Nathan Jessop is a columnist for Pharmaceutical Technology Europe.

Nathan Jessop

Parallel trade involves the crossborder trade of a given product in parallel to a manufacturer's official supply chain in that country. With respect to pharmaceuticals, the trade is a controversial issue in Europe and has led to several legal battles. Parallel traders purchase medicines at low prices in one country (often in southern Europe) and then subsequently resell the product at higher prices in another country. Companies seeking to create a profit from price differentials have been active since the 1970s when trademarks and patents were considered not to be lawful obstacles for repackaging and resale (1). However, parallel trade has surged as the EU has widened and created more opportunities for profit. Recently, it was suggested that price differentials of just 10% between EU member states was sufficient enough for pharmaceutical traders to make a profit (2). 

Although pharmaceutical manufacturers are firmly against parallel trade, there is little they have been able to do to prevent it. Parallel trade of goods, including pharmaceuticals, is based on the EU principle of free trade (3), which means that there should not be any obstacle to the free movement of goods between individual EU member states. The legalities of parallel trade also depend on what is known as the "exhaustion of intellectual property rights." Basically, commercial exploitation for a given product is considered to have ended in the EU after the product's first sale (4), meaning that the original manufacturer cannot actively prevent another party, such as a parallel trader, selling exactly the same product within the EU and benefiting commercially. 

The European Federation of Pharmaceutical Industry Associations (EFPIA) acknowledges the benefits of the EU principle of free trade, but believes that its application to the field of pharmaceuticals is not appropriate (3). Manufacturers have frequently argued that public safety could be compromised through parallel trade because products are not following the intended supply chain with its builtin measures for quality assurance. Indeed, EFPIA has often highlighted examples of safety and quality issues arising from parallel traders' handling of pharmaceutical products (3).  

Parallel traders angrily reject accusations by pharmaceutical companies that their activities compromise patient safety. The European Association of EuroPharmaceutical Companies (EAEPC) states that its members add value to society by introducing price competition and that precautions are taken to guarantee product safety (2). They consider arguments from certain pharmaceutical companies as part of a smear campaign to suppress their activities (5). Ironically, the EAEPC has recently collaborated with EFPIA and other parties in the pharmaceutical industry on a joint European stakeholder model to prevent falsified medicines from entering the European supply chain and improve patient safety (6). 

Unfortunately for pharmaceutical companies, rulings concerning parallel trade by the European Court of Justice have tended to leave enough room available for parallel traders to continue. Even when decisions appear favourable to pharmaceutical companies, they are not final and appeals can continue. For example, to deal with the issue of parallel importation, GlaxoSmithKline (GSK) adopted a dual-pricing mechanism in its Spanish distributor agreements. The company charged one fixed price for products sold domestically and a higher price for products sold outside Spain. At first, a ruling from the European Commission went against GSK, primarily because its agreement was considered to restrict trade between member states. Appeals led to the European Commission's ruling being partially annulled, leading to optimism among pharmaceutical companies that their views on parallel trade were finally being listened to. However, it turned out that the partial annulment centred mainly on the fact that GSK's arguments for their dual pricing system had not been properly addressed. Consequently the case continues. Although pharmaceutical companies continue to mount legal challenges against parallel trade whenever possible, there is a feeling that success is unlikely. 

Although parallel trade has received backing from the legal establishment, opinions from the industry may be changing. One of the complaints from pharmaceutical companies has been that parallel trade can lead to product shortages in certain countries as medicines are diverted elsewhere (3). Such views have relied on anecdotal evidence and so have easily been countered by parallel traders, who have blamed manufacturers for product shortages (7). However, the ongoing eurozone crisis in Greece and a parliamentary report in the UK have provided the sort of evidence that the pharmaceutical industry has needed to directly link parallel trade with shortages. 

 Austerity measures have placed huge pressures on the healthcare system in Greece. Traditionally, the country has always been a lowpriced market, but in 2011, the Greek government cut drug prices further to reduce the country's medical expenditures. These price cuts have led to a documented surge in parallel trade out of the country (8). Faced with domestic customers, including hospitals, who cannot afford to pay for medicines, many wholesalers have turned to the European market to make a profit. The PanHellenic Association of Pharmacists has reported that 500 commonly used drugs are now in short supply (8). These include products for hypertension, gastroenterological disorders, cancer, kidney diseases and painkillers, placing patients in a dangerous position. 

Greece's National Organisation for Medicines (EOF) has become so alarmed at the situation that it has launched a hotline for reporting shortages and tried to introduce a temporary ban on the export of 28 identified medicines (8). Since March 2012, wholesalers have been required to submit their sales per product and per client to EOF. This information is to be used to provide guidance on how to distribute the drugs. The EOF has also begun to electronically tag medicines to track usage, identify shortages and control parallel exports (9). So far, these official measures have failed to counteract the shortages and have been beset by other problems. In April, the electronic tracking system had to be taken offline as hackers uploaded around 1.5 million fake prescriptions (9). 

 In May 2012, the British Parliament's All-Party Pharmacy Group (APPG) published a report calling for restrictions on the practice of parallel trade (10). APPG states that the UK has been experiencing shortages of prescription medicines available on the UK's National Health Service for four years and that exporting by speculators, although legal in the EU, is responsible for this occurrence. In compiling its report, the APPG heard evidence of vulnerable patients not receiving the medicines they needed, including patients with mental health problems, epilepsy sufferers, diabetics and pregnant women. Although the APPG recognised that the Department of Health had tried to prevent shortages by informing supplychain participants of their obligations to maintain a supply and issuing best practice guidance, they concluded that none of the measures had succeeded. In 2010, the Department of Health held a Ministerial summit to address the issue and announced that the UK's Medicines and Healthcare products Regulatory Agency (MHRA)would tackle the shortages. It was also announced that action would be taken against those in the supply chain who were not fulfilling their supply obligations. However, the APPG pointed out that the MHRA has little market data to determine which products are in short supply and who is exporting them. The APPG was highly critical of the Department of Health, believing that many personnel were resigned to the current state of affairs and even blamed the problems on the previous government rather than trying to act and remedy the situation (10). 

The evidence that the APPG gathered regarding parallel trade impacting drug supply appears compelling (10). For example, the group heard that demand for Novartis' Emselex (darifenacin), for overactive bladder syndrome, rose to 350000 packs over a fivemonth period, vastly outstripping any possible UK patient demand. In fact, it was calculated that this amount was equivalent to an astonishing 26-year supply of the drug. The APPG also heard directly from pharmacists who described how the situation was causing stress to their patients, as well as excess work for staff in trying to source medicines in short supply. According to the report, many pharmacists were spending on average between two and five hours a week sourcing out-of-stock medicines. 

The APPG has called for immediate action from the government to ensure patient safety. First of all, it has asked the government to unequivocally state that patient health must come before meeting legal obligations concerning the free movement of goods in the EU. In addition, the government has been recommended to examine EU law to determine exemptions that will allow it to prevent current medicines shortages caused by parallel trade.  

The APPG has noted that the French government has been facing a similar situation and is examining measures that would place restrictions on the export of medicines. Because France also has to contend with the same EU legal constraints regarding the free movement of goods, it would be logical for the UK government to review the French proposals and see whether they could be employed to ensure that patients in the UK are not deprived of medicines. 

Parallel trade continues to irritate pharmaceutical companies in Europe, who view the trade as unfair competition and a danger to public health. To date, the EU legal position regarding the free movement of goods has enabled parallel trade to continue despite frequent court battles with pharmaceutical manufacturers. Naturally, parallel traders have cited such cases as highlighting their legitimacy and have rejected criticism of their business. However, emerging information is associating parallel trade with drug shortages in different EU countries. If patient safety is considered to be a risk, then the public will not accept the stated view of parallel traders that their business adds value to European healthcare by providing competitive prices. In fact, they could be seen as benefiting financially while patients struggle to access prescribed medicines. Parallel trade representatives have yet to issue a response regarding current EU drug shortages, but they will need to react quickly as pharmaceutical companies will cite such information as evidence of their previous warnings of the perils of parallel trade.			

1. T. Staton, "Austria racks up millions from parallel trade in EU" (Fierce Pharma, 

2. J. Kilick, "Parallel trade in Europe - the tide is turning

4. C. Heath, "Parallel imports and International trade" (World International Property Organisation, 1999). 

5. European Association of Euro-Pharmaceutical Companies, "Cutting the costs of medicines in Europe" (European Association of Euro-Pharmaceutical Companies website, 2012). 

6. European Association of Euro-Pharmaceutical Companies, Anon (2012). "EAEPC-EFPIA-GIRP-PGEU working for better patient safety

(European Association of Euro-Pharmaceutical Companies website, 2012).  

7. European Association of Euro-Pharmaceutical Companies, "What challenges do parallel distributors face?" (European Association of Euro-Pharmaceutical Companies website, 2012). 

9. Pharmaceutical-Technology, "Greece hit with essential medicine shortage caused by mounting drug debt" (Pharmaceutical-Technology website, 2012). 

10. APPG, "APPG Medicines Shortages Report

Articles

Parallel trade has frustrated pharmaceutical manufacturers for years and now evidence has linked such trade to drug shortages in Europe. Parallel trade representatives have yet to respond, but will need to react quickly to salvage their reputation.

Parallel Trade's Emerging Image Crisis

Traditionally, clinical trials were predominantly conducted in North America, Western Europe and Japan, but over the past decade there has been a dramatic shift towards using other regions. The extent of this international trend was illustrated in a global analysis of the period between 2002 and 2006, which examined the regional share of total sites and the growth rates for different regions (1). According to this analysis, the share of global sites accounted for by Western Europe increased by a modest 3%, whereas for Eastern Europe the share rose by 24%. Meanwhile, both Asia and Latin America's shares increased by around 20%. The trends come as little surprise, since it is now almost standard practice to incorporate so-called emerging market regions and rapidly developing countries in clinical development programmes (2).

Faster patient recruitment and lower trial operational costs are factors that have attracted companies to newer regions. In addition, many of these areas represent pharmaceutical markets in their own right and products may be looked upon more favourably if they have been tested in local populations. Many governments in emerging markets have recognised this interest from global companies and have taken measures to attract investment by decreasing bureaucracy and improving their regulatory systems. In China, for example, centralising the regulatory agency helped to decrease the number of conflicting standards between the central and local governments, and has led to improvements in approval times (3). 

While the pharmaceutical industry has expanded its clinical trials internationally, this shift has been viewed with concern in some quarters. Some observers believe that there has been too much emphasis on economic benefits and that the ethical angles of globalisation have not been fully explored (2). In particular, there have been several media reports criticising the use of developing world regions for clinical trials. In a television programme called "Dying for Drugs," which aired in the UK, Pfizer was heavily criticised for the manner in which it conducted a trial in Nigeria (4–7).

The anti-industry slant of the programme prompted a furious response from the Association of the British Pharmaceutical Industry (ABPI) and Pfizer said that the coverage of the company's activities was "misleading" (8). Nevertheless, unfavourable media coverage continues to emerge. In 2011, the UK's Independent newspaper ran a series of articles highlighting a series of clinical trial violations in India (9-11). The newspaper highlighted how drug trials were carried out on survivors of the 1984 Bhopal gas disaster without their knowledge and how certain Indian hospitals were generating considerable revenue from UK, US and French pharmaceutical companies for clinical trials (10). The resulting outcry led to pressure on India's regulatory agency to tighten regulations and protect subjects from exploitation. However, the media coverage then expanded to highlight examples in different countries, including those in Europe (10).  

The Dutch nongovernmental organisation, Wemos, which advocates for the right to health of people in developing countries, together with international partner organisations and journalists, began to document cases of unethical trials and lobby European politicians and policymakers to address the highlighted problems (12). Wemos' campaign has involved collecting and publishing testimonies from trial subjects, their relatives and others investigating the issue, but the organisation has not singled out individual companies (12). 			

These campaigns have had an effect, with groups of influential European MEPs raising the issue in the European parliament and calling for an appropriate response from the European regulators (9–11). Dr Peter Liese, a German Christian Democratic MEP was of the opinion that the European ban of an unethically tested drug would serve as an appropriate deterrent to wrongdoers in the pharmaceutical industry (10). He believed that appropriate laws to prevent breaches in conduct existed, but were not being implemented. Meanwhile, Margrete Auken, a Danish Green Party MEP, was quoted in the media as equating unethical clinical trials with organ trafficking and called for companies to be "named and shamed" (10).  

The EMA has received criticism from several MEPs for its perceived lack of action (9–11). In 2011, the EMA responded directly to the media, arguing that the globalisation of clinical trials was presenting it with a huge regulatory challenge that it was ill equipped to deal with. The EMA expressed the need for more resources and improved cooperation from the pharmaceutical industry to respond to the matters raised in the European Parliament, pointing out that all clinical trials, regardless of their nature, are required to meet internationally agreed ethical and data quality standards or their equivalent.  

However, critics of the EMA are not satisfied. Wemos has argued that the regulatory agency is not being proactive and should be closely questioning companies about their conduct before granting regulatory approval for products (10, 11). In March 2012, MEPs on the Environment, Public Health and Food Safety Committee renewed demands for answers from the EMA regarding allegations of informed consent, inadequate investigation of deaths, conflicts of interest and other breaches for several trials conducted in India (11). The EMA acknowledged that there were still problems and promised to increase transparency to show how it was trying to enforce standards, but Dr Fergus Sweeney, the EMA's head of inspections, appeared to reject the demands of certain MEPs to refuse market authorisation for any ethical breaches (11). 

Perhaps as a response to this criticism, the EMA has been keen to highlight the recent work it has been doing to ensure a robust global framework for the conduct and oversight of clinical trials. In April this year, the EMA's Working Group on Clinical Trials conducted outside of the EU and European Economic Area published a final reflection paper on the issue (13). The paper entered into force on 1 May 2012, with the aim of making sure that all standards are formally enforced, regardless of where in the world clinical trials are conducted. 

One of the key steps that the EMA believes will enable it to enforce standards is better international cooperation. The agency recommended that a common international approach to the oversight of clinical trials be adopted, particularly with respect to countries where ethical and regulatory systems are not fully developed. A clear difficulty identified in the paper is for countries where EU regulators have limited existing formal contacts or experience in the local conduct of clinical trials (10). 

As a starting point to prioritise its international focus, the EMA has collected data on the numerical distribution of patients participating in pivotal trials included in regulatory applications submitted to the Agency (10). In Africa, it identified South Africa as the major contributing country, whereas in Asia it was India, the Philippines, Thailand and China. In Latin America, a number of countries were highlighted including Brazil, Argentina, Mexico, Costa Rica and Peru. However, the EMA's data can only account for centrally authorised products, and so it is continuing to collect information at a Member State level and from international sources, such as the World Health Organisation (WHO) to create up a better picture of the situation.  

From the available and emerging information, the EMA has proposed that high level "mapping" of information should be established in cooperation with individual European regulatory authorities and other international organisations (10). The exercise will effectively grade countries on the basis of the strengths and weaknesses of their regulatory systems, and whether the EMA can offer any assistance in the field of clinical trial regulation.  

There will also be discussion on opportunities for collaboration based on the needs identified in the countries included in the priority list. The EMA already runs international collaborative projects in other areas, such as GMP inspections (14). The success of these programme can serve as a suitable framework to build collaboration for the purposes of enforcing clinical trial regulations. 

The EMA has also noted that there are existing collaborative programmes in other regulatory areas, which may feature aspects of clinical trial regulation. Therefore, the agency is keen to look for synergies with other initiatives and to avoid the duplication of effort. However, the EMA has acknowledged that the results of some of the initiatives that have been conducted to date have not always been well documented, so there may be gaps in knowledge to overcome if its proposed international work is to complement existing programmes (13). There are also some basic, practical issues that the EMA must deal with such as developing a contact list of representatives of the foreign organisations it wants to deal with and determining appropriate communication measures. 

For the EMA to become a stronger force for the enforcement of clinical trial regulations, it will also need greater resources and training. The final reflection paper mentions that training will involve courses, workshops and support for the preparation of guidelines and SOPs (10). However, it is not clear where the EMA will be getting additional resources from to cope with the growth of its activities or how they will be financed. 

The globalisation of clinical trials is now an accepted trend, although not all observers are content about the way it has developed and continues to progress. Documented cases of unethical conduct during clinical trials have led to both public and media outcry, and have prompted calls in the European Parliament for the stronger enforcement of international standards. The EMA has comeunder heavy criticism over its role in overseeing trials conducted on foreign territories, although it argues that it is responding to the need for better regulation and intends to become transparent regarding its future activities in this field. 

3. China Clinical Trials Outsourcing Congress, "Welcome to the 4th Annual China Clinical Trials Outsourcing Congress" (Event website, 2012). 

5. BBC News Anger at deadly Nigerian drug trials. 

www.news.bbc.co.uk/2/hi/africa/6768799.stm

http://news.bbc.co.uk/2/hi/africa/6768799.stm

6. BBC News. Pfizer denies dirty tricks claims in Nigeria. 

http://www.bbc.co.uk/news/world-africa-11971805

7. The Guardian, 2012. Pfizer pays out to Nigerian families of meningitis drug trial victims. 

http://www.guardian.co.uk/world/2011/aug/11/pfizer-nigeria-meningitis-drug-compensation

8. I. Hall, "Pharma firms hit back at C4's drugs documentary" (PR Week, 2003). 

9. N. Lakhani "From tragedy to travesty: Drugs tested on survivors of Bhopal" (The Independent, 2011). 

10. A. Buncome, "Delhi to examine weak regulation' of clinical trials" (The Independent, 2011). 

11. N. Lakhani, "Europe targets drug firms over unethical practices" (The Independent, 2011). 

12 Wemos, "The Globalization of Clinical Trials: Testimonies from Human Subjects" (Wemos website, 2010). 

13 EMA, "Towards a robust global framework for conduct and oversight of clinical trials" (EMA website, 2012). 

14. EMA, "International collaboration on good manufacturing practice inspections expanded" (EMA website, 2012). 

The globalisation of clinical trials is putting pressure on the European Medicines Agency.

European regulators Struggle with Globalisation of Clinical Trials

The French pharmaceutical sector is a recognised force within the healthcare system. As well as representing a source of medicines, it is a major employer and contributor to the economy. However, the pharmaceutical industry has grown increasingly concerned that its contributions to the nation are being taken for granted and has been using the French Presidential campaign as an opportunity to highlight its views.  

On 1 March, the Alliance for Research and Innovation in Health Industries (ARIIS) issued a petition asking all presidential candidates to support the industry in the national interest (1). ARIIS represents a collaboration between different companies in the healthcare sector, pharmaceutical and diagnostic, to make the sector a greater priority for the government. Since political candidates are engaging with French businesses about how to revitalise the faltering economy, the pharmaceutical industry hopes that its views will make an impact. Even the Socialist party, which has argued for more intensive cost cutting in the healthcare sector, has met with representatives of the pharmaceutical industry.  

Pharmaceutical companies operating in France have long expressed concern that they are being unfairly targeted by the government as part of its cost-containment drive to reduce healthcare expenditure. According to the French pharmaceutical industry association, Les entreprises du médicament (LEEM), which represents more than 270 pharmaceutical manufacturers nationally, price cuts in 2011 cost the industry €1 billion (2). It also suggested that cost-containment policies dissuade companies from making further investments in France and that companies are already looking at cutting jobs – although it has declined to name which companies.  

A longstanding complaint has been that, over the past two decades, a series of taxes have been introduced with a specific focus on the pharmaceutical industry. LEEM has calculated that these measures account for 5.5% of annual turnover, in addition to other burdensome levies imposed upon all industrial sectors (2, 3). Officially, the taxes are described as "contributions", and were introduced to reduce the French health system's huge deficit, for which the pharmaceutical industry was partly blamed because of high product prices (4). Pharmaceutical companies have rejected such accusations, pointing out that since they must negotiate in advance with the government about product pricing, the government is fully aware of, and involved in, the decision-making. The industry believes that the government should pay more attention to the non-pharmaceutical costs within the healthcare system. 

Pharmaceutical-specific tax rates have increased steadily, and are likely to continue to do so for the foreseeable future. They secure substantial revenue for the government, which is struggling to deal with the eurozone crisis (highlighted by the January 2012 loss of its top AAA credit rating from Standard & Poor [5]). These types of industry-focused taxes are likely to continue in a bid to avoid imposing tax rises on the general population. Currently, 13 pharmaceutical-specific taxes generate vital revenue for the government, but are an irritant to the industry since they can represent between 50% and 100% of companies' annual corporate income tax (4, 6).  

The Promotion Tax is a tax on promotional expenses for medicines that have a marketing authorisation in France and are included on the official list of reimbursed medicines. As the government reimburses much of the product costs in France, there has been a steady drive to curtail the promotional activities of pharmaceutical companies, with the costs associated with medical representatives, such as salaries, being a favoured tax target. Initially, the Promotion Tax rate was set at 5%, but it is now charged at 19–39%, depending on the nature of the company's promotional expenses. Currently, it brings in between €130 million and €165 million per year for the government. The types of activities deemed eligible for the tax are frequently disputed between the industry and the government. For example, the government stated that all advertising would be subject to Promotion Tax and indicated that this even included pens and giveaways bearing logos and trademarks at conferences (4).  

Not surprisingly, the level of promotional activities has sharply declined because of a combination of government pressure and company desire to minimise their exposure to such taxes and other restrictions. Recently, a proposal to allow limited television advertising for over-the counter medicines was rejected at a joint industry–government forum, as the two parties could not agree about how such measures should be governed (7). 

One general criticism of the Promotion Tax is its lack of clarity and ambiguous wording, about which certain companies have challenged the government. For example, a number of disputes have centred on the term 'medical representatives'. In 2009, Janssen-Cilag successfully argued in court that the Tax could not be applied to medical representatives who had not yet graduated (4). The government continues to challenge this ruling, arguing that the Law did not specifically set out to exclude medical representatives who worked in the absence of any graduate qualification or diploma. It believes that professional experience should be considered in the same manner as an official qualification. 

Another pharmaceutical tax (introduced by Article 12 of the law for Health Insurance Financing of 2004) is levied on sales of pharmaceutical products, and nets annual revenue from €215 million to €250 million. This tax is charged at 1%, but does not apply to exported, generic and orphan products. Since 1999, companies have also had to pay a tax on the basis of the annual increase of sales to prevent an unaffordable increase in health expenses caused by product sales. The nature of these payments is determined by confidential negotiations with the government. 

The pharmaceutical companies continuing complaints against the tax system appear to be making their mark on the government, which is worried that companies are reducing their investment in the French market. In 2009, the French President, Nicolas Sarkozy, gave a keynote speech to the Health Industries Advisory Board (CSIS), in which he publicly acknowledged that healthcare expenditure could not be viewed solely on the basis of cost containment (8). The pharmaceutical industry was heartened that this might signify a shift in government attitudes to the sector, and as far as the taxation issue goes, there have been positive developments. The CSIS was set up in 2004 and usually meets under the chairmanship of the French Prime Minister, who works below the President, as an open forum for the industry and government to air their views about the operational environment. 

In January 2012, the CSIS reviewed the tax system and agreed that a simplification of the various measures was required (2, 7). It recognised that the industry's views were not being taken into account, and that some of the tax provisions did not appear to align with other branches of government policy to stimulate industrial competitiveness.  

The French government has been particularly keen to promote biotech SMEs and has been particularly worried that the taxation system may stifle growth of this emerging sector. After its latest meeting, the CSIS recommended that the General Inspectorate of France and the General Inspectorate of Social Affairs should examine how other countries are taxing the pharmaceutical industry and apply their findings to the French market to incentivise companies toward local investment. The audit and development of recommendations to be implemented by these bodies has been set for 2013 (7), although it is unclear whether the election will influence this timeline. The pharmaceutical industry has also complained about the changing rates of pharmaceutical taxes and hopes that the future recommendations will also feature stabilisation of the tax levels (2). 

The French pharmaceutical industry has been taking advantage of the Presidential political campaign to reiterate its calls for more favourable policies for the sector and to boost its public image following the recent Mediator scandal (1, 2, 7). To date, it has been worried by the narrow focus on cost containment by successive governments, which is most apparent in the form of 13 different taxes on the pharmaceutical sector. The pharmaceutical industry believes that encouraging pharmaceutical innovation is the best means for the government to help revive the economy, since improvements in healthcare affect the population at large.  

Although the current government has altered its stance in public to become more positive about the industry, it still has to make difficult cost-cutting decisions to deal with eurozone crisis. In fact, the French Finance Minister François Baroin was quoted, prior to the election, as stating that the government would not back down from a policy of containing medical spending (2). Any incoming French government will face the same financial challenges. Since considerable revenue comes from the long-standing taxation measures, it is unlikely that reform will be quick or to the satisfaction of the pharmaceutical industry. The government dilemma is that the slowing economy has already reduced revenue from corporate sources. 

Companies have warned that they may reduce their investment in France on the basis of unfavourable operating conditions. However, they face similar cost-containment pressure in other European markets as their respective governments are also dealing with the global financial crisis. They may not be able to offer sufficiently attractive incentives to prise companies away from the French market. 

1. ARIIS, "Pétition d'ARIIS pour les présidentielles 2012" (ARIIS Website, 2012). 

2. A. Torsoli, "French Drugmakers Say Pricing Policy May Hamper Industry" (Bloomberg Website, 2012). 

3. The Pharma Letter, "Tax system for French drug firms to change" (The Pharma Letter Website, 2012). 

4. J. Cuadrado and C. Damiano, "French taxes specific to the pharmaceutical industry: cutting the health expenses or a different way of taxing the profitability of the pharmaceutical industry in France" in Tax on Transactions multi-jurisdictional guide (Practical Law Company Website, 2011). 

5.  Anon, "France loses AAA rating as euro governments downgraded" (BBC News Website, Jan. 12, 2012). 

http://www.bbc.co.uk/news/business-16552623

6. H. Israël and C. Guionnet-Moalic, "France: How the Reform of the Tax Applicable to Pharmaceutical Product Turnover Will Affect Entities in this Field" (mondaq Website, 2005). 

7. CSIS, Meeting of the Health Industries Strategic Advisory Board (Ministère de l'Économie, des Finances et de l'Industrie website, 2012). 

8. Focus Reports, "France: The French Revolution" (Focus Reports Website, 2010). 

As the French Presidential campaign is underway, and politicians collaborate with businesses to revive a flagging economy, the pharmaceutical industry seizes the chance to lobby for equitable taxation to give the sector a much-needed boost.

Taxing Times for French Pharma

The economic crisis in Greece has dominated headlines in Europe for the past few years. The country recently secured a bailout worth €130 billion, but no one believes this will solve the crisis given that previous bail out loans of €110 billion in May 2010 and €109 billion in July 2011 proved insufficient. Greece's public sector has been hit hard by the ongoing austerity measures imposed on it and even now the government is spending more than it can receive through taxes. This perilous state of affairs is having a wide range of negative impacts on society. Unemployment and homelessness is rising, as is crime, and there have also been outbreaks of violence on the streets. 

The economic crisis has devastated the Greek healthcare system, with austerity measures introduced by the government resulting in significant budget cuts for hospitals. The Greek healthcare system was already suffering from understaffing and under resourcing before the crisis. Now, treatment waiting times have increased further and many people are turning to street clinics that had originally been set up by non-governmental organisations for those outside the mainstream system. Médecins du Monde has estimated that the proportion of Greeks now seeking medical attention at such street clinics is around 30%. Before the crisis, it was only 3–4% (1). There have also been warnings of a rise in infectious diseases such as tuberculosis, malaria, hepatitis and HIV (2). These findings are a shocking development considering that the Greek healthcare system was highly ranked by the World Health Organization in 2000 (3).  

Another sign of decline in the country's healthcare system is the disruption of the pharma supply chain. The government cutbacks have resulted in shortages of many medicines around the country. In January, the Panhellenic Association of Pharmacists described 500 commonly used drugs as being in short supply, including painkillers and products for hypertension, gastroenterological disorders, kidney disease and cancer (4). A commonly cited point in the media was that some pharmacies had even run out of aspirin (5). 

Previously, strikes by pharmacists had accounted for drug shortages, but the current supply problems are more complicated. In 2011, the Greek government enforced heavy price cuts for pharmaceuticals. According to the new law, a drug's price is set according to the average of the three lowest priced countries in the EU. As a result, Greece's spending on pharmaceuticals only amounted to €4.1 billion in 2011 compared with €5-6 billion in 2010 (6). The national spending on pharmaceuticals for 2012 has been predicted to be around €2.8 billion. Recently, Greece's health minister, Andreas Loverdos was quoted as saying that excessive spending on unnecessary drugs amounted to a value of €1 billion per year (6). 

The government-enforced price cuts mean that wholesalers prefer to sell their stocks in other countries where they can make higher profits. The problem has also been exacerbated by public insurers delaying payments to pharmacies, which have then been unable to pay their suppliers. The lack of funding has been detrimental for the pharmacy sector. Out of the 12000 pharmacies that operate, 800 are facing closure and a further 200 have severe operational difficulties (4). 

Rather than keep their stock lying around in warehouses or waiting for payment from pharmacies, wholesalers are maintaining their business by re-exportation. In 2011, the amount that public insurers owed pharmacists exceeded €400 million (5). As payments can take three months, pharmacists recently announced that they could only supply medicines to patients who paid with cash. For many patients, this is impossible due to their financial circumstances. 

Media reports suggest that Greece has become a pan-European source for parallel trade products. Prior to the economic crisis, parallel trade was described as having plateaued in Greece because pharmaceutical companies had imposed supply quotas for the country. However, pharmacies in other countries often turn to Greece to replenish their supplies when they are low on stocks. In effect, the financial incentive to supply a drug outside Greece rather than for domestic customers is creating new clients across Europe. This situation has also led to cases of fraud where a bill is still submitted for reimbursement to public insurers as if the drug had been prescribed to a patient locally. Reimbursement fraud has been estimated by the European Federation of Pharmaceutical Industries and Associations (EFPIA) to cost Greece more than €500 million, which places further strain on the healthcare system (5). 

Many drugmakers are adopting a negative view of Greece's pharmaceutical market, which is also contributing to difficulties. On the one hand, companies have to conform to the low prices demanded by the government, but then they also find their own products in circulation in other European markets. Consequently, some manufacturers have stated that they are competing against their own products in these foreign markets (5). Another concern has been the influence that Greek prices might have on the way other countries set their prices. As some countries use Greece as a reference point, there could be a steady lowering of prices throughout Europe. 

The restrictions of the Greek pricing system were so severe when first introduced that some manufacturers started to reduce supply. In 2010, Novo Nordisk took some of its insulin products off the Greek market, claiming that as well as price cuts reducing profits, it was also owed around €26.1 million by the Greek government (7). An estimated 50000 diabetic Greek patients were using these products and the company's move led to an outcry. Novo Nordisk responded forcefully, accusing the government of mishandling the economy and putting patients and the company in the difficult position.  

Another Danish company, Leo Pharma, took a similar approach and issued a Notification Letter of Discontinuation covering the potential withdrawal of 18 of the company's 29 products on the Greek market (8). The company also claimed that it was owed $300 million (€223.4 million) by the Greek government. However, Leo Pharma was particularly worried about the impact of Greek prices on pricing decisions in other countries that use Greece as a reference market. 

In 2011, Roche halted delivery of some of its anticancer products and other therapies to some of the public hospitals that had not paid their bills (9). It stated that some hospitals had failed to pay the company for more than four years, but that it was boosting supply to pharmacies that had been reliable clients. In general, privately-run pharmacies have had a better track record of fulfilling payment than public hospitals. Patients could take their prescriptions to these pharmacies and, in the case of intravenous or injected cancer drugs, take them back to a hospital to have them administered. In this way, the company believed that patients would not be deprived of their medicines. 

Representatives of the Greek pharma industry have also complained about the government's attitude (9, 10), arguing that pharmaceuticals only account for a small proportion of the healthcare expenditure and that little is being done about other aspects of spending, such as diagnostic tests and medical procedures.  

As Greece already has some of the lowest prices in Europe, the government has already exhausted all possibilities to extract savings from medicines. They have also stated that the pharmaceutical industry understands how critical the current circumstances are and the need for flexibility, and therefore seeks sincere dialogue with the authorities. However, the representatives add that the current approaches being used will do nothing to resolve long-term problems. It has also been suggested that the government is basing its decisions on flawed data. One recommendation was to harness the benefits of information technology so that a full picture of the waste in the healthcare system could be revealed (9). By studying the way in which the supply chain was monitored from product distribution to use of medicines by patients, the effectiveness of the whole system could be improved. 

The situation in Greece continues to look bleak. As it is unclear what comes next for the economy as a whole, it is difficult to see how the healthcare sector will receive improved funding. In the short term, Greece will remain an unattractive market for companies seeking to launch innovative medicines with high prices. However, pharmaceutical companies already have experience of operating in tough markets. They will likely continue their presence in Greece, but will be highly selective in the products they bring to market there.			

1. A. Kentikelenis, "Health effects of financial crisis: omens of a Greek tragedy" (Lancet website, 2011) 

2. A. Carassava, "Euro crisis: Why Greece is the sick man of Europe" (BBC News website, 2011). 

3. Healthcare Economist, "Health Care Around the World: Greece" (Healthcare Economist website, 2008). 

4. E. Karamanoli, "Greece's financial crisis dries up drug supply" (Lancet website 2012). 

5. N. Kresge, "Greek Crisis Dries Up Drug Supply as Even Aspirin Can't Be Found" (Bloomber GusinessWeek website, 2012). 

6. Pharmaceutical-Technology, "Greece confirms state pharmaceutical spend" (Pharmaceutical-Technology website, 2012). 

7. Pharmalot, "Novo Nordisk Pulls Insulin From Greece Over Money" (Pharmalot website, 2010). 

8. L. Taylor, "Danish drugmakers' "no" to Greek price cuts" (Pharma Times, 2010). 

9. A. Roy, "America's Future? Greece Defaults on Cancer Treatments in State-Owned Hospitals" (Forbes, 2011). 

10. C. Papachlimintzos, "Medicine in Greece is cheap" (Athens News, 2011). 

Greece’s economic crisis has battered the country’s healthcare system, resulting in medicine shortages, market withdrawals and falling profits for the pharma industry.

Greece’s Financial Crisis and Devastated Healthcare System

Despite receiving increased regulatory attention, counterfeit medicines remain a serious and ongoing global health threat. The World Health Organization (WHO) defines them as medicines that have been deliberately and fraudulently mislabelled with respect to their identity and/or source (1). Such illicit products range from random mixtures of harmless, inactive substances to toxic preparations that can result in death. Counterfeit medicines are found everywhere in the world, although the scale of the problem varies from region to region.  

Criminal gangs are attracted to pharmaceuticals because of the high value of medicines and the relatively low risk of prosecution (2); as the counterfeiting business operates on an international scale, it is difficult to tackle the source of the problem and apprehend the parties involved. Furthermore, since many countries have failed to enact deterrent legislation, counterfeiters have felt free to act with impunity and have often managed to evade justice. 

Counterfeiting has traditionally been most prevalent in regions where the regulatory and enforcement systems for medicines are at their weakest, which includes many African countries, as well as parts of Asia and Latin America. In contrast, counterfeiting levels in most industrialised countries (e.g., EU countries, the US, Australia, New Zealand, Canada and Japan) tend to be low thanks to effective regulatory systems and market control. Consequently, many anticounterfeiting strategies have tended to focus on the areas where counterfeit pharmaceuticals are most prevalent.  

However, the supply chains of industrialised regions are now under threat, with several highprofile court cases in 2011 highlighting the efforts that counterfeiters are willing to make to break into high-value pharmaceutical markets. These cases have brought a renewed sense of urgency to the fight against counterfeiters. 

In 2011, the Medicines and Healthcare products Regulatory Agency (MHRA) revealed the extent to which the UK is now being targeted by counterfeiters. In one country-wide crackdown, the agency reported that over a million doses of medicines worth approximately €2.4 million were seized in raids by enforcement investigators (3). Counterfeit Valium and Viagra were the most commonly sold fakes, but counterfeiters were also targeting major therapeutic areas such as cancer, cardiovascular disease, respiratory disease and depression. 

The MHRA's success against counterfeiters was illustrated by the culmination of a case that has been described as the most serious counterfeit medicine fraud in the EU (4). A criminal gang had attempted to target the UK by bringing in two million doses of counterfeit drugs from China. The plot was highly sophisticated, with the products closely resembling genuine medicines, and was considered the worst breach of the UK's regulated medicines system. Approximately 72000 packs of counterfeit medicines with a retail value of around €5.6 million actually managed to enter the UK supply chain between December 2006 and May 2007. It was only thanks to international cooperation over a tip off that the criminal network was broken up. In May 2007, a licensed pharmaceutical packager in the UK was repacking a wholesale consignment of the antipsychotic drug Zyprexa when he noticed anomalies in the packaging (5). He informed the drug's manufacturer, Eli Lilly, who were suspicious about the findings and immediately contacted the MHRA. The regulator's enforcement team then impounded the consignment. Upon testing, it was found that the fake Zyprexa tablets contained various impurities, as well as only 55–80% of the API (5). This led to the MHRA's first ever Class One Drug Alert recall for the fake batch of Zyprexa as it ordered all pharmacies and healthcare staff to ensure that the product was taken off the shelves. Over the following months, the investigation revealed a complex international supply route that led from Ireland via Belgium and Mauritius, and then to a location in London. At the same time, US investigators began to investigate the matter and revealed the Chinese source of the counterfeits.  

Despite this success, the UK's BBC news has recently reported that not all the counterfeit products that entered the country's supply chain have been recovered. Following questioning of the MHRA using a Freedom of Information request, the regulators admitted that although the vast majority of counterfeit products had been recovered, some had been dispensed to patients (6). Eight patients who had received counterfeit Zyprexa or Plavix were identified, but the authorities are continuing to look for other patients who may have received such products. According to the BBC, the numbers could run into the thousands.  

There are also continuing reports of other breaches of the system. At the end of last year, the MHRA announced that counterfeit versions of the HIV medicine Viread had been discovered in the UK market alongside earlier-reported Truvada counterfeit products (7). At around the same time, a Danish parallel importer withdrew stocks of Truvada following consultations with the Danish regulatory agency. So far, full details of the nature and source of the products have not been made public and there is no evidence that they reached patients. 

Illegal online pharmacies have been a particular problem for the authorities. In November 2011, two men who had been running an illegal online pharmacy business were sentenced to 24 months in prison. The MHRA had run a 2-year surveillance initiative called Operation Aimee to expose the set up (8). Over this period, MHRA intelligence officers made large numbers of online test purchases of products to build up evidence for their case. When raids were finally conducted, 99220 tablets of counterfeit Viagra, Cialis and a number of other controlled substances were seized. 

Fortunately, the MHRA were able to expose and close down this particular criminal network, but the consequences of the illegal online trade ended up being deadly for one unfortunate victim. In a tragic case, a young paramedic who was having trouble sleeping between shifts decided to look online to get quick access to medication. She bought an anti-depression drug that is also used for insomnia from an online site, but died after taking a few tablets (3). The case served as a reminder of the fine line between success and failure against the counterfeiters and the need for concerted action. 

The fact that counterfeit products have managed to enter highly regulated markets has led to renewed efforts to tackle counterfeiting. Much hope has been placed in Europe's Falsified Medicines Directive, which will come into force in January 2013 and increase controls across the EU. The Directive was approved by the European Parliament last year and introduces new rules that will require prescription medicines to have safety features that enable verification of individual packs throughout the supply chain (9). Under the new system, all importers, manufacturers and distributors will become brokers of medicinal products, which confers greater responsibility on them to be vigilant and proactive. The Directive also targets illegal online pharmacies, which remain a major threat. In the future, all websites offering medicines for sale will need to be clearly linked to the website of the competent authority in that particular country. The regulatory body will also display a list of approved online sales sites, which will be required to display a common, recognisable logo (9, 10). 

The pharmaceutical industry has also been working on a number of initiatives with other stakeholders. In January 2012, the European Federation of Pharmaceutical Industry Associations (EFPIA), the European umbrella organisation of pharmaceutical full-line wholesalers (GIRP), the European Association of Euro-Pharmaceutical Companies (EAEPC) and the Pharmaceutical Group of the European Union (PGEU), which represents pharmacists, issued a joint press release calling for practical and cost-effective solutions to implement the requirements of the EU's Falsified Medicines Directive (11). The organisations have been developing a European Stakeholder Model (ESM) that can be adapted to individual national systems. ESM employs a product verification system that is run by pharmaceutical manufacturers, pharmacists and wholesalers, as well as parallel distributors. A unique serial number will be featured on each product pack that can be checked with ease against a central database at the point of dispensing. A pilot of the system was conducted in Sweden during 2009 to 2010 and a further pilot is planned for Germany in 2013 (11). 

Another major development that has received the industry's backing is the MEDICRIME Convention launched by the Council of Europe. In December 2011, a high-level conference was held in Moscow where members signed up to binding international legal agreements to combat counterfeiting. In particular, it was felt necessary to tighten the definition of what constituted a counterfeit in order to fill gaps in certain national legislation. For example, in certain countries, it has been difficult to bring legal action against those manufacturing, distributing and selling falsified medicines because the existing legislation only covered breaches of trademark and patent legislation (12). EFPIA hopes that the timing of the MEDICRIME initiative will boost efforts at the EU level and has also stated that it is ready to help any members in meeting their obligations for the MEDICRIME Convention (12). 

The threat posed by counterfeits to the European supply chain cannot be underestimated and the number of cases in the UK alone last year shows that counterfeiters are continuing their efforts to break into regulated markets. On a positive note, the level of international cooperation to defeat the criminals behind counterfeiting is at an all-time high. The EU's Falsified Medicines Directive, the MEDICRIME Convention and the ESM initiative by industry stakeholders are just some of the notable cooperative measures that are set to improve protection of the supply chain. 

1. WHO, "Medicines: spurious/falsely-labelled/ falsified/counterfeit (SFFC) medicines" (WHO website, 2010). 

3. T. Symonds, "Fake medicine trade: UK crackdown on drug importers" (BBC News, 2011). 

4. BBC News, "Man jailed for £4.7m counterfeit medicine fraud" (BBC News Website, 2011). 

5. N. Siva, "How investigators unravelled Europe's biggest-ever fake-medicine scam" (Wired, 2011). 

6. P. Kemp, "Fake drugs given to NHS patients still untraced" (BBC News, 2012). 

7. MHRA, "Counterfeit drug peddlers sentenced" (MHRA Press Release, 2011). 

8. P. Taylor, "Counterfeit Viread also on market, says MHRA" (Securing Pharma Website, 2011). 

9. G. MacDonald, "EU falsified meds act formally adopted" (In-Pharmatechnologist Website, 2011). 

10. "Q&A: Directive on falsified medicines" (European Commission, 2011). 

11. EFPIA, "EAEPC-EFPIA-GIRP-PGEU working for better Patient Safety" (EFPIA Website, 2011). 

12. EFPIA, "MEDICRIME Convention Position Paper of the European Federation of Pharmaceutical Industries & Associations" (EFPIA Website, 2011). 

Traditionally more prevalent in less industrialised regions, counterfeit medicines are now more frequently entering the heavily regulated supply chains of EU countries.

Stepping Up the Fight Against Counterfeits

However 2012 ends up, it will be a dramatic year for Servier. The French company has a number of ongoing collaborations that could lead to a new generation of products, but any positive news from these developments is likely to be overshadowed by the ongoing safety scandal of its diabetes treatment Mediator (benfluorex hydrochloride), which was withdrawn from the market in 2009. A major court case is set for mid-year and the controversy continues to implicate an ever-growing list of prominent people in France. The scandal receives regular coverage in the French media, some of which has drawn an angry response from Servier's legal team (1). It is also worrying for the pharmaceutical industry as a whole because the developments are prompting changes in the way that drugs are approved in France (2). 

Servier has always prided itself as being different to other pharmaceutical companies (3). Although it is among the top 10 companies in Europe and ranks among the top 30 worldwide, it remains an independent company. In 2004, Servier's ownership structure was changed to a foundation to prevent takeovers. According to the company's founder, Jacques Servier, this is the best way to enable continuity for the company's mission.

Its publicly available information highlights the difference between itself and other companies and this has been emphasised by its founder in his rare interviews (4, 5). For example, Servier states that it reinvests a higher proportion of its turnover back into its research. Whereas the top ten pharmaceutical companies reinvest 14% of turnover, and French industry as a whole reinvests 9%, Servier reinvests 25% (3). Servier refers to this as the "invent or die" principle, citing the fact that it has synthesised 50 000 chemical entities as evidence of its innovation credentials.

Another aspect of the company's independent approach has been its internationalisation strategy. It is now present in 140 countries and 90% of its medicines are used internationally. This success stems from adopting a global strategy early on. For example, the company established itself in eastern Europe before the fall of the Berlin wall, which meant that it was well positioned in the aftermath. In 1998, a major economic crisis hit Russia and prompted a number of US companies to withdraw from the market, but Servier chose to stay and has since benefited from the market resurgence. 

At present, the company is banking on a number of collaborations bearing fruit in the near future to continue its strong growth. In January 2012, Servier announced a deal with the Swedish company BioInvent International under which Servier will use BioInvent's technology to select an antibody candidate for the development of an unspecified oncology target (5). At the end of 2011, Servier also entered into an agreement with MacroGenics, a US biotech company, for the development and commercialisation of MGA271, a first-in-class monoclonal antibody candidate that is being studied in Phase I for the treatment of solid tumours. The deal is potentially worth $470 million (5, 6). Servier also has an ongoing alliance with Belgian biotech firm Galapagos to develop a novel osteoarthritis drug, which led to a milestone payment of €4 million from Servier in December 2011 (7).

Unfortunately for Servier, most mention of its name at present is connected with Mediator. The drug was originally on the market as a diabetes treatment, but became widely used off label for weight loss (8). In 2009, it was revealed that the drug might be linked to 500 deaths in France, and media and public outcry led to its removal from the market (2). Astonishingly, Jacques Servier was quoted in the French media as saying that there had been no more than three deaths due to Mediator, which prompted an angry reaction from the Health Minister Xavier Bertrand (9). 

The French regulator, the Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSAPS), was criticised for not acting on earlier information that structurally similar drugs could cause valvular heart disease and pulmonary arterial hypertension (8). Regulators in other European markets and the US had taken strong action over related agents and there is still anger as to why similar action was so slow to take place in France. The Mediator scandal has also had a dramatic effect on the regulatory mechanisms of the French healthcare system. In January 2011, the head of the French regulatory agency was forced to resign and the agency has since also been renamed the National Agency for the Safety of Medicines and Health Products (ANSM) (10).  

Although acknowledging that safety regulators had missed a series of warning signs in previous years, the French government has pointed the finger at Servier. However, it has been difficult for the government to totally shift the blame after an interministerial commission revealed that voting members of the approval committee had been allowed to simultaneously serve as consultants or employees of the companies they were supposed to be regulating (11). 

Such revelations have led to an overhaul of the French system, and in December 2011, a law to reform how drugs are approved and regulated was adopted by the parliament (2). Under the new system, potential new drugs must be compared with existing approved therapies rather than just with placebos, if they are to be reimbursed under the public health insurance system. Furthermore, greater transparency is being insisted on, with pharmaceutical companies being forced to declare their links with outside organisations and individuals or face criminal sanctions for failure to comply (2). The new law is still in development, but has been criticised over certain aspects, such as an additional clause that states that a drug will be reviewed every five years regardless of problems. The French pharmaceutical industry body, les enterprises du medicament (LEEM), has also expressed concerns at clauses in the new law intended to restrict visits by sales representatives and ban company-funded medical education (12).  

Patient groups have launched a number of legal cases against Servier and in December 2011, the Cour de Cassation, France's highest criminal and civil court of appeal, rejected a request from Servier, for all lawsuits being brought against the company to be consolidated into a single trial (13). This is a major setback for Servier as the cases are likely to drag on for several years. One of the first cases will be a trial before the correctional court of Nanterre, where Jacques Servier himself and several executives of the company will face charges of "deception", which they were charged with in September 2011 (13). Beyond this, the company's executives face more serious charges for "involuntary homicide and injuries" (13).  

Public demand for someone senior to be held accountable is high and the authorities will be keen to be seen as dispensing justice. Jacques Servier risks a maximum prison sentence of four years and the company is likely to face huge claims for damages. The worst-case scenario could see the company lose its operating license. 

Servier's R&D successes this year will be pushed into the background as further details about Mediator emerge. The ongoing case also has wider ramifications because it may set a precedent for future cases involving drug safety issues. It is unusual for a company's top executives to be named and shamed, and the Servier case shows that in serious cases involving public health, senior people may find themselves on trial. Equally, regulators will be under greater scrutiny and are likely to become increasingly conservative because any oversight may come back to haunt them.  

The pharmaceutical industry as a whole will also be concerned that the fallout from the Mediator case will cloud the public's views over what can be considered acceptable regarding the risk–benefit profile of products. The industry's interactions with regulators and healthcare professionals will also come under greater scrutiny. Servier has often publicly highlighted how it differs from other pharmaceutical companies in the way it operates its business, but the irony is that critics of the pharmaceutical industry will consider Servier's actions as typical of the sector. The Mediator case has already led to changes in the way that France approaches the regulation and promotion of medicines. Whatever emerges over the next year also has the potential to influence markets in other countries, which will be keen to safeguard against any flaws proven in the French system.

1. E. Lanez, "Mediator : l'effarante boîte à mensonges" (Le Point.fr, 2011) 

2. B. Casassus, "With New Law, France Revamps Drug Approval" (

3. Servier, "Research is as vital as being an industry " (Servier website, 2011). 

4. J. Upton, "Servier: patience and passion," 

5. Focus Reports, "Interview—Jacques Servier" (2011). 

6. K. Grogan, "Servier signs cancer deal with Sweden's BioInvent" (

7. European Biotechnology Science & Industry News "Galapagos gets €4 million in alliance with Servier" (2011). 

9. Le Point.fr, "Mediator, un jugement pour 2012?" (2011). 

10. S. Sayare, "Scandal Over Mediator, a French Weight-Loss Drug, Prompts Calls for Wide Changes" (

www.assemblee-nationale.fr/13/rap-info/i3552.asp

12. InPharm, "2011 Year In Review" (2012). 

, "Mediator: la cour rejette le regroupement des procédures" (2011). 

The scandal surrounding Servier's diabetes drug, Mediator, continues to unravel in France and could have implications for the whole pharmaceutical industry as the country scrutinises its regulatory systems.