contributed new insights on the mechanisms underlying and helping mitigate oncology drug shortages today. Third, data on the effectiveness of the identified mitigation strategies was not available, preventing the assessment which of these interventions tended to be the most successful. Although most drugs in this study were linked to more than one cause of shortage and more than one mitigation strategy, the inter-relations between such factors were not examined. Further research should examine how the various factors may inter-relate in determining the risk of shortages, shortage duration, and response to various mitigation strategies.

A final limitation is that the mitigation strategies examined in this study were all implemented after a shortage—and yet, in many cases, the shortage continued. Clearly more needs to be done given the continued shortages in spite of all the actions. Policymakers should therefore prioritize shortage prevention. Many of the policy targets identified in this study offer pathways for shortage prevention: buildup of buffer stocks or stockpiles, implementing financial incentives for manufacturers to build resilient supply chains, and increasing transparency in the supply chain. Preventive and mitigation strategies should be implemented in tandem to bolster system-wide resilience.

Clinicians and policymakers should find it unacceptable that drugs go years or even a decade in short supply without appropriate resolution. Shortages leave patients in poorer health and overburden providers. Improved monitoring of supply chain vulnerabilities, promoting preventative infrastructure, and engaging stakeholders across regulatory, manufacturing, clinical, and distribution domains are essential to strengthening the resilience of the US oncology pharmaceutical supply.