How to alleviate the shortage: a scoping review of prevention and management of global drug shortages

Abstract

Background

Drug shortages have been reported to lead to insufficient treatment, delays or cancellations in care, poor medication adherence, prolonged hospital stays, increased medication errors, adverse events related to alternative therapies, and even deaths, posing a serious threat to public health. Despite ongoing and substantial efforts to address this issue, many drug shortages continue to persist. Against this backdrop, this study aims to conduct a scoping review of the mechanisms for preventing and managing global drug shortages, to offer insights and recommendations for countries seeking to resolve this pressing problem.

Methods

Seven online literature databases were systematically searched, including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese biomedical literature database (CBM), China Science and Technology Journal Database (VIP), and Wanfang Database, from inception to October 2022. Supplementary searches were conducted using Bing and other public search engines. We included studies that discussed prevention, early warning, or response strategies for managing drug shortages in various countries. Thematic synthesis was used to analyze and categorize the extracted data on early warning and response measures.

Results

Our search strategy retrieved 7,821 references, of which 69 studies published between 2008 and 2022 met the inclusion criteria. The majority of included articles were reviews or systematic reviews (50 studies), providing comprehensive insights into drug shortage prevention, warning mechanisms, and response measures across different countries. Regarding preventive and early warning strategies, interventions at the production stage received significant attention, with regulatory recommendations focused on minimizing the risk of disruption. Regarding response strategies, the literature primarily addressed necessary actions at production, distribution, clinical use, and regulatory levels.

Conclusion

This review underscores the urgent need for an integrated, cross-sectoral approach to drug shortage prevention and response. Strengthening connections across the pharmaceutical supply chain, refining stakeholder incentive structures, and leveraging technological innovations are essential for building systemic resilience. In practice, this calls for the establishment of international data-sharing agreements, investment in real-time monitoring infrastructure, and policy frameworks that balance regulatory oversight with market sustainability.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12889-026-26834-2.

Background

In 1998, the 51st World Health Assembly of the World Health Organization (WHO) proposed the global health strategy of " Health for all by the year 2000”: promoting health equity both between and within countries and enhancing the life expectancy and quality of life for all [1]. Access to essential medicines for treatment fairly and sustainably is a crucial prerequisite for achieving universal coverage of basic health services. Regrettably, the frequent shortage of medicines has become a major obstacle to realizing this goal [2]. Drug shortages have been reported to be leading to insufficient treatment, treatment delays or cancelations, poor medication adherence, increased length of hospitalizations, an increase in medication errors for patients, and adverse events related to the use of alternative therapies, and even deaths, posing a serious threat to health [3–10]. Healthcare systems spend resources to manage or mitigate shortages, which have been estimated to be at least $359 million per year for labor resources and $200 million per year to purchase alternative treatments [3].The serious adverse outcomes, such as patient deaths caused by medicine shortages, have become a severe challenge faced globally [9].

American Society of Health-System Pharmacists (ASHP) Drug Shortages Statistics (January 2001 to December 2024) reported that the number of active drug shortages was 271 in end of 2024, down from an all-time high of 323 in the first quarter of 2024 [11]. However, nearly half of all active shortages (48%) began in 2022 or earlier. French regulators managed 871 shortages in 2018, while there were 769 shortages in the Netherlands. In 2019, Australia prescribers faced critical shortages of 56 medicines, and around 5% of licensed medicinal formulations were unavailable in Belgium [12].It can be seen that many drug shortages persist despite the ongoing and significant resources invested in addressing them.

Although many reviews have summarized the preventive and response measures for drug shortages, some of these studies were not based on systematic searches or double-blind literature verification, and some only focused on a specific aspect of the shortage issue (e.g., early warning) or only included guidelines. This may make it difficult to comprehensively summarize the global measures for addressing drug shortages from the pre-event early warning to the post-event response throughout the entire process. Based on this, this paper hopes to conduct a scoping review of the mechanisms for prevention and management of global drug shortages in order to provide ideas and suggestions for countries to solve the problem of drug shortages.

Methods

Data sources and searches

Seven online literature databases were systematically searched, including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese biomedical literature database (CBM), China Science and Technology Journal Database (VIP), and Wanfang Database, from inception to October 2022. Supplementary search Bing and other public search engines. The search terms used were as follows: medicine shortage, drug shortage, out-of-stock drug, shortage of medicine, and stockout of medicine. The retrieval formula was designed according to the different databases’ retrieval requirements and characteristics (Supplementary appendix 1). We adhered to PRISMA for Scoping Reviews guidelines.

Inclusion criteria

For the breadth of the analysis, we chose to define the scope of drug shortages as drugs that have applied for registration and marketing, with insufficient or unstable supply within a certain period of time or a certain region. Hence, papers were included if they satisfied all of the following eligibility criteria:

1. Contents of literature: prevention or early warning and response strategies for drug shortage management in various countries, the strategies have been implemented in practice, rather than a theoretical suggestion;

2. Research types: original research and review of any type;

3. Papers published in Chinese and English were included.

Exclusion criteria

Duplicate publications or articles with unavailable original texts were excluded.

Selection and data extraction

Three authors screened the literature and extracted data independently. In literature screening, the title of the literature was first read to exclude irrelevant literature. Then the abstract and full text were further read to screen according to the inclusion and exclusion criteria. The decision of inclusion was made after discussion of inconclusive literature. The detailed selection process is illustrated in the PRISMA flow diagram (Fig. 1).

Fig. 1.

PRISMA Flow Chart

A standardized data extraction table was designed through brainstorming and discussion. After literature screening, two researchers extracted the information of the included literature back-to-back, with discrepancies resolved through discussion with the third author. The information included: (1) basic information: title, first author, of publication, country based on the first author; and (2) the links involved in the shortage of drugs, the main body of measures, and the specific measures.

Synthesis and analysis

For the extracted data, the thematic synthesis method was used to summarize the main information of the literature related to the early warning and response measures of drug shortage, and it was included in the literature classification. In this study, the relevant information in the literature will be included to form a table, and the original data from the literature will be extracted. Based on the common theme of the original data, the first-level theme will be summarized. Based on the common themes of the first-level themes, the second-level themes were summarized. Based on the common theme of the first-level theme and the second-level theme, the third-level theme was formed by induction and summary.

Results

Literature characteristics

As illustrated in the PRISMA diagram (Fig. 1), in this scoping review, a comprehensive search was conducted across seven databases using a carefully designed search strategy, yielding 7,821 articles. After screening the titles and abstracts, 492 articles were initially selected, and full-text evaluations ultimately led to the inclusion of 69 studies [2, 13–80], comprising 38 in English [13, 15–51] and 31 in Chinese [2, 14, 52–80]. The publication years for these studies spanned from 2008 to 2022, with a noticeable concentration of publications (11 studies) emerging in 2020.

Regarding the study design, the majority of included articles were reviews or systematic reviews (50 studies), providing comprehensive comparisons on drug shortage prevention, warning mechanisms, and response measures across various countries. In addition, 12 studies employed qualitative methods to explore specific aspects of drug shortage interventions in detail, while 7 studies used cross-sectional designs to provide descriptive or comparative insights into national strategies and institutional practices.

The scope of these studies is broad and globally representative, with drug shortage mitigation strategies documented across multiple countries, including the United States, the United Kingdom, the European Union, Canada, China, Australia, and Pakistan, among others. This geographic diversity enriches the review by allowing for cross-national comparison of measures and facilitating an understanding of both global and region-specific approaches.

Strategies in drug shortage management

According to the included literature, thematic synthesis was conducted from the perspectives of drug shortage prevention, early warning and response measures. Five links of research and development, production, distribution, clinical use, and regulation were integrated.

The studies addressed various measures focused on preventive and responsive aspects of drug shortage management. For preventive and early-warning strategies, a significant focus was on interventions at the production stage, with regulatory recommendations to minimize disruption risks. Regarding response strategies, the literature mainly discussed necessary actions at the production, distribution, clinical use, and regulatory levels. This holistic approach highlights the complexity and interdependence of stakeholders involved in addressing drug shortages, emphasizing the need for coordinated, multi-level interventions to ensure drug availability and accessibility across healthcare systems.

Preventive and early-warning strategies

In research and development (R&D)

In the reviewed studies, preventive or early-warning measures at the R&D stage have been infrequently addressed in the context of drug shortages. Notably, the U.S. government has implemented targeted incentive policies to encourage R&D for drugs vulnerable to shortages, particularly orphan drugs. These policies include a seven-year market exclusivity period, tax credits, research funding support, and fee reductions for regulatory submissions [70, 74]. In the European Union, Article 23a of Directive 2001/83/EC mandates that all relevant stakeholders notify the national regulatory authority at least two months in advance of any anticipated temporary or permanent interruption in supply [40]. In the United Kingdom, an advance notification system is in place for the cessation of pharmaceutical production, requiring manufacturers to submit notifications 12 months prior to the planned discontinuation [58].Such incentives are instrumental in supporting the sustainable development of the orphan drug industry, offering vital support to prevent shortages in this category.

In production

At the production stage, preventive or early-warning measures for drug shortages are primarily focused on the reporting or registering of drugs nearing discontinuation. For example, manufacturers in the United States and marketing authorization holders in the European Union are required to report any plans for permanent or temporary discontinuation, enabling government authorities to assess shortage causes and assist other relevant stakeholders, such as alternative manufacturers, in making timely adjustments to mitigate potential shortages [23, 33, 40, 49, 58, 59, 70].

In the United Kingdom, the Department of Health mandates that manufacturers appoint a designated drug shortage liaison to forecast, evaluate, and report the potential shortages and their impacts [58]. Additionally, some studies reported using risk-based identification methods to detect early signals of production disruptions and predict demand, providing a proactive approach to managing supply chain vulnerabilities [24].

Additionally, in China, a proactive measure to address drug shortages was introduced in 2014 through the “National Essential Medicines Designated Production Pilot“ [57]. Under this initiative, the government selected specific companies via a bidding process to produce small-volume but clinically essential drugs, ensuring their steady supply and reducing the risk of shortages. This program targets essential medicines that are crucial for healthcare yet have limited demand, helping stabilize availability and prevent supply interruptions.

In distribution

In the distribution stage, the role of suppliers and retailers is prominent in preventing or early-warning drug shortages. Key measures include ensuring multi-channel supply options and closely monitoring the shortage signals [25, 37, 50]. For instance, in Canada, the government encourages Group Purchasing Organizations (GPOs) to establish contracts with backup suppliers or require them to have contingency plans, reducing the reliance on single-source suppliers [63]. Additionally, Canada reviews and assesses drug pricing policies to understand and mitigate their impact on drug supply [35, 63].

Wholesale and retail enterprises implement an immediate alert system in Iran for proactive shortage detection. This system collects shortage data and utilizes historical drug usage patterns to predict future demand. Furthermore, formal monthly meetings are held among domestic manufacturers, wholesalers, and retailers to enforce strict inventory control and monitor the supply chain closely, ensuring effective management of drug availability [45].

In clinical use

At the clinical use stage, healthcare institutions and pharmacies play a critical role in implementing preventive and early-warning measures for drug shortages. For example, healthcare providers, patients, and professional organizations serve as key reporting entities in bottom-up drug shortage monitoring systems, as seen in countries such as the United States and the European Union [32, 48, 66]. Pharmacy personnel, in particular, are responsible for verifying suspected or actual shortages and assessing their potential impact. This involves gathering detailed information on affected patients or departments, the estimated duration and severity of the shortage, current usage rates, available inventory, and potential alternative manufacturers or therapies. Equipped with this data, pharmacy staff can collaborate with multidisciplinary teams to formulate effective response strategies, ensuring continuity of care and minimizing the clinical impact of shortages [48].

In supervision

Government-led regulatory initiatives are pivotal in designing system-level frameworks to manage and prevent drug shortages. Key measures include establishing drug supply information management and shortage reporting systems, creating essential medicines lists to ensure baseline supply, and setting up dedicated organizations to monitor, respond to, and assess the shortage signals [18, 24, 39, 41, 42, 55, 67, 80]. Additionally, governments have developed information-sharing channels among stakeholders to improve coordinated responses [2, 42].

Countries like the United States have implemented a shortage-tracking database to support early-warning systems. This database uses data analytics to identify potential shortages by evaluating risk factors associated with production, such as limited active pharmaceutical ingredient (API) or formulation manufacturers and quality defects. Other factors, such as market share, market capacity, and external environmental influences (e.g., natural disasters or regional conflicts), are also incorporated into shortage assessment models to predict and address vulnerabilities in the drug supply chain [67].

Response strategies

In R&D

In response to early signals of drug shortages or new shortage notifications, various governments have implemented proactive measures at the research and development stage to incentivize pharmaceutical production and ensure timely market access. Common strategies involve accelerating regulatory review processes through streamlined evaluation procedures, shortened approval timelines, or special expedited pathways to facilitate the rapid introduction of essential medicines [16, 28, 49, 53]. Additionally, specific regulatory frameworks allow drug shortage declarations to serve as supplementary evidence for new drug marketing authorization, thereby accelerating the approval and distribution of shortage drugs [49]. Furthermore, the United States and Canda have adopted policies aimed at increasing the number of generic drug manufacturers to enhance market competition and bridge the supply-demand gap caused by shortages [2]. These comprehensive strategies reflect concerted efforts to mitigate the impact of drug shortages by optimizing regulatory mechanisms and expanding manufacturing capacities.

In production

Governments worldwide have implemented a range of measures at the production stage to address drug shortages, focusing on capacity adjustments, alternative sourcing, and regulatory interventions. A key strategy involves identifying and facilitating alternative manufacturers to initiate or scale up production of shortage drugs, depending on the urgency of clinical needs and the exclusivity of supply sources [19, 34, 55, 71]. Authorities also assist suppliers in resolving production challenges and, when necessary, engage with additional suppliers to stabilize the market [26, 49]. To further mitigate supply disruptions, governments actively seek alternative active pharmaceutical ingredients and provide technical consultations or recommendations to manufacturers on overcoming production bottlenecks [65].

Country-specific measures demonstrate diverse approaches to enhancing manufacturing resilience. In the United States, regulatory agencies expedite the documentation review for new production facilities and suppliers, ensuring a rapid response to emerging shortages [23]. A national organization in Denmark attempted to mitigate the risk of drug shortage by signing contracts that obligate suppliers to pay compensation for replacement purchases in the event of shortage [29]. Meanwhile, Canada adopts a more flexible approach by allowing manufacturers to produce, use, or sell patented drug versions without negotiating with patent holders when responding to public health emergencies of national concern [18]. These strategies collectively highlight the proactive and multifaceted nature of governmental interventions in securing pharmaceutical production and mitigating supply chain vulnerabilities.

In distribution

At the drug distribution stage, governments and healthcare institutions have implemented targeted strategies to optimize inventory management, ensure equitable drug allocation, and facilitate access to alternative supplies. A primary governmental approach involves refining stock management systems, establishing structured distribution plans for surplus inventory, and enhancing coordination among distributors to mitigate regional disparities in drug availability [23, 27, 38, 47]. In addition, several governments approved temporary imports to supplement domestic shortages or restricted exports of medicines, thereby preventing serious gaps in patient treatment [18, 23, 36, 40, 49]. For countries that regulate pharmaceutical pricing, timely adjustments to pricing strategies are employed as an intervention to stabilize supply and incentivize continued production and distribution [24].

Healthcare institutions are crucial in mitigating supply chain disruptions through proactive procurement strategies. Personnel responsible for drug supply must remain vigilant to fluctuations in the healthcare system’s supply chain, verifying suspected shortages with distributors or manufacturers to inform response strategies and assess institutional resilience. Upon confirmation of a shortage, facilities are required to conduct an immediate stock assessment, estimating coverage duration to guide allocation decisions [21, 23, 30, 55]. Where feasible, collaborative frameworks are established within healthcare networks or across regional institutions, such as inter-hospital coordination, to redistribute scarce resources efficiently [23, 25, 26].

In clinical use

At the clinical use stage, healthcare institutions and professional associations have implemented collaborative strategies to mitigate the impact of drug shortages on patient care. A critical component of institutional response involves strengthening communication with media, national professional bodies, patient organizations, and government agencies to raise awareness of shortages and their potential consequences [15, 17, 28, 56]. Transparent information-sharing ensures that stakeholders remain informed, facilitating coordinated responses and reducing uncertainty among healthcare providers and patients.

Multidisciplinary teams within healthcare institutions play a central role in assessing the clinical implications of shortages and identifying viable alternative therapies. These teams work collaboratively to evaluate substitute treatments, ensuring that proposed alternatives align with clinical efficacy and patient safety standards [13, 16]. Additionally, structured prioritization frameworks are developed to optimize the allocation of shortage drugs, ensuring that patients with the most urgent medical needs receive prioritized access [19, 20, 23–25, 33, 51].

Professional associations further contribute by fostering inter-institutional dialogue, facilitating the exchange of critical information on alternative treatment options, stock substitutions, and restricted drug-use guidelines [26]. By reviewing and standardizing best practices for managing shortages, these associations help healthcare providers navigate treatment decisions with greater confidence and consistency. Collectively, these measures underscore a proactive and coordinated approach to sustaining high-quality patient care amid pharmaceutical supply challenges.

In supervision

In response to drug shortages, governments have established specialized agencies and regulatory frameworks to ensure continuous oversight across the entire drug supply chain. These agencies, such as the FDA Drug Shortage Staff (DSS) in the United States, are tasked with monitoring, coordinating, and addressing drug shortages at the national level [28, 68]. Through these institutions, governments have clarified their roles and responsibilities, ensuring that regulatory flexibility is maintained to adapt to emerging shortages and to facilitate rapid responses when necessary [26, 36, 42, 46, 79]. This includes the enactment of specific legislation, such as the FDA Safety and Innovation Act in the U.S., which mandates the timely reporting of drug shortages and provides regulatory mechanisms to mitigate their impact on patient care [24, 44, 64].

Furthermore, Canada, the European Union, and China have prioritized transparency in shortage reporting by promptly disclosing information on current and resolved shortages through public databases [13, 48]. These databases are essential tools for healthcare providers, enabling them to access up-to-date information on the status of drugs in short supply, facilitating informed decision-making in clinical and procurement settings. By releasing this data in real-time, these regions promote accountability and support proactive management of drug shortages, contributing to a more resilient healthcare infrastructure. These comprehensive oversight strategies underscore the importance of transparency, institutional flexibility, and timely communication in ensuring continued access to essential medicines during times of supply disruptions.

Discussion

By synthesizing evidence from 69 studies spanning 15 years and multiple countries, this scoping review provides a comprehensive synthesis of global drug shortage prevention and response strategies, highlighting the interconnectedness of key stakeholders across drug R&D, production, distribution, clinical use, and regulatory oversight. The findings reveal the characters and reality existing frameworks, emphasizing the necessity for coordinated, multi-stakeholder interventions to mitigate supply disruptions and ensure equitable drug access.

Effectiveness of coordination mechanisms

Current measures to address drug shortages predominantly focus on production adjustments and regulatory interventions, while few policies systematically encourage the development of potentially vulnerable drugs before shortages arise, particularly for those with low commercial profitability but high clinical necessity. Strengthening early-phase interventions, such as targeted funding for essential drug R&D, adaptive regulatory pathways, and risk-sharing mechanisms, could help preempt shortages rather than merely responding to them once they occur.

Drug shortage monitoring systems have been established in some regions, allowing for enhanced visibility and timely supply adjustments. However, the effectiveness of these systems is highly dependent on seamless coordination among regulatory agencies, manufacturers, and distributors. Over-reliance on regulatory mandates without fostering industry collaboration may lead to compliance-driven responses rather than sustainable supply chain resilience. Therefore, a more inclusive governance model that actively involves pharmaceutical companies, healthcare providers, and distribution networks in shortage prevention strategies is essential. Encouraging voluntary cooperation, data sharing, and incentive-driven participation could enhance the adaptability and responsiveness of the overall system.

Balance of interests

The governance of drug shortages involves multiple stakeholders, including regulatory bodies, pharmaceutical companies, healthcare providers, and patients, each with distinct priorities and constraints. While mandatory shortage reporting has improved transparency, concerns regarding regulatory burden, commercial confidentiality, and compliance costs persist.

Technological and regulatory interplay

Advancements in digital technology present opportunities for improving drug shortage management. However, their widespread adoption is often limited by regulatory and infrastructural constraints, particularly in areas with insufficient digital infrastructure or restrictive data-sharing policies. While these technologies have the potential to enhance supply chain transparency and improve forecasting accuracy, their impact is contingent on institutional flexibility and regulatory adaptability. Overly rigid regulations may slow technological adoption, whereas insufficient oversight could raise concerns about data security and reliability. Balancing these factors is essential to leveraging technological innovations effectively while ensuring robust governance frameworks.

Global governance, equity, and ethical considerations

Differences in healthcare infrastructure, regulatory capacity, and economic resources influence the effectiveness of drug shortage mitigation strategies across different regions. Some areas benefit from advanced data-driven monitoring systems and well-established regulatory mechanisms, while others face challenges in securing stable supply chains for essential medicines. Disparities in access to shortage-related information and response resources highlight the need for more inclusive and equitable global drug supply management approaches. Efforts to strengthen international collaboration and facilitate cross-border data sharing could help bridge these gaps and improve collective responses to shortages. Additionally, ethical considerations surrounding equitable access to medicines must be integrated into policy discussions to ensure that commercial interests do not compromise the availability of essential drugs.

Limitations

While this review synthesizes a broad spectrum of literature, certain methodological limitations must be acknowledged. Given that only English and Chinese publications were included, the inclusion criteria may have introduced language bias and may have overlooked insights from other language backgrounds. Additionally, the review focused on identifying existing measures rather than evaluating their effectiveness, leaving the actual impact of these measures across different practical settings unexamined. Future research should prioritize assessing the efficacy of these interventions and include quantitative evaluations to establish causal links, while also considering a broader range of stakeholder perspectives, including those of non-governmental organizations and patient advocacy groups.

Conclusion

This scoping review underscores the urgent need for an integrated, cross-sectoral approach to drug shortage prevention and response. Strengthening interlinkages across the pharmaceutical supply chain, refining stakeholder incentive structures, and leveraging technological innovations will be critical in enhancing systemic resilience. In practice, this calls for establishing international data-sharing agreements, investment in real-time monitoring infrastructure, and policy frameworks that balance regulatory oversight with market sustainability. Moving forward, a more adaptive, evidence-based governance model will be essential to ensuring sustainable access to the medicines on a global scale.

Authors’ contributions

YQS and YN: Methodology, Data analysis, Writing-original draft. ZLN, ZK, DS: Methodology. CJJ, LJF, ZM: Literature screening, data extraction. YQ, HL: Data analysis, ZYZ: Writing-review and editing. HL, ZLL: Topic selection, Writing-review and editing. All authors reviewed the manuscript.

Funding

This work was supported by a project entrusted by the Pharmaceutical Administration Department of the National Health Commission in 2022.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.