Causes Of Drug Shortages Research Articles

Extent of a valsartan drug shortage and its effect on antihypertensive drug use in the Canadian population: a national cross-sectional study.

Background:Drug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada.Methods:We conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period.Results:After the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes.Interpretation:Our findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.

Kebijakan Industri Farmasi pada Masa Pandemi COVID-19

Drug shortages has been global problem since 2000s until now, and it become in serious condition by the presence of the pandemic COVID-19. The main causes of drug shortages were economic and regulation, business problem, manufacture and supply chain. During this pandemic, the main causes of drug shortages are many pharmaceutical industries closures due to quarantine, logistical problems caused by border closure, export bans, quarantine of exporting active subtances and drugs’countries, increased demand and pilling up. However, this problem has been overcome by making policies and good cooperation between governments, regulatory institution and the pharmaceutical industry throughout the world. Several policies like increasing production capacity, restrict quantity of drugs purchased by the public, facilitate the process of industrial license and making a systems such as i-SPOC (Industry Single Point of Contact). It is expected to reduce drugs shortages problem during this pandemic.

Drug shortages in Saudi Arabia: Root causes and recommendations

Drug shortages are a multifaceted problem that has been recurring in Saudi Arabia over the past decade with its significant negative impact on patient care. However, there is a dearth of evidence about possible domestic reasons, if any, behind this recurring problem. Recently, the Pharmacy Education Unit at King Saud University College of Pharmacy has called for a meeting with multiple stakeholders from academia, pharmaceutical care, pharmaceutical industry, purchasing and planning, and regulatory bodies to unveil the root domestic causes of the drug shortages in the Kingdom. Four major topics were used to guide the discussion in this meeting, including: current situation of drug shortages in Saudi Arabia, major factors contributing to drug shortages, challenges and obstacles to improve drug supply, and stakeholders’ recommendations to manage drug shortages. The meeting was audio-recorded and transcribed into verbatim by five authors. The text was then reviewed and analyzed to identify different themes by the first and third authors. Multiple causes were identified and several recommendations were proposed. The main domestic causes of drug shortages that were explored in this study included poor medication supply chain management, lack of government regulation that mandates early notification of drug shortages, a government procurement policy that does not keep pace with the changes in the pharmaceutical market, low profit margins of some essential drugs, weak and ineffective law-violation penalties against pharmaceutical companies and licensed drug importers and distributors, and overdependence on drug imports. The participants have also proposed multiple recommendations to address drug shortages. Policy makers should consider these factors that contribute to drug shortages in Saudi Arabia as well as the recommendations when designing future initiatives and interventions to prevent drug shortages.

Drug shortages in Israel: regulatory perspectives, challenges and solutions

BackgroundPharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients’ wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013–2015, assessing their etiology and exploring the steps taken for their mitigation and prevention.MethodsThe database of the Israeli Ministry of Health (MoH) on drug shortages contains all the DSs recorded in Israel since 2013, detailing the cause of the DS, its duration, steps taken in its’ management and the availability of generic or therapeutic alternatives. Selected examples of DSs from the database are described in this paper in order to identify the causes of DSs, the scope of the problem and possible solutions. Additionally, we have reviewed the recent activities performed by European Medicine Agency (EMA) and the American Food and Drug Administration (FDA) in their efforts to minimize this problem.ResultsSeveral factors contributing towards DSs in Israel were identified, including quality problems in both the final drug product and in the raw materials, upgrades and improvements of the manufacturing process required by the MoH, manufacturing by a sole supplier, dramatic price decrease in off-patent medications causing the manufacturer to discontinue the distribution of the product in Israel, just-in-time inventory control, and others.One of the most important steps in managing drug shortages was identified to be early notification of the shortage by the Marketing Authorization Holder (MAH) to the MoH. In 2013, the Israeli MoH updated the regulation on drug shortages instructing MAHs on their obligation of early notification to the MoH.Furthermore, various steps dealing with marketing withdrawal of drugs and temporary drug shortages are being implemented in Israel, such as suspending any further reductions in drug prices below 17 new Israeli shekels, instructing all MAHs to maintain no less than 1 month supply of all registered and non-registered drugs in Israel and allowing an expedited registration pathway for well-established use/grandfather drugs.ConclusionsDrug shortages pose significant public health hazards worldwide. Early notification to the MoH and open dialog with MAHs are essential for managing DSs and mitigating their impact. Despite the efforts carried out by health regulatory authorities worldwide, DSs still pose a significant threat to public health.

The new regulatory tools of the 2016 Health Law to fight drug shortages in France

Drug shortages are becoming worrying for public health in the European Union. The French public authorities first took action against the causes of drug shortages in 2011 with a law, followed by a decree in 2012 to overcome the dysfunctions of the pharmaceutical distribution channel. These texts would establish emergency call centres implemented by pharmaceutical companies for pharmacists and for wholesalers to inform of shortages, and would oblige pharmaceutical companies to inform health authorities of any risk of potential shortage situation; they would also reinforce the declaration regime of the territory served by wholesalers. Through the Health Law of January 2016, France acquired new regulatory tools in order to fight against these shortages and wanted to target the drugs for which they are the most detrimental: the major therapeutic interest (MTI) drugs. Furthermore, this new text reinforces the legal obligations of pharmaceutical companies and of wholesalers for drug shortages and sets out the enforcement of sanctions in case of breach of these obligations. France’s goal is ambitious: to implement coercive measures aiming at making the actors of the drug distribution channel aware of their responsibilities in order to take up the public health challenge triggered by drug shortages.

Impact of Drug Shortages on Health System Pharmacies in the Southeastern United States.

Drug shortages have become all too common and affect all aspects of the health care delivery system. The increased number of drug shortages has had a negative impact on patient care as well as costly financial implications. This article identifies the current problems and negative outcomes drug shortages have caused and provides a framework for how to best prepare for and combat future shortages. It highlights specific problems faced by health care system pharmacies in the Southeastern United States and the managerial responses to address these shortage situations. A 34-question, multiple-choice survey was distributed to pharmacy directors in North Carolina, South Carolina, Georgia, and Florida. Of 549 surveys distributed, 219 (40%) responses were received. Respondents reported that drug shortages cause 1% to 5% error rates in hospitals and that 60% of the time drug shortages create unsafe conditions for patients and staff. Many of the respondents reported a 300% to 500% markup on medications on the shortage list. Seventy-six percent of institutions have autosubstitutions for drug shortages that have been preapproved by Pharmacy & Therapeutics Committees. The causes of drug shortages are multifaceted, and the safety and financial implications can be costly. In the short term, health care institutions can utilize pharmacists to assist in circumventing the drug shortage problem. The combined efforts of all health care professionals, the US government, manufacturers, and the lay public are necessary to bring awareness and plausible solutions to the drug shortage problems in the long term.

Causes of drug shortages in the legal pharmaceutical framework.

Different causes of drug shortages can be linked to the pharmaceutical legal framework, such as: parallel trade, quality requirements, economic decisions to suspend or cease production, etc. However until now no in-depth study of the different regulations affecting drug shortages is available. The aim of this paper is to provide an analysis of relevant legal and regulatory measures in the European pharmaceutical framework which influence drug shortages. Different European and national legislations governing human medicinal products were analyzed (e.g. Directive 2001/83/EC and Directive 2011/62/EU), supplemented with literature studies. For patented drugs, external price referencing may encompass the largest impact on drug shortages. For generic medicines, internal or external reference pricing, tendering as well as price capping may affect drug shortages. Manufacturing/quality requirements also contribute to drug shortages, since non-compliance leads to recalls. The influence of parallel trade on drug shortages is still rather disputable. Price and quality regulations are both important causes of drug shortages or drug unavailability. It can be concluded that there is room for improvement in the pharmaceutical legal framework within the lines drawn by the EU to mitigate drug shortages.

Critical drug shortages: implications for emergency medicine.

Prescription drug shortages have become increasingly common and more severe over the past decade. In addition, reported shortages are longer in duration and have had a greater effect on patient care. Some of the causes of current drug shortages are multifactorial, including the consolidation of drug manufacturers, quality problems at production plants that restrict the supply of drugs, and a lack of financial incentives for manufacturers to produce certain products, particularly generic medications. Generic injectable medications are most commonly affected by shortages because the production process is complex and costly for these drugs, and profit margins are often smaller than for branded medications. Many commonly used emergency department (ED) generic injectables have been affected by shortages, including multiple resuscitation and critical care drugs. Several reports have shown that shortages can potentially have major effects on the quality of medical care, including medication errors, treatment delays, adverse outcomes, and increased health care costs. Currently, no published data exist outside of case reports that directly link ED-based drug shortages to overall patient safety events; however, there are several examples in the ED where first-line therapies for life-saving medications have been in short supply, and alternatives have higher rates of adverse events, narrower therapeutic indexes, or both. Aside from increasing notification about shortages, the U.S. Food and Drug Administration has little power to coerce manufacturers to produce medications during a shortage. Therefore, ED providers must learn to mitigate the effects of shortages locally, through active communication with pharmacy staff to identify safe and effective alternatives for commonly used medications when possible. Particularly given the effect on critical care medications, therapeutic alternatives should be clearly communicated to all staff so that providers have easy access to this information during resuscitations. This review focuses on the etiology of drug shortages, their effect on the ED, and potential solutions and mitigation strategies.

An audit of drug shortages in a community pharmacy practice

There are no firm data on drug shortages in Irish community pharmacy. This prospective observational study aimed to characterise the drug shortage problem in an Irish community pharmacy. The primary aim was to determine numbers and durations of drug shortages. Secondary aims included comparing these shortages with Irish Pharmacy Union (IPU) drug shortage lists and determining the frequency with which notifications were received prior to shortages. Further secondary aims were to examine relationships between causes of drug shortages and drug costs and between causes of drug shortages and shortage durations. The study took place in a community pharmacy in a Limerick City suburb between October 2012 and February 2013. Data were collected daily regarding drugs that were dispensed, but unavailable to purchase. Suppliers/manufacturers provided data on the reasons for shortages. 65/1,232 dispensed drugs (5.3%) were in short supply over the study period. Median shortage duration was 13 days (interquartile range 4-32 days) and median cost was <euro>8.10. Numbers of unavailable drugs by month varied from 13 to 38. Monthly IPU drug shortage lists identified between six and eight of these shortages depending on the month. Two notifications were received from suppliers/manufacturers regarding shortages. Parallel exports had the highest mean costs (mean <euro>38.05) and manufacturing problems were associated with the longest durations (mean 57.44 days). This study highlights the drug shortage problem in an Irish community pharmacy. We propose that enhanced communication between all stakeholders is the most worthwhile solution. Further studies are needed.

Pediatric Oncology Drug Shortages: A Multifaceted Problem

* Abbreviations: FDA — : Food and Drug Administration WG — : working group The consensus statement by Unguru et al1 concerning national shortages of therapies used to treat children with cancer accomplishes 2 important tasks: it highlights a serious public health threat and proposes steps to address the problem. The working group (WG) has outlined 6 recommendations. All are constructive approaches and, in the case of the recommendations that are within US Food and Drug Administration’s (FDA’s) purview, the FDA has already taken steps to implement actions. The first recommendation (Support Current and Develop Innovative Measures to Prevent Drug Shortages) might be perceived as primarily in the FDA’s purview. Addressing the complex issue of drug shortages continues to be a high priority for the FDA. On October 31, 2013, the FDA released a strategic plan to improve the agency’s response to imminent or existing shortages and to identify longer-term approaches for addressing the underlying causes of drug shortages.2 This plan also highlights opportunities for drug manufacturers and others to prevent drug shortages by promoting … Address correspondence to Dianne Murphy, MD, FAAP, Food and Drug Administration, Office of Pediatric Therapeutics, Office of the Commissioner, 10903 New Hampshire Ave, WO32-5150, Silver Spring, MD 20993. E-mail: dianne.murphy{at}fda.hhs.gov

An analysis of communication-centered policy alternatives to address the anesthesia drug shortage

Provision of safe and effective anesthesia relies on an adequate and uninterrupted supply of anesthetic drugs and drugs used to manage complications throughout the perioperative period. The confluence of regulatory and communication barriers impede the ability of the pharmaceutical industry, government and healthcare institutions to effectively respond to anesthetic drug shortages. These impediments directly threaten the health and safety of patients undergoing surgical and diagnostic procedures in the United States. The most common causes of drug shortages are product or quality issues and manufacturing capacity issues.This paper presents 2 policy alternatives directed towards the most common causes of drug shortages; an FDA-operated stakeholder communication center and a public/private partnership communication center. The feasibility of the 2 alternatives was assessed against 5 criteria including population benefit, ethics and equity, cost feasibility, administrative feasibility and political feasibility. Selection of the most favorable alternative was based on the final score from a decision matrix presenting evaluation criteria weighed against each proposed alternative.The final result reveals the public/private communication center as the most feasible alternative. This is consistent with stakeholder agreement that early, accurate communication and coordination will help mitigate and prevent present and future shortages. Specifically, the public/private center will improve the current state of communication, protect proprietary information and provide stakeholders with information regarding manufacturing, supply, distribution, and business issues encouraging coordination of action to attack the root causes of drug shortages.

History of sterile compounding in U.S. hospitals: Learning from the tragic lessons of the past

The evolution of sterile compounding in the context of hospital patient care, the evolution of related technology, past incidents of morbidity and mortality associated with preparations compounded in various settings, and efforts over the years to improve compounding practices are reviewed. Tightened United States Pharmacopeial Convention standards (since 2004) for sterile compounding made it difficult for hospitals to achieve all of the sterile compounding necessary for patient care. Shortages of manufactured injections added to the need for compounding. Non-hospital-based compounding pharmacies increased sterile compounding to meet the needs. Gaps in federal and state laws and regulations about compounding pharmacies led to deficiencies in their regulation. Lapses in sterility led to injuries and deaths. Perspectives offered include potential actions, including changes in practitioner education, better surveillance of sterile compounding, regulatory reforms, reexamination of the causes of drug shortages, and the development of new technologies. Over the years, there have been numerous exhortations for voluntary better performance in sterile compounding. In addition, professional leadership has been vigorous and extensive in the form of guidance, publications, education, enforceable standards, and development of various associations and organizations dealing with safe compounding practices. Yet problems continue to occur. We must engage in diligent learning from the injuries and tragedies that have occurred. Assuming that we are already doing all we can to avoid problems would be an abdication of the professional mission of pharmacists. It would be wrong thinking to assume that the recent problems in large-scale compounding pharmacies are the only problems that warrant attention. It is time for a systematic assessment of the nature and the dimensions of the problems in every type of setting where sterile compounding occurs. It also is time for some innovative thinking about ensuring safety in sterile compounding.

Drug shortages: Can we resolve that problem?

Although drug shortages have been an issue for several years, based on the unavailability of a number of drugs, 2012 has been the worst year for drug shortages in recent memory. The results of the national survey by Hall et al. published in this issue of the Journal highlight that fact. This increase in drug shortages is due in no small part to the unplanned partial closure of the Sandoz plant (Boucherville, QC, Canada) in early February 2012 and the downstream consequences of such a closure. It would be easy to blame Sandoz for all the problems relating to their poorly planned decision, but there are many factors that help explain why we are in such a difficult situation today. Recent publications have summarized some of the causes of drug shortages, not only in Canada but also in the United-States and Europe. Issues regarding the availability of raw material, especially when obtained outside of North America, can cause disruptions in the manufacturing process. At the manufacturing level, there are problems such as surge capacity limitations, inspection failures, outdated equipment, and voluntary recalls for batches not meeting the standards of good manufacturing practices. When the American Food and Drug Agency tightens the regulatory requirements for drug manufacturing plants that distribute to the USA, such regulations affect Canada when the same plant produces drugs for our market. Business and market factors also affect the vulnerability of the system. Having more and more generic drugs produced by only one manufacturer (also called ‘‘sole source’’ drugs) in Canada decreases alternate options when the manufacturer faces a drug shortage. Large contracts with group purchasing organizations (GPO) also reduce the incentive for other manufacturers to continue producing a drug that has not won an award with the GPO. The Canadian government is also changing some of its regulatory requirements, which is slowing down the approval of manufacturing changes requested by drug companies. The result is a longer time needed to implement improvements and potentially being unable to meet current demand. There are many drugs on the lists of drug shortages in Canada and the USA. On February 24, 2013, the drug shortage section of the Web site for the American Society of Health-System Pharmacists (ASHP) listed 238 drugs that were affected by a shortage. On the same date, the Canadian Web site www.drugshortages.ca listed 282 formulations. These lists are getting longer every year, yet no clear strategy is in place to help reduce or eliminate them. At the Drug Shortages Summit in November 2010, the American Society of Anesthesiologists, the American Society of Clinical Oncology, the ASHP, and the Institute for Safe Medication Practices met to discuss different aspects of the problem and to develop an action plan. The following top three drug shortage difficulties were identified: the absence of information on the duration of a specific shortage, the lack of advance warning of an impending problem, and the absence of information on the cause of the shortage. In Canada, the Sandoz partial closure has put pressure on the provincial and federal governments to improve our regulatory system relating to drug approval. It has also shone the spotlight on an issue that has been growing in recent years but, until recently, was not publicly known. The survey by Hall et al. is significant for the fact that it measured, quite by chance, the impact of the Sandoz partial closure in the early days of the shortage crisis in February M. Bedard, PharmD, RPh (&) Department of Pharmacy, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada e-mail: mbedard@toh.on.ca

Drug shortages: Canadian strategies for a complex global problem

Drug shortages are a complex global problem. Increasingly intricate global supply chains, stricter drug regulations and current economic conditions, have exposed Canadians to greater shortage risks. That Canada represents only a limited share of the global drug market means that all stakeholders—hospitals, shared service organizations, group purchasing organizations, supplier networks and governments—must coordinate their efforts to find an effective market solution to recurring shortages. Based on ongoing collaboration between HealthPRO Procurement Services Inc. and multi-level national healthcare stakeholders, this article examines the primary causes of drug shortages in Canada, with recommendations for ensuring reliable sources of supply. Group Purchasing Organizations (GPOs) are vitally important in this regard. By building contracting processes that support market competition, GPOs can improve the reliability of supply for medically-necessary products, while creating a more flexible procurement strategy that supports competition, leverages innovation, creates value and adapts more readily to volatile global markets and changing patient needs.

Canada falls short on safeguarding its drug supply

Canada falls short on safeguarding its drug supply

Drug Shortages: What Can Hospital Pharmacists Do?

Hospital pharmacists have become accustomed to drug shortages over the past few years. For example, in 2010, 94% of Canadian pharmacists surveyed claimed that they had had difficulty locating a medication during the previous week. A 2010 survey of members of the American Society of HealthSystem Pharmacists indicated that both pharmacists and pharmacy technicians were spending an average of 8–9 h/week dealing with issues related to drug shortages. Furthermore, drug shortages are not limited to North America, but rather are a worldwide problem. The causes of drug shortages are multifactorial and include supply disruptions, changes to regulatory requirements, shortages of raw materials, recalls, government pricing strategies, and monopolization of manufacturing. With the current shortages of Sandoz products (first announced in February 2012), hospital pharmacy managers spend most of their days monitoring the drug supply and working with clinicians to deal with the shortages. The question considered here is, What can hospital pharmacists do to prevent further exacerbation of the human-caused crisis we are currently facing? In this era of globalization, drug manufacturers, like hospitals, are always seeking to save money. One way to reduce costs is the concentration of manufacturing. However, if production within a particular company slows down, the whole world may be affected. In a recent study published by the US Food and Drug Administration, 55 (43%) of 127 shortages were attributed to manufacturing quality problems. Does this sound familiar? What role did hospital pharmacists play in the development of the current situation? Hospitals are mandated to provide high-quality care while saving money. As pharmacy managers, many of us deal with a group purchasing organization, such as SigmaSante in Quebec and Medbuy or HealthPRO in the rest of Canada. These 3 buying groups represent about 90% of the Canadian hospital pharmacy market. So what is the connection between group purchasing and the current drug shortages? It arises from the concept of “winner take all”. Currently, group purchasing organizations put out requests for proposals (RPFs) for a 3to 5-year term, which allows the single supplier chosen to reduce its production costs and submit a lower bid on the next RFP. As an example, assume there are 3 manufacturers of a specific injectable product, drug X. Bids submitted in response to an RFP are assessed, and the contract is given to the lowest bidder, supplier Y. When the next RFP is put forward, supplier Y already has a secure production line for drug X, which allows it to bid at a lower price than the other 2 suppliers. Over time, supplier Y may get contracts with all 3 major group purchasing organizations. At that point, it may no longer be cost-effective for other suppliers to keep producing drug X, because their production costs will be too high, and they will probably stop producing drug X. In this way, trying to save money on hospital drug budgets leads to decreased competition and a situation in which supplier Y is the only manufacturer of drug X. If this supplier’s plant goes “down” for some reason, we are in trouble. In fact, this is what is happening right now! What can we learn from the current drug shortages? The simple answer is that we need to maintain healthy competition in the Canadian drug market to secure the chain of supply of essential drugs. This is not a new concept. For example, the federal, provincial, and territorial vaccine contracting group understood the risk years ago. This contracting group is responsible for nationwide procurement of vaccines. To maintain Canadian manufacturing capacity for the influenza vaccine, the group has been awarding a split contract for many years, giving the majority of the business to the lowest bidder and the remainder to the secondand possibly third-lowest bidders. The split may be 50%–25%–25% if there are 3 suppliers or 70%–30% if there are only 2. This approach ensures that more than one manufacturer is able to maintain a production chain. In contrast, New Zealand had a single-source provider for influenza vaccine

Drug Shortages: Causes and Cautions

Drug shortages have increasingly been a problem for pharmacists and clinicians over the past decade. Clinicians need to be aware of the various causes of drug shortages and the issues that may arise as a result, particularly as they relate to medication safety. Numerous resources and strategies are available to mitigate the effects of drug shortages, and clinicians should work with their health care team and the patient to determine the best option when faced with a drug shortage that affects patient care.