AIDS). Director, Infectious Disease Division, Pistoia Hospital, Pistoia, Italy

Transcription

1 1 PROFIT RULES AND THE RIGHT TO APPROPRIATE ANTIRETROVIRAL TREATMENTS: SUITABILITY OF INCENTIVE-BOUND WHO-MEDIATED VOLUNTARY LICENSES FOR EQUITABLE LONG-TERM SOLUTIONS Daniele Dionisio 1 * 1 Coordinator, Access to Drugs: International Policies branch - CLIA (Network for International Fight against AIDS). Director, Infectious Disease Division, Pistoia Hospital, Pistoia, Italy *Address correspondence to this author at the Infectious Disease Division, Pistoia Hospital, Piazza Giovanni XXIII 1, Pistoia, Italy; Tel: ; Fax: ; d.dionisio@usl3.toscana.it Summary AIM: To explore the suitability of incentive-bound WHO-mediated voluntary license agreements (VLs) for equitable long-term solutions attuning together the profit rules and the right of poor populations to appropriate antiretroviral treatments (ARVs). METHODS: Model potentials were assessed through concurrently considering: 1) the expected impact on current regulatory obstacles (enforced TRIPS rules and TRIPS-plus measures such as free-trade agreements and exacerbated data exclusivity), 2) the advantages over compulsory license, differential pricing and donation options, both in the sake of kids and adult end-users and in terms of feasibility, equity and sustainability, as well as safeguard of the generic and brand name manufacturers s interests, 3) the interplay dynamics with the drug trading policies of deeply involved countries (China, India, US, Brazil, South Africa and Thailand), 4) the suitability for helping new home plants for ARVs in Sub-Saharan Africa take off and engage in research & development (R&D) partnerships encompassing technological catch-up, exploitation of TRIPS flexibilities, raised job opportunities, as well as improved marketing power. RESULTS: Incentive-bound VLs look superior to other options and able to secure, as long as they entwine with WHO s brokerage, equitable and sustainable access to ARVs by poor populations, while boosting R&D, expanded drug provision, domestic industry plants development, as well as penetration of the wealthy and under-served markets by generic competitors, along with slashing of drug prices linking to a stably growing economy. Unaffordable drug prices are still among the major obstacles to antiretroviral (ARV) treatment access in the income-constrained countries. Cost of second-line combination treatments with protease inhibitors (PIs) is ten times the average amount of first-line combination generic antiretrovirals (ARVs) which is US $ per adult person per year. Actually, the cost of first-line generic combinations should be reduced too to help fill the monetary gap between overall needs and the funding available. Challenges are all the more complicated by regulatory obstacles bound up with enforcement of TRIPS (Trade-Related Aspects of Intellectual Property) rules inside the World Trade Organisation (WTO) [1] (Table 1). Definitely, patent rules, along with exacerbated data exclusivity rules (Tables 1, 2), do hamper the development of any new generic ARV formulation, either individual ARVs or fixed-dose combinations (FDCs) that contain drugs with exclusive status [2]. Insightfully, this is a worrisome situation based on second generation medicines, as well as any new drugs are crucial to HIV treatment programs once first line ARVs fail [3]. A core problem with current patent system is that it allows brand name enterprises to charge the price that the market will endure and not a price consistent with the real manufacturing and research & development (R&D) costs. At the same time, current patent protection, by eliminating competition, does skyrocket drug prices. Even worse, unceasing pressing by European Union, Japan and the United States (US) on the Geneva based World Intellectual Property Organization (WIPO) towards global harmonisation of patent laws could herald less autonomy in national decision-making about patents, loss of TRIPS flexibilities (Table 1), and too expensive medicines on the poor countries horizon [4 ]. This stifling backdrop mostly damages children. The market for paediatric ARVs in the US and Europe is very small compared with the developing world [5, 6]. Consequently, there is no incentive for brand name corporations to develop new ARV formulations for children because they aren t a lucrative market. On the other hand, generic manufacturers are discouraged because paediatric formulations are still a niche product in income-constrained countries where achievement of accurate demand forecasting still remains difficult (even though new data indicate that the market for paediatric ARVs is already substantial and will only grow with

2 2 improved and scaled up diagnosis and monitoring of children) [6]. Difficulties are further compounded by the fact that treating children implies much higher costs than adults [7, 8]. On the flip side, TRIPS rules do encompass flexibilities as mentioned (including compulsory licenses-cls, voluntary licenses-vls, as well as parallel importation and bolar exceptions) to help poor populations equitably access low-priced ARV treatments (Table 1). Actually, some flexibilities could act, if appropriately harmonised through combination incentives, as equitably balanced tools for trade agreements securing all counterparts sustained advantages (see later). Enforcement of these favourable perspectives is conditioned hugely by long-term trade and drug policy directions of China and India due to frontier crossing implications of their TRIPS management, along with their mushrooming penetration of the wealthy and under-served markets the world over. Again, enforcement substantially depends on feasibility of measures to effectively offset protectionist US drug trading policy. Eventually, to extensively be put into effect, these favourable perspectives also depend on the policy directions of at least Brazil, South Africa and Thailand. Implications from India and China s management with TRIPS rules Almost all countries are requested, as WTO member states, to conform to the 1994 WTO Agreement on TRIPS (Table 1) [1]. China implemented patent regulation in 2002, while TRIPS compliance took effect in India on 1 st January Overall, big industrial plants of these two countries supply most of home needs while exporting high volumes of drugs to the under-served markets. China and, to a lesser extent, India are, moreover, the major suppliers of active pharmaceutical ingredients (APIs) for ARV drugs to both developed and developing countries [9]. Definitely, this faculty assigns both countries a crucial power in influencing evolution of ARV drug prices. Indeed, as APIs represent the largest components of direct manufacturing costs (55-99%) [10], significant price variations for APIs would predictably be followed by a same extent ARVs price fluctuation. India s thwarting trend: what escapes? Recently revised Indian patent law [11] has, regrettably, posed a threat to keeping on affordable ARV treatment access. According to the new Bill, mailbox medicines (Table 1) and newer drugs whose generic versions have not yet made by Indian firms can only be sold as branded originals unless CLs or straightforward agreements between the patent holders and Indian generic manufacturers have been undertaken. On the contrary, Indian companies now producing generic versions of medicines for which patent applications were submitted prior to 1 st January 2005 are allowed to keep on with manufacturing and marketing, provided that they have made a significant investment and pay a reasonable royalty to the patent owner [11]. Definitely, this backcloth alerts that, without incentives by Indian government, the prices of generics produced under such a royalty imposition will only increase making these drugs unaccessible by the poor. This environment also means that CLs will hardly be issued by Indian government mainly because of threats to keeping on with partnerships with research-based enterprises along with risks of blackmail by wealthy country governments and multinational corporations (Table 3). Conversely, TRIPS-bound VLs (Table 1), if offset in their royalty imposition through incentives to firms, could actually help Indian companies overcome handicaps by TRIPS rules while keeping drug prices low (see later). What on China s horizon? China could possibly become, in the next future, the ARV factory for the poor world because of both its cheapest APIs for ARVs and its accelerating industrial scale-up coupled with steady penetration of the under-served markets [12, 13]. Chinese producers are already making first-line ARV formulations, as well as the raw materials for a wide array of first and second-line ARV drugs [12]. China s research into innovative drugs is rapidly enhancing, particularly in the biotechnology sector, while its drug development industry has a number of advantages: a large patient population, lower costs of labour and clinical trials, approval process shorter compared with US [12]. Regrettably, however, while no Chinese ARV drugs have been World Health Organization (WHO) pre-qualified so far, China is under pressure nowadays for its weak pursuance of TRIPS rules [14, 12]. Nonetheless, Chinese government, aside from

3 3 disinclination to streamline burdensome and risky CLs (Table 3), should definitely be attracted by TRIPS-bound VL flexibilities just for the following needs: - technological catch-up while aiming to compete with the multinational drug giants. - trustworthy relations with research-based companies while looking for the standard above. - enhanced domestic production of suitable ARVs including FDCs and paediatric formulations, both of which are not produced in China yet. - sustainable self-sufficiency in pharmaceutical manufacturing, so breaking away from dependence on fickleness and price fluctuations by foreign enterprises. Implications from conflicting US drug trading policy Appropriate strategies must be able to measure with protectionist US drug trading policy currently torn among 1) keen defence of brand name home product ( free trade agreements with coercive TRIPS-plus clauses are mushrooming) [15], 2) shy acknowledgment of generic ARVs, unfortunately without any reliableness for their routine use in the PEPFAR (US President s Emergency Plan for AIDS Relief) programme, 3) incidental opening towards generic ARVs as a result of US government strategic agreements on the international chessboard: actually, March 2 nd, 2006 US-India signed civil nuclear power agreement [16] is expected to substantially play as a boost to expand PEPFAR exploitation of Indian generic ARVs. Really, free trade agreements with TRIPS-plus clauses, nothwitstanding US touted acknowledgment of generic medications, do actually threaten to prevent future production of low-cost, generic ARV alternatives for use in PEPFAR. That s why closer cooperation is urged between the United Nations system and the Office of PEPFAR Global AIDS Coordinator. Actually, something has stepped forward, and boost to expand ARVs access by children is expected by the newly PEPFAR-released public-private partnership for paediatric AIDS treatment encompassing innovator and generic pharmaceutical companies along with the United Nations Children Fund (UNICEF) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) [17]. Implications from Brazil, South Africa and Thailand s policies Brazil, South Africa and Thailand, though unreliable to equal India and China s predictability in securing poor countries second-line ARVs for paediatric and adult needs, appear, however, with some chance to do so. This, based on worst-off minded government directions, will mainly depend on whether national companies will be capable of negotiating profitable agreements with the multinational counterparts [18]. To this aim, VL flexibilities, along with WHO brokerage, should always be experienced in transactions [19]. Towards a working combination incentive strategy Generic companies look currently as the most fitting target for incentives to tackle ARV treatment needs in the poor world. Intriguingly, support to generic companies would spur competition with research-based corporations as far as control of the underserved markets is concerned. In such a perspective, western multinationals should necessarily try to enter these markets through negotiating partnership agreements aiming to recoup lost time and reduce the gap with high-level technology, market penetration and attraction power already achieved by their generic counterparts. These processes, by enhancing competition among all involved parties, would ultimately slash the drug prices. According to insights above, combined incentives for generic manufacturers must be explored and should encompass public, private and/or intergovernmental subsidies using public-private partnerships, as well as fiscal drug softening, funding and simplification of patent rules. Funding should be raised by governments and major international donors, based on generic companies do accept WHO pre-qualification check. Funding could even arise through giving African governments support to meet their commitment, as in Abuja Declaration, to set aside 15% of national GDP (Gross Domestic Product) for health sector spending [20]. This would quite be achievable if debt cancellation to poor countries by G8 Heads of State and Finance Ministers will fully be met [21, 22].

4 4 Incentive-bound VLs as a key option Coherently with overall thoughts here, VLs do appear as a fitting strategy nowadays, notwithstanding they impose royalties on generic firms: these licenses, indeed, only imply direct agreements between firms; they do not require changes in national legislation, while including non-exclusivity, openings towards technology transfer, access to owner s data for branded medicines, as well as consent for export (Table 1). In South Africa and, more recently, Kenia VLs were signed between patent-holding companies and generic industries for ARVs production [19, 23]. Really, VLs look fruitful because research-based corporations are secured economic profits, while advantages to developing country firms are enjoyable as well: these include domestic market growth as well as technology transfer and R&D partnerships which act as prerequisites for enhanced competition capability in the western and under-served markets. This model, again, by letting developing country-based (Brazil, Singapore, Chile, Thailand, South-Africa...) generic firms depending on major APIs producers be secured low-cost APIs, would help allow these firms to keep on with domestic ARV drug production. Such a policy would also be crucial in helping least-developed countries with no manufacturing capability still import affordable generic ARVs without undertaking hardly doable CL-bound changes in national law (Table 1). Likewise, predictability of HIV resistance mutations in the developing world does allow VLs to be assigned another spin-off which links in with urgency for second-line and newer ARV drugs [7]. Clearly, owing to royalty imposition, VL frames must secure combination incentives to generic firms. These incentives, aimed to keep prices as lowest as possible, are first awaited by country governments and international players, including the Global Fund to Fight AIDS, TB, Malaria, World Bank, WHO and UNAIDS. Based on complementarity with all of these institutions, the recently launched UNITAID-International Drug Purchase Facility [24] is expected, if stably implemented in its dedicated revenues, to substantially help combination incentive strategy succeed. Under such a perspective, country governments could be assigned UNITAID revenues to finance fiscal relief to national generic companies. Additionally, UNITAID revenues could serve multi-year large-volume purchasing programmes with generic drug companies be negotiated by international players. This strategy is expected to spur R&D and marketing power, while slashing drug prices and accelerating WHO pre-qualification and drug distribution in developing countries. It would also let international organisations be borne by a new player bringing together several contributors. In detail, combination incentives should comprise: -Generic ARVs exclusive bulk purchasing by international donors, based on acceptance by firms of WHO prequalification surveillance These agreements would result in reduced drug prices thanks to the certainty of a growing market. Transparency enjoyed through WHO prequalification check would make this model quite trustworthy. -Fiscal relief by country governments Sources of tax allowance: enhanced disbursement by international donors, domestic expenditure priority reallocations, debt relief savings from debt cancellation to poor countries. WHO and UNAIDS, following acknowledgement of country pledges to channel debt relief savings towards tax allowances, should engage in promoting approval of debt cancellation and closely checking for pursuance of the pledges. -WHO brokerage in VL agreement negotiations with research-based corporations These regulated agreements mean as incentive for technological catch-up and easier access to profitable wealthy markets by generic firms while ensuring equitable drug access by poor people as well. VLs and domestic drug plants development in Africa: a fruitful link Overall insights above also highlight the reasons for setting up, following already working examples [7], country-owned plants for generic ARVs in Sub-Saharan Africa as well. Home plants would play as a prerequisite for negotiating, through WHO brokerage, profitable VLs encompassing equitably expanded ARV drug access. Really, a credible industrial potential would act as a boost for drawing branded drug producers into technology transfer agreements the terms of which would let all counterparts enjoy substantial advantages. Under such a perspective, China s cheapest APIs could definitely serve as an affordable source for allowing domestic

5 5 sub-saharan plants to take off. These insights sound consistent with Chinese increasing interests in Africa as documented by China s multi-pronged bilateral agreements currently being signed with many African countries and encompassing -though not limited to- trade, energy supply, investments, as well as infrastructure and health cooperation [13]. Final remarks The model explored here looks able to secure, as long as it entwines with WHO s brokerage [25], equitable ARV drug access by the poor while boosting R&D, expanded drug provision, national industry plants development, as well as penetration of wealthy and under-served markets by generic competitors, along with slashing of drug prices thanks to the certainty of a stably growing economy. Incentive-bound WHO-mediated VL use should be enhanced in transactions between western multinationals and generic companies as far as second-line ARV drugs, including newer FDCs for children and adults, are concerned. VL use, indeed, would allow generic manufacturers to overcome patent protection rules while being not barred by coercive data exclusivity rules which do hurdle, instead, CL use (Table 2). Additionally, VL use would bear countries against the risk that 6 December 2005 CL-bound public health waiver (Table 1) might not be formally built into the TRIPS agreement. This concern arises from slow progress made, as of November 2006, into ratification of the waiver by WTO membership [26]. Based on their potential including suitability for meeting requirements and needs by all parties, incentive-bound VLs do appear, under WHO s brokerage, as a key formula nowadays with advantages over CLs, differential pricing or donations (Table 3) [27, 7]. Really, other ways seem hardly feasible. As an example, the suggested transferable market exclusivity model (by the International Federation of Pharmaceutical Manufacturers & Associations-IFPMA), grounding on granting a company patent extension for products that are marketed in the developed world, in exchange for performing R&D on neglected diseases for the developing world, looks actually unreliable as far as urgent need for life-saving medicines is concerned [28]. Likewise, the proposed US legislation Medical Innovation Prize which suggests new drugs to be treated as generics and patent owners be rewarded from a US award fund for coming up with innovations for better health, does sound quite hard to be put into force [28]. Again, patent donation and pooling do not appear as routine measures and look almost restricted to university centres [28]. To conclude, dynamics highlighted here also mean that the trade and profit rules cannot basically be given up if long-term results are the goal to look for. Only agreements securing all contractors lasting advantages will be able to shift such a goal from vision to sustainable achievement.

6 6 Table 1 TRIPS REGULATORY TERMS AND DATES FOR PATENT STATUS OF DRUGS IN LOW-INCOME COUNTRIES Patent A twenty- year warranty securing inventor exclusive rights on the overall drug production and marketing aspects. When countries signed up to World Trade Organisation (WTO) they accepted to protect the patent rights of corporations selling drugs within their boundaries. TRIPS (Trade-Related Aspects of Intellectual Property Rights) 1994 WTO Agreement to the safeguard of Intellectual Property Rights (IPRs) around the world. It protects companies by stopping anyone from copying their products for twenty years at least. Drugs invented before 1995 No need for patent protection by a WTO member State if drugs were not patented before 1995, i.e. before TRIPS came into force mailbox drugs It refers to invented drugs (including second-line ARVs) for which WTO members which did not recognise drug patents before 1995 were offered diversified time limits to become TRIPS-compliant. Transitional countries have to hold patent applications on these drugs in a so-called mailbox and secure patent applicants exclusive marketing rights (EMRs) for five years once drug was in the mailbox and registration was made by the national drug regulatory authority. Post-2005 drugs All WTO members, with exception of least-developed countries (LDCs), are requested TRIPS compliance. Dates for LDCs Doha Declaration November 14, 2001 Compulsory license (CL) Voluntary license (VL) Decision August 30, 2003 Parallel importation LDCs have to become TRIPS-compliant by 2006 but, if national legislation has been consistently amended, they are exempted from accepting patent protections and TRIPS enforcement until Aside from this flexibility, even LDCs have to issue compulsory licenses (see below) for importing copies of drugs already patented in pre-trips domestic law. It stated that each WTO member has the right to use TRIPS-enompassed flexibilities (which include compulsory and voluntary licenses) to secure universal access to drugs in the face of a public health need. It is when a poor country government allows to manufacture domestically or to import copies of patented drugs at prices much cheaper than those imposed by the patent holder and without his consent. Both importing and exporting countries need to have enabling legislation in place (a corresponding CL for export has to be issued by the exporting country). Prior negotiation with the patent owner for voluntary license first is required unless for situations including extreme health crisis and not-for-profit government use. Payment of a royalty to the patent owner is encompassed by CL rules. Agreement negotiated with the patent s owner for manufacturing and marketing. Notwithstanding royalty rates imposition on generic firms, these licenses only imply straightforward agreements between companies; they do not require changes in national legislation, while including non-exclusivity, openings towards technology transfer, access to owner s data for branded drugs as well as permission for export. It allows non-manufacturing countries to issue a CL to import a generic version of a particular medicine based on a CL for export issued by the exporting country government. Declaration by the non-manufacturing country of insufficiency in manufacturing the specific drug is required. WTO amendment approved on 6 December 2005 made the Decision permanent, based on two thirds of WTO members have ratified it by December 2007 [26]. So far, Norway, Canada, India, the EU, Korea and China have altered their laws to meet conditions for export. Importing of fairly priced patented drugs for which the rights of the patent owner have been exhausted by the first sale. Bolar exception Permission to a generic firm for copying and registering a patented medicine before patent expiry. It could exceptionally be applied only if the normal rights of patent holder are pledged. Data exclusivity Data protection against unfair commercial use only (but five and eight year protection have been respectively requested by U.S. and Europe).

7 7 Table 2 Data exclusivity (exacerbated) Term refers to a practice which temporarily bars registration files of an originator from being used to register the generic copy of a brand-name medicine. As long as fixed time period ( five years in the U.S. and eight years in the Europe), Drug Regulatory Authorities are prevented from registering such generic equivalents unless generic producer has carried out independently the required safety and efficacy tests, or bilateral agreements encompassing Voluntary License (VL) use (Table 1) have been undertaken. Data exclusivity impact does actually consist in barring Compulsory License (CL) use (Table 1) until the expiry of data exclusivity itself and, mainly, in securing research-based companies a monopoly period in countries agreeing to data exclusivity even when a medicine is not patented in the specified country. Definitely, this practice goes far beyond WTO request for data protection against unfair commercial use only (Table 1).

8 8 Table 3 VOLUNTARY LICENSE ADVANTAGES OVER COMPULSORY LICENSE, DIFFERENTIAL PRICING AND DONATION OPTIONS VOLUNTARY LICENSES (VLs) - suitable for attaining (through technology transfer) technological catch-up while securing transparent relations with research-based companies. - suitable for breaking away from dependence on fickleness and drug price fluctuations by foreign corporations. - suitable for keeping generic drug prices more affordable than those of branded originals even after cutting by patent s owners. - suitable for securing both research-based and generic industries lasting advantages which may include market expansion, economic gains as well as manufacturing and R&D partnerships. - suitable (as per export authorization) for expanding access to affordable ARV drugs in foreign under-served markets lacking capability for domestic manufacturing. - suitable for enhancing manufacturing of appropriate fixed-dose ARV combinations for children. - suitable for achieving, by native language instruction enclosed, the proper use of medicines. - suitable (through making generic copies of new and second-line ARVs really available) for appropriately tackling impending viral resistance expansion in the developing world. -suitable for helping domestic plants for ARVs in sub-saharan Africa take off and engage in R&D partnerships encompassing technological catch-up, exploitation of TRIPS flexibilities, raised job opportunities, as well as improved marketing power. - suitable for supporting markets development in resource-constrained countries while bringing these countries into the global pharmaceutical market. In economic terms this means as incentive for either research-based or leading generic companies to enter these markets with existing products while concurrently investing in new products for them. REQUIREMENTS (UNDER VLS) FOR EFFECTIVELY EXPANDING ACCESS BY THE POOR INCLUDE: 1) WHO S BROKERING ROLE IN NEGOTIATIONS, 2) SUBSTANTIAL INCENTIVES TO GENERIC FIRMS (e.g. GENERICS EXCLUSIVE SALES AGREEMENTS WITH MAJOR DONORS, FISCAL RELIEF BY COUNTRY GOVERNMENTS). COMPULSORY LICENSES (CLs) - frequently feared by governments in the developing world because of risks of blackmail and withdrawal of investments based on multinational corporations and wealthy country governments would be detracted from profits. - unwieldy and burdensome (drug-by-drug, country-by-country) decision-making processes requiring enabling national legislations already into force. DIFFERENTIAL PRICING (GOAL: PRICES CLOSE TO THE MANUFACTURING COST) - promotion of local market by keeping competition with domestic and foreign manufacturers. - support to R&D. - risks that offers are not available in the private sector notwithstanding most people in developing and least developed countries access healthcare through private organisations (lack of transparency). - risks that discounts might preclude the use of generics (exclusion from the market of generic competitors: lack of transparency). - risks for drug price fluctuations depending on fickleness and policy strategies of research-based corporations. - drug prices unlikely to be as affordable as those of generics domestically manufactured. - risks for diversion and leakage (need to modify packages, formulations and instruction languages). - discounted drugs not always available in every country. - discounted drugs sometimes not registered in specified countries. - cumbersome distribution channels for some discounted medicines. - discounted price quoted by the manufacturers may not constitute the final price for reasons including (though not limited to) exceeding mark-ups and lack of monitoring. DONATIONS - no suitability to long-term needs in the developing world where consistency of supply is crucial for chronic conditions. - risks to undermine the development of local markets by locking out competition. - no sustainability: it would be impossible by the patent s owners to give away their products indefinitely.

9 9 References 1. World Trade Organisation (2005). Overview: the TRIPS Agreement 2. Correa CM. (May 2006). Implications of bilateral free trade agreements on access to medicines. Bull World Health Organ vol 84 n.5 Genebra 3. Kim JY, Gilks G. (2005). Scaling up treatment why we can t wait. New England Journal of Medicine. 353: New W (May 2006). Rich and poor countries divided on patent treaty. Bull World Health Organ vol 84 n.5 Genebra 5. UNAIDS, Report on the Global AIDS Epidemic (June 2006) Dionisio D, Gass R, McDermott P, Racalbuto V, Madeo M, Braghieri G, Crowley S, Dos Santos Pinheiro E, Graaff P, Vasan A, Eksaengsri A, Moller H, Khanna AK, Kraisintu K, Juneja S, Nicolaou S, Sengupta A, Esperti F, Messeri D (2007). What strategies to boost production of affordable fixed-dose antiretroviral drug combinations for children in the developing world? Current HIV Research. In press 7. Dionisio D, Cao Y, Hongzhou L, Kraisintu K, Messeri D. (2006). Affordable antiretroviral drugs for the under-served markets: how to expand equitable access against the backdrop of challenging scenarios? Current HIV Research 4: UNAIDS/WHO/MSF (June 2005). Sources and prices of selected medicines and diagnostics for people living with HIV/AIDS [online: last access February 2006]. [last access 2006 February] 9. Grace C (2004). The effect of changing intellectual property on pharmaceutical industry prospects in India and China: considerations for access to medicines. DFID Health Systems Resource Centre Pinheiro E, Vasan A, Kim JY, Lee E, Guimier JM, Perriens J (2006). Examining the production costs of antiretroviral drugs. AIDS 20 (13): (April 5 th, 2005). Revised Patent Law. 12. Tanner JA (February 2006). WTO TRIPS and its effect on the supply and development of medicines in China. Hong Kong Med. J. vol.12 n China s African Policy, January WTO scrutinises China s trade policies. ICTSD Bridges (1 November 2006) vol 10 n Westerhaus M., Castro A. (2006). How do intellectual property law and international trade agreements affect access to antiretroviral therapy? PLoS Medicine 3 (issue 8): US, India clinch nuclear deal, call pact historic (2 March 2006) U.S. builds new public-private partnership for paediatric AIDS treatment (March 13, 2006) India, China or Brazil who will produce the second line ARVs? (July 12, 2005) Aspen and BMS conclude strategic ARV deal (16 February 2006) Abuja Declaration on HIV/AIDS, tuberculosis and other related infectious diseases (27 April 2001) Gleneagles Implementation Plan for Africa (October 2006 update) Report of the Special Summit of African Union on HIV/AIDS, TB and Malaria (Abuja, May 2-4, 2006) Wise J (May 2006). Access to AIDS medicines stumbles on trade rules. Bull World Health Organ vol 84 n.5 Genebra

10 Presentation of the UNITAID Initiative (20 September 2006)- French Mission to the United Nations De Cock K, Grubb I (July 2006). Towards universal access: WHO s role in HIV prevention, treatment and care. Bull World Health Organ vol. 84 n. 7 Genebra Members OK amendment to make health flexibility permanent (6 December 2005) Department for International Development (March 2005). Increasing people s access to essential medicines in developing countries: a framework for good practice in the pharmaceutical industry. A UK Government policy paper Gerhardsen TI (May 2006). Meeting the need for treatment: the initiatives. Bull World Health Organ vol 84 n.5 Genebra