DRUG INDUSTRY

“World’s pharmacy” faces new challenges from Western drug companies Is India’s role as the “world’s pharmacy” under threat? And what effect will this have on affordable access to medicines? Andrew Jack reports

n two courtrooms at opposite ends of India, ries,” says Paul Herrling from Novartis. “But if the difficult both to win patents and for foreign drug pivotal legal battles with Western drug com- situation doesn’t change on patents, we will not companies to operate within the country. The panies over patents are coming to a head this invest in any major drug discovery work there.” result was a drop in investment but a fillip for month. The outcomes will have wide ranging For critics such as Médecins Sans Frontières domestic generic drug companies. consequences for millions of patients across (MSF), however, the decisions offer a stay of exe- As a result, companies like thrived, taking Ithe developing world. cution against what they see as a steady erosion medicines still patented abroad and re-engineer- In New Delhi, the Supreme Court is con- of India’s historical resistance to patents, which ing them for more efficient manufacture and sale sidering Novartis’s last ditch argument that it gave it a central role in the production of low cost far more cheaply for the local market. “I’m not should be granted patents to protect imatinib generic medicines that provide affordable access against patents, but a country like India simply mesylate (Glivec), its treatment for ­leukaemia, to patients both domesti- cannot afford them,” says despite a series of rejections by the patent cally and internationally. “I’m not against patents, but Yusuf Hamied, head of the office and in subsequent appeals since the Michelle Childs, from a country like India simply company. middle of the last decade. the charity’s essential cannot afford them” In other poor countries, Separately in Chennai, the Intellectual medicines campaign, says: Yusuf Hamied, head of Cipla similarly weak intellec- Property Appellate Board is considering a case “These are the biggest test tual property laws—or the brought by Bayer after India’s patent control- cases. We’re very concerned about the sustain- absence of filings by Western drug companies ler took an unprecedented decision in March ability of generic competition. We are a medical even where there was strong protection—created this year to issue a “compulsory licence,”­ organisation and we want new molecules, but valuable export markets for the Indian generic ­substantially undermining the patent Bayer we don’t want monopolisation. Newer drugs are producers without fear of legal challenge. had ­previously been granted for its cancer drug going to be priced out of reach.” As a result, Cipla and its peers have brought sorafenib (Nexavar). India’s drug manufacturers are divided on the treatment to millions of people, notably those The and patient issue, with some generic companies that thrived with HIV in Africa. Lack of patent protection advocacy groups worldwide are watching in the past lamenting a longer term trend towards meant they could not only sell drugs cheaply but the cases closely, as India becomes a global tougher patent protection, while others side with also combine medicines from different companies ­battleground for the fight over intellectual the foreign developers of innovative drugs that into “fixed dose combinations,” making the treat- ­property rights and their effect on innovation they are seeking to emulate. ments easier to take and more effective. and affordable access to medicines. The feud The reality is that both legal cases represent But MSF warns that India’s role as the “world’s is taking place in courtrooms, but there is also extremes, against a backdrop of growing cooper- pharmacy” is under threat from political changes high level lobbying over trade rules between ation between local and Western pharmaceutical to open up its economy since the 1990s. Most India and the US and Europe. companies. But they highlight continuing diffi- significantly, its membership of the World Trade Some Western multinational drug companies culties of affordable pricing and of investment Organisation included the condition that by 2005 argue that the current situation is casting a chill in drug development even as India’s commercial it would enforce innovative medicine patents. on their willingness to invest in drug research in attractiveness as a market for medicines grows. India and jeopardising their broader ability to New approach to patents develop new medicines and be fairly rewarded Growth of generic market Since then, India has been granting even more for their efforts and risks. In the 1960s and 1970s, legislation—partly for patents, restricting the ability of generic compa- “There is no doubt that India has the talent— protectionist reasons and in response to perceived nies to copy new drugs and reducing competitive we have lots of Indian scientists in our laborato- exploitation by foreign businesses—made it more pressures as a way to push down prices.

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Weak intellectual property laws created valuable export markets for the Indian generic producers without fear of legal challenge

Under the Trade Related Aspects of Intellectual Cooperation Property conditions of the World Trade Organi- In reality, such spats have not prevented intensi- sation, India is legally permitted to issue such fying commercial activity and partnership in the a licence. A few other countries have done so, country in recent years. Indian generic compa- and many more have issued the threat in order nies are an increasing source of low cost phar- to negotiate cheaper prices, including the United maceutical ingredients, including as suppliers to States when it sought affordable access to cipro- multinational innovative businesses. They have floxacin, Bayer’s antibiotic, after the post-9/11 also become significant exporters, selling their anthrax scare. cut price versions of drugs in the US and Europe Judging the price of imatinib to be too high, once patents expire. the Indian patent controller authorised Natco, At the same time, Western drug companies an Indian generic producer, to sell the drug for have been expanding their operations in India. just 3% of Bayer’s price in the country ($5500 Mylan, a US generic producer, acquired the (£3400; €4200) a month per patient), while Indian producer Matrix in 2006, and has just requiring it to pay the company a royalty.1 started selling its medicines within the coun- try. In 2008, Daiichi Sankyo of Japan bought MSF Maintaining affordable access Ranbaxy for $4.6bn and two years later Abbott New Delhi, February: protests against an EU-India The ruling has sparked fears that other patents acquired the generic arm of Piramal for $3.7bn. deal that threatens to limit the production of will be undermined. But it has also triggered Sanofi has since bought Shanta, and Glaxo- affordable generic medicines fresh reflection on how to make drugs available SmithKline, Pfizer, Forest, and Merck have all in India when so much of the population lives in formed alliances with local companies. Novartis argues that imatinib should be enti- poverty, unable to pay for medicines themselves Much of their interest is in tapping into the tled to patent protection. Its difficulty is that the and inadequately served by under-funded gov- country’s generic expertise in low cost manu- drug pre-dated eligibility for India’s tougher new ernment healthcare or insurance schemes. facture for export. But they are also buying into patent laws. Rather than seeking protection on Drug companies argue they should be able India’s fast growing domestic demand for medi- the initial molecule identified by researchers, it to generate a return from India’s emerging mid- cines, which industry forecasts suggest will be instead had to file a patent application for the dle classes, who can afford to pay, while find- worth at least $50bn by 2020, making it one of slightly modified “salt” form it ultimately used ing other ways to supply the poor, who cannot. the world’s 10 largest markets. to treat patients. They have responded by creating patient assist- Even so, Indian companies have yet to show But India’s patent system seeks a higher stand- ance programmes to provide free drugs to those significant medical innovation of their own, while ard of originality and inventiveness than that of judged eligible. foreign companies have largely concentrated their most other countries. The system was designed to They point out that many more potential activities on clinical trials work or specialist serv- prevent the practice of “evergreening,” whereby patients remain untreated in the country not ices such as contract chemistry rather than early drug companies make minor modifications to because of the absence of cheap medicines, but stage research and development. their products in order to extend the market because the inadequate health system means The continuing cloud over intellectual prop- exclusivity. that many people are never even diagnosed or erty may be among the reasons, although observ- Herrling rejects any suggestion that the offered treatment and support by doctors. ers also point to other factors, from the country’s approach applies to imatinib. “Evergreening is not To tackle affordability, other companies have lack of traditional focus on drug research, to the something we want, but improvements that trans- taken different approaches. GlaxoSmithKline absence of sufficient risk capital, limited govern- late into tangible advantages should be included,” and, more recently, Roche have introduced ment funding for science or health, and a slug- he says, arguing that even incremental changes “tiered pricing,” for example, selling drugs in gish regulatory bureaucracy. that result in improved safety, efficacy, compli- India at a discount to Western prices, and even In the coming years, that may well change. But ance, or quality of life for patients deserve patents. offering a range of deeper discounts within India like the battle over patents, there is unlikely to Childs replies: “We recognise that the basic to reflect patients’ ability to pay. US company be much clarity until long after imatinib’s patent molecule was inventive, but Novartis’s prob- Gilead has taken another tack, fostering a form of expires in 2014. The broader issues of affordabil- lem is that India’s new law came into force in managed competition to reduce price by licens- ity and access for low income patients around the 2005 while its really innovative discovery of the ing its antiretroviral medicines to several Indian world will be felt for far longer yet. m­olecule took place before.” generic manufacturers in exchange for guaran- Andrew Jack pharmaceuticals correspondent, Financial Even some rival Western drug company exec- tees on quality control and payment of a royalty. Times, , UK [email protected] utives suggest that Novartis’s case is an outlier, But legal clashes between generic companies Competing interests: None declared Provenance and peer review: Commissioned; not externally and point to the growth in subsequent successful and innovators over patents continue, leading peer reviewed. patent awards—including Bayer’s sorafenib. But to rulings that often appear confusing. In early 1 Jack A, Fontanella-Khan J. India approves generic cancer they are nervous about the broader implications September, for instance, a court upheld Roche’s drug. 2012 Mar 12. www.ft.com/ cms/s/0/13d79d3c-6c50-11e1-8c9d-00144feab49a. now the monopoly on sorafanib has been under- patents on erlotinib (Tarceva) but also allowed html#axzz26QdSEA7Z. mined with a “compulsory licence.” Cipla to continue producing it. Cite this as: BMJ 2012;345:e6207

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bmj.com ЖЖBMJ Careers: Vary pay increases for different groups of doctors, suggests government IS THERE EQUAL PAY IN HEALTHCARE? NOT IF YOU ARE A DOCTOR The gap may be closing between men and women’s pay, but in medicine the gender divide persists, finds John Appleby

Last year, for the latest release of data from The real eye opener is the 28.6% on average with no real discernible decrease its annual survey of hourly earnings, the pay gap between men and women (fig 2). Office of National Statistics (ONS) announced among medical practitioners But what explains the big gap in pay a continued closing of the pay gap between between male and female doctors? A 2009 men and women in the United Kingdom. study for the BMA suggested that some By April 2011, the difference in median respectively. But at 16% less than men’s pay, of the difference may be “legitimate” and hourly earnings between men (£13.11; the gap for pharmacists is nearly treble this. explained by factors such as experience, €16.40; $21.10) and women (£11.91) in Interestingly, female medical radiographers type of specialty, grade, and administrative full employment stood at 9.2% (of men’s seem to earn 5.3% more than their male duties (although why men end up with average pay)—a drop of one percentage point counterparts on average. more experience or on higher grades—and compared with April 2010.1 2 At this rate, by Perhaps the real eye opener (although hence more pay—raises some questions).6 2021 women can expect to be on a par with perhaps not for most female doctors) is the Nevertheless, a substantial part of the pay men—a mere 51 years after the Equal Pay Act 28.6% pay gap between men and women gap seemed to be unexplained by such passed on to the statute book. among medical practitioners. In 2011, male factors. Doctors questioned as part of Unfortunately, a change in methods led to doctors’ median earnings were £33.17 the BMA analysis suggested that female the ONS publishing revised figures in March per hour—£9.49 more than their female doctors were disadvantaged because 2012, The change increased the 2011 gender colleagues. Trends in this gap since 2000 are of caring roles, a “hostile culture,” and pay gap to 10.5% and makes comparison erratic but suggest a pay gap of around 25% geographical limitations that reduced with 2010 figures impossible.3 4 On the basis of recent trends since 2000 it might seem 40 likely that the gap has continued to close, but we don’t know for sure. The annual survey of hourly earnings 35 (ASHE) is based on a 1% sample of employee jobs taken from Her Majesty’s Revenue and 30 Medical Customs pay as you earn (PAYE) records. practitioner Information on earnings and hours is pay gap: 2011 obtained from employers and treated 28.6% 25 confidentially. The survey does not cover the self employed or employees not paid during the reference period. It covers hundreds of 20 occupations, including many healthcare jobs. So how does men and women’s pay compare in healthcare? Gender pay gap (%) 15 For those health related occupations for All which samples were large enough not to be occupations pay gap: 2011 classified as “unreliable” by the ONS, nursing 10 10.1% auxiliaries and assistants show the smallest bias in pay towards men, with women’s 5 median hourly pay being 0.1% less than men’s (£9.40 v £9.41). For nurses the pay gap widens to 1.9% (£15.97 v £16.28). Not 0 perfect, but good news for the largest NHS 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 staff group (fig 1). Year Female paramedics’ and health service managers’ pay also lags behind that of Fig 1 | Gender pay gap in median hourly earnings, selected healthcare and other occupations, their male colleagues—by 4.9% and 5.8% 2011, UK (full time employees, excluding overtime)4

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BMJ BLOG Athene Donald Women earn 10% more than men EU website own goal 35 Equal pay The European Union scored an own goal a few Women earn 10% weeks back when it launched its new website less than men “Science: It’s a Girl Thing,” aimed at getting 30 more teenage girls to consider science as Women earn 20% less than men a career. If you look at the site now, it looks innocuous enough—indeed, possibly rather 25 Women earn 30% interesting and informative—but on the day less than men it was launched it also hosted a so-called “taster video” that set the airwaves alight 20 with horrified comments. The video was pulled within 24 hours because of the vitriol tossed in its direction. men (£) Suffice to say, if you hadn’t known in Wo 15 advance it was intended to make teenage girls take science seriously, you might have been forgiven for thinking it was a rather bad 10 pop video aimed at teenage boys. The three females who “starred” in the film, wearing miniskirts and high heels, were obviously an object of interest (or possibly astonishment) 5 to the only clearly identifiable scientist in the film, a man (needless to say in a white coat), who looked up from the microscope he was 0 peering down apparently in amazement at 0 5 10 15 20 25 30 35 the sight of this female trio. The girls seemed Men (£) more interested in their poses than in the occasional large “molecule” that wafted All full time employees Medical radiographer past them. I had little idea what most of the Higher education teaching professionals Nurses video was meant to convey, but it was wildly Hospital and health service managers Nursing auxiliaries and assistants inappropriate and deeply disappointing. For further commentary—and a lot was Journalists, newspaper and periodical editors Paramedics written about it, none that I saw in the least Medical and dental technicians Pharmacists bit complimentary—I’ll refer you to Curt Rice in . He was one of the original Medical practitioners “gender expert group” charged with providing recommendations for the campaign. Fig 2 | Gender pay gap in UK median hourly earnings, all full time employees and “medical practitioners,” But, as he says, “The video was so shocking 2000-11. (Data from ONS annual survey of hourly earnings) that the European Commission had to deny that it was an attempt at irony.” It’s a shame this was such a public relations disaster, since there remains a crying need women’s ability to change jobs (a key way 1 Office for National Statistics. Gender pay gap falls below 10 per cent in 2011 Press release, release 23 November to get more girls into science. Medicine is to increase pay). Of course women in other 2011. www.ons.gov.uk/ons/rel/mro/news-release/ actually less badly off than disciplines like occupations face these problems too. But annual-survey-of-hours-and-earnings-2011/ashe- 2011-nr.html. physics and engineering. In my own field of it may be that these factors are more acute 2 ONS. Annual survey of hourly earnings (SOC 2000).2011 physics, although the numbers of girls taking for female doctors. The BMA report noted www.ons.gov.uk/ons/dcp171778_241497.pdf. the subject at A level this year has increased that more research is needed to explain 3 ONS. Annual survey of hourly earnings, 2011 provisional results (SOC 2010). Table 14.6a: Occupation. 2012. by a little bit more than for boys (and the the apparently inexplicable and persistent www.ons.gov.uk/ons/publications/re-reference-tables. numbers of both have been increasing over gender gap in doctors’ pay and hence to html?edition=tcm%3A77-256648 4 Gainsbury S, Cadman E. Gender pay gap larger than the past few years), they still represent only point to policies to eradicate the difference. expected. Financial Times 2012 Mar 21. www.ft.com/ about a quarter of A level entrants. This Maybe there are lessons to be learnt from cms/s/0/32f63230-735a-11e1-9014-00144feab49a. html#axzz24SrpvbZg. is a problem for the medical profession, some other healthcare professions—nurses, 5 Fairfield H, Roberts G. Why is her paycheck smaller? which undoubtedly needs well trained paramedics, and managers—where gender New York Times 2010 May 18May 18, 2010May 18, 2010. www.nytimes.com/interactive/2009/03/01/ physicists to become the medical physicists, pay differences are closer to zero. business/20090301_WageGap.html. radiographers, and the like of the future, 6 Connolly S, Holdcraft A. The pay gap for women supporting doctors in the hospitals. John Appleby chief economist, King’s Fund, London, UK in medicine and academic medicine: an analysis [email protected] of the WAM database. BMA, 2009. www. Athene Donald has been a professor of physics at the medicalwomensfederation.org.uk/files/pay%20 Competing interests: None declared. University of Cambridge since 1998. gap%20report.pdf. Provenance and peer review: Commissioned; externally peer ̻̻Read this blog in full and other blogs at bmj.com. reviewed. Cite this as: BMJ 2012;345:e6191

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