Assessing the magnitude and nature of shortages
of essential medicines and vaccines
Focus on the WHO European Region
Assessing the magnitude and nature of shortages
of essential medicines and vaccines
Focus on the WHO European Region
ABSTRACT
Access to affordable quality-assured essential medicines and vaccines has been recognized as a crucial element of the solutions to numerous important public health problems in World Health Assembly resolutions. It also represents one of the targets of the Sustainable Development Goals and is essential to achieving universal health coverage.
Unfortunately, availability is not always guaranteed, and more and more countries are facing shortages of essential medicines and vaccines. In order to gain a better, more comprehensive understanding of the national mechanisms in place and of strategies used by countries to mitigate the risk of shortages, WHO developed a survey to assess the extent and impact of shortages across countries and sent it to all Member States in the WHO European Region in 2018. This report summarizes the main findings and considerations arising from the responses.
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iii
Contents
Acknowledgements ...iv
Executive summary ... v
1. Introduction ...1
2. Methodology ...3
3. Findings ...5
3.1 Reponses to the survey ...6
3.2 Definitions of shortages ...6
3.3 Factors associated with reporting of data ...7
3.4 Policy and legislative context ...8
3.5 Reporting mechanisms in place ...10
3.6 Number and nature of reports per country ...11
3.7 Information provided in notifications ...12
3.8 Action taken in response to shortages ...15
3.9 Main communication barriers and challenges ...16
3.10 Examples of best practice ...17
4. Overview of areas for further consideration ...19
Annex 1. National medicines agency or ministry reporting system ...21
Annex 2. Example of a national initiative to address shortages ...24
iv ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES
Acknowledgements
The WHO Regional Office for Europe would like to thank all national representatives who contributed data to the survey on which this report is based. The report was developed by the WHO Regional Office for Europe with support from WHO headquarters.
v ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES
Executive summary
This report was commissioned to support WHO’s work implementing the Sixty-ninth World Health Assembly resolution WHA69.25 of 2016 on addressing the global shortage of medicines and vaccines. It builds on a report that analyses the results of a worldwide WHO survey. Given the particularly high survey response rate from countries in the WHO European Region, this further regional analysis was carried out to examine the structures in place and the mechanisms for reporting on the magnitude and nature of shortages in the Region.
The global survey was distributed in May 2018 through WHO country offices for the attention of national authorities with responsibility for monitoring shortages of medicines and vaccines. The standardized survey tool, in English and Russian, was developed by staff at the Department of Essential Medicines and Health Products at WHO headquarters and included five major sections, covering:
• national mechanisms for reporting
• watch lists or other reference lists
• policies on and actions taken in response to notifications of shortages
• communication strategies
• the medicines and vaccines most frequently affected by shortages.
Questions were designed to offer the opportunity to provide both qualitative (open-ended, descriptive) information and quantitative data. Of the 53 countries in the WHO European Region, 38 responded to the survey.
The survey data collection and analysis and writing of the report were coordinated by the WHO Regional Office for Europe Health Technologies and Pharmaceutical Programme, in partnership with the Vaccine-preventable Diseases and Immunization Programme.
The main themes explored in this report include:
• policy context or legislation framing notification processes
• the number and nature of reports submitted
• information provided in notifications of shortages
• action taken in response to shortages, including best practices
• main communication barriers or challenges.
Reporting of data on shortages was statistically associated with the existence of policies and a mandatory requirement to report, but it was not associated with the existence of relevant legislation. While a combination of legislative, policy and reporting mechanisms was in place in most countries, there was an issue with coherence between the various mechanisms within countries as the systems did not align. Addressing coherence requires a nuanced approach, taking into account the detail of national systems. National and regional stakeholders should share best practices, including those related to strengthening national analytical capacity and supporting coherence along the policy continuum regarding reporting and responding to shortages of medicines and vaccines.
Of the 38 countries in the WHO Europe Region that responded to the survey, 21 provided data on the number of shortages. An additional 10 countries either indicated that they had a mechanism for reporting shortages but did not provide data, or responded that they had no such mechanism but provided an annual number of reports. This apparent discrepancy related to clarity of definitions and to coherence across systems.
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES vi
The number of shortages reported in the previous 12 months varied considerably: the median number of reports per country was 150, with a range from 2 to 7335. The distribution was uneven, skewed towards a small number of reports: around 65% of countries reported fewer than 210 shortages per year. The number of reports did not appear to be associated with market size, but the absence of contextual information on demand, market size or relative risk for both shortages and different medicines made it difficult to assess and fully respond to the impact of shortages.
Countries faced a variety of challenges in providing updates on shortages, include insufficient information to identify the product, and indications of when a shortage started and the time frame. Information is gathered in some but not all countries in the WHO European Region, highlighting the need to understand and address specific bottlenecks based on individual country situations. Further emphasis should be placed on improved data sharing around shortages within regulatory collaborations, including a set of minimum common datasets and definitions.
Good examples of best practice were seen in publicly available reporting systems. The Latvian Regulatory Agency, for example, provides detailed information on shortages on its public website, as well as indications of therapeutic alternatives. Countries with more limited capacity also have communication tools at their disposal, such as web-based medicines registers; these could eventually be expanded to include notices on shortages as reporting capacity increases.
To understand the potential impact of a shortage, countries could consider developing systems further to profile risks for different medicines; they could also strengthen roles and responsibilities for identifying the level and nature of response. Several such mechanisms exist in both high- and low-income countries, including the use of lists outlining the importance of medicines by categorizing vital, essential and necessary (VEN) medicines. For example, Germany uses such a list for vaccines. Countries could, in collaboration with WHO, optimize the use of analytics to predict emerging risks, including the use of alternative data sources.
This report also highlights examples of best practice from several countries, noting how data on shortages are used by stakeholders to put in place mitigation and response strategies. For instance, Ireland has developed a health sector-wide framework response to deal with shortages. Examples for informing and engaging governance mechanisms to prevent shortages also exist at the European Union level, such as the European Commission’s guidelines to avoid shortages during the COVID-19 outbreak.1
Results of the survey, feedback from countries and existing best practices clearly highlight some essential components to address shortages. Advance notification of shortages facilitates risk assessment and allows corrective actions to be taken. Data systems are required; these should be able to flag potential shortages weeks or months in advance. Finally, systems should highlight issues across the supply management process, going beyond reporting of stock levels to include issues with the manufacturing level, with procurement and with regulatory factors.
1 Guidelines on the optimal and rational supply of medicines to avoid shortages during the COVID-19 outbreak. Brussels: European Commission;
2020 (2020/C 116 I/01; https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv:OJ.CI.2020.116.01.0001.01.ENG&toc=OJ:C:2020:116I:TOC, accessed 18 May 2020).
vii ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES
The report suggests the following areas for further consideration:
• assessing and supporting national-level policy alignment around monitoring, reporting and response to shortages;
• expanding consensus around common definitions for key data points to facilitate data gathering, sharing and analytics;
• including data sharing around shortages within regulatory collaborations, incorporating a set of minimum common datasets and definitions;
• regular analysis of the situation across groups of regulators, similar to the European Union’s Heads of Medicines Agencies discussions within the European Medicines Agency;
• sharing of regulatory measures taken to avert or minimize the negative public health consequences of a shortage and promoting collective monitoring of any unintended consequences;
• development of analytics to predict emerging risks (in collaboration with WHO), including the use of alternative data sources;
• developing capacity within responsible agencies to detect and respond to shortages, including strengthening reporting systems;
• developing or using legislation or guidelines similar to those shared by European Union Member States for other countries in the Region.
1 INTRODUCTION
Introduction 1
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 2
This report was commissioned by the WHO Regional Office for Europe, with support from WHO headquarters, as part of a body of work responding to the Sixty-ninth World Health Assembly resolution WHA69.25 of 2016 on addressing the global shortage of medicines and vaccines. The resolution asked the WHO Director-General “to develop an assessment of the magnitude and nature of the problem of shortages of medicines and vaccines”.
In response, WHO organized a global survey of Member States to collect details on existing notification systems and perceptions of shortages of medicines and vaccines.
Given the particularly high response rate from countries in the WHO European Region, a regionally specific analysis was carried out to support the 53 countries in the Region. This report provides an assessment of the situation and the structures in place to report on the magnitude and nature of shortages. It highlights areas for further consideration for national and global notification systems on shortages, including sharing best practice, training and data monitoring. This report complements the global report on the same topic.
3 METHODOLOGy
Methodology 2
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 4
A survey tool was developed by staff at the Department of Essential Medicines and Health Products at WHO headquarters. This was distributed to all WHO Member States through the intermediary of WHO country offices. The survey was completed between May and June 2018 by officials from national ministries of health and national procurement agencies. Those completing the survey included senior policy-makers, pharmacists, coordinators of national extended programmes for immunization, regulatory authorities and staff responsible for central medical stores or national medical supplies.
The standardized survey tool was developed in English and translated into Russian. It comprised five major sections, covering the existence of:
• a national mechanism for reporting shortages, including the components and the frequency of reporting;
• watch lists or other reference lists;
• policies on and actions taken in response to notifications of shortages;
• communication strategies;
• the medicines and vaccines most frequently affected by shortages.
Questions were designed to offer the opportunity to provide both qualitative (open-ended, descriptive) information and quantitative data. Completed surveys were returned by email as PDF documents and were entered into a Microsoft Excel spreadsheet for analysis.
The main themes explored in this report include:
• policy context or legislation framing notification processes
• the number and nature of reports submitted
• information provided in notifications of shortages
• action taken in response to shortages, including best practices
• main communication barriers or challenges.
Where possible, recognizing the limited sample size, statistical analysis was carried out. The dependence between factors was tested using regression analysis to identify which factors were most highly associated with reporting. Example of questions asked for the analysis include:
• Does reporting increase with national income level?
• Is mandatory reporting associated with having legislation in place?
• Are countries that have legislation more likely to have data on shortages?
Descriptive analysis was also carried out, focusing on the qualitative information provided by countries in the survey and augmented by external research. This sought to tease out some explanatory factors, which might indicate:
• the common drivers or contributors within a group
• common challenges or bottlenecks faced
• any stated or inferred data gaps influencing reporting decisions and practice
• best practices and possible sharing across different groups
• unusual or unexpected findings.
Areas for further consideration, including capacity development options, are proposed at the end of the report to promote further discussion among countries in the Region.
5 FINDINGS
Findings 3
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 6
3.1 Reponses to the survey
A total of 45 responses were received from 38 countries of the 53 in the WHO European Region. Six countries completed the survey more than once (for example, submitting separate answers for medicines and vaccines).
Of those responses, 22 were received from the 28 member countries of the European Union(EU),2 and 16 from non-EU countries. The survey results were therefore somewhat skewed by data from high-income countries – and particularly from EU countries, which are members of a common economic and legislative block.
Multiple responses were received from the following countries: Georgia, Germany, Hungary, Romania, Tajikistan and the United Kingdom. Georgia provided three responses; all the others provided two. Responses from these countries were analysed for differences between respondents and merged if possible. Where the responses differed, the nuances between respondents from the same country were examined.
All respondents completing the survey represented a government or official agency: 44% of responses came from medicines regulatory agencies; 33% from ministries of health; 13% from other government agencies, including centres for disease control; 7% from research institutes and one response from a national central medicines store. In line with this, 89% of respondents described themselves as civil servants.
3.2 Definitions of shortages
Recognizing the importance of a common nomenclature, in response to resolution WHA69.25, WHO provided a draft definition of shortages in 2017, taking into consideration both supply and demand components:
On the supply side: a “shortage” occurs when the supply of medicines, health products or vaccines identified as essential by the health system is considered to be insufficient to meet public health and patient needs. This definition refers only to products that have already been approved and marketed, in order to avoid conflicts with research and development agendas.
On the demand side: a “shortage” will occur when demand exceeds supply at any point in the supply chain and may ultimately create a “stockout” at the point of appropriate service delivery to the patient if the cause of the shortage cannot be resolved in a timely manner relative to the clinical needs of the patient.3
The question of defining a shortage came out clearly as a challenge in the global survey responses. As such, the issue was examined further in this regional report. The absence of a common definition – or at least definitions that allow comparison across outputs – makes it difficult to tailor responses. Variability of definitions across countries affected the usability of the information at a national level. More importantly, it also affected the ability to assess situations where a regional market failure could be at play.
The survey responses clearly identified the difficulty of comparing data. For example, Greece indicates both the number of reports and the number of product codes, while Georgia reports on a defined list of essential
2 Note that at the time of the survey in 2018, the United Kingdom was still a member of the EU. It left the EU on 31 January 2020.
3 Addressing the global shortage of, and access to, medicines and vaccines: report by the Secretariat. Geneva: World Health Organization; 2017 (A70/20;
https://apps.who.int/iris/handle/10665/274799, accessed 18 May 2020).
7 FINDINGS
medicines rather than on all products. In other countries, such as Germany and Norway, data regarding medicines and vaccines are reported to different institutions.
Not all countries offered an easily accessible definition of a medicine shortage, and where they did, these did not always align. For example, the Latvian Medicines Agency clearly acknowledges the issue of definition:
There is no definition of medicinal product supply disruption included in the normative acts of Latvia, but in essence it is a situation where none of the medicinal product wholesalers in the Republic of Latvia are able to purchase a medicinal product.4
This particularly highlights the supply side of the problem.
The Irish Health Products Regulatory Agency has set out its own definition of shortages: “a shortage is when the supply of a medicinal product is inadequate to meet the needs of the patient”.5 This is closely aligned with the WHO and European Medicines Agency6 definitions, and highlights the importance of both the supply and demand perspectives when considering the issue of shortages – indicating a need for both supply and demand data.
3.3 Factors associated with reporting of data
Acknowledging challenges in the absence of common definitions, the data were next analysed to identify the factors emerging as the most significant barriers to reporting shortages. Analysis was based on qualitative and quantitative data from the survey, as well as additional information gathered through desk research.
While much of the information was qualitative, requiring descriptive analysis, statistical regression analysis was also carried out on the quantitative data to assess the factors most strongly associated with reporting data on shortages. It should be noted here that the limited sample size and the structure of the survey itself did not allow for very detailed statistical analysis.
The statistical analysis considered the association of reported data against the existence of national reporting mechanisms (p=0.027); reporting of shortages being mandatory (p=0.00002); the country being a member of the EU (p=0.001); World Bank income group (p=0.02 for high-income countries and upper-middle-income countries and p=0.03 for lower-middle-income countries). A negative association was found between reporting of data and income level – that is to say that upper-middle-income, lower-middle-income and low-income countries were all less likely to report data.
It is interesting to note that, statistically speaking, there was an association between the existence of national policies and reporting of shortages (p=0.007) but this did not hold true for the existence of legislation. The existence of national legislation on reporting of shortages was not associated directly with the availability of reported data (p=0.95). The reasons for this are discussed further in the report and relate mainly to the systems
4 Regarding timely reporting of medicinal product supply disruptions. In: State Agency of Medicines [website]. Riga: State Agency of Medicines; 2020 (https://www.zva.gov.lv/en/news-and-publications/news/regarding-timely-reporting-medicinal-product-supply-disruptions, accessed 18 May 2020).
5 Medicinal Product Shortages. In: Health Products Regulatory Agency [website]. Dublin: Health Products Regulatory Agency; 2014 (https://www.hpra.
ie/homepage/medicines/medicines-information/medicines-shortages, accessed 18 May 2020).
6 “A shortage of a medicinal product for human or veterinary use occurs when supply does not meet demand at a national level.” Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders (MAHs) in the Union (EEA). Amsterdam: European Medicines Agency; 2019 (https://www.ema.europa.eu/en/human-regulatory/post-authorisation/availability-medicines, accessed 2 June 2020).
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 8
used for reporting and the public availability of reported data. This highlights the importance of assessing and supporting national-level policy alignment, as well as the importance of strengthening reporting structures and analytical capacity.
3.4 Policy and legislative context
Overall, 25 of the 38 (65%) respondent countries indicated that they have legislation on reporting shortages.
Among these were 17 EU Member States, so EU legislation was examined to identify any tools for notification schemes that could provide best practice information for others in the Region.
Article 81 of Directive 2001/83/EC states:
The holder of a marketing authorization for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered. 7
The Directive requires notification of a shortage to be made no less than two months before the interruption of supply. National requirements may reduce this further. Reports from countries indicate that 11 of the EU countries in this survey either referred directly to the EU legislation when asked about timelines for reporting or referenced the two months stated in the legislation. Seven countries either did not provide a timeline or had a one longer than two months. Most non-EU countries either had no timeline for reporting or one was specified in procurement contracts.
Since the time of the WHO survey, the European Medicines Agency complemented the EU Directive with a guidance note issued in July 2019.8 This includes a definition of a shortage and outlines what should be notified, by whom, to whom and when. It also includes a template reporting form that may serve as a reference for others.
The initial hypothesis for the analysis had been that there would be a correlation between levels of reporting and the existence of both policy and legislation. This was, however, not the case, as indicated in the statistical analysis results in section 3.3. Legislation is important but not sufficient to ensure reporting of shortages.
The authors therefore dug deeper into the issue of coherence across policy components, and noted a general principle that policy-making frequently faces issues with:
• ensuring that appropriate legislation and policies are in place
• coherence across legislation, policy and implementation
• standardized definitions to ensure that comparisons can be made across data.
7 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use; OJ L 311, 28.11.2001:67–128 (https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX%3A32001L0083, accessed 18 May 2020).
8 Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders (MAHs) in the Union (EEA).
Amsterdam: European Medicines Agency; 2019 (https://www.ema.europa.eu/en/human-regulatory/post-authorisation/availability-medicines, accessed 18 May 2020).
9 FINDINGS
The degree of consistency across national legislative, policy and implementation relative to countries’ reporting patterns was examined (Table 1) to find national nuances. This analysis highlights that most countries do in fact have many of the key components already in place. It underscores three issues to consider further:
• a nuanced approach to policy that considers the detail of national systems
• systematic definitions in structures, data and reporting systems
• the implementation of simple, accessible and reliable mechanisms for reporting.
Table 1. Consistency across legislation, policies and implementation on reporting Country World Bank
income group Legislation exists Policy exists Mechanism exists Data are reported
Armenia UMIC Yes Yes No No
Austria HIC No Yes Yes Yes
Belarus UMIC Yes No No No
Belgium HIC Yes Yes Yes Yes
Croatia HIC No No Yes Yes
Cyprus HIC Yes Yes Yes Yes
Czechia HIC No Yes Yes Yes
Denmark HIC Yes Yes Yes Noa
Estonia HIC Yes Yes Yes Yes
Finland HIC Yes Yes Yes No
Georgia UMIC Yes Yes No Noa
Germany HIC Yes Yes Yes Yes
Greece HIC Yes Yes Yes Yes
Hungary HIC Yes Yes Yes Yes
Iceland HIC Yes No Yes Noa
Ireland HIC Yes Yes Yes Yes
Israel HIC No Yes Yes Yes
Kyrgyzstan LMIC No No No No
Latvia HIC Yes Yes Yes Yes
Lithuania HIC Yes Yes No Yes
Luxembourg HIC Yes No No No
Malta HIC Yes Yes Yes Yes
Monaco HIC No No No No
Montenegro UMIC No No No Yes
Norway HIC Yes No No Yes
Portugal HIC No Yes Yes No
Republic of
Moldova LMIC Yes No No No
Romania UMIC No Yes Yes No
Russian Federation UMIC No Yes Yes Yes
San Marino HIC No No No Noa
Serbia UMIC Yes Yes Yes Yes
Slovenia HIC Yes Yes Yes Yes
Spain HIC Yes Yes Yes Yes
Sweden HIC Yes Yes Yes Yes
Switzerland HIC No Yes Yes Yes
Tajikistan LIC No No No No
Turkmenistan UMIC Yes No No No
United Kingdom HIC Yes Yes Yes No
Notes: HIC = high-income country; UMIC = upper-middle-income country; LMIC = lower-middle-income country; LIC = low-income country.
a Where cells are orange, countries may have reporting systems but not provide public reports.
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 10
The national nuances regarding consistency across the policy continuum are particularly important in countries that have all the other parts of the policy process in place. For example, both Denmark and Finland have both policies for reporting shortages and relevant national legislation. Data are gathered and submitted to the national authorities by the marketing authorization holder.9 However, as no centralized system/database exists for reporting, retrieval and analysis of the data may be challenging. Similarly, some smaller countries such as San Marino rely on the systems in place in larger neighbouring countries; their data may therefore have been aggregated into other systems.
3.5 Reporting mechanisms in place
The analysis in section 3.4 highlights the importance of having the policy and legislation framework in place, along with coherence across the policy continuum. It also emphasizes the need to have mechanisms in place to support reporting. While the survey showed that some countries without reporting mechanisms do not provide data on shortages (10 of 13), a detailed assessment of the qualitative responses and supplemental information suggests that many of those countries without mechanisms do in fact gather some level of data (including those with cells coloured orange in Table 1 above). The gaps relate mainly to systems that would produce meaningful information: the mechanisms in place.
The Preamble of EU Directive EC/83/2001 states that:
It is however necessary, in order to control the complete chain of distribution of medicinal products, that pharmacists and persons authorized to supply medicinal products to the public keep records showing transactions in products received.
Thus, in an EU context, marketing authorization holders have a responsibility to ensure the supply of medicines, while pharmacists and suppliers of medicines should have the ability to track volumes. EU Member States should therefore be in a position to gather information on supplies of medicines. Access to such data may be restricted by commercial confidentiality, but the existence of core supply and demand data should allow national authorities and suppliers to have a good overview of supply, from which they can anticipate or identify shortages.
Among the 25 countries with a reporting mechanism in place, 20 (80%) are EU Member States. Three of these (Cyprus, Ireland, Latvia) made explicit reference to EU legislation, while three more (Denmark, Slovenia and Romania) referenced national legislation. Non-EU countries with mechanisms in place included Iceland, Israel and Switzerland (high-income countries) and the Russian Federation and Serbia (middle-income countries).
Among the 10 countries with no mechanism in place, only three are high-income countries, but these share a common characteristic of having very small populations (Luxembourg, Monaco and San Marino) and of frequently collaborating with neighbouring countries on legislative and sanitary mechanisms. The remaining seven countries are located in eastern Europe and central Asia.
Finally, the countries that did not provide an answer to this question include Lithuania, Norway and Turkmenistan.
The multiple answers received from countries such as Georgia and Germany highlighted the nuances across different types of products. In Germany information on vaccines is collected by the Paul-Ehrlich-Institut, while
9 Note: a full list of the websites of regulatory agencies, including the pages where shortages are reported, is included in Annex 1.
11 FINDINGS
data on medicines are the responsibility of the Federal Institute for Drugs and Medical Devices. Information on shortages must therefore be gathered from both or either of the institutes, depending on the question under discussion.
Overall, it is clear that high-income countries are more likely to have a national reporting mechanism than middle- or low-income countries (Fig. 1). Section 3.6 explores what components (data points) are reported by these countries. Consistency across these components could improve comparisons across countries that currently report; it could also aid in creation of guidelines for countries intending to set up reporting systems.
Fig. 1. Existence of reporting mechanism, by World Bank income group
0 5 10 15 20 25
High-income
countries Upper-middle-income
countries Lower-middle-income
countries Low-income
countries Yes No No Response
Note: HIC = high-income country; UMIC = upper-middle-income country; LMIC = lower-middle-income country; LIC = low-income country.
3.6 Number and nature of reports per country
Of the 38 countries in the WHO European Region responding to the survey, 21 (55%) provided data on the number of shortages. The numbers reported in the previous 12 months varied considerably: the median number of reports per country was 150, with a range from 2 to 7335. The distribution was uneven, skewed towards a small number of reports: around 65% of countries reported fewer than 210 shortages per year. Seven countries reported under 100 shortages per year, while three reported between 1000 and 2000 notifications in a similar time period (Fig. 2).
The number of reports does not appear to be associated with market size, but without a reference to market size, patient demand or product risk category, it is difficult to estimate the impact of these shortages.
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 12
Fig. 2. Number of reports submitted by countries (annual)
0 1 2 3 4 5 6 7 8
Number of countries reporng
Number of reports submied
Among the 19 countries indicating both that they have a reporting mechanism and that reporting is mandatory, six (30%) did not provide data on shortages: Denmark, Finland, Greece, Hungary, Portugal and Romania. Once again, however, the nuances are important. In Denmark, for example, reporting is only required for “serious”
shortages, highlighting the importance of definitions. In addition, as indicated above, the reporting mechanism is based on an email system that is not aggregated into a centralized database, thus reducing access to and analysis of such data.
Finally, the following countries either indicated that they did not know whether a reporting mechanism exists or did not answer this question, but they did provide data on the number of shortages: Lithuania, Montenegro, Norway and Romania. The United Kingdom indicated that a reporting mechanism was due to start the year following the survey (in 2019). Germany has reporting mechanisms – for example, information on vaccines is reported to the Paul-Ehrlich-Institut. Shortages there are defined as “an interruption in delivery of a licensed product which is expected to last more than two weeks, or an unexpected, significantly increased demand that cannot be adequately met by the license holder”.10
3.7 Information provided in notifications
The availability and detail of information on shortages varies considerably. Some countries provide very detailed data, easily accessible on the website of the national medicines regulatory agency; others provide no information on shortages at all. Countries were initially categorized into five groups, based on publicly available information on shortages gathered through desk research (Table 2).
A full list of the websites of national regulatory agencies is provided in Annex 1. The European Medicines Agency provides an overview of shortages affecting EU Member States, with a list of ongoing and resolved shortages, which complements national reports.11 Its website also provides links for online registers in several EU countries.
10 Report of suspected supply shortages. In: Paul-Ehrlich-Institut [website]. Langen: Paul-Ehrlich-Institut; 2019 (https://www.pei.de/EN/medicinal- products/vaccines-human/supply-shortages/supply-shortages-node.html?cms_gts=12733774_list%253DdownloadNr_str_sort%252Basc&cms_
tabcounter=2, accessed 28 May 2020).
11 EMA shortages catalogue. In: European Medicines Agency [website]. Amsterdam: European Medicines Agency; 2020 (https://www.ema.europa.eu/en/
human-regulatory/post-authorisation/availability-medicines/shortages-catalogue#ema-shortages-catalogue-section, accessed 18 May 2020).
13 FINDINGS
Table 2. Publicly available information on shortages, by country
Available information Countries
Database of products facing shortage: searchable, with
details Belgium, Croatia, Finland, Ireland, Latvia (not in English),
Spain
• No list of products facing shortage
• Online medicines register
• Reference to shortages (e.g. information on where to submit notification)
Romania, Slovenia, Sweden
• No list of shortages
• Online, searchable database of registered products Armenia,a Austria,a Cyprus,a Czechia, Denmark, Estonia,a Georgia, Greece,a Hungary, Malta,a Montenegro,a Norway, Portugal,a Republic of Moldova, Serbia, Switzerland
• List of registered products (not a publicly searchable
database) but no reference to shortages Germany, Lithuania, Luxembourg, United Kingdom
• No list of shortages
• No publicly available list of registered products Belarus, Iceland, Israel, Kyrgyzstan, Monaco, Russian Federation (site only in Russian), San Marino, Tajikistan, Turkmenistan
a Register is available in English.
An example from a detailed reporting system is given below: Fig. 4 shows a report of a shortage on the Finnish Medicines Agency website. Note that this image was selected for demonstration purposes only as a real post on the website; it may not constitute an active shortage.
Fig. 4. Example from the Finnish Medicines Agency website
Source: Fimea [website]. Kuopio: Finnish Medicines Agency; 2020 (https://www.fimea.fi/web/en/databases_and_registers/fimeaweb?humanmed=true&self care=true&receptmed=true&marketedmed=true&availability=true&prefillonly=false, accessed 18 May 2020).
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 14
In order to monitor, and therefore respond to, shortages a proactive system requires a minimum set of key data points. These include sufficient information to identify the product, an indication of when a shortage started, and an indication of the time frame – either duration or date of resolution (from which the duration can be calculated if the start date is known). It is also critical to be able to investigate the root cause of the shortage. An effective solution to a shortage – whether short, medium or long term – cannot be developed without relevant parties considering the complete details.
This information is gathered in some, but not all countries in the WHO European Region, as shown in Table 3.
Table 3. Time-related data points provided in national systems Start, end, duration and
resolution Start, end and
resolution End or duration and
resolution No report or no information available
• Denmark
• Germany
• Ireland
• Latvia
• Portugal
• Romaniaa
• United Kingdom
• Belgium
• Croatia
• Israel
• Luxembourg
• Norway
• Slovenia
• Spain
• Sweden
• Switzerland
• Austria
• Cyprusb
• Czechia
• Estonia
• Finland
• Greece
• Hungary
• Lithuaniab
• Malta
• Montenegroa
• Republic of Moldova
• Serbia
• Armenia
• Belarus
• Georgia
• Kyrgyzstan
• Icelandc
• Monaco
• Russian Federationc
• San Marino
• Tajikistan
• Turkmenistan
Notes: a Country did not provide information on resolution; b Country did not provide information on end date of the shortage; c Country did not provide reports.
Of the 38 countries in the WHO European Region responding to the survey, 16 reported using a “vital, essential, necessary” (VEN) or similar list to identify which medicines to monitor for shortages: Armenia, Belarus, Finland, Georgia, Kyrgyzstan, Lithuania, Montenegro, Portugal, the Republic of Moldova, Romania, the Russian Federation, Slovenia, Sweden, Switzerland, Tajikistan and Turkmenistan. Among these, four countries identified government-procured or reimbursed lists as a priority for reporting, three identified essential medicines lists and five monitored the supply of vaccines. The survey did not request information on how often the VEN list was updated.
It is important to note that some countries distinguished between notifications of vaccines and medicines, often with a more stringent process for the notification of shortages of vaccines – perhaps as a result of information available from international vaccine support programmes such as Gavi, the Vaccine Alliance.
Such notification requirements are often set out in procurement contracts with individual suppliers.
Similarly, certain countries impose stricter reporting in cases where there is no known or easily available substitute, or where the shortage is likely to result in a therapeutic gap. Other global efforts to review the demand and supply of vaccines include WHO’s Market Information for Vaccines studies12 and the UNICEF Supply Division’s market notes and updates.13
12 MI4A: Market Studies. In: World Health Organization [website]. Geneva: World Health Organization; 2020 (https://www.who.int/immunization/
programmes_systems/procurement/mi4a/platform/module2/en/, accessed 18 May 2020).
13 Market notes and updates. In: UNICEF Supply Division [website]. Copenhagen: UNICEF Supply Division; 2020 (https://www.unicef.org/supply/market- notes-and-updates, accessed 18 May 2020).
15 FINDINGS
3.8 Action taken in response to shortages
All countries except two indicated that they take action in response to notification of shortages. It should be noted that one of the two countries not taking action is a small country (population less than 100 000), with high interdependence on a neighbour; thus, action in the case of shortages would be taken in that larger country.
Responses by countries coalesced around a small number of actions. Two thirds (65%) of respondents indicated they would look for appropriate substitutes, either with the same active ingredient offered by other manufacturers or an alternative with an appropriate clinical indication. A similar proportion stated that they would make use of specific legislation or implement special legislative measures, such as:
• authorizing importing unregistered medicines on a one-time or other limited basis;
• offering exemptions from labelling and packaging requirements, such as language requirements;
• reducing marketing fees;
• expediting registrations.
One third emphasized the importance of communicating with a wide range of stakeholders, and around 20%
mentioned offering guidance to clinicians on alternatives.
Information on alternatives highlights the possibility of a potential “quick win” for many countries and regulatory agencies. In their capacity as regulatory authorities, national medicines agencies have full lists of registered products, allowing unique insight into the current market situation. The Latvian Medicines Agency website, for example, provides an interesting model for consideration: it not only provides information on shortages but also gives a clear indication of any substitutes and their supply situation (Fig. 5). Note that this image was selected for demonstration purposes only as a real post on the website; it may not constitute an active shortage.
Other countries could explore the feasibility of replicating such an approach.
Fig. 5. Example from Latvian Medicines Agency website
Source: Medicinal Product Register of Latvia (https://www.zva.gov.lv/zvais/zalu-registrs/?iss=1&lang=en&q=Daleron&s-CWP=on&ON=Daleron&NAC=on&ES C=on&ESI=on&SAT=on&DEC=on&PIM=on&e-CWP=on&SN=&RN=&AK=&DIA=&RA=&LB=&MFR=&MDO=&IK=, accessed 18 May 2020).
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 16
Germany provides an example of best practice in managing vaccine shortages. The Paul-Ehrlich-Institut, the national regulatory agency, collects and publishes this information, providing a form on its website that can be filled in by pharmacists, doctors and members of the public.14 It engages with the Standing Committee on Vaccination at the Robert Koch Institute to provide guidance on how to manage shortages programmatically.
The Committee’s recommendations15 are linked to each shortage notification published by the national regulatory agency.
It is interesting to note that around 50% of respondents would use an assessment of the importance of a product as the starting-point for action. This response may have been influenced by the design of the survey tool, but it nonetheless highlights the importance of:
• having capacity to assess the risk of the impact of shortages of different medicines;
• having a clear strategy on the capacities needed to implement a response safely and effectively – such as monitoring regulatory flexibilities for alternate sources.
Risk profiles are already familiar for decision-makers in most countries; they include both clinical risks and supply-related risks. Such risk profiles may also take into account associated products and services (such as ventilators, oxygen and qualified staff).
3.9 Main communication barriers and challenges
Over 80% of respondents to the survey indicated that they communicate information about shortages. Most of this was done by posting information to websites, with some additional information sent out to specific stakeholder groups as and when required. Updates were generally posted on a daily or weekly basis, depending on the volume and urgency of notifications. Press releases or media statements might occasionally be used, but this was not commonly cited as a communication tool.
There was a significant difference in approach between most western European or high-income countries and most eastern European countries. Respondents from Armenia, Belarus, Cyprus, Montenegro, the Russian Federation, Tajikistan and Turkmenistan indicated that they do not generally communicate information about shortages.
The most frequently mentioned challenges were adequately describing and identifying possible alternatives, while managing information flows to avoid panic or hoarding. Other issues included getting sufficiently detailed information on the shortage, limited feedback from stakeholders, systems for communication (such as appropriate or centralized information systems), coordinating information and timely provision of information.
While only one person mentioned understanding the impact of a shortage in terms of patient outcomes, this was indirectly referred to in many answers.
14 Report of suspected supply shortages. In: Paul-Ehrlich-Institut [website]. Langen: Paul-Ehrlich-Institut; 2019 (https://www.pei.de/EN/medicinal- products/vaccines-human/supply-shortages/supply-shortages-node.html?cms_gts=12733774_list%253DdownloadNr_str_sort%252Basc&cms_
tabcounter=2, accessed 28 May 2020).
15 COVID-19 in Germany. In: Robert Koch Institut [website]. Berlin: Robert Koch Institut; 2020 (https://www.rki.de/EN/Home/homepage_node.html;jsessi onid=F22F7DCA680D315FA558A92C78750A5C.internet091, accessed 28 May 2020).
17 FINDINGS
3.10 Examples of best practice
The health implications of medicine shortages are clear. Further, the numbers of shortages are growing in frequency and increasing in impact in many contexts, whether high- or low-income. A wealth of information is available, but it is frequently underutilized owing to low prioritization, limited resources or structures that are not well adapted to simplifying reporting and responses to shortages.
This section briefly draws attention to six examples of measures taken to respond to shortages, including one outside the WHO European Region that nevertheless maintains strong technical collaboration with the European Medicines Agency. Similar examples may exist in each of the countries responding to this survey and, indeed, in all 53 countries in the Region. National authorities should be encouraged to explore, document and publish their own best practice case studies.
Heads of Medicines Agencies: addressing shortages
The EU’s Heads of Medicines Agencies network has identified shortages as a priority issue. It provides an overview of the issues, including definitions, and a summary of different best practices and solutions.16
Germany: managing shortages of vaccines
In view of the importance of routine childhood immunization programmes for national public health goals, the Paul-Ehrlich-Institut in Germany monitors stocks and reports on shortages of vaccines. The Institute offers a definition of a shortage of vaccines:
A supply shortage is defined as an interruption of a delivery from the manufacturer to its usual extent or an unexpected significant increase in the demand which cannot be met adequately by the manufacturer, if such a situation is likely to last more than two weeks.
Shortages are reported by the vaccine manufacturer to the Institute, which compiles the information, publishes it on its website, tracks trends in shortages and coordinates information-sharing with key stakeholders.17
Ireland: a multistakeholder framework and case study
Recognizing the increasing frequency and impact of shortages of key medicines in Ireland – notably after some high-profile shortages and incidents of high pricing of medicines negatively affecting access – stakeholders from across all parts of the Irish health sector came together to develop a framework for dealing with medicine shortages.18 This outlines the definition of a shortage, including which products may be concerned and under what circumstances. It also describes the roles of different stakeholders and details the steps to take in reporting
16 Availability of medicines. In: HMA [website]. Langen: Heads of Medicines Agencies; 2020 (https://www.hma.eu/599.html, accessed 19 May 2020).
17 PEI is taking positive stock – four years of commitment for vaccines supply. In: Paul-Ehrlich-Institut [website]. Langen: Paul-Ehrlich-Institut; 2019 (https://www.pei.de/EN/newsroom/hp-news/2019/191015-pei-is-taking-positive-stock-four-years-of-commitment-for-vaccines-supply.html, accessed 19 May 2020).
18 Medicines shortages framework. Dublin: Health Products Regulatory Authority; 2018 (https://www.hpra.ie/homepage/about-us/publications-forms/
guidance-documents/item?id=d21f0b26-9782-6eee-9b55-ff00008c97d0, accessed 19 May 2020).
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 18
and responding to a shortage. The framework may be read in parallel with a case study of a shortage response, addressing a shortage of adrenaline autoinjectors in late 2018.19
Latvia: using existing infrastructure to identify alternatives
As demonstrated in the case highlighted in section 3.7, the Latvian authorities have used existing tools – in the form of the register of authorized medicines database, the website of the medicines authority and shortages reporting mechanisms – to improve responsiveness to shortages of medicines and vaccines. By optimizing the tools at their disposal, they are able not only to flag shortages but also to provide quick and easy access to information on appropriate alternatives, thus allowing clinicians, pharmacists and suppliers to respond quickly to patient needs.
Denmark: a national initiative to address shortages
In Denmark, Amgros, the national procurement agency for medicines and medical equipment for hospitals, started to work with manufacturers and suppliers to decrease the number of shortages. It created a working group and had regular meetings with suppliers and manufacturers to review their performance and to better understand the challenges (see Annex 2 for further details).
United States: averting drug shortages
The American Food and Drug Administration (FDA) has oversight of medicines in the United States and takes the issue of medicine shortages very seriously. The FDA provides a detailed overview of the kinds of actions and responses it can facilitate, and notes that it has successfully intervened to avert shortages since 2011. Since the reporting requirements were put in place, the number of shortages has declined. A total of 50 shortages were notified in 2018, while 146 shortages were averted thanks to this intervention.20
19 Adrenaline autoinjectors (AAIs) – a shortages case study. In: HPRA [website]. Dublin: Health Products Regulatory Authority; 2018 (https://www.hpra.ie/
homepage/medicines/medicines-information/medicines-shortages/adrenaline-auto-injectors-(aais)-a-shortages-case-study, accessed 19 May 2020).
20 Drug shortages infographic. In: FDA [website]. Silver Spring, MD: Food and Drug Administration; 2019 (https://www.fda.gov/drugs/drug-shortages/
drug-shortages-infographic, accessed 19 May 2020).
19 OVERVIEw OF AREAS FOR FURTHER CONSIDERATION
Overview of areas for further 4
consideration
ASSESSING THE MAGNITUDE AND NATURE OF SHORTAGES OF ESSENTIAL MEDICINES AND VACCINES 20
In countries in the WHO European Region, the differences in capacity to detect, investigate and report appear to correlate most strongly with economic status, and in some cases with the size of the market. Members of the EU were more likely to have reporting mechanisms; this also correlated with improved reporting and use of information. While these structures do not apply to all countries, this evidence nonetheless highlights the capacity that exists within the Region to learn from the best practices demonstrated in key elements of these systems.
Results of the survey, feedback from countries and existing best practices clearly highlight some essential components to address shortages, and this report aims to promote further discussion on these among countries in the Region. Recommendations of areas for action that could most readily be explored for future consideration, including capacity development options, include:
• assessing and supporting national-level policy alignment around monitoring, reporting and response to shortages;
• ensuring coherence and consistency across the policy continuum;
• expanding consensus around common definitions for key data points to facilitate data gathering, sharing and analytics;
• developing a template of core components of a national reporting mechanism, including systems for identifying key products where appropriate;
• including data sharing around shortages within regulatory collaborations, incorporating a set of minimum common datasets and definitions;
• regular analysis of the situation across groups of regulators, similar to the Heads of Medicines Agencies discussions within the European Medicines Agency;
• sharing of regulatory measures taken to avert or minimize the negative public health consequences of a shortage and promoting collective monitoring of any unintended consequences;
• developing analytics to predict emerging risks (in collaboration with WHO), including the use of alternative data sources;
• strengthening national capacity to identify alternative products in case of shortages;
• developing capacity within responsible agencies to detect and respond to shortages, including strengthening reporting systems;
• developing or using similar legislation or guidelines on shortages to those shared by EU countries for other countries in the Region;
• engaging relevant national technical advisory mechanisms (such as national immunization technical advisory groups) in policy decisions, dissemination of messages, linkages and referencing;
• authorities taking advantage of technology developments (such as social media tools) to target messaging and engaging with relevant stakeholder groups to optimize engagement around addressing and eliminating shortages.
The number of countries in the WHO European Region that responded to the initial global survey and had publicly available information enabled development of this additional analysis. Availability of transparent information on shortages was considerably stronger than in other regions responding to the survey. Both the global report and this regional report highlight the fact that information on the type and magnitude of shortages at the level of specific products is insufficient. Not enough countries worldwide participate in monitoring and reporting shortages, and availability of data appears to be among the most persistent challenges that all countries need to consider.
