On the 15th of December 2022 the European Medicines Agency announced that almost every EU country was facing medical replenishment gaps. It was known that a harsh winter was ahead for European countries facing both the Covid-19 pandemic and other seasonal viruses that were testing their health systems anew. However, what actually happened this year exceeded all forecasts.
“To be honest, what took place this winter was that European countries were taken by surprise with such a large mismatch between supply and demand, especially for antibiotics”, admits to MIIR Steffen Thirstrup, Health Head of EMA (the European Medicines Agency) – the competent body that guarantees the scientific assessment, supervision and monitoring for medicines safety in the EU.
From 2000 to 2018 there has been a 20-fold increase in recorded drug shortages in Europe. It is like a disease that gets worse every year without – yet – a cure. The war in Ukraine and the energy crisis were used as a convenient excuse in various countries for political leaders to attempt to cover reality. But the problem seems to have other, timeless, causes.
Worse and worse
According to the latest 2022 European Pharmaceutical Union (PGEU) report, all EU countries that responded to the survey (including pharmaceutical chambers and pharmacy associations of 29 countries in Europe) experienced drug shortages in pharmacies in the last 12 months. The majority of countries reported that the situation worsened compared to the previous 12 months (75.9%) or remained the same (24.1%). No country recorded an improvement.
“Medicines shortages are increasing in Europe and have a huge negative impact on patients. They occur across all healthcare settings and involve both essential life-saving medicines and very commonly used medicines. Community pharmacists are very concerned about this phenomenon, which can compromise patients’ health. Moreover, pharmacies and pharmacists invest a lot of resources dealing with shortages which constitutes not only a financial burden, but also a loss of opportunity to spend time with other patient-centered tasks and to improve the quality of care”, Ilaria Pasarani, General Secretary of PGEU, tells MIIR. On average, each pharmacy in the European Union spends 6.3 hours a week looking for missing medicines. In some countries this number reaches 20 hours per week.
“At present the situation is that most European countries are still reporting shortages. This is observed in 28 out of the 30 countries of the European Economic Area. The result would have been the same if you had also asked me two weeks ago,” EMA’s Steffen Thirstrup points out to MIIR.
Which countries record the greatest drug shortages in recent years? Is the data reliable? What are the real reasons and why are we increasingly unable to find the medicines prescribed by our doctor in pharmacies? Which categories of drugs, which active substances are missing, and above all, why are they missing? The answers are not unequivocal, they are often difficult to find and they are not always the same for all countries.
Inhomogeneity in records
At a pan-European level there is not yet a homogenized database recording drug shortages, showing data in real time in the same language. There is not even a definitive European agreement on how a shortage is defined. Several European states have adopted the 2019 definition given by the European Medicines Agency: “A shortage of a medicine for human or veterinary use occurs when the supply does not meet the demand at national level”.
Assessments for the actual duration of medicinal shortages are often difficult to be determined, precisely because of the gaps and inconsistencies in national medical association registries. Many listings do not even provide an (assessed) expiration date for each shortage. Most European countries have only started collecting standardized information on shortages in the last five years. There are also notable differences in the obligations surrounding the reporting of shortages. For example, in Denmark notifications are made only for “severe” shortages, while in Sweden only shortages with an expected duration of more than three weeks are required for notification by the system.
There are countries that do not even provide a registration website, while in others the database includes in parallel human, hospital, veterinary, and vaccine medicines. Furthermore, not all countries publish their data in the same way. For example, the Greek National Organization for Medicines (EOF) does not publish the shortages annually, does not mention the classification of drugs, and does not systematically provide data about the duration of shortages. The lack of standards for recording and reporting shortages hinders information-sharing and comparative analysis between countries.
We asked the European Medicines Agency (EMA) whether it keeps aggregated data for all EU countries, but the answer was negative. Instead, the EMA referred us to the websites of the national medicine’s registries. “Some states have a very detailed network of information collection from community pharmacies and from hospital pharmacies. But not everyone has it to the same degree. Some states have sophisticated IT systems to look at supply and demand, and can therefore respond much more quickly”, EMA’s Steffen Thirstrup explains, hoping this gap will be bridged in the future.
Building our own database
In an attempt to partially fill this information gap, MIIR, together with collaborating media teams from EDJNet, spent a three-month period looking for data and managed to create an updated database on drug shortages in Europe, as homogeneous as possible.
We recorded 22,107 different entries over a five-year period (2018-23) in a total of nine European countries (Germany, Italy, Spain, Slovenia, Czechia, Greece, Romania, Austria, and Belgium), from which it was possible to gather reliable data, either by extracting data from published statistics in the national medicine’s associations or by submitting data requests. In many of the above countries, we traced the Anatomical Therapeutic Chemical (ATC) classification, the marketing authorisation holder, the starting & ending date of the shortage and reasons for it being taken off circulation.
Among the aforementioned countries, when adding up the new shortages for each year between 2018 and 2023, it appears that Italy cumulatively registers the most shortages in absolute number (10,843) for human medicines, quite far from the second, Czechia (2,699), and the third country, Germany (2,355). Greece (389) is the country with the fewest shortages in absolute numbers.
Similarly, 371 vaccine shortages were recorded in the countries under review in the period 2018-23, with Italy leading (144 vaccine shortages), followed by Germany (102) and Czechia (57). Belgium recorded the fewest shortages (8).
However, to observe the absolute number of medicines and vaccines in short supply is not always the best way to draw safe conclusions, given that not all countries keep record of their stocks with the same consistency and the same criteria. In addition, these are different reference populations and countries with different levels of demand, while the different pharmaceutical import-export balance must also be taken into account.
The recording indicator that best describes the situation in each country is the duration of a shortage. In order to find the average duration of shortages in the European countries that we examined, we excluded extreme values by calculating the median. Of the 22,107 drug entries we processed in total, we had data on shortages’ duration for 16,945. Based on these, the European average duration of shortages is 94 days, meaning that it takes about three months for a drug to be back on the market.
From the analysis MIIR conducted on the data collected, it appears that Greece has the longest median duration of shortages (130 days), followed by Germany (120 days) and Belgium (103 days). Czechia may have been second in absolute numbers of shortages, but it registers the shortest amount of time with drugs in shortage (41 days).
The European average of vaccine shortages, again excluding extremes, amounts to 84 days, less than that for medicines. For vaccines, the longest median duration of shortages is traced in Italy (111 days), Germany (68 days) and Czechia (66).
Shortages lasting more than 13 years
The most comprehensive study carried out in recent years on medicine shortages was that of the Technopolis Group consultancy on behalf of the EU (Future-proofing pharmaceutical legislation – study on medicine shortages), which was published in December 2021. In that research, the Netherlands and Portugal turned out to be the “champions” of medicines shortages in 2019 (over 1,600 different drug shortages). In contrast, that year Austria, Croatia, Iceland, and Greece recorded fewer than 100 shortages, relating to 60 or less different medicines.
The same survey ascertained that the average duration across all shortages notices was 137 days and that 66 percent of all shortages were resolved within the first three months. The minimum duration of the shortage was one day, the maximum duration was about 13.5 years (!) and is related to amoxicillin which was in short supply in Spain from September 2005 until March 2019. Amoxicillin is still today among active substances that are missing mostly from the European market.
However, it should be noted that in all nine countries for which data was collected by MIIR and EDJNet, very significant increases in shortages were recorded in 2022 compared to the previous year.
The largest percentage increase in the absolute number of drug shortages from 2021 to 2022 was recorded in Greece. This was perhaps due to previous under-reporting by the Greek National Organisation for Medicines (EOF), as pharmaceutical associations in Greece complain that the real shortages are much more than those declared by EOF.
“The shortages are neither 80 nor 130. They start from 400 and upwards. This is the image I have from running a pharmacy; I don’t care what EOF tells me. I find it reasonable for any government not to want to be exposed. If I were in the position of the respective government, I would do the same. I would call the EOF president and tell him to declare that we have at most 100 shortages. I don’t think you can have an objective view from EOF, its presidents are always appointed by the respective government,” says Konstantinos Lourantos, who has been the president of the Pharmaceutical Association of Attica for 27 years. For this story we contacted and repeatedly sent written questions to the president of the Greek National Registry, D. Filippou, without receiving any answer.
Which medicines are missing?
According to our analysis, in a total of six countries (Germany, Spain, Greece, Austria, Slovenia, Czechia), the drugs missing the most are those related to the neural system (1,718 drugs, 19.0% of the total), such as anesthetics, psychotropics, antidepressants, anxiolytics, antiepileptics, antiparkinsonian drugs, etc.). In second place we find cardiovascular drugs (1,307, 14.5% of all shortages) and in third place the anti-infectives for systemic use, i.e. antibiotics (1,126 drugs, 12.5% of all). On the contrary, almost zero shortages are recorded in the same sample in the category of antiparasitic, insecticides, and insect repellents.
“I have been searching for eight months and have not been able to find my medicine. The pharmacists tell me to be patient, it may come but we don’t know when”, 25-year-old Eleftheria, who suffers from a rare disease, tells MIIR. “They don’t even give me an explanation as to the reason why it suddenly stopped being available, all I hear is that this medicine is imported and that the multinational company that produces it hasn’t sent it,” she adds. As a substitute she takes another drug that does not fully cover her for the condition, and on the advice of her endocrinologist she has adjusted her diet to make up for the substances she lacks. She works as a babysitter in homes taking care of young children. “Especially this winter, I have been told by parents that not only simple medicines, respiratory and antibiotics for viruses are not easy to find, but even a simple serum,” she says.
The impact of Covid-19
All researches point at an increase of the problem, which concerns millions of patients on the European continent. “During the pandemic, but also in the post-pandemic era, with the post-COVID syndrome hitting a large part of the population, the need for medicines and treatments has increased. This fact led to an increase, to a certain extent, of the shortages of medicines”, underlined Ioulia Tseti, CEO of the Tsetis Pharmaceutical Group of Companies and general secretary of the Hellenic Federation of Enterprises (SEV).
But this explanation is not enough. As she explains, “the problems of the supply chain and the dependence of the European Union countries on raw materials from third countries made the problem even more explosive. As well as the fact that countries such as India and China banned the export of raw materials for their own needs. And it is known, when raw materials are scarce the price gets higher. We must not forget that the shortage of raw materials and the increase in energy costs were reinforced by the war in Ukraine, as the (once) rich and sufficient grain silo of Ukraine is a raw material for medicine production. Unfortunately, Europe is dependent on third countries and at some point, it must become independent, acquire sufficiency and self-sufficiency in raw materials.”
The war is not the only one to blame…
The root causes of the problem are the result of different economic, structural or regulatory causes, Ilaria Passarani, general secretary of the PGEU, underlines at MIIR. She herself summarizes these as follows:
- The increasingly globalized nature of pharmaceutical manufacturing, including Active Pharmaceutical Ingredients (API), with production concentrated in fewer sites distributed around the world;
- Shifts in demand, resulting from longer term factors such as demographic change, but also short-term factors such as tendering of medicines leading to difficulties in providing sufficient quantities of medicines for some markets;
- Pricing strategies and regulatory changes that in some cases may have an impact on supply;
- The imposition of fixed quotas of medicines by the pharmaceutical industry, often not sufficient in relation to patients’ actual needs;
- The removal of the traditional role of the full line wholesalers as a result of Direct to Pharmacy (DTP) schemes in some markets;
- The abolition and ineffectiveness of public service obligation/minimum national stock keeping requirements in some countries;
- The lack of priority given to smaller markets;
- The effects of the European internal market dynamics (e.g., exports).
Dependance and friction point
As it turns out, at European level the over-reliance on a small number of suppliers for active pharmaceutical ingredients and other raw materials has made it difficult for manufacturers to meet current demand. China and India together account for more than 60 percent of the world’s supply of active pharmaceutical ingredients in 2020. Parallel exports are often seen by pharmacists and the pharmaceutical industry as part of the problem.
“It is a fact that parallel exports magnify the problem as the more expensive prices of the same products in European countries push pharmacies to export in order to take advantage of their price difference and, by extension, increase their profitability”, Ioulia Tseti, CEO of the Tsetis Pharmaceutical Group of Companies, tells MIIR.
At the same time, however, at the European level, pharmaceutical companies seem to have reduced the stocks they keep in their warehouses. Thus, when a problem occurs in a manufacturing plant, the stocks are not sufficient to meet the needs until the problem is overcome and drug production returns to normal.
“Parallel exports” are a challenging point between pharmaceutical manufacturers and drug dealers, since through them the pharmacies get a part of the profits of the pharmaceutical industry. For this reason, the multinational pharmaceutical companies strictly control the quantities they give to the domestic pharmacies, in order to limit the chances of exporting their products and the loss of profits in developed markets with high prices. All of this encourages any pharmacists who can obtain drugs directly from the companies to do so, even though this happens at an extremely slow pace.
But what is Europe doing to deal with a problem that looks like a difficult balancing act in an industry with huge competing interests? Within the next few weeks, the European Health Commissioner Stella Kyriakidou will submit the long-awaited proposals for the revision of the pharmaceutical regulations, after a long period of dialogue with the pharmaceutical industry, the relevant government authorities, health professionals, the academic community and representatives of patients.
“This dialogue and resulting policy analysis showed that shortages of medicines have become a systemic challenge with numerous vulnerabilities, including the increased complexity and specialisation of supply chains, the lack of geographical diversification of sourcing for certain products and perceived regulatory complexity”, a Commission spokesperson admits to MIIR, adding that the upcoming bill will include “stricter procurement obligations, timely notification of shortages and withdrawals and enhanced transparency of stocks”.
This cross-border data-based investigation was coordinated by the Mediterranean Institute for Investigative Journalism (MIIR) within the framework of EDJNet. Data analysis and visualizations were conducted by Corina Petridi.
The research was implemented between January and March 2023 and seven more EDJNet members participated in it: Deutsche Welle (Germany), Il Sole 24 Ore (Italy), PressOne (Romania), Deník Referendum (Czechia), El Orden Mundial (Spain), Pod črto (Slovenia), BIQdata (Poland).