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Abstract
Introduction To protect patients against falsified medicines, countries around the world implement stringent regulations. Despite efforts to protect supply chains in the European Union (EU), authorities continue to find falsified medicine. We studied how in Romania, one of the poorest EU countries, political and economic factors influence the risk of patients being exposed to falsified medicines.
Methods For this case study, we reviewed 131 documents and interviewed 22 purposively selected key informants.
Results In Romania, several politically and economically motivated policies have led to persistent medicine shortages. Following the 2007 accession to the EU, fierce competition led to a decline in domestic medicine production. Soon after, the government introduced a tax on reimbursed medicines to support the national health budget. Prior to the 2015 elections, medicine prices were abruptly lowered to provide voters with the cheapest medicine in Europe. The low prices incentivised traders to buy medicines in Romania and sell them elsewhere in the EU. The high taxes and low prices led manufacturers to withdraw medicines from the market and impose product quotas to limit parallel trading. The accumulated effect of these market responses translated into persistent shortages of essential medicine, which have pushed patients and health professionals to unregulated markets with a high risk of exposure to falsified medicine.
Conclusion Strategies against falsified medicine with a narrow focus on safeguarding quality in the regulated supply are insufficient. To protect patients, governments must also ensure that patients have access to affordable medicines, as shortages provide an opportunity for those selling fake products.
- Health systems
- Health policy
- Health services research
- Pharmacology
- Public Health
Data availability statement
Data are available on reasonable request. Data can be made available on request. Due to the fact that the interviews contain sensitive information (i.e. unethical practices), the interviews will not be disclosed. We worked under an informed consent procedure, whereby the respondents were ensured complete anonymity. The detailed coding structure is available at https://doi.org/10.7910/DVN/CVPSBB. Specific coding queries can be submitted to the first author, AN. The requested results will be redacted in order to ensure the anonymity of the respondents. Additionally we provide a downloadable bibliography of all references reviewed during this research.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Being part of European Union (EU)’s harmonised system of medicine regulation guarantees good quality medicine for Romanian patients from the regulated supply chain.
At the time of conducting the study, reports from private, non-governmental organisations indicated that many Romanian patients were purchasing medicines from illicit sources, which often sold counterfeit products.
The question that arose was: why would patients in Romania step outside the safety of the regulated supply chain and purchase medicine from illegitimate sources?
WHAT THIS STUDY ADDS
European Medicine Agency (EMA) regulations ensure the quality of medicines produced or imported into the region, nevertheless, according to EU rules, medicines are just another commodity that can be freely traded in the EU’s internal market.
Medicine price differences among EU countries lead to parallel trade which, coupled with withdrawal of certain medicine often leads to shortages of essential medicines.
While the regulated supply chain is protected from falsified medicines, shortages lead desperate patients to step out of the regulated supply chain and purchase medicine from illicit sources, thus exposing themselves to falsified medicines.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The findings of this study indicate that regulating the production and distribution of medicines within the EU is insufficient in eliminating the issue of falsified medicine as long as persistent shortages push patients to buy medicine from illicit suppliers. This has implications not just for EU countries, but also for other regional institutions across the globe who are implementing the model set up by EMA in order to ensure the quality of medicine.
Introduction
In many countries, governments implement strict regulations to assure the quality of medicines that reach patients. The European Union (EU) offers an example of how such a system works at a regional level, through its European Medicine Agency (EMA). The Agency’s role is to evaluate marketing-authorisation applications submitted through the centralised procedure and harmonise the work of existing national medicines regulatory authorities in 27 EU Member States. However, even in this highly regulated single market, falsified medicines (defined by WHO, the European Falsified Medicines Directive and this paper as medicines that are deliberately and fraudulently mislabelled with respect to identity, composition or source)1 2 are reaching patients.
Falsified medicines have a long history, but they appear to be flourishing recently through technological developments, including in the printing of packaging and on-line sales. Definitional challenges have hampered a correct estimation of the scale of the problem, but the number of cases of suspected falsified medical products reported to the WHO has been rising.1 3 Many of these products are found on the internet or in informal markets, where regulation is problematic.4 5
Between 2013 and 2018, the European Commission received over 400 notifications of 'falsified’ medicines, which they defined as medicines which ‘may contain ingredients, including active ingredients, which are of low quality or in the wrong dosage—either too high or too low.’6 According to Europol, a wide variety falsified medicine are sold in the EU, including opioids, treatments for heart disease and cancer, psychotropic drugs, as well as performance-enhancing medicine. Every year, numerous illegal websites where such medicine are traded are tracked down and shut down. To strengthen the legal supply chain, the EU has adopted the Falsified Medicines Directive, which introduces harmonised, pan-European safety and control measures that are designed to make it easier to identify falsified medicines and improve verifications and checks and controls at borders and within the EU.
While strict and well-implemented regulations are important to keep poor-quality products out of regulated supply chains, they may not suffice to protect patients from exposure to falsified and substandard medicine procured from unregulated sources, either on the internet or elsewhere. Studies in several countries show that the likelihood of falsified medicine reaching patients is also influenced by market-related factors, especially shortages, which may result from rapid changes in prices, supply chain disruptions, market withdrawals, lack of competition and poor forecasting and inventory management.7–10 These market and planning related factors can lead to problems with the supply of affordable products, which in turn provide an opportunity for those trying to sell medicine through illegal channels. In short, these studies suggest that planning and market regulation may be as important as product regulation in securing the quality of medicines.
In this study, we focus on Romania, one of the poorest EU Member States, which, despite all EU-wide product regulations, still faces the problem that patients are getting exposed to falsified medicines. In 2017, Romania was shaken by a massive scandal of falsified disinfectants that were used in almost every public hospital in the country. The scandal sparked a national debate on health safety and raised concerns about the quality of medical products.6 In July 2017, the first report on medicine procured from online markets that are used by many Romanian patients estimated that around 50% of the drugs sold online are counterfeited.11
It is not clear why, while EU Member States try to ensure the quality of medicine through stringent product regulation, patients in Romania step outside the safety of the regulated supply chain and buy medicines from illegal sources.
The aim in this study is to examine how in Romania, political and economic factors influence the risk of patients being exposed to falsified medicine. The results show that a siloed approach that focuses on ensuring the quality of medicine in the regulated supply chain is not sufficient, as long as poor access to affordable products push patients to buy medicine from unregulated channels.
A better understanding of the factors that contribute to making a country vulnerable to falsified medicine is not just relevant for Romania and other EU member states. Several countries in other regions are currently developing and implementing medicine regulation and market strategies that are similar to the European model. A clear understanding of how product and market regulation interacts and shape the demand for medicine may help identify vulnerabilities and design policies that reduce the risk that patients are exposed to poor quality medicine.
Methods
Study setup and participants
For this case study, we combined literature review and document analysis and in-depth interviews with purposively selected key informants. We define falsified medicines as those which deliberately and fraudulently misrepresent their identity, composition or source, regardless of patent or registration status.
Document review
The Romanian case study was part of a broader multicountry study of political and economic factors shaping markets for substandard and falsified medicines.12 13 To prepare for the study, we conducted a semistructured literature review to gather an overview of the factors that increase the risk of substandard and falsified medicines to reach patients. For the general background information, search engines such as PubMed, MEDLINE, the WHO Essential Medicines and Health Products Information Portal and Google Scholar have been browsed for articles containing the keywords “falsified”, “substandard”, “poor quality” and counterfeit in combination with “medicine(s)”, “medical products”, “pharmaceutical”. The resulting publications were subjected to an interpretative review, a method of synthesising the results which involves both induction and interpretation of data. The primary concern of this method is to develop theories that integrate the concepts. The initial literature review for this study produced a coding structure centred on factors that created a market opportunity for poor-quality medicines, as well as factors that motivate, facilitate, or deter their production or trade.
The second part of the literature review focused on understanding Romania’s political and economic landscape in relation to medicine production, procurement and distribution, in relation to its EU membership and what that entails. As the reading progressed, the coding structure was refined in order to include specific concepts that impact medicine production and procurement in Romania such as ‘price referencing’, ‘claw-back tax’ and ‘parallel trade’. Documents analysed included academic articles, technical reports, regulations and press reports related to medicine production, procurement, pricing and quality assurance from government, EU and WHO sources, relating both to Romania and more global settings. We also reviewed records related to Romania’s political and economic landscape and its EU membership. Documents were coded using NVivo V.11, a qualitative data analysis computer software. As the reading progressed, two authors (A-LN and EP) refined the coding structure in order to include specific concepts that impact medicine production and procurement in the Romanian context, including issues related to EU membership.
Interviews
Interview participants were purposively selected for their knowledge of different aspects of the regulation, production, trade and use of medicines in Romania. We aimed to include medicine regulators, employees of multinational and Romanian pharmaceutical companies, medicine distributors, retail pharmacists, doctors, patient organisations and investigative journalists. The first author identified and contacted potential interviewees by email, phone or LinkedIn. Potential participants were provided with detailed information about the study purpose and confidentiality procedures, as well as an outline of interview topics. Those that agreed to participate provided written consent (see the Results section, table 1 for details).
Interview participants
Using a topic list (see online supplemental annex 1), the first author (A-LN) conducted interviews in person between January and March 2018. Most were conducted at the respondent’s place of work or in a public place. Interviews were conducted face to face in Romanian language and lasted between 35 and 125 min. The interviews were recorded (21 out of 22 respondents). In the one case where permission to record was not granted, detailed notes were taken during the interview. Additional field notes on contextual factors prior, during or after the interviews were kept in a logbook.
Supplemental material
Full details of our methods reported following COnsolidated criteria for REporting Qualitative research criteria, together with topic guides and coding tree, can be found in our study archive.12
Data analysis
The interviews were transcribed verbatim and translated to English. Interviews were coded iteratively by the first author (A-LN) against the structure developed during the literature review; another author (EP) coded a subset of interviews in parallel—differences in coding were discussed until a shared understanding was reached. Key themes and concepts found across multiple documents and transcripts were recorded by A-LN and EP. Themes identified in early interviews were verified either through other interviews or by comparison to documents. The resulting data were used to map the interaction between national and regional regulation, and the outcomes in terms of medicine availability and quality.
The preliminary findings were presented and discussed in April 2018 in London, at the Wellcome Trust with invited experts from WHO, Médecins sans Frontiers, Wellcome Trust, Erasmus Rotterdam, Oxford University and the London School of Hygiene and Tropical Medicine. The preliminary results were presented at a conference on medicine quality organised in Oxford in September 2018.14
Results
We identified and coded 131 documents that were directly relevant for this case study. A total of 36 individuals were approached for interview, and 22 participated. Table 1 shows the occupations of both groups. The participants who refused were predominantly key individuals working at that time at the Ministry of Health or Technical/Reimbursement Agencies, as well as pharmaceutical companies representatives.
In the remainder of this section, document references are given for findings arising from the literature review. Other findings come from interviews.
Transitioning from communism
Romania’s centralised social health insurance system was decentralised after the fall of communism in 1989.15 While the percentage of good distribution practices (GDP) allocated to healthcare increased significantly, it continued to be underfunded compared with its European neighbours.16 Simultaneously, state subsidies for local pharmaceutical producers were eliminated, and medicine production fell dramatically.17
In 1997, social health insurance became mandatory for all Romanians, with some groups (eg, the retired) exempted from paying insurance contributions. The system has since 2002 been administered by CNAS (the Romanian acronym for National Health Insurance House), a central quasi-autonomous body. Insured citizens are legally entitled to receive a basic benefits package that includes health services and the reimbursement of medicine and medical device costs.
The benefits package and the conditions for service delivery are laid out in a yearly framework contract proposed by CNAS, agreed by the Ministry of Public Health and approved by the government.15 CNAS initiated a nationwide electronic tender process, through which hospitals and other public health institutions could procure medicines at the approved prices, which are published in national catalogue and on the Ministry of Health website.18 The price of medicines that are dispensed in pharmacies without a prescription, or for medicines not listed in the catalogue, is freely set by the manufacturers.19
Joining the EU
When Romania joined the EU in 2007, its pharmaceutical manufacturers were obliged to adhere to EU regulations concerning good manufacturing and GDP (see figure 1). Some local producers were unable to make the investment needed to upgrade facilities to meet these stringent regulations; others could not absorb the resulting increase in production costs, which averaged 34%. Around 40 companies were pushed out of business.17
Timeline of key events. GDP, good distribution practice; GMP, good manufacturing practice.
In 2009, the Ministry of Health set the price of reimbursed medicine at the minimum of their prices in 12 European countries: Austria, Belgium, Bulgaria, Czech Republic, Germany, Greece, Hungary, Italy, Lithuania, Poland, Slovakia, Spain.20 21
A 2006 law dictated that these prices should be reviewed annually, based on changes in the market as well as exchange rate fluctuations. Typically, the average price of medicines within the EU drops by at least 7.1% between 6 months and 3 years after they are first authorised for sale in Europe,22 so annual revision would imply a fall in prices in Romania. However, despite repeated political promises, no price review was undertaken in Romania until 2015. As prices fell elsewhere, Romania was soon in practice paying more than richer European countries were for many medicines.23
The 2008 economic recession and governmental response
As the global economic recession begun to engulf Europe in 2008, public funding in Romania was deeply affected. Romanian authorities implemented an ample programme of cost containment in health. Fee-for-service payments to health providers was replaced by payment by diagnostic group. Rather than reimbursing medicines by prescribed active ingredient, CNAS reimbursed for the cheapest drugs in a therapeutic class. Less overt cost containment measures included late payment of suppliers and a reduction of medicines that were on the prescription list.24
Finally, the government in 2009 introduced a ‘claw-back’ tax on medicines reimbursed by CNAS.25 26 This caps the profits market authorisation holders can make on reimbursed medicines, requiring them to return any additional profits to the Romanian state. Controversially, profit margins added by distributors and pharmacies were included in calculations of ‘profits’, increasing the tax burden on market authorisation holders. The tax was announced in 2009 and implemented in 2011 as a temporary measure to alleviate pressure on the health budget.25 However, in 2022, it is still in place.
Political promises for the lowest price
Aware that prices in Europe were dropping faster than they were in Romania, the Social Democratic party (PSD) rose to popularity in the 2012 legislative elections with promises to restore medicine prices to the lowest levels in Europe.27 PSD was and still is the largest social democratic political party in the country and the largest overall political party in Romania. Although PSD won the elections, they took no action until 2015, just months before the next legislative elections. It was only then that the Minister of Health finally ordered the updating of reimbursed medicine prices from their 2006 levels.28
It was a political ploy every time. Historically in Romania, the first category of voters is retired people. So, elderly people who, unavoidably, consume most drugs. And then the political stakes are given by cheaper drugs. Every electoral campaign has so far had the issue of cheaper drugs. (Multinational Manufacturer)
Prices dropped by 16%–25% overnight.29 The party that implemented the price revisions retained power, but the dramatic fall in prices had knock-on effects across the Romanian medicine market.
Pharma industry response to squeezed profit margins
Interviewees explained how the medicine pricing policies, coupled with a regressive claw-back tax, led to several responses: bankruptcy; market withdrawal of unprofitable medicines (in particular cheap generics); and the parallel trade of innovator medicines. These in turn led to overall medicine shortages.
Insolvency and price rises
In Romania as in other countries, manufacturers and distributors commonly sell medicines to large clients at a discount to the list price, reducing actual spending on medicines in the health system, (especially for innovator medicines not covered by public auctions). Faced with the claw-back tax on public insurance medicines, manufacturers reduced these discounts, raising prices for all clients. Others went out of business.
When this tax was introduced there was a major change in terms of behaviour of the producer and distributor, and of the people who work here. So, after it was introduced and 2–3 months after discounts disappeared from the market or decreased, companies merged, people were laid off. So the impact was felt very fast. (Technical Agency Advisor)
Medicine withdrawal
A more common response to the squeeze on profit margins from local manufacturers was to stop manufacturing unprofitable products—mostly low-cost generics which are the bedrock of the public health system. Importers also stopped supplying these products. In 2017, the Association of Generics Medicine from Romania estimated that more than 2000 (of around 6200) medicines completely left the Romanian market since the price revisions of 2015.30 One interviewee explained why:
Authorities [explaining supply interruptions] say 'no, no, you've had production problems'. But the truth is that it’s very simple to explain the decision not to produce a drug as long as it brings you losses.’ (Technical Agency Advisor)
Companies, especially those with substantial sales in higher-priced markets, also started withdrawing higher-value medicines from Romania, or cancelling product launches because they were concerned that other countries might point to the very low Romanian prices, and benchmark their own offers at similarly low levels.31
Parallel trade
Under EU law, medicines may be traded freely between countries. This allows wholesalers to buy medicines in a member state where medicine prices are low, and sell into another member state where medicine prices are higher—a practice known as ‘parallel trade’. In the case of innovative medicines, the price difference between Romania and more affluent countries like Germany or the Netherlands created arbitrage opportunities for distributors and drained medicines out of the Romanian market. The situation was aggravated by manufacturers, who sometimes restricted supply of medicines (especially higher-value products) to the Romanian market to avoid fuelling parallel trade, which benefits middle-men rather than producers.
Commenting on the fallout of politically motivated medicine pricing policies, one manufacturer said:
If you ask someone: do you want to buy cheaper drugs? Of course, they say yes, everyone wants this. But this has unwanted side effects. One of them is parallel export. And the second is the withdrawal of some medication from the market because it goes below the profitability threshold set by the company and the only solution is to withdraw the drug. (Multinational Manufacturer)
Consumer responses to medicine shortages: unregulated sourcing
The market responses described above, coupled with manufacturing issues which also lead to the temporary unavailability of certain medicines, have led to several medicine shortages over the past 10 years.
Healthcare providers and patient representatives said that when they could not get medicines from regulated sources, they sought them elsewhere. One of our respondents, a healthcare provider described procuring vials of magnesium sulphate with no expiration date on them for his patients, via a former patient who smuggled them in from abroad. A 2015 television documentary, The Network, describes an employee at the Minister of Finances (who later became Minister of Health in 2016 and 2020) setting up an informal buyers' club through which Romanians travelling abroad volunteered to carry medicines back for patients at home.32–34
According to a July 2018 report, oncology medicines were among the most affected by shortages caused by the price drops of 2015 and other reforms.35 A year earlier, the first report on medicines procured from online markets in Romania estimated that around 50% of the drugs sold online are counterfeited. The report which was conducted by Media Kompass, a Romanian healthcare company that focuses on regulatory affairs and pharmacovigilance, indicated that Romanian patients were purchasing medicines from illicit sources.11
A patient representative described buying cancer medicines online:
Patients buy medicines from the internet, and the majority of them do this in full knowledge [of the risks], because the state does not provide them with a treatment in time. They are desperate and take the risk and buy medicines from wherever they can. Desperation pushes them into consciously aggravating their own situation, because is it known that many of these meds are fakes. I met patients that ingested chalk, chalk that was made to look exactly like a pill, or medicinal charcoal, in various forms and packages. And they bought them online. And also, around the corner from the hospital. And the saddest thing is that this trade also takes place next to the oncology institute. (Patient Advocate)
Policy responses to medicine shortages: ad hoc and incomplete
Respondents said that policy responses have tended to be ad hoc, or only partially implemented, in part because of very high turnover of governments and ministers.15 Since 2007, Romania had 22 different Ministers of Health. In 2017–2018 alone, there were three governments and two Ministers of Health.36 In an attempt to limit shortages caused by parallel trade, the government in 2016 required producers, distributors and pharmacies to report medicine stocks daily. This should allow authorities to invoke provisions in EU law that allow governments to ensure that the national demand for medicines is satisfied before any surplus can be exported.37 However, even respondents within national technical agencies were unable to say whether the data were ever analysed or acted on.
When reports surfaced in late 2017 of a critical shortage of immunoglobulin products following withdrawal of the products from the Romanian market, policy-makers resorted to imports through a special needs acquisition system which is used in cases of emergency, also providing relief from claw-back tax for these products.38 Similarly, a special needs import programme was eventually put in place for magnesium sulphate, but only after media attention to the longstanding shortages had reached a critical point.39 Respondents said the structural problems underlying these shortages remained unaddressed.
Discussion
This study looked at how national price regulation, in the context of regional medicine regulation and the EU single market, influences the risk of patients being exposed to falsified medicines, by focusing on the situation in Romania, one of the poorest EU member states.
The results show how a combination of politically and economically motivated policies have led to persistent problems with the availability of essential medicines. After accession to the EU in 2007, fierce competition and EU quality requirements led to a rapid decline in domestic drug production. Starting in 2009, the government levied a tax on reimbursed medicines to support the national health budget, making the Romanian market less attractive for producers and distributors. In the run-up to the 2015 elections, medicine prices were abruptly lowered to provide voters with the cheapest medicine in Europe. The low prices and free movement of goods in the EU market made it attractive for traders to buy medicines in Romania and sell them at a profit in other EU countries. Due to the low prices and high taxes in Romania, foreign manufacturers took medicines from the local market or imposed product quotas to limit unwanted parallel exports. The accumulated effect of these market responses, combined with a lack of sector-wide planning, translated into persistent shortages of essential medicine. Shortages in legal channels have pushed patients and health professionals to unregulated informal markets with a high risk of exposure to falsified and substandard medicine.
The findings of this study indicate that, while important, a narrow focus on tightly regulating the production and distribution of medicine is not sufficient to eliminate falsified medicine. To prevent exposure to poor quality medicine, governments, at multiple levels, need to collaborate and ensure that patients have effective access to affordable medicine.
In almost every market, the quality of medicines is regulated by a specialised authority, which also controls access to the market through product authorisation. In the EU, this function is mostly performed by a regional body, the EMA, in collaboration with national authorities. Trade in commodities is also regulated regionally, through the single market. Broadly speaking, therefore, once authorised by the EMA, medicine may be freely traded throughout the bloc. National governments, however, generally control access to the public sector market through national formularies or procurement practices.40 The price of medicines, especially in the public sector, may also be regulated. In most countries, including those of the EU, price regulations are set at the national level, according to a country’s budget, needs and political priorities.
The Romania case study demonstrates the pitfalls of this situation. Romanian politicians seeking popular approval promised the cheapest medicines in Europe. But they had to implement the cost and profit-control policies to deliver on that promise within the context of a single market, where sellers are free to offer to the buyer that yields greatest profit. The populist pricing strategy undermined the domestic pharmaceutical industry, and drained medicines away into other, higher-paying EU countries, leaving Romanian patients short of medicines and exposed to informal suppliers.
The measures taken by the politicians have been ad hoc, focusing on rapidly bringing down prices, without a clear strategy for ensuring access to affordable medicine in the long term. For example the claw-back tax which was introduced in 2009 was supposed to be a temporary measure that would alleviate the national budget. However, 13 years later, it is still in place. In 2020 the claw-back tax has been capped and differentiated across three categories of drugs which alleviated the financial burden from Romanian medicine producers, but not for foreign producers.41 42 In 2022, the Romanian Association of Generics maintains that the claw-back tax, along with the policy of having the lowest medicine price in Europe represent a burden for the generic producers and ultimately do not benefit patients.43 44
The EU wants both the free movement of medicines in the internal market and equal access to medicine for EU citizens. As long as countries within the EU continue to set medicine prices at different levels, these two goals are contradictory, because medicines will generally flow to higher-paying markets. This may restrict access in lower-paying countries. Countries such as Bulgaria45 or Poland46 equally face medicine shortages, which can be traced to low health spending per capita, pricing policies47 and parallel export.46 One study comparing prices for cardiovascular diseases in Romania and Bulgaria revealed that while both countries joined the EU19 and have been following EU regulations, there are significant differences in patient co-payment, producer and retail prices, due to the fact that the price for medicines is decided as a matter of national policies. What makes Romania particularly vulnerable is that medicine prices are set at the lowest among other EU countries with similar socioeconomic profile. Furthermore, its specific political climate rife with instability and a lack of a long term systemic perspective is not helping to ensure that essential medicine are both available and affortable.
Different options for addressing the problems caused by parallel trade have been formulated, such as the exclusion of pharmaceuticals from the internal market rules and unitary pricing in the EU.48 However, each of these options causes other issues such as increasing medicine prices in some countries and reducing the bargaining power of the distributors when dealing with pharmaceutical companies. In addition to further research into the benefits and problems that result from parallel trade, a political debate is needed on what trade-offs should be made.
This case study shows one of the demonstrable downsides of parallel trade in the current situation: the risk of shortages in ‘cheap’ markets. If patients are able conveniently to access the medicines they need for free or at prices they can afford in the regulated supply chain, they are likely to do so. If there are shortages of affordable medicines in that supply chain, however, patients may turn their need (and their increasing familiarity with online shopping) into an opportunity for falsifiers. Because necessary medicines were not available through mainstream channels, Romanian patients and health professionals purchased medicines from unregulated sources, both online and through informal markets, increasing their risk of buying falsified products.
Parallel trade has in the past allowed falsified products to seep into national supply chains.1 The EU Falsified Medicines Directive which came into force in February 2019, was intended in part to lower this risk.49 The directive requires states to adhere to stringent regulatory standards and track and trace regulations. These include serialisation, compliance reporting and verification requirements.2 Anecdotal evidence suggests that in practice, the directive was implemented with delay and is still not fully operational everyhwere. According to a public statement made by the president of the Organisation of Medicine Serialisation in Romania, Dan Zaharescu, in July 2019 only half of the pharmacies from Romania had been registered into the national system of medicine verification.50 At the present time, the situation seems to have been remedied and the serialisation has been implemented.51
Between 2016 and 2021, several pharmaceutical companies operating in Romania withdrew from the market due to commercial reasons. Around 70% of total drug discontinuity notifications monitored by the National Agency for Medicines and Medical Devices of Romania during the aforementioned period have been caused by financial considerations.52 In 2022, Romanian patients are still confronted with shortages of essential medicine such as antibiotics.53 Continuing roll-out of the Falsified Medicine Directive is likely further to constrain the opportunities for fake products to enter the regulated supply chain. However, the directive does not address risks in the unregulated supply chain, such as sales through websites and social media platforms. In October 2021, as the COVID-19 pandemic continued to spread, a hidden-camera investigation in Romania revealed the sale of medicine purporting to be COVID-19 treatment and other pharmaceuticals. Arbidol, an antiviral that was not to be found on the Romanian market at the end of 2021 was sold online and the investigative reporters met with sellers purporting to be patients in need of medicines.54 Most recently, in March 2022, reports of falsified medicines being sold on the internet prompted an investigation by the Minister of Health in cooperation with the police.55 A coherent national strategy to address the root causes of the persistent medicine shortages has not yet been developed.
Our qualitative study would have benefited from a larger and more diverse number of views from practitioners, including those concerned with EU trade relations. However, we believe the Romanian experience described in this paper may serve as a reminder to those planning other regional initiatives that medicine regulation, trade and pricing must be considered holistically to avoid undesirable fall-out of well-meant ‘harmonisation’ efforts.
A central implication of this study is that to counteract falsified medicine, it is essential that pharmaceutical markets and supply chains function properly and patients have effective access to affordable medicines. In the fight against poor quality medicines, the WHO and others emphasise the importance of strengthening the capacity of national medicine regulators (NRAs). Our study suggests that, while well-functioning NRAs are very important, a siloed strategy against falsified medicine that primarily focuses on product regulation is insufficient. Most of the factors which contributed to Romania’s vulnerability to falsified medicines were the result not of regulatory action but of commercial responses to political decisions.
Effectively combating falsified medicine requires coherent intergovernmental coordination between departments and a systemic perspective that takes into account product regulation, market regulation, pharmaceutical management in the health system and law enforcement. In addition to promoting regional cooperation between NRAs, it may be useful to examine how, within countries, multisectoral coordination across sectors and between departments can best be designed, governed and institutionalised. Existing and new studies of multi-sectoral collaboration for other health issues may provide useful lessons.56
Data availability statement
Data are available on reasonable request. Data can be made available on request. Due to the fact that the interviews contain sensitive information (i.e. unethical practices), the interviews will not be disclosed. We worked under an informed consent procedure, whereby the respondents were ensured complete anonymity. The detailed coding structure is available at https://doi.org/10.7910/DVN/CVPSBB. Specific coding queries can be submitted to the first author, AN. The requested results will be redacted in order to ensure the anonymity of the respondents. Additionally we provide a downloadable bibliography of all references reviewed during this research.
Ethics statements
Patient consent for publication
Ethics approval
Daily Board of the Medical Ethics Committee of Erasmus approved the protocol with ID number MEC-2018-016. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
The authors are grateful for the input provided by all the experts who took part in this study, both through interview and through participation in the preliminary results presentation and discussion hosted by the Wellcome Trust in London, in April 2018.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Handling editor Seye Abimbola
Twitter @nistornis, @elizabethpisani, @MaartOKok
Contributors All authors contributed to the design of the study, analytical methodology and the conceptualisation and writing of the paper. A-LN led the data collection for this case study, conducted the analysis of the data and drafted the first version of this paper. MK is responsible for the overall content as the guarantor and accepts full responsibility for the finished work.
Funding This work was funded by the Research Excellence and Innovation Grant of Erasmus University Rotterdam, Netherlands. Elizabeth Pisani was funded by the Wellcome Trust (grant number 209930).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.