Elfi De Weerdt

Causes of drug shortages in the legal pharmaceutical framework.

INTRODUCTION 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Toward a European definition for a drug shortage: a qualitative study.

Background: Drug shortages are currently on the rise. In-depth investigation of the problem is necessary, however, a variety of definitions for ‘drug shortages’ are formulated in legislations, by different organizations, authorities, and other initiatives. For international comparison, the underlying definition for drug shortages is important to allow appropriate interpretation of national databases and the results of scientific studies. The objective is to identify the different elements which should be considered in a uniform definition for drug shortages in the European Union (EU) and to detect the different conditions for reporting drug shortages. Materials and Methods: Definitions of drug shortages were searched in the scientific databases as well as in the gray literature. Similar topics were identified and organizations were contacted to formulate the reasoning underlying the definitions. Results: Over 20 different definitions for drug shortages were identified. A distinction is made between general definitions of drug shortages and definitions used for the reporting of drug shortages. Differences and similarities are observed in the elements within the definitions, e.g., when does a supply problem become a drug shortage, permanent and/or temporally shortages, the typology and time frame of a drug shortage. The moment a supply problem is considered as a shortage, can be defined at four levels: (i) demand side, (ii) supply side, (iii) delivery of a drug, and (iv) availability of a drug. Permanent discontinuations of drugs are not always covered in definitions for drug shortages. Some definitions only consider those drugs used for the treatment of serious diseases or drugs for which no alternative is available. Different time frames were observed, varying between 1 day and 20 days. Conclusion: Obtaining a uniform definition for drug shortages is important as well as identifying which conditions are preferable to report drug shortages in order to facilitate international benchmarking. This paper can be used as a guidance to point out all the different elements which should be considered to formulate a uniform definition to be applied in the EU.

Time spent by Belgian hospital pharmacists on supply disruptions and drug shortages: An exploratory study

Introduction Supply problems of drugs are an increasing and worldwide problem, also in Belgium. Hospital pharmacists try to manage drug supply problems to minimize the impact on patient care. This study aims to quantify in a detailed manner how much time employees of 17 Belgian hospital pharmacies spend on drug supply problems. Methods During six months, employees of Belgian hospital pharmacies filled in the daily time spent on drug supply problems using a template containing all steps which can be executed to manage drug supply problems. Additionally, Belgian hospital pharmacists were asked to report the drugs which experienced drug supply problems together with the solution for this problem. Results Hospital pharmacists spent a median of 109 minutes a week on drug supply problems, with a minimum of 40 minutes per week and a maximum of 216 minutes per week. Fifty-nine percent of the total time spent on drug supply problems was executed by hospital pharmacists, 27% by pharmacy technicians; the rest was performed by logistic or administrative personnel. About one third of the total time spent was invested in gathering information on the supply problem. About two third of the supply disruptions caused drug shortages, meaning there was a need to switch to another (generic) therapeutic alternative. For most drug shortages, a Belgian generic medicine could be found. However in some cases, the alternative had to be ordered abroad or for some drug shortages, no alternative was available. Conclusion These exploratory results on time spent by hospital pharmacists on drug supply problems in Belgium highlight the economic impact of drug supply problems for hospital pharmacies. A fully reliable, daily updated list on the federal agencies websites would be a major help to hospital pharmacists.

Clinical, Economic and Policy Implications of Drug Shortages in the European Union

Drug shortages are an international problem, which seems to worsen. In this paper, the clinical, economic and policy implications of drug shortages are discussed, based on data available for the EU. Research on the clinical impact is scarce. Most data describe that patients will experience more side effects or need to postpone their treatment. However, more detailed research such as case studies and the number of patients affected are lacking. Information on the economic impact is described as an estimation of the time spent by hospital pharmacies. Other stakeholders are also burdened: manufacturers loose part of their profit, patients may pay more for the alternative treatment and society pays for additional health-care costs. However, no data are available. Again more detailed and objective research is necessary to know where the problem is situated and how solutions can be proposed. Policy implications are also rather scarce. However, once more detailed and objective research has been conducted, policy changes will follow. All stakeholders should be involved in the discussions, prior to the implementation of policy measures.

Time Investment in Drug Supply Problems by Flemish Community Pharmacies

Introduction: Drug supply problems are a known problem for pharmacies. Community and hospital pharmacies do everything they can to minimize impact on patients. This study aims to quantify the time spent by Flemish community pharmacies on drug supply problems. Materials and Methods: During 18 weeks, employees of 25 community pharmacies filled in a template with the total time spent on drug supply problems. The template stated all the steps community pharmacies could undertake to manage drug supply problems. Results: Considering the median over the study period, the median time spent on drug supply problems was 25 min per week, with a minimum of 14 min per week and a maximum of 38 min per week. After calculating the median of each pharmacy, large differences were observed between pharmacies: about 25% spent less than 15 min per week and one-fifth spent more than 1 h per week. The steps on which community pharmacists spent most time are: (i) “check missing products from orders,” (ii) “contact wholesaler/manufacturers regarding potential drug shortages,” and (iii) “communicating to patients.” These three steps account for about 50% of the total time spent on drug supply problems during the study period. Conclusion: Community pharmacies spend about half an hour per week on drug supply problems. Although 25 min per week does not seem that much, the time spent is not delineated and community pharmacists are constantly confronted with drug supply problems.

The necessity for a European definition of drug shortages

Drug shortages are a known problem for all stakeholders involved in the pharmaceutical supply chain. However, the term ‘drug shortage’ is not uniquely defined. Different stakeholders use different definitions and even within one stakeholder group, opinions on how to define a drug shortage are inconsistent. This use of different definitions confuses any debate on drug shortages and complicates the comparison of research results. Art. 23a of Directive 2001/83/EC obliges market authorisation holders (MAHs) to report drug shortages to national competent authorities, as drug shortages may result in a temporary cessations of the supply to pharmacies and their patients. National authorities are free to decide how to adapt their legislations to comply with the goals of Directives, leading to different definitions and reporting requirements at national levels. Thus, a direct comparison of the reported drug shortages across countries is impossible, as it is like comparing apples with oranges. To avoid these problems, it is essential to develop a uniform definition for drug shortages and uniform reporting requirements for EU member states. Patients should be the central focus of this uniform definition, but also other potentially affected stakeholders should be considered. Additionally, to prevent and mitigate drug shortages, stakeholders should be able to react as soon as possible. Therefore, we recommend that the European definition of a drug shortage should be applied at the earliest point that a MAH experiences supply problems. This would maximise the time available for national competent authorities (and other involved stakeholders) to react appropriately and thus mitigate the problem or even prevent the drug shortage. Creating a European definition and reporting conditions for drug shortages would be just a first step towards creating a more efficient system for managing drug shortages. For research purposes, we suggest it might be useful to define drug shortages at two levels: ‘drug shortages at supply side’ and ‘drug shortages at demand side’. A drug shortage at supply side is defined at ‘pharmacy level’ and is defined as the situation ‘when the MAH is unable to supply to wholesalers/pharmacies, or when the wholesaler is unable to supply to pharmacies’. A drug shortage at demand side implies a supply problem at ‘patient level’, that is, when pharmacies are unable to supply the drug to patients. This distinction is both interesting and important if we are to understand better complex problem of drug shortages and their ramifications (how many drug shortages at supply side resulted in drug shortages at demand side; what prevented a drug shortage at supply side to result in a shortage at demand site, etc.). In conclusion, to prevent and mitigate drug shortages at European level, it is important to understand them. The main challenge remains creating a single definition so that we can compare national reported drug shortages at a European level, to facilitate our understanding of this complex problem. Whilst the inconsistent definitions of a drug shortage and variation in reporting requirements remain in place, our ability to make recommendations to minimise the effects will be severely hampered, and patients may continue to suffer.

Systemic Measures and Legislative and Organizational Frameworks Aimed at Preventing or Mitigating Drug Shortages in 28 European and Western Asian Countries

Drug shortages have been identified as a public health problem in an increasing number of countries. This can negatively impact on the quality and efficiency of patient care, as well as contribute to increases in the cost of treatment and the workload of health care providers. Shortages also raise ethical and political issues. The scientific evidence on drug shortages is still scarce, but many lessons can be drawn from cross-country analyses. The objective of this study was to characterize, compare, and evaluate the current systemic measures and legislative and organizational frameworks aimed at preventing or mitigating drug shortages within health care systems across a range of European and Western Asian countries. The study design was retrospective, cross-sectional, descriptive, and observational. Information was gathered through a survey distributed among senior personnel from ministries of health, state medicines agencies, local health authorities, other health or pharmaceutical pricing and reimbursement authorities, health insurance companies and academic institutions, with knowledge of the pharmaceutical markets in the 28 countries studied. Our study found that formal definitions of drug shortages currently exist in only a few countries. The characteristics of drug shortages, including their assortment, duration, frequency, and dynamics, were found to be variable and sometimes difficult to assess. Numerous information hubs were identified. Providing public access to information on drug shortages to the maximum possible extent is a prerequisite for performing more advanced studies on the problem and identifying solutions. Imposing public service obligations, providing the formal possibility to prescribe unlicensed medicines, and temporary bans on parallel exports are widespread measures. A positive finding of our study was the identification of numerous bottom-up initiatives and organizational frameworks aimed at preventing or mitigating drug shortages. The experiences and lessons drawn from these initiatives should be carefully evaluated, monitored, and presented to a wider international audience for careful appraisal. To be able to find solutions to the problem of drug shortages, there is an urgent need to develop a set of agreed definitions for drug shortages, as well as methodologies for their evaluation and monitoring. This is being progressed.