Access to essential medicines for sexual and reproductive health care: the role of the pharmaceutical industry and international regulation

Abstract

The range of medicines and technologies that are essential for sexual and reproductive health care is well established, but access to them is far from universally assured, particularly in less developed countries. This paper shows how the pharmaceutical industry plays a major role in the lack of access to essential medicines for sexual and reproductive health care, by a) investing in products for profit-making reasons despite their negative health impact (e.g. hormone replacement therapy), b) marketing new essential medicines at prices beyond the reach of countries that most need them (e.g. HPV vaccines), and c) failing to invest in the development of new products (e.g. microbicides and medical abortion pills). Small companies, some of them non-profit-making, struggle to fill some of that demand (e.g. for female condoms). International patent protection contributes to high prices of medicines, and while international agreements such as compulsory licensing under TRIPS and the Medicines Patent Pool allow for mechanisms to enable poorer countries to get access to essential medicines, the obstacles created by “big pharma” are daunting. All these barriers have fostered a market in sub-standard medicines (e.g. fake medical abortion pills sold over the internet). An agenda driven by sexual and reproductive health needs, based on the right to health, must focus on universal access to essential medicines at prices developing countries can afford. We call for greater public investment in essential medicines, expanded production of affordable generic drugs, and the development of broad strategic plans, that include affordable medicines and technologies, for addressing identified public health problems, such as cervical cancer.

Résumé

La panoplie de technologies et de médicaments essentiels pour les soins de santé génésique est bien établie, mais on est loin de l'accès universel, en particulier dans les pays les moins avancés. Cet article montre comment l'industrie pharmaceutique joue un rôle majeur dans le manque d'accès aux médicaments essentiels pour les soins de santé génésique a) en investissant dans un but de rentabilité en faveur de produits,malgré leurs conséquences négatives sur la santé (par exemplele traitement de substitution hormonale), b) en commercialisant les nouveaux médicaments essentiels à des prix hors de portée des pays qui en ont le plus besoin (par exemple les vaccins contre le VPH) et c) en n'investissant pas pour le développement de nouveaux produits (par exemple les microbicides et les pilules d'avortement médicamenteux). Les petites compagnies, dont certaines sans but lucratif, luttent pour combler une partie de ces besoins (par exemple le préservatif féminin). La protection internationale des brevets contribue au prix élevé des médicaments et si des accords internationaux, comme la concession de licences obligatoires au titre des ADPIC et la Communauté de brevets pour les médicaments, offrent des mécanismes permettant aux pays les plus pauvres d'accéder aux médicaments essentiels, les obstacles créés par les grandes compagnies pharmaceutiques sont redoutables. Toutes ces limitations ont encouragé un marché de médicaments de mauvaise qualité (par exemple de fausses pilules d'avortement médicamenteux vendues sur Internet). Un programme guidé par les besoins de santé génésique et fondé sur le droit à la santé doit se centrer sur l'accès universel aux médicaments essentiels à un prix abordable pour les pays en développement. Nous demandons un investissement public accru pour les médicaments essentiels, une production élargie de médicaments génériques abordables et la mise au point de vastes plans stratégiques, notamment des médicaments et des technologies à bon prix, pour répondre aux problèmes de santé publique, comme le cancer du col de l'utérus.

Resumen

Aunque se ha establecido claramente la variedad de medicamentos y tecnologías que son esenciales para los servicios de salud sexual y reproductiva, el acceso a estos está lejos de ser garantizado universalmente, en particular en los países menos desarrollados. En este artículo se muestra cómo la industria farmacéutica contribuye a la falta de acceso a estos medicamentos a) al invertir en productos por razones comerciales a pesar de su impacto negativo en la salud (p. ej. terapia de reposición hormonal), b) al comercializar nuevos medicamentos esenciales a precios inasequibles para los países que más los necesitan (p. ej. vacunas contra el VPH) y c) al no invertir en la creación de nuevos productos (p. ej. microbicidas y tabletas de aborto con medicamentos). Las pequeñas empresas, algunas sin fines de lucro, luchan por satisfacer parte de la demanda (p. ej. de condones femeninos). La protección de patentes internacionales contribuye a los elevados precios de los medicamentos y, aunque los acuerdos internacionales como las licencias obligatorias bajo el acuerdo TRIPS y la Reserva de Patentes de Medicamentos permiten mecanismos que les facilitan a los países más pobres obtener acceso a los medicamentos esenciales, los obstáculos creados por las “grandes farmacéuticas” son desalentadores. Todas estas barreras han fomentado un mercado de medicamentos de calidad inferior (p. ej. la venta por Internet de falsas tabletas de aborto con medicamentos). La agenda impulsada por las necesidades de salud sexual y reproductiva, basada en el derecho a la salud, se debe centrar en el acceso universal a los medicamentos esenciales a precios asequibles para los países en desarrollo. Hacemos un llamado para una mayor inversión pública en los medicamentos esenciales, mayor producción de medicamentos genéricos asequibles y la formulación de planes estratégicos más amplios, que incluyan medicamentos y tecnologías asequibles, con el fin de tratar los problemas de salud pública identificados, como el cáncer cervical.

Key Words:

• essential medicines
• pharmaceutical industry
• reproductive and sexual health care
• hormone replacement therapy
• human papillomavirus and vaccination
• medical abortion pills
• female condoms
• microbicides

In 2004, the World Health Assembly adopted the first global Reproductive Health Strategy, designed to guide member states to achieve universal access to sexual and reproductive health.¹ The Strategy describes five overarching activities necessary for accelerated progress: strengthening health systems capacity ; improving information for priority setting; mobilizing political will; creating supportive legislative and regulatory frameworks; and strengthening monitoring, evaluation and accountability. Under each of these overarching activities, more specific actions are described. For example, under “strengthening health systems capacity” actions include setting in place sustainable financing mechanisms specific to sexual and reproductive health, and determining the essential requirements at all levels for number and distribution of health workers with the skills needed to perform prioritized sexual and reproductive health interventions. Appropriate medicines and devices are mentioned only once, in the context of creating supportive legislative and regulatory frameworks:

“To ensure that regulations and standards are in place so that necessary commodities (i.e. medicines, equipment and supplies), which meet international quality standards, are available on a consistent and equitable basis.” ¹

The same section speaks of the need for an effective regulatory environment “to ensure public and private sector accountability for providing high-quality care for all the population.”¹ This meagre reference needs elaboration, as access to appropriate medicines, equipment and supplies is an essential piece of realising sexual and reproductive health for all.² And while it is heartening that the target “in cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing countries” has been added to Millennium Development Goal 8, with an indicator of “proportion of population with access to affordable essential drugs on a sustainable basis”³, little progress has been made towards achieving this target over the past decade.

Pharmacist at Dissikou health post, Central African Republic 2008

⁴

Gross inequity in access to appropriate, essential, quality medicines exists globally. There is over-medicalization in some parts of the world and a severe lack of essential medicines in others, with high prices, profit-making and other vested interests often driving developments alongside, or even above, concern for public health. These issues became a focus of activism both in the feminist women's health movement and the essential medicines movement in the 1960s and 70s, and are still highly pertinent today, with elements such as international trade agreements, competition between multinational pharmaceutical companies, southern-based companies producing generic drugs, small and non-profit NGOs struggling to produce medicines and devices that make little profit, and producers of sub-standard and fake drugs. To this, in the past decade, has been added massive investment in vertical programmes to deliver technological solutions to epidemic levels of illness by private foundations and global health initiatives, the latter supported by global institutions such as the World Bank, adding to the complexities.

Access to essential medicines for sexual and reproductive health

Contraception, abortion and protection of sexual health

In no other area of health is there so much “medication” for people who are well. Contraception and prevention of sexually transmitted infections (STIs) using condoms are about prevention in a very different way from prevention in other aspects of health and illness. Childhood immunisation, for instance, is a one-off or infrequently-repeated event, whereas protection against unintended pregnancy and STIs is something that people may need throughout their sexually active years. Between 700 and 800 million women or couples (there are no figures available for men alone) around the world are currently using some form of contraception.⁵ Condom sales in China alone reached 6.3 billion in 2008, indicating a massive market at the global level.⁶ Yet some 215 million women have an unmet need for contraception,⁷ lacking either the information or the means to obtain a method, or the ability to access services. This number is continuing to grow as population increases, contributing (along with contraceptive failure), to unintended and unwanted pregnancies.

Induced abortion methods have been hugely improved in the past three decades, making them among the safest procedures available in health care, especially early manual vacuum aspiration and medical abortion pills. While the types of contraceptive methods have not greatly increased during that same period, considerable refinements have been made, for example, improving the safety of both female and male sterilisation and IUDs, reducing the dosage of oral contraceptive pills, developing new routes of administration for hormonal contraception (injections, implants, vaginal rings) and new compounds for emergency contraception, making many of these methods both safer and simpler than previously.⁸⁹

However, the development of new and improved methods is only one factor in improving people's access to contraceptives. The pharmaceutical industry has probably never been interested in delivering contraception to developing countries, and official development assistance for family planning programmes was used to purchase large quantities of contraceptives for distribution in the developing world during the 1980s and 1990s. Such assistance has declined sharply since 1995¹⁰ and many national governments are now struggling to meet demand. Viet Nam, for example, which has a high modern contraceptive prevalence (68%), with most services received through the public sector, faces a large projected shortfall in the family planning budget. In response, the Ministry of Health decided to prioritize free or subsidized contraceptives for poor and vulnerable groups, and is debating whether and how to enhance social marketing and sales of contraceptives in the private sector.¹¹ Social marketing has stepped in because the industry stayed out, presumably perceiving too low a return for investment. However, as Ravindran has shown in Pakistan, social enterprises may not be able to overcome deep-rooted systemic weaknesses, overall lack of availability of equipment and supplies of contraceptives, and many other aspects that are needed to ensure access to contraception, let alone other reproductive health services.^{12 *}

Management of pregnancy and childbirth

Each year, globally, approximately 210 million women become pregnant: over 135 million of them deliver liveborn infants. The remaining 75 million pregnancies end in stillbirth, or spontaneous or induced abortion. It was estimated that in 2003 approximately 42 million pregnancies were voluntarily terminated: 22 million safely and 20 million unsafely.¹³ Based on 2008 estimates, more than 358,000 women die each year from pregnancy-related causes,¹⁴ of which 47,000 are from the complications of unsafe abortion.¹⁵ Morbidity and mortality related to pregnancy and childbirth account for one of the ten leading sources of “disease burden” in women aged 15–44 years and are responsible for 8% of the total global burden of disease for women aged 15–49 in the sub-Saharan African and South-East Asian regions.¹⁶ Although pregnancy and childbirth are natural conditions in themselves, complications can rapidly become life-threatening if not treated in a timely manner. Fortunately, the essential medicines and technologies needed for helping women safely through pregnancy, and for terminating a pregnancy, are not sophisticated or expensive and include: oxytocin for inducing contractions, misoprostol for the management of post-partum haemorrhage, mifepristone + misoprostol and manual or electric vacuum aspirators (MVA or EVA) for induced abortion and uterine evacuation, magnesium sulphate for the management of hypertensive disorders, along with standard health care supplies such as antibiotics, high-grade disinfectants, and blood.¹⁷ Ultrasound and labour monitoring machines help but are not essential. Yet, there are still large numbers of health centres in developing countries that do not have MVA, EVA or misoprostol, oxytocin or magnesium sulphate, blood supplies or antibiotics.¹⁸ Their absence is not only a technical issue of the supply of medicines, but also occurs in the absence of a health systems approach to maternity care that includes antenatal care, skilled attendance at delivery (including for miscarriage and stillbirth), post-partum care, safe abortions, and timely access to emergency obstetric care if required.

Treatment of STIs and HIV/AIDS

More than 448 million new cases of four bacterial STIs – gonorrhoea, chlamydia, syphilis and trichomoniasis – are estimated to have occurred in 2005¹⁹, all of which are curable with antibiotics. However, many remain untreated because they go undetected. The tests themselves are expensive; competent, affordable services are lacking; and stigma attached to STIs often deters people from seeking care, particularly women. Untreated gonococcal and chlamydial infections in women will result in pelvic inflammatory disease in up to 40% of cases, one in four of which will result in infertility. Worldwide, up to 4,000 newborn babies become blind every year because of eye infections attributable to untreated maternal gonococcal and chlamydial infections.²⁰ Most of these infections can be prevented through personal hygiene and use of condoms for sexual intercourse, but this can only be achieved if people have information and condom supplies, and access to treatment if needed.

UNAIDS estimates that at the end of 2009, there were 31–35 million people living with HIV (human immunodeficiency virus), and 2.3–2.8 million people became newly infected. AIDS is the world's leading infectious killer, claiming – to date – more than 27 million lives; an estimated 1.8 million of them in 2009 alone.²¹ The vast majority of those who died lived in low- and middle-income countries. Even though the number of newly infected people is one fifth fewer than the 3.1 million people newly infected in 1999, halting and reversing the spread of HIV has a long way to go. Highly active antiretroviral (ARV) treatment prevents the virus from multiplying in the body, enabling people to stay healthy and live longer, and greatly reduces the risk that they will transmit HIV. About 5 million HIV-positive people had access to ARV medicines in low- and middle-income countries in 2009, a 13-fold increase in treatment coverage since 2004, reducing deaths by 19% between 2004 and 2009.²¹ But global coverage is still reaching only 35% of those who need ARVs.²¹

Globally, deaths among children younger than 15 years of age are also declining.²¹ Nonetheless, more than 2.5 million children under 15 years were living with HIV and AIDS in 2009.²¹ Most of them lived in sub-Saharan Africa and were infected vertically during pregnancy, childbirth or breastfeeding. Yet in spite of increased access to services for preventing vertical HIV transmission, most pregnant women with HIV still do not have access to appropriate treatment.²¹ Recent WHO guidelines recommend that all HIV-positive pregnant women (with a CD4 count of <350) be put on ARVs and that they and their infants take ARVs during breastfeeding to prevent HIV transmission.²²²³ However, few pregnant women living with HIV are screened for their own health. The proportion of pregnant women who tested positive for HIV and were assessed for their eligibility to receive antiretroviral therapy for their own health increased from 34% to 51% between 2004 and 2009. But only 15% of pregnant women living with HIV whose HIV status was detected while attending maternal and child health services were also provided antiretroviral therapy for their own health at the same time as for their babies.²¹

New attention to sexual health problems of men

The sexual health problems of men have been seen largely as relating to infectious diseases, particularly STIs and HIV. This focus has finally begun to shift, as drugs developed for erectile dysfunction are proving useful as adjunct treatments for prostate disease and sexual recovery from invasive prostate cancer treatments such as radical prostatectomy, as well as their other uses. Awareness of the extent of prostate cancer is growing (it generally kills the same number of men each year in Western countries as does breast cancer in women), but calls for national screening programs are controversial, as the technologies are by no means perfect and the evidence for and against is yet to be conclusive. This in turn has shed light on younger men's susceptibility to testicular cancer, for which regular physical examination is now regarded as important. Fertility issues for men are now sometimes considered in relation to assisted reproductive technologies, e.g. concerning sperm donor policies. The ageing process in men has also become the subject of research and biomedical intervention concerning testosterone therapy (HRT for men), but is yet to be subjected to the scrutiny, debate and discussion surrounding HRT for women. In this regard, oestrogen therapy for late stage prostate cancer is showing promising results, but begs questions of bodily and psychological changes, side effects and issues of masculinity (Gary Dowsett, Personal communication, August 2011).

Access to essential medicines: a constant struggle

Access to essential medicines, including those for sexual and reproductive health, is one of the pillars of the right to the highest attainable standard of health, guaranteed through the International Covenant on Economic, Social and Cultural Rights,²⁴ now ratified by some 160 states. Yet it is an extremely long way from being realised, being one more graphic demonstration of the enormous inequities between developed and developing countries. As the history of efforts to bring ARV drugs to the developing world has proven, the ownership and price of medicines and the programmatic infrastructure to deliver them are critically important and among the main barriers to access. In 1977, in an effort to address the lack of access to medicines in the developing world, WHO set up the “Action Programme on Essential Drugs”, whose aim was to assist countries in formulating national medicines policies, selecting essential medicines and setting in place appropriate procurement mechanisms and a system of public sector pricing to ensure the availability, affordability and rational use of medicines that were safe, effective and of good quality.²⁵

In the three decades since, the Essential Medicines Programme (as it is now called) has contributed greatly to increasing people's access to essential medicines. While the Model List itself is not impervious to political pressures,^* the programme has played a crucial role in trying to redress the highly inequitable system of access to essential medicines, and has often stood up to heavy pressure from the pharmaceutical industry, most significantly in the global battle to introduce generic antiretroviral drugs, which at the time was highly controversial as large pharmaceutical companies used their extensive power to defend their patents. This is an ongoing battle.

Consequences of the profit motive for access to medicines

It is no surprise that the pharmaceutical industry's investment in innovations and developments in medicines, while grounded in health concerns, is driven first and foremost by profits. A pharmaceutical company will not be inclined to invest in products from which it will not be able to recover the costs and make enough profit. This means that investments in medicines tend to be targeted mainly to developed country populations, who can pay for them. Once the investment has been recouped, the industry may not be interested in making the products more affordable for people in other parts of the world, which probably explains why there has been very little innovation in contraceptive products or promotion of existing contraceptives by industry in developing countries in the past decade or so. In 2008, the hormonal contraceptive market was worth US$6.2 billion to the major pharmaceutical companies manufacturing such products in seven countries,²⁶ but this is comparatively low in market terms, where, in contrast, the global market for cardiovascular diagnostics and therapy was US$111 billion in 2006 and is estimated to reach $192.4 billion through 2012, a compound annual growth rate of 9.9%.²⁷ Such calculations have an impact on which medicines are developed and indeed how much they are promoted.

Another striking example of the bias in pharmaceutical priorities is the case of hormone replacement therapy (HRT). An examination of the rise in popularity of HRT shows the pharmaceutical industry cultivating women's fears of losing their femininity with menopause,²⁸ and a systematic downplaying of the known risks of HRT in favour of its purported benefits,²⁹ leading to a rapidly expanding market among older women in developed countries. The industry even managed to persuade the drug regulatory authorities in France, the US and UK to expand the off-label use of HRT based on untested claims regarding prevention of cardiovascular disease.²⁹ It was only with the publication of a large randomized, controlled trial demonstrating significantly increased risk of venous thromboembolism, coronary events, stroke and gall bladder disease, as well as an increased risk of both endometrial and breast cancers,³⁰ that the dangers of HRT started to be widely recognized. Yet in spite of these findings, the market for HRT remains brisk and is expected to grow considerably. A market research company reported in 2008 that: “The global market for HRT will increase from US$14.7 billion in 2007 to an estimated… US$25.9 billion in 2013, a compound annual growth rate of 10.4%.³¹ This could not happen without many doctors continuing to write HRT prescriptions. Fortunately, access to HRT for women in developing country settings has not been an industry priority.

A pertinent example for the developing world is the case of human papillomavirus (HPV) vaccines. Two major companies developed two different vaccines, both of which are highly effective in preventing two high-risk types of HPV associated with cervical cancer, while one of the two vaccines also prevents HPV types associated with genital warts. Cervical cancer, diagnosed in about 490,000 women annually, causes an estimated 240,000 death every year.³² Inequalities in the burden of cervical cancer incidence and mortality are striking, due to near universal screening and treatment in the developed world and their virtual absence in the developing world. Incidence rates in Europe, North America and Japan are around 10 per 100,000 women, while those for southern Africa are as high as 69.³³ The cervical cancer mortality rate is only about 2 per 100,000 in Canada, due to a high quality screening and treatment programme. Similar low rates are found in the Nordic countries, following the introduction of nationwide screening in the 1960s. The greatest fall was in Iceland, where the screening interval was the shortest and the target age range the widest.³⁴ Building on the success of these programmes, HPV vaccination of adolescent girls is growing rapidly in developed countries. The vaccines are only effective against two strains of HPV, however, so further development of the vaccines may be needed. Even with high vaccine coverage, a certain amount of screening will still need to be undertaken, because some women will already have HPV, but it is likely that the need for screening will be greatly reduced once there is high vaccination coverage.

Nonetheless, at this writing, neither HPV vaccine is yet available at an affordable price in the developing world – where vaccination would do the most good and is most urgently needed. In Uganda, evidence has been found of significantly higher prevalence of HPV in both HIV-positive women under age 25 (42–75% compared to 24–67% in HIV-negative women) and HIV-positive men (55–77% compared to 39–48% in HIV-negative men),³⁵ and greater expression of HPV infection and more rapid progression to cervical cancer in HIV-positive women.³⁶ This means that vaccine coverage, or early and regular screening, should be treated as essential in areas with high HIV prevalence.

The cost-effectiveness of HPV vaccination of men is still contested, even in developed countries, and greater coverage in young women as the way to protect young men is still being recommended.³⁷ However, both the strong association between HPV and HIV and the needs of men who have sex with men must be taken more into account. As one US study points out, HPV is the most common sexually transmitted infection worldwide, with 6.2 million new infections each year, and it has been implicated in a host of cancers, including oral, cervical, penile and anal cancers. Although the incidence of HPV infection drops in women older than 30 years, it remains high for men who have sex with men in all age groups. Indeed, in the US the incidence of anal cancer among men who have sex with men is higher than the incidence of cervical cancer among women. Yet few men who have sex with men are identified as high-risk patients in primary care or have been vaccinated against HPV.³⁸ Further research in other countries and reconsideration of vaccination policy regarding men is clearly called for.

In the US, the three-shot vaccination costs US$360, bringing in substantial revenue for the company. The promotion of these vaccines in the US when they first came on the market demonstrated a singularly narrow approach, carried out in a rush and in isolation from existing screening and treatment programmes and other developments in the field, presumably to recoup investments through aggressive marketing.^{39 *} On the other hand, if the companies were to work in concert with initiatives to introduce a comprehensive prevention, screening and treatment approach to cervical cancer in the developing world by making the vaccines widely available at an affordable price there, they would be making a major contribution to reducing the global incidence of cervical cancer.

Protest about this situation has been followed by considerable efforts on the part of the international health community to negotiate affordable public sector prices, reportedly for 75 developing countries (Jeffrey O'Malley, personal communication, August 2010). For example, the PAHO Revolving Fund for Vaccine Procurement for the Latin American and Caribbean region, which acts as a financial and management intermediary for vaccines, has helped Mexico negotiate a price of US$34 for the three doses.⁴¹ Nevertheless, even a price of US$15 for three doses would represent a major budgetary challenge for the region's poorer countries. On the other hand, even priced at US$30–60 for three doses, paying for prevention would be more cost-effective than treating late stage cancer at tertiary hospital level.

The new HPV DNA blood test, if used as a “pre-screening” test to identify women with high-risk strains of HPV, is expected to make an important contribution by seriously reducing the numbers of women needing to be screened, and therefore costs, thus potentially improving access for those who need cervical screening and early treatment. Visual inspection of the cervix has been field tested in a growing list of developing countries, as a lower-cost alternative to cervical cytology from India to Zambia to Mexico. But unless these screening modalities are scaled up in developing country settings where incidence is highest, but where no cervical cancer programmes currently exist, the high global rates of cervical cancer will persist. While the pharmaceutical industry is only one player on the scene, it appears able to block the possibility of reducing cervical cancer by pricing the vaccines out of reach where they are most needed. This poses fundamental questions about “ownership” of essential medicines and treatments from an ethical and human rights, as well as a public health, point of view. The need for public sector pricing is essential.

International trade agreements, licensing and generics

The high cost of many medicines is largely due to the international patent system, which grants monopoly protection to the innovator of a product, who can then completely control the price of the medicine, where it should be sold and in what quantities. The patent system is codified by the Trade Related Intellectual Property Rights (TRIPS) Agreement (a part of the World Trade Organization agreements), one of whose objectives is to balance the rights of the inventor with those of the consumer. The inventor is given a monopoly of 20 years as a reward for developing a new product, after which generic manufacturers are free to enter the market and reduce prices through competition.⁴² As a result, generics are always cheaper than the original patented product.

The TRIPS Agreement also allows for a mechanism called compulsory licensing before the 20 years is up. A compulsory license allows developing country governments to legally suppress a patent as a means of making medicines more affordable in their country. Such a license can be granted by a government to private or state-run firms without the permission of the patent owner. Licenses are typically motivated by a patent owner's refusal to license the patent or to make available the patented product at a price affordable for that country. The government issuing the license, or the firm making use of the license, must then pay the patent owner reasonable compensation. Regardless of who uses the license, the result is the same for the patent holder: manufacture and sale of its product without permission.⁴³ For those needing the medicine, the result is that it is available at a considerably lower price. For instance, in 2000 the best discount that originator companies were willing to offer for first-line ARVs was US$10,349, but Indian companies started marketing generic versions of the medicines for US$350.⁴⁴

A number of countries – Brazil, South Africa and Thailand among them – have declared compulsory licences particularly for antiretroviral treatment for HIV, in good part due to the enormous push by HIV activists globally for access to treatment for people living with HIV.^* Brazil has developed a very successful programme to provide free, universal access to treatment for HIV and AIDS. Its National STD/AIDS Programme reduced AIDS-related mortality by more than 50% between 1996 and 1999, and in two years, saved the country US$472 million in hospital costs and treatment costs for AIDS-related infections.⁴⁵ In 2006, the Thai government issued a compulsory licence for efavirenz (an antiretroviral) and within two months it had imported 16,000 bottles from an Indian company.⁴⁶ In 2001, South Africa was requested by another Indian manufacturer to issue compulsory licenses to patents on several HIV medicines. This, together with a complaint filed by the Treatment Action Campaign in South Africa against two big pharmaceutical companies for charging excessive prices for the same medicines, resulted in a settlement with one company to grant a voluntary license to national pharmaceutical companies.⁴⁷ All these actions have helped to improve access to HIV medicines.

In reaction, there are various initiatives by western governments, presumably backed by the pharmaceutical industry, to negotiate separate free trade agreements with provisions on international pharmaceutical patents that severely limit compulsory licensing. The European Union (EU) is currently negotiating with the Indian government for them to accept a “data exclusivity” provision that would force India's drug manufacturers to submit their own data on safety and effectiveness to be able to register their generic products, even though this information is already known, seriously hampering their capacity to produce and market generic versions of vital medicines at low prices.⁴⁸ Another initiative, the “trans-Pacific partnership” (TPP), led by the United States but involving Australia, Brunei, Chile, Malaysia, New Zealand, Peru, Singapore, and Viet Nam, proposes that patents be available for any new forms, uses or methods of using a known product, another way to effectively prevent poorer countries from eliminating patents on new forms of older products, to produce generic versions.⁴⁹ In March 2011, 11 advocacy groups from different parts of the world filed a complaint with the UN Special Rapporteur on the Right to Health, alleging that this proposed regional “free trade” accord violates human rights. This complaint is supported by guidelines for pharmaceutical companies with regard to access to medicines, issued by the Special Rapporteur in 2008, which include, amongst others, the obligation that:

“The company should refrain from any conduct that will or may encourage a State to act in a way that is inconsistent with its obligations arising from national and international human rights law, including the right to the highest attainable standard of health.” ⁵⁰

It is unclear to what extent these guidelines can be enforced, but their very existence provides an international legal basis for advocacy groups and others to demand compliance and accountability.

Of course, once original branded products come off patent after 20 years, other companies are at liberty to manufacture and distribute generic versions. A good example is Indian generic contraceptive manufacturers who contribute to the supply of quality, low-cost contraceptives on the international market, mostly through international tenders for government programmes.⁵¹

It is interesting to note that some large pharmaceutical companies have started programmes that appear to be geared towards providing cheaper medicines but only to “eligible” developing countries.^{52 *} In its 2006 Annual Report, a German company reported that it was donating nevirapine to some 156 programmes in 59 countries in Africa, Asia, Latin America and Eastern Europe.⁵³ And in 2009, the manufacturer of the quadrivalent HPV vaccine “made a commitment to donate at least 3 million doses… to organizations and institutions in developing countries, where more than 85% of the world's cervical cancer cases occur”.⁵⁴ The same company also reported that it has been making “affordable contraceptives available to ministries of health and non-governmental organizations in low- and middle-income countries around the world” for more than 25 years. Nonetheless, such “charitable” initiatives do not cover the great bulk of essential medicines needed nor are they open-ended.

Mobile pharmacy, Tahoua village, Niger 2005

A more recent initiative to address the crippling costs of patented medicines for poorer countries is the Medicines Patent Pool. Established in 2010 by the international health financing mechanism, UNITAID, the Pool aims to stimulate innovation and improve access to HIV medicines through the negotiation of voluntary licences on medicine patents that enable generic competition and facilitate the development of new formulations. The US National Institutes of Health was the first patent holder to join the Pool when it licensed darunavir (an ARV) in October 2010,⁵⁵ and since then another company manufacturing antiretrovirals has also joined. Unfortunately, the licensing agreement also excludes middle-income countries like Brazil and China, restricting its coverage.⁴⁹

Cost of medicines, sub-standard and fake products

In the developed world, the cost of medicines is usually reimbursed, at least in part, by government or private health insurance schemes; because of this, prices may even be bumped up, although there is a push for more and more generic medicines on grounds of cost-saving. On the whole, there is strict quality control for both branded and generic medicines. In Australia the prices of all medicines used in the public health system are a matter of negotiation between the government and the pharmaceutical industry, and prices tend to be a matter of compromise and somewhat cheaper than in comparable countries. In developing countries, broadly speaking, insurance schemes are few and far between, and even with the use of mechanisms such as compulsory licensing, prices are disproportionate to people's incomes. There is thus huge scope for the manufacture and sale off prescription of cheaper, unregistered medicines, some of which may be of acceptable quality, but many of which are sub-standard.

Sub-standard medicines can be found nearly everywhere in the world, and range from inactive, ineffective preparations to random mixtures of harmful toxic substances. Sub-standard medicines may also be “counterfeit”, that is, “deliberately and fraudulently mislabelled with respect to identity and/or source.”⁵⁶ The marketing of counterfeit medicines is a criminal activity with the specific intent to defraud that involves infringement of trademarks,⁵⁷ and “anti-counterfeiting” legislation has been recently introduced in many countries.⁵⁶ However, counterfeit medicines may not be sub-standard, but only represent an infringement of trademark. Generic medicines are, by definition, off patent, but with TRIPS flexibilities allowing the use of compulsory licensing, they are not “counterfeit”. However, there is considerable confusion about this and generic medicines may be at risk under the proliferation of anti-counterfeiting legislation in countries of East Africa (Burundi, Kenya, Rwanda, Tanzania and Uganda) that are susceptible to US and EU pressure.⁵⁸ One of the most effective measures to lower the prices of medicines is to encourage generic competition, and placing patent infringement under the rubric of counterfeit medicines potentially handcuffs countries from using one of the most effective means of depriving counterfeiters of a space from which to operate.⁵⁶

Procurement and distribution of medicines is haphazard and open to corruption in many low-income countries, resulting in many health centres – particularly in rural areas – having no medicines at all.⁵⁹ Low salaries may also lead to some health workers selling medicines privately that should be free.⁵⁹ Another major cost-related issue is that the same medicines are sold by the same companies at different prices in different countries. AIDS activists pointed this out in relation to HIV treatments years ago, but it is true in many other instances as well.

It is the nature of industry generally to respond to market demand and to make profits from their products and investments. Positive benefits include promoting innovation, fostering competition to bring prices down, providing products that people need and providing employment. In the case of the pharmaceutical industry, however, the stringent protection of “intellectual property” plays a key role in keeping prices high, and in fostering the manufacture of alternatives which are often sub-standard. Strategies such as compulsory licenses and generic manufacturing are essential mechanisms for countering the enormous power of this industry.

Internet trade in medicines

The internet trade in medicines now represents a huge, unregulated (and perhaps unregulatable) market globally, which needs more research and attention. Legitimate products that do not require a prescription are available. However, in over 50% of cases, medicines purchased over the internet from illegal sites that conceal their physical address have been found to be counterfeit or fake.⁵⁶ Spam e-mails selling what they claim is viagra and other drugs and devices said to enhance sexual performance are common. Unverified brands of medical abortion pills are another case in point, as a study by Women on Web found. Internet sale of drugs are here to stay and in many cases the web may be the only source of a product such as medical abortion pills or emergency contraception, where these are restricted. However, people need to be advised to be cautious when purchasing any medicine on the internet from an unknown source, since it may be ineffective or even dangerous, and the seller may charge unjustifiably high prices (see ICMA statement at <www.medicalabortionconsortium.org/icma-statement-on-misoprostol-internet-sale.html>).

Non-profit and public-private initiatives: their potential and actual impacts

When big pharma fails to develop or market an essential medicine, an alternative path is a non-profit or public-private initiative. There are a number of examples of non-profit research and development projects and of non-profit companies launched to manufacture, promote and distribute essential medicines for sexual and reproductive health. Most have met with many obstacles along the way. The microbicides story is an example of a need perceived by women's health advocates, which was taken up by supportive scientists and eventually led to the setting up of the International Partnership for Microbicides, a well-funded global health initiative, who took over research and development of a number of formulations and delivery systems. After years of research, for which there has been no industry involvement or funding, a microbicide formulation, using the ARV tenofovir, already being used to treat HIV disease and prevent vertical transmission, has given proof of concept in a clinical trial. It was shown to offer women some protection against sexual transmission of HIV, and a vaginal gel and vaginal ring may well emerge from this research.⁶⁰

The development of the female condom, first introduced in 1984, and of the Female Health Company as a public-private partnership to manufacture and distribute it, is another story of a method intended to be controlled more by women, produced by only one small company that has been struggling for years to survive without the financial backing needed for widespread promotion and distribution. Global public sector agencies, country governments and public and private donors have been instrumental in helping the Female Condom gain greater acceptance. Female condoms are now available in 100 countries worldwide, but access to them is still severely limited and demand is not being met. However, it took 18 years of losses before the company became profitable, and was finally able to consider expanding production and marketing (see <www.femalehealth.com/aboutus/companyhistory.html>). While unwillingness to use these condoms has often been cited as the main reason for the company's difficulties, a recent evaluation on access to new health technologies in poor countries argued that:

“universal access to female condoms is not primarily hampered by obstacles on the users' side, as is often alleged, nor by unwilling governments in developing countries, but that acceptability of the female condom is problematic mainly at the international policy level”. ⁶¹

A recent initiative to expand access to the female condom has been created through a product development partnership between a technology research NGO and the manufacturer of the new “woman's condom” in China. Activities of the partnership include development of a market in sub-Saharan Africa as well as China, obtaining international regulatory clearance, building evidence of effectiveness, and creating and sustaining advocacy initiatives to raise awareness of demand for the female condom.⁶²

The Concept Foundation is another example of an initiative set up to respond to decades of obstacles to making medical abortion pills mifepristone and misoprostol available to women, which has only been possible since the pills (which had only previously been produced by different companies) came off patent. The Foundation has worked with colleagues to develop a pill packet with the approved dosage of both pills, which is being produced by an Indian generic manufacturer. The Foundation, as a non-profit NGO, is promoting both the registration of the drugs in developing countries and their sale and distribution at low prices in conjunction with the manufacturer, with the support of donors. This has been a long, slow, sometimes agonising process as all the forces still ranged against abortion, and the controversy manufactured around abortion to keep it stigmatised, come into play in countries. The Foundation is similarly involved in manufacturing and distributing injectable contraceptives (see <www.conceptfoundation.org> and <www.medabon.info>).

Although not involved in the sexual and reproductive health field, the Drugs for Neglected Diseases initiative (DNDi) is another interesting alternative model for research and development of new medicines. Set up to respond to the fact that essential medicines to treat many diseases that affect the world's poor are either too expensive, no longer produced, highly toxic, or ineffective, DNDi is a collaborative, non-profit research and development organization, driven by patients' needs, consisting of five public health institutions, including in Brazil, India and Kenya, the Malaysian Ministry of Health, and one humanitarian organization, working in partnership with NGOs, industry and academia. (see <www.dndi.org/index.php/overview-dndi.html?ids=1>).

While not a non-profit initiative, the Health Impact Fund has been proposed by some as a way of providing pharmaceutical innovators financial incentives to develop new medicines based on a global health impact assessment exercise. Such a fund would enable companies to sell such medicines worldwide at no more than the lowest feasible cost of production and distribution and compensate the innovator through a share of fixed remuneration from a reward pool.⁶³ However, this proposal appears to be some way from being realised, and it is unclear whether any new medicines essential for sexual and reproductive health would be included in the impact assessment.

The long-term goal: an agenda driven by public health needs

Making essential medicines available through appropriate mechanisms can dramatically change people's lives and health, but as this paper has shown, access to medicines for sexual and reproductive health care, particularly essential medicines, is subject to the same forms of scarcity and inequity as access to every other aspect of health care services. Unless funding is forthcoming, as an example from Myanmar testifies, nothing will happen. A pilot study in a rural area of Myanmar demonstrated that community-based midwives were able to administer oral misoprostol for the prevention of post-partum haemorrhage as part of active management of the third stage of labour, with no case of post-partum haemorrhage occurring. The author of a paper on this study says:

“Thus, we have now found one way to help to bring down maternal mortality, especially in the remote rural areas, by introducing this simple, cost-effective, appropriate and feasible intervention. However, the challenge is how to achieve universal coverage. It will cost US$1.5 million annually to provide misoprostol tablets for every delivery. We believe inter-sectoral coordination, community participation and social marketing are part of the answer.” ⁶⁴

While the last 50 years have seen progressive moves towards defining a universal list of essential medicines, manufacture of generic drugs and negotiation of public sector prices for essential medicines, the vast bulk of research and development, manufacture and distribution of products supporting sexual and reproductive health, remain in the hands of multinational, private, profit-making companies.

An agenda driven by sexual and reproductive health needs and based on the right to health must focus on closing the gap between what medicines are needed and what low-income countries actually have and can afford. The fact that a specific target to provide access to affordable essential drugs in developing countries “in cooperation with pharmaceutical companies” has been added to MDG 8 is important,³ but far more work needs to be done to achieve it. Greater public investment in the alternatives to “big pharma” monopoly would be an important contribution. Use of the TRIPS flexibilities in patent law must be reinforced and protected. Promising new mechanisms such as the Medicines Patent Pool must be promoted and expanded beyond protecting HIV medicines to all essential medicines, including for sexual and reproductive health care. Different ways of supporting countries to ensure adequate and regular supplies essential for sexual and reproductive health must be found. Some mechanism through which pharmaceutical companies would develop products within a broader strategic plan of addressing identified public health problems, such as cervical cancer, would be yet another important contribution. The further development of generic medicines with rigorous quality control, used in tandem with the WHO Model List of Essential Medicines, is also something to promote, together with sufficient and reliable financing, research and development of new products targeted for use in resource-poor settings. Governments and inter-governmental agencies must be called upon to live up to their obligations to protect access to medicines as a fundamental component of the human right to health.⁶⁵

At this point in time it is hard to imagine how such mechanisms can be put in place in a sustainable manner, given the extraordinary wealth and power of “big pharma”. Nonetheless, there was a time not so long ago when it was also hard to imagine the growth in generic medicines, the incredible increase in access to treatment that has been achieved for people living with HIV and AIDS in developing countries, or the successful appearance of medical abortion pills in places where all the forces on earth ranged against women's right to a safe abortion have not been able to stop women getting access to them.

Acknowledgements

An earlier version of this paper was presented at the meeting Repoliticizing sexual and reproductive health and rights, Langkawi, Malaysia, 3–6 August 2010. We thank Kajal Bhardwaj, Jeffrey O'Malley and Gary Dowsett for valuable comments at that meeting and since.

Notes

* The components of a comprehensive family planning programme included by UNFPA in the ICPD costed population package are as follows: contraceptive commodities and service delivery; capacity-building for information, education and communication regarding family planning and population and development issues; national capacity-building through support for training; infrastructure development and upgrading of facilities; policy development and programme evaluation; management information systems; basic service statistics; and focused efforts to ensure good quality care. (At: <www.unfpa.org/webdav/site/global/shared/documents/publications/2006/resources_flows_2006.doc> p.7).

* Various hormonal contraceptives are included on the WHO Model List of Essential Medicines, including levonorgestrel for emergency contraception. However, the two medical abortion pills, mifepristone and misoprostol, which are most effective when taken together, were only approved for inclusion after several years' delay because of concerns that WHO might be seen as “promoting” abortion. Even now, the entry for these pills carries the rider “where permitted under national law and where culturally acceptable”, the only medicines on the entire list that carry such a disclaimer. Fortunately, the more specific “Essential Medicines for Reproductive Health”, published in 2006, includes a full description of mifepristone with misoprostol for medical abortion, with no such “rider”.⁸ Nonetheless, even though it has been available since 1988, mifepristone was approved in only 46 countries as of June 2010 (see <http://gynuity.org/resources/info/list-of-mifepristone-approval>). Hence, most women must still use misoprostol alone.

* The quadrivalent vaccine (that protects against the four HPV types) received US Food and Drug Administration (FDA) approval in June 2008, before the final safety evaluation trials were complete, and it was then mass-marketed on TV and in cinemas in the US through advertisements pitched to young girls. The manufacturer also lobbied state legislators to introduce mandatory vaccination in schools for girls from age 11.³⁹ It has also given extensive financial support to various professional medical associations to promote the vaccine, providing lecture kits, slides and various rewards for educators.⁴⁰

* E.g. the Treatment Action Campaign in South Africa, who work to hold government accountable for health care service delivery, cultivate community leadership on HIV and AIDS, campaign against official AIDS denialism, and challenge the world's leading pharmaceutical companies to make treatment more affordable (see <www.tac.org.za>).

* “Eligible” here may mean excluding middle-income countries. According to the 2011 Médecins Sans Frontières report, Untangling the Web of ARV Price Reductions, presented at the 6th International AIDS Society conference on HIV pathogenesis, treatment and prevention, Rome, 17–20 July 2011, a number of pharmaceutical companies will no longer be providing preferential pricing for AIDS drugs to middle-income countries like Brazil, China, India and Thailand. At: <http://utw.msfaccess.org/>.