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Action against AIDS Aktionsbündnis gegen AIDS Indian Generics and Aids
A Fact Finding Mission in the "Pharmacy of the Poor"
Indische Generika und Aids
Eine Erkundungsreise in der „Apotheke der Armen" Das Aktionsbündnis gegen AIDSDas Aktionsbündnis gegen AIDS will mit seiner Kampagne das Schweigen über HIV/Aids brechen und setzt sich ein für eine „Jeder Mensch hat das Recht auf einen Lebensstandard, der seine und Welt ohne Aids und Armut. Mit HIV/Aids zu leben, beeinträchtigt seiner Familie Gesundheit und Wohl gewährleistet, einschließlich Nahrung, alle persönlichen Bereiche der Betroffenen. Weltweit bedroht die Wohnung, ärztlicher Versorgung und notwendige soziale Leistungen (.)." HIV/Aids-Epidemie Entwicklungschancen. Das Risiko, in noch größere Armut zu geraten, steigt durch die Krankheit. So fordert Artikel 25 der Allgemeinen Erklärung der Menschenrechte der Vereinten die HIV/Aids Epidemie weltweit ein gesellschaftliches Umdenk- Mit seinen Forderungen beruft sich das Aktionsbündnis gegen ihrer Verantwortung im weltweiten Kampf gegen HIV/Aids stel- AIDS auf die HIV/Aids-Ziele der Vereinten Nationen vom Juni len. Das Leben von Millionen Menschen hängt davon ab, ob diese 2001 und wendet sich gezielt an die Bundesregierung und die Versprechen eingelöst werden. Pharmaindustrie. Im Mittelpunkt der Forderungen steht der Ein- satz für das Menschenrecht auf Leben und Gesundheit, die Be- Das Aktionsbündnis gegen AIDS ist ein bundesweiter Zusammen- reitstellung zusätzlicher Mittel für die weltweite Aids-Prävention schluss von über 100 Nichtregierungsorganisationen der Aids- und -Behandlung durch die Bundesregierung, sowie die Reduk- und Entwicklungszusammenarbeit sowie über 280 Basisgruppen. tion der Kosten für die lebenswichtigen Medikamente durch die Zur Koordination seiner Lobby- und Öffentlichkeitsarbeit wurde Pharmaindustrie. Mit bundesweiten Aktionen und im politischen 2002 ein Kampagnenbüro beim Deutschen Institut für Ärztliche Dialog erinnert das Aktionsbündnis gegen AIDS an die interna- Mission (DIFÄM) in Tübingen eingerichtet und mit dem Auf- tionalen Vereinbarungen und Versprechen der Regierungen von bau eines bundesweiten Kampagnennetzwerkes begonnen. Das UNMitgliedsländern und der G8. Es fordert deren Umsetzung, zivilgesellschaftliche Netzwerk finanziert sich ausschließlich denn Politik, Pharmaindustrie und Öffentlichkeit müssen sich über Mitgliedsbeiträge.
Indian Generics and Aids Indische Generika und Aids Das Aktionsbündnis gegen AIDS Hrsg.: Aktionsbündnis gegen AIDSRechtsträger Difäm Neue Erkenntnisse zu Aids-Medikamenten aus Indien Paul-Lechler-Straße 24, 72076 TübingenTel.: +49 7071 206 504, Fax: +49 7071 206 510 Introduction to Patents and Aids in India [email protected], www.aids-kampagne.de Indian Generic Industry and ARVs Redaktion: Astrid Berner-Rodoreda, Christiane Fischer,Beate Ramme-Fülle (V.i.S.d.P.) Indian Patent Law and ARVs Layout: Kai-Uwe Dosch (Titelfoto: www.pixelio.de)Druck: [email protected]

Neue Erkenntnisse zu Aidsmedikamenten aus IndienIn der ersten Märzwoche 2009 besuchte eine internationale Auch wurden die inzwischen sehr stark gesunkenen Preise der Delegation1 des Aktionsbündnisses Generikafirmen und Nichtr- ersten Therapielinie der Aidsmedikamente problematisiert. Auf egierungsorganisationen (NROs) in Indien, um die Situation der diesem Niveau wären viele Generikafirmen gezwungen, bald aus neueren Aidsmedikamente genauer zu erforschen. In den näch- manchen Produktionslinien auszusteigen, da sie keinerlei Profit sten Jahren werden immer mehr Menschen aufgrund von Resist- mehr machten. Sollte sich diese Aussage bewahrheiten, hätten enzen neuere Aidsmedikamente benötigen. In den Gesprächen wir in Entwicklungsländern bald ein riesiges Versorgungs- und kristallisierten sich folgende Punkte heraus: Finanzierungsproblem mit den Aidsmedikamenten der ersten Therapielinie. Und dies in einer Situation, in der knapp 70 % der HIV-Positiven, die diese Medikamente benötigen, immer noch keinen Zugang dazu haben. Kann Indien die Produktion der neueren Aidsmedikamente aus- bauen? Keine Frage – alle besuchten Firmen könnten mit sicheren Patentanträge Absatzmärkten ein Vielfaches der heutigen Menge produzieren. Viele der Firmen sprachen sich gegen Ausschreibungsverfahren Auf die meisten neueren Aidsmedikamente haben die Original- aus, da in einigen Ländern die heimische Industrie stark fa- hersteller Patentanträge in Indien gestellt. Laut indischen NROs vorisiert werde, wie dies wohl vor kurzem in Südafrika der Fall kommt es jedoch einer Schatzsuche gleich, herausfinden zu wol- war. Die Firmen bevorzugen gemeinsame Lieferabkommen für len, für welche Substanz ein Patentantrag in Indien gestellt wurde. den Medikamentenbedarf mehrerer stark von Aids betroffener Biochemiker werden benötigt, um das jeweilige Präparat aufgr- und der chemischen Substanz identifizieren zu können. Außerdem gibt es bisher noch kein zentralisiertes Antragsverfahren. Wer in Delegierte aus dem Aktionsbündnis gegen AIDS (Kampagnen- Indien rechtzeitig Widerspruch gegen Patentanträge einlegen büro, action medeor, Brot für die Welt, BUKO Pharma-Kampagne, medi- möchte, muss aufwendig recherchieren - die indische NRO Law- co international, MSF), zwei afrikanischen Partnerorganisationen von yers Collective hat dies in 15 Fällen getan. Laut indischem Pat- BfdW (TAC und EPN), einem indischen Partner von medico (LOCOST) entgesetz (Section 3d) erhält eine leichte chemische Veränderung sowie der englischen Stop AIDS Campaign Internationale Delegation des Aktionsbündnisses gegen AIDS und seiner Partner unter den Augen Mahatma Gandhis.
Aktionsbündnis gegen AIDS Action against AIDS eines Medikaments kein neues Patent. So gehen viele indische zierter herzustellen und benötigen oft 17-18 chemische Verfahren Generikafirmen z.B. davon aus, dass die hitzestabile Form von – diese Technologie nach Afrika zu transferieren und die Fabriken Abbott's Kaletra® in Indien kein Patent erhalten wird. Oftmals international zertifizieren zu lassen, halten die indischen Herstel- werden jedoch trotzdem Patente vergeben. Die Indian Pharma- ler für äußerst schwierig.
ceutical Alliance, der Zusammenschluss indischer Generikaher- steller, fordert das Aktionsbündnis deshalb auf, sich dafür einzu- setzen, dass die Klausel 3d des indischen Patentrechts beachtet Rufschädigung und fälschlicherweise genehmigte Patente rückgängig gemacht In der Vergangenheit wurden mehrere Ladungen generisch herg- estellter Aidsmedikamente, die von Indien über Europa nach Af- Die einzelnen indischen Generikafirmen reagieren unterschied- rika oder Lateinamerika transportiert wurden, beschlagnahmt. lich auf die Rechtsunsicherheit, die durch die Patentanträge Weder in Indien noch im Importland stehen sie unter Patentschutz vorliegt. Einige gehen davon aus, dass viele Patentanträge auf – ein Zeichen dafür, dass man das Wort „Fälschung" wohl be- Aidsmedikamente der zweiten Therapielinie abgelehnt werden, wusst falsch gebraucht. Die Medikamente entsprechen höchsten da es sich oftmals um keine wirklich neuen Medikamente han- Qualitätsstandards, sind von WHO2 und FDA3 anerkannt und delt. Viele Generikafirmen bemühen sich jedoch vorsorglich um somit ganz klar keine Medikamentenfälschungen. Sie befinden freiwillige Lizenzen des Originalherstellers, um Rechtssicherheit sich in Europa lediglich im Transit. Dennoch werden sie von eu- zu haben. Dies ist beispielsweise bei Tenofovir Disoproxil Fuma- ropäischen Behörden als ‚Fälschungen‘angesehen. Wohin führt rate (TDF), einem wichtigen Medikament der ersten und zweiten dieser irreführende Fälschungsbegriff? Therapielinie, der Fall. Der Originalhersteller legt bei freiwilligen Lizenzen jedoch häufig fest, wohin exportiert werden darf, beans- Die Regierungen der Länder Uganda und Kenia sind dabei, Ge- prucht Rechte auf alle Neuerungen der Generikafirmen für sich setze zu entwerfen, die Kopien eines Produkts, das irgendwo auf und erhebt eine Lizenzgebühr. Im Fall TDF steht das Medikament der Welt patentiert ist, automatisch als „Fälschung" (counterfeit) in Indien noch gar nicht unter Patentschutz, trotzdem müssen die im eigenen Land ansehen und deshalb in ihren Ländern nicht zu- Generikafirmen, die unter freiwilliger Lizenz produzieren, eine lassen wollen. Dies hätte verheerende Folgen für die zukünftige Gebühr an den Originalhersteller Gilead zahlen. Versorgung mit preisgünstigen indischen Aidsmedikamenten in Für die ganz neuen Aidspräparate kommen die indischen Generi- kafirmen um Lizenzen nicht herum. Entweder sie müssen sich um Das Aktionsbündnis gegen AIDS wird sich deshalb weiter dafür freiwillige Lizenzen bemühen oder aber die indische Regierung einsetzen, dass getestete, qualitativ hochwertige und preisgün- muss eine Zwangslizenz verhängen. Das hat sie bisher jedoch stige Generika verschiedener Therapielinien hergestellt und in noch nicht getan.
andere Länder exportiert werden können, so dass eine lebens- lange Behandlung mit Aidsmedikamenten im öffentlichen Sektor Technologietransfer in Länder mit niedrigem Einkommen, die erst in Ländern niederen und mittleren Einkommens realisiert werden 2016 den vollen Patentschutz gewähren müssen, wäre theoretisch kann.
eine Option für die indischen Firmen. Die meisten von uns be- suchten Generikafirmen sahen dies jedoch als problematisch an. Astrid Berner-Rodoreda, Brot für die Welt, Sprecherin im Aktionsbündnis Die Rohstoffe, die für die Produktion der Medikamente benötigt gegen AIDS werden, kommen fast ausschließlich aus Indien und China. Generi- World Health Organisation – die Zulassung der Medikamente kaproduzenten in anderen Ländern müssten deshalb weiterhin die durch die WHO ist z.B. für Global Fund Programme wichtig Rohstoffe aus diesen beiden Ländern beziehen und hätten somit schon Fixkosten, die eine Preissenkung der Medikamente erschw- Food and Drug Administration – diese US-amerikanischen Zu- eren würden. Außerdem sind die neueren Medikamente kompli- lassungsbehörde ist für Lieferungen über das US-amerikanisch finanzi- erte PEPFAR-Programm wichtig Aktionsbündnis gegen AIDS Action against AIDS

Introduction to Patents and AIDS in IndiaIn March 2009, ten delegates of Action against AIDS Germany including three international guests visited India to meet four Patents and profits generic companies (Cipla, Hetero, Aurobindo and Matrix) that A patent is a set of exclusive rights granted by a state to an inven- produce first and second line generic antiretroviral drugs (ARVs) tor for a limited period of time in exchange for the disclosure of and members of civil society groups (Lawyers Collective, Alter- an invention.1 To be granted a patent the invention must be new, native Law Forum, MILANA, LOCOST, All India Drug Action inventive, and industrially applicable. Therefore it is not enough for a patent being granted just to discover a substance or object (such as neem, a plant product used in agriculture) The patent This fact-finding mission had the following objectives regarding grants the patentee monopoly over the production, use and sale patents applications on ARVs in India as well as prices and rea- of the invention for a given period of time. Therefore the patent sons for prices for improved first line and second line ARVs in excludes others from making, using, selling, offering for sale or India and African countries: importing the patented product. The patentee can thus exploit the patent to increase prices by limiting quantity. This monopoly is in • What are the effects of granting patents on second line ARVs fact the basic idea of granting any patent.
on the production and marketing inside India and the exports to other (e.g. African) countries? Any grant and enforcement of patent is governed by national laws and can be granted (or denied) by national authorities only within • What role does the Indian generic industry play for affordable the authority of that country. • What role does the Indian civil society play for access to TRIPS and public health While patents are valid only within the country of their issue, In this document, we provide articles that reflect opinions and po- international treaties seek to harmonize patent laws. The World sitions of members and friends of Action against AIDS Germany.
Discussing patents at the Lawyers Collective HIV/AIDS Unit Bangalore. Aktionsbündnis gegen AIDS Action against AIDS

Indian Patent Act of 1970 Indian Patent Amendment of 2005 No product patents on pharmaceuticals were allowed, only process patent- Product patents are encouraged ingThe maximum time for patentability was seven years from the date of ap- Patents are granted for a minimum period of 20 years plication and five years from the date when the patent is grantedImported products were not patentable No discrimination between local and imported products The patent holder has to prove the patent infringement.
The filed generic company has to prove that no patent infringement took place.
Trade Organization (WTO) plays an important role in this proc- ess. The TRIPS Agreement (Trade Related Intellectual Property Indian Patent Law Rights) coerces all WTO member countries to manipulate their "Transition countries" like India had to amend their national law national laws to conform to the TRIPS agreement. In general this in 2005 to conform to the TRIPS agreement whereas "least devel- enforces a minimum period of 20 years for product patents. In oped countries (LDCs)" still have time until 2016. India did not regard to drugs such exclusivity rights can prevent affordable ge- allow product patents on pharmaceuticals from 1970 until 200 nerics to enter the market and therefore lead to maintenance of and therefore the most important generic industry developed to high prices.2 This means, that those most in need of basic essential provide cheap generics for the global south. This role is now un- medicines are unable to afford it. Survival becomes a commodity der threat as with the beginning of 2005 India had to change its available only to the rich.
For striking a balance between TRIPS and the basic human right • However, the Patents (Amendment) Bill of 2005 allows the of access of essential medicines, TRIPS includes important safe- use of the TRIPS flexibilities to the largest possible extent6: guards to protect public health. These rights were reaffirmed by Compulsory licence for the use within India and for export of the Doha Declaration on the TRIPS Agreement and Public Health, medicines to countries which have insufficient or no manufac- which was adopted in November 2001 by the WTO Ministe- turing capacity is part of the amendment. Interesting to note is rial Conference. To assure better access to essential medicine it that both possibilities were never used until now.
recognises: "We agree that the TRIPS Agreement does not and should not prevent Members from taking measures to protect pub- • Section 3 (d) excludes inventions from discovery, which are lic health." Crucially, the Doha Declaration reaffirms the right of only of a new form of a known substance without any addi- national authorities to grant Compulsory Licences (CL). CLs are tional therapeutic value. This is meant to prevent "evergreen- non voluntary licences allowing a government to force the pat- ent holder to grant use. In case of pharmaceuticals, governments to medicines before Hong Kong ministerial meeting.
can grant CLs on a second line ARV in case of a health crises 5 Jean O. Lanjouw: The Introduction of Pharmaceutical Product such as HIV/AIDS, but also in case of many other reasons.3 One Patents in India. „Heartless Exploitation of the Poor and Suffering?", remaining problem is that CLs are meant mainly for the domestic NBER Working Paper, No. 6366, Yale University and the NBER, 7-8 market, thus a solution is needed for countries without substantial manufacturing capacity to access compulsorily licensed drugs, 6 The Patents (Amendment) Bill 2005 passed by Indian Parlia- like importing them. On 30 August 2003, a compromise was ment, http://www.indianembassy.org/press_release/2005/Mar/12.htm found to allow WTO members to issue compulsory licences to export generic versions of patented medicines to countries lack- ing manufacturing infrastructure. However this 'solution' works only on paper: Since 2003 only one small consignment of drugs was shipped from Canada to Rwanda. The requirements of the Andrea Czekanski/AgA compromise are extremely unwieldy and since inception only four countries have implemented them into their national law; the burdensome drug-by-drug and country-by-country process discourages the use.2 D.H. Banta (2001): Worldwide interest in global access to drugs. The Journal of the American Medical Association, No. 285 (22), 28- WTO Ministerial Conference (Fourth Session, Doha, 9-1 No- vember 2001): DECLARATION ON THE TRIPS AGREEMENT AND PUBLIC HEALTH§5(b) Each Member has the right to grant compulsory licences and the freedom to determine the grounds upon which such licences are granted.
§5(c) Each Member has the right to determine what constitutes a national emergency or other circumstances of extreme urgency, it being under- stood that public health crises, including those relating to HIV/AIDS, tuberculosis, malaria and other epidemics, can represent a national emer- gency or other circumstances of extreme urgency.
Astrid Berner-Rodoreda, Beate Ramme-Fülle, and Christiane Fischer planting a MSF Press Release (12 December 2005): WTO sacrifices access tree of hope against AIDS in India.
Aktionsbündnis gegen AIDS Action against AIDS ing" of patents.
• The generic production could be stopped, as only branded products would be on the market, the price would be likely to • It is possible for civil society groups and generic industry to increase, this would be likely to happen in case of the heat sta- file a post or pre-grant opposition against a patent application. ble Lopinavir/Ritonavir, as Abbott has the policy not to grant A hearing is compulsory. These possibilities are widely used by groups such as the Lawyers Collective7 or generic companies such as Cipla to fight patents be- Treatment of HIV Patients ing granted on essential medicines. A good example is the second line ARV, the heat stable form of Lopinavir/Ritonavir, where Ab- HIV slowly destroys the immune system of the body, the so-called bott has applied for a patent.8 CD immune cells. If the number of these cells decreases below a certain threshold, the patient needs to start and continue treatment In other cases, such as the patent application of Boehringer In- for the rest of his/her life. A cocktail of at least three ARVs from gelheim on the paediatric suspension of Nevirapine9 the Positive different drug classes has to be swallowed. If the patient does not Women's Network filed a pre-grant opposition and won the case. take his/her drugs regularly and/or the drug supply is not constant, As Nevirapine is a "a new form of a known substance" it is not resistances develop and the patient has to be switched to second patentable under Sec 3(d) of Indian Patent Law. Thus generic line treatment. Even under the conditions of strict adherence at production of Nevirapine will be continued to be produced. To some point in time resistances will develop and second line treat- summarize on what has been written: Indian Patent Law, although ment needs to be started. In poor countries standard drug regimes allowing product patents and therefore limiting the scope of ge- are used, which make it simpler to assure continuous drug supply. neric production, allows for the possibility to counter evergreen- The World Health Organisation (WHO) recommends the most af- fordable and qualitative best combinations with less side effects. The old recommendation by WHO were of Stavudine, Aciclovir As it is by now, once a patent would be granted on drugs such or Lamivudince and Nevirapine or Evaviranz. In the new recom- as second line ARVs, the situation, whether affordable generic mendation Tenofovir replaces Stavudine due to a more favour- production can continue, remains unclear. There are several pos- able toxicity profile and less adverse side effects. However the price increase, even using Indian generics, is huge. While the old regime is available for 87 US$ per patient per year the best price • The generic company will depend on voluntary licences (VL) for the Tenofovir based regime is 39 US$ per patient per year. from Big Pharma to continue production. This would be likely In case the patient needs to be switched to second line treatment to happen in case of Gilead, which granted a VL to Indian the price for Lopinavir/Ritonavir alone is 7 US$ per patient per generic companies for Tenofovir. However also a VL would year.10 In the case patents are granted, the expected price increase increase the price as the generic firms need to pay a royalty to would further threaten access to these drugs for the poor in the Gilead. Gilead would therefore be in the position to dictate the global south.
conditions for the VL.
In conclusion, to guarantee access to affordable generics for the • The Indian government could issue a compulsory licence (CL) global south we as Action against AIDS demand that the phar- for local needs and for export. Whether the Indian government maceutical companies Abbott, Bristol-Myers Squibb and Gilead is willing to go this step, remains unclear.
withdraw their applications in India for patents on new, essential AIDS medicines, as patents can be deadly and the human right to life needs to be prioritised before pharmaceutical profit. Abbott Patent 339/MUM/2006, Filing date: 26.8.200 Christiane Fischer, BUKO Pharma-Kampagne, Action against AIDS, Germany Patent number 285/DEL/1998, case decided on 31.8.2007 by MSF, Untangeling the Web of Price Reductions, Geneva, July the Patent office Aktionsbündnis gegen AIDS Action against AIDS Indian Generic Industry and ARVs Assessment by Indian Generic Firms and Civil SocietyFor many years the Indian generic industry flourished and made it possible for Sub-Saharan Africa to have access to affordable Volume and Tendering ARV drugs of the first generation. This was mainly due to the The generic firms put volume (large-scale production) at about Indian Patent Law of 1970 which enforced process but no product 10 % of the cost. Thus, whilst assurance of having a large market patents on medicines1. for the product would certainly bring down the price, the produc- tion process in their opinion was much more significant for pric- According to an observational study carried out between January ing a drug. 200 and March 2006 on 2,162 orders of AIDS drugs for Sub-Sa- haran Africa reported to the Global Price Reporting Mechanism at All of the generic companies we talked to were of the opinion the World Health Organization, generic companies supplied 63 % that the present tendering system needs to be reformed for various of the drugs, at prices that were on average about a third of the reasons: prices charged by brand companies. 85 % of the generic drugs came from India.2 • It gives the contract to the lowest bidder. If a company wants to get rid off surplus stock, it can go below production costs India has been the world's pharmacy for the poor with regard to which will make it impossible for others to compete.
first line ARVs – will this be the case for second line ARVs as well? What are the factors that impede production of generic sec- • Some countries (South Africa was given as an example) seem ond line and newer ARVs? In our talks with Cipla, Hetero, Matrix to protect their own market in favouring bids from their own and Aurobindo as well as in our talks with the Lawyers Collective national companies. These bids, according to some generic and the Alternative Law Forum we explored the barriers to large- firms, were up to 30 % higher than those from India and they scale production of newer ARVs. still won the tender. Some Indian firms decided not to take part in the tender, as they knew they would not have a chance in Complex production procedures competing against the domestic South African firms. Cipla, Hetero and Matrix unanimously declared that the cost of • It is a short-term contract – sometimes only for a few months the newer ARVs largely depends on the cost of the raw material which gives no security to the firms with regard to the invest- and the chemical processes necessary to manufacture the drug. ments they need to make for producing the newer ARVs. The production of the API (active pharmaceutical ingredient) is one of the major factors which influences pricing. Whilst a prod- Alternatives which were discussed were a meeting with high-bur- uct like first line Nevirapine only takes -5 chemical processes, den countries to find out what their needs are over the next few the second line ARV Lopinavir/Ritonavir takes 17 to 18 chemical years and to work out with generic firms what price and volume steps to manufacture. All three companies agreed that 90 % of the they can offer, i.e. a pooled procurement system similar to the costs of second line ARVs are due to complex production pro- Clinton Foundation negotiations.
cedures. However, according to Matrix, costs can be reduced by optimizing these procedures. They felt that a 10-20 % reduction might be possible.
For further information on the Indian patent law, see "Introduc- From the discussion we held with the generic firms and civil so- tion to Patents and AIDS in India" on p. 5 and "Indian Patent Law and ciety organisations, it became clear that for the newer and espe- ARVs" on p. 12.
cially the very new drugs – those for which patent applications PLoS ONE. 2007; 2(3): e278 - published online 2007 March 1. have recently been lodged in India - we increasingly face a huge problem with patents.
Percentage Total Percentage Generic Avg. Brand Price Avg. Generic Price year equivalents) N = 2,162 ordersVolumes calculated on the basis of WHO daily dosing guidelines to generate patient year equivalents. Average prices in US$ per patient per year and calculated on the basis of total US$ paid for drugs/total drugs in category.
Aktionsbündnis gegen AIDS Action against AIDS

Andrea Czekanski/AgA Quality check of the Indian generics firm Cipla.
tween 1995 and 2005. Here we have to look at the applications almost on a case-by-case basis to see if the ingredients of these For the newer drugs (mostly third line ARVs) which were patent- drugs were known and patented in the past so that the new version ed elsewhere in the world after 2005, the amendment to the Indian might only be a minor modification either in form or in combining Patent Act fully applies, that is to say they will in all likelihood be various known chemical substances – i.e. cases in which clause 3 granted product patents. For these drugs, most generic firms in In- (d) or (e) of the Indian Patent Act would apply. dia prefer to apply for voluntary licences from the originator com- pany. Some generic firms also hope for the Indian Government One of the first challenges which civil society and the generic to issue a compulsory licence in cases where a voluntary licence firms face is to identify the originator firm and the product for may not be granted. However, up to now, the Indian Government which the patent is applied for as the publishing of the data is of- has not made use of these TRIPS flexibilities. Thus, lower prices ten quite cryptic and put in bio-chemical terms. Whilst pre-grant for these drugs in developing countries will only be possible un- opposition has been a successful instrument in not getting patents der voluntary or compulsory licensing. granted which fall under section 3 (d) and (e), there is no guaran- tee that the patent is refused. The option of establishing a patent pool as planned by UNITAID was something most generic firms have not heard of and that they All of the firms visited seemed confident that they would be able had misgivings about on the grounds that it was still unclear who to continue producing LPV/r– currently one of the most impor- would put their patents in and what patents would be put into the tant second line ARVs. Cipla, Hetero, Matrix and Aurobindo have pool (all process patents or only the end product patent), what produced LPV/r as a generic product. Matrix is so far the only countries the patent pool covered, who could draw on it, if all generic firm to have received WHO approval for its generic ver- patents put in the pool had the same conditions, etc. Most thought sion of LPV/r in February 2009.3 It is also the only firm which is it was an unworkable model.
confident of selling LPV/r in the near future below the price set by the originator company, i.e. US$ 500/pp/pa. Both Aurobindo and The only other option for producing the latest ARVs – transferring Matrix received tentative FDA approval in March 2009. Most production to least developed countries which have until 2016 to firms think, it is unlikely that a patent on LPV/r will be granted become fully TRIPS compatible – was not seen as a viable op- under the Indian Patent Act. Even if it were granted, most firms tion by most generic firms. Cipla was one of the very few Indian seemed confident that the Indian Government would issue a com- generic companies interested in the issue and might even consider pulsory licence (CL) so that they could continue producing the opening an API plant in Africa to make prices more competitive. generic version of LPV/r. Their confidence is based on the roll-out The other firms regarded capacity in Africa as too limited to try of LPV/r as a second line drug in India in 20085 – India therefore and produce the substantially more complex chemical substances has an interest in having access to the drug at an affordable price for newer ARVs and to get the production sites pre-qualified by for its own domestic market. So far, however, India has not issued a CL. One would have to see, if the Indian Government would 3 For most of the second line ARVs, the patent applications went es/200931268993.htm into the so-called mail box, i.e. the applications were lodged be- Aktionsbündnis gegen AIDS Action against AIDS

use the flexibilities of the TRIPS agreement. At this stage it seems • There is only a patent application for TDF for which pre-grant more likely that the patent application for the tablet form of LPV/r opposition has been filed – so why should a royalty fee of 5 % will not be granted based on sections 3(d) of the Indian Patent Act. be paid whilst there is no patent on the drug in India? Abbott has so far not issued a single voluntary licence to a generic firm for producing LPV/r and has not expressed any intentions of • If the patent application gets rejected in India, the firms who doing so in the near future. It has recently sued Mylan for plan- have signed the contract with Gilead may not get out of that ning to sell the tablet form of LPV/r at low cost prices before the contract which, according to Cipla, was made under British patent has expired in 2021.6 The Indian Pharmaceutical Association and Cipla believe that out • There are grant-back licences to Gilead for all improvements of the more than 7500 patent applications in the mailbox, 5000 on methods and modifications relating to the API or the fin- are frivolous meaning that no patent should be granted. Whilst ished product.
Cipla is confident that the exemptions in the Indian Patent Act will block frivolous patents, other generic firms would rather play • Export to certain middle-income countries of the finished it ‘safe' and apply for voluntary licences even before the patent product or the API is not possible. is granted. The conditions of these voluntary licences and their long-term implications need to be studied in detail to predict the In addition, the following issues are seen as detrimental by inter- effect on pricing of second line and other newer ARVs in develop- national experts to ensuring access to TDF at affordable prices The American originator firm Gilead has issued voluntary licenc- • Gilead seeks to impose royalties on all product sales for TDF es to 11 generic firms for the production of TDF, a substance used from the licensed suppliers of APIs, including sales where pat- in improved first as well as second line ARV regimens. Matrix, ents do not exist, as the licence covers over 90 countries.
Hetero and Aurobindo produce TDF under this voluntary licence. Matrix got tentative FDA approval for TDF in November 2007; • Gilead seeks to cut off the supply of generic APIs of TDF Aurobindo got tentative FDA approval for TDF in February 2009. outside of the licensed territories.
Matrix sells TDF for 1 US$/pp/pa and expects further reduc- tions through pooled procurement with Clinton Foundation. Cip- • The partitioning of the generic TDF API market between la was the only generic firm visited which challenged Gilead's approved and non-approved sellers and licensed and non-li- patent application on TDF7 and is confident that TDF will not be censed territories will lead to less competition and less efficient granted a patent. Cipla was therefore not interested in applying for economies of scale in the market for generic TDF APIs.8 a voluntary licence from Gilead, as they see a number of problems with this contract others have signed: Even if the patent on TDF should get granted, Cipla is prepared to fight it out in court. The other firms see the advantage of being able to export TDF without any legal hassle. However, the long see James Love, Knowledge Ecology International, http://www.
Andrea Czekanski/AgA Aids drug production of the Indian generics firm Cipla.
Aktionsbündnis gegen AIDS Action against AIDS offer prices below production, the sustainability of providing first line ARVs in developing countries would be severely threatened. Keeping in mind that at present 97 % of people receiving ARVs in developing countries are on first line and that this constitutes te Ramme-Fülle/AgA only 31 % of those in need of ARVs,9 first line needs to be around for the long-term and to come at affordable prices. Remedies that were suggested by generic firms in India were to have fixed prices for certain ARVs and ARV regimens. These suggestions should be discussed with Clinton Foundation, PEPFAR, Global Fund and other major ARV purchasing/distributing agencies.
Counterfeit Issue - Defaming the Indian Generic Industry?In recent months a number of shipments of ARVs from India to Latin America and Africa were seized in Europe because they were regarded as "counterfeits". These drugs were under patent in Europe. Under the EC directive 1383/2003 they were regarded as violating European patents, even though they were not meant for any European country but were merely in transit at European airports. The term "counterfeit" is a total misnomer, as the drugs had been pre-qualified by the WHO or FDA and therefore been declared safe and of high quality; neither were they shipped under a false name. They also did not violate patents as the drugs were not patented in India or the importing country. So why call them "counterfeits"? Is it to discredit the Indian generic industry? No doubt, sub-standard drugs exist and some may well be produced in India. Yet, any drug tested and declared safe by the WHO and FDA is not a counterfeit drug. Attempts to ruin the reputation of Dr. Yusuf K. Hamied, CEO Cipla, signing a petition of Action against AIDS.
high-standard generic firms in India have already succeeded to some extent. Both Kenya and Uganda are working on anti-coun- term implications of the voluntary licences may well mean that terfeit bills which label any copy of a product that enjoys patent middle income countries pay much higher prices than they would protection anywhere in the world as "counterfeit".10 This would need to and that the price for APIs is high in countries which do bring to an end all generic imports of ARVs and have tragic con- not have patents on TDF as well as the non-licensed territories.
sequences for the scale-up of ARV treatment and will therefore need to be opposed.
Non-enforcement of patents in India for these drugs would cer- tainly make the long-term availability and pricing more secure. However, we also need to look at the production processes and Summary the costs involved in buying the machinery to produce the newer ARVs. In order for generic firms to invest in producing newer Whilst production processes and volume play an important part drugs, they need to be certain of having a market and of being in pricing and need to be addressed in terms of finding alterna- able to sell the product cheaper than the originator firm but with tives to the present tendering processes, patent issues will be the enough of a profit margin to sustain production. Pooled procure- main obstacle for producing and marketing the newer ARVs. Civil ment might be the way forward here. For middle income coun- society needs to remind governments to uphold the full TRIPS tries the import of cheaper drugs may only be possible by issu- flexibilities (including compulsory licences), to support pre- and ing a compulsory license. Thus, the full flexibilities of the TRIPS post-grant opposition to patenting ARVs whose substances are agreement need to be upheld in India and elsewhere. already known and see to it that free trade agreements do not ex- acerbate the patent situation in developing countries. Also, the im- India and China are the countries which produce the APIs for pact of voluntary licences needs to be critically assessed in cases, ARVs and any attempt to restrict access to APIs in other countries where the originator firm has too many strings attached. Civil as is allegedly taking place in connection with the Gilead volun- society needs to fight against attempts by originator companies, tary licensing should be scrutinized and publicly criticized.
individual states and the EU to mislabel high-quality products as "counterfeits" – instead the "counterfeiting of patents" in terms of Conventional first line ARVs ever-greening substances needs to be exposed.
Astrid Berner-Rodoreda, HIV Advisor, Bread for the World, Action against What about the older ARVs? Here a number of Indian generic AIDS, Germany firms felt that rock bottom had been reached with regard to pric- ing and that many generic firms would pull out of producing first line regimens, if prices were further pushed. For civil society it 9 is difficult to know exactly what the production costs of generic 2008.pdf firms are. One can assume that the machinery has long been paid 10 off and so the actual production costs are rather low. However, if html and http://www.essentialdrugs.org/edrug/archive/20090/msg0001.
no profit margin is made anymore or generic firms are pushed to php Aktionsbündnis gegen AIDS Action against AIDS Indian Patent Law and ARVsBackground of Indian Patent Law ability of Indian pharmaceutical companies to continue to provide Until the early 1970s, India primarily imported most drugs and less expensive, generic medicines to patients in India and other prices of drugs in India were amongst the highest in the world. developing countries.
Recognising that this was due to the product patent protection available to pharmaceuticals, India changed its patent regime. In 1970, India enacted a new patent law. The Patents Act, 1970, Post 2005 Impact on ARVs which came into force in 1972, sought to remedy the problem by Atazanavir, Lopinavir (PIs) and Tenofovir (NRTI) are antiretro- only recognising process patents in relation to drugs and agro- viral drugs used as second line ARVs, as recommended by World chemicals. This change, coupled with other regulatory changes, Health Organization. Atazanavir and Lopinavir are part of the sec- enabled the growth of a robust Indian pharmaceutical industry ond line regimen, which was recently initiated in the 2008 ARV (generic companies). The consequent competition resulted in the roll out programme in India. To our knowledge, none of these lowering of prices of medicines in India. By 1988-9, India became drugs are patented in India and generic versions of these drugs are a net exporter of drugs1. available. However, foreign multinational pharmaceutical com- panies have filed patent applications in respect of all these drugs In 1995, India became a signatory to the WTO. This required India in India. to comply with the minimum mandatory requirements set out in the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS). By 2005, it was to introduce a TRIPS-compliant Atazanavir product patent regime for pharmaceuticals. Thus, in 2005, India amended its patent law to provide for product patent protection Generic Atazanavir is marketed as Atazor®2 (100, 150, 200 and for pharmaceuticals. In light of this, concerns have arisen over the 300 mg) and Atavir® by Indian companies such Emcure, Cipla and Aurodindo in India. Generic active pharmaceutical ingredi- Sudip Chaudhuri: The WTO and India's Pharmaceuticals Indus- Andrea Czekanski/AgA Lopinavir/Ritonavir is marketed as Lopimune® by Cipla.
Aktionsbündnis gegen AIDS Action against AIDS ents (APIs) are also available. The main advantage of this drug is once-a-day dosing, tolerability and favorable effects on lipid te Ramme-Fülle/AgA Bea So far, we have traced two applications relating to Atazanavir in the Indian patent official journal. Patent Application No. 805/MAS/1999 bearing title "HETEROCYCLIC AZAHEXANE DERIVATIVES" filed by We filed a pre-grant opposition against this patent application. As Novartis AG did not reply to the examination report issued by the Patent Office within the stipulated time, the patent application has been deemed to be abandoned by the patent office in August However, Novartis AG has filed a divisional application No. 310/ CHE/2007 bearing title "HETEROCYCLIC AZAHEXANE DE- Patent Application No. 625/DELNP/2006 bearing ti- tle "PROCESS FOR PREPARING ATAZANAVIR BISULFATE AND NOVEL FORMS" filed by Bristol-Myers Squibb. Lopinavir/Ritonavir (Kaletra®)Kaletra® is available as soft gel capsules in India. Generic versions are marketed as Lopimune®, Ritocom®, Ritomax-L® and V-Letra® Ramya Sheshadri, Lawyers Collective, signing a petition of Action against AIDS.
by generic companies such as Cipla, Hetero, Alkem (Cytomed) and Ranbaxy respectively3. TDF (Tenofovir Disproxil Fumarate) The new heat stable Kaletra® is considered as a better option when compared to soft gel capsules due to its non refrigeration aspect. TDF is an important first line and second line drug which is wide- Recently, Mylan received approval by World Health Organization ly used. Generic versions are marketed as Tenvir5, Tofovir6, by under prequalification program, for the heat stable form of Kale- generic companies such as Cipla and Alkem (Cytomed). Even tra® (Aluvia®). Matrix is the Indian subsidiary of Mylan. In light other generic companies like Ranbaxy, Hetero and Matrix are of this, it would need to be seen if the generic version of Aluvia® manufacturing TDF7. will be made available in India. Gilead, the originator company, has entered into voluntary license with several generic companies in India, even when there is no patent on the drug. There are nearly 15 patent applications filed by Abbott for both individual drugs (Ritonavir and Lopinavir) or as combination Patent Status (Kaletra®) drugs in India. Of these, civil society groups have filed pre-grant oppositions to four patent applications—one application We have been able to identify five applications pertaining to TDF. relates to Ritonavir, one relates to Lopinavir, one relates to soft The civil society group has filed pregrant opposition's against gel Kaletra® and one relates to heat stable Kaletra®. three applications. Presently two oppositions are pending in the The patent application relating to soft gel Kaletra® is deemed to be abandoned, as Abbott did not respond to the examination report To our knowledge, no patent has been granted with respect to issued by the Indian patent office. The other three applications are these applications. As mentioned earlier we have to monitor the still under examination.
applications and scrutinize if the claims in these applications could potentially block generic versions. To our knowledge, no patent has been granted with respect to these applications. However, we need to peruse all of the applica- tions closely to identify if the claims in these applications could Impact of Product Patents in India potentially block generic versions. Patenting of even one of the individual drugs, either Lopinavir or Ritonavir, could have an ad- If these key drugs are patented in India the impact will be disas- verse impact on the availability of all fixed dose combinations of trous as it would stall the production of generic drugs. It can have Indian Drug Reference (No. 3, 2008, updated till 31 May 2008) MSF (2008): Untangling the Web of ARV Prices Aktionsbündnis gegen AIDS Action against AIDS an impact on the Indian government second line ARV programme consultation with affected stakeholders. In light of this, the DCGI initiated in 2008, as Kaletra® and TDF are the key drugs of the decided against introducing the patent linkage system until the second line ARV roll put programme. It will also freeze the import issue was discussed and debated.9 of drugs to developing and least developing countries. In the meantime, Bayer filed a writ petition in Delhi High Court When drugs are patented, the patentee can exclude other generic against the Union of India, the DCGI and Cipla, seeking an or- companies from manufacturing, consequently due to monopoly der that the DCGI should consider the patent status of its drug and absence of competition drugs will be exorbitantly priced. Sorefenib Tosylate before granting marketing approval to Cipla. The court thereby directed the DCGI to not grant marketing ap- Under these circumstances the options available for the Indian proval to Cipla until the final order was passed10 in the matter. civil society and patient groups is to file a pre-grant opposition against these key drugs. However if the patent is granted we need Concerned about the consequences of this litigation Cancer Pa- to lobby with the government to issue compulsory license and file tients Aid Association (CPAA), represented by Lawyers Col- of post-grant opposition.
lective HIV/AIDS Unit, filed an intervention application in the matter. In January 2009 the hearing was held, CPAA argued that Patent Linkage: Bayer Case patent linkage raised a grave public health concern and would have implications on the public at large. CPAA pointed out that Bayer was attempting to introduce a policy change, which is oth- Another cause of concern have been the attempts of pharmaceu- erwise the prerogrative of the Legislature, through the court. It tical companies to introduce TRIPS-plus provisions, including further argued that the patent and drug regulatory systems are two patent linkages, in India. Patent Linkage is a system aiming at independent systems under Indian law and it is not permissible to preventing the registration and authorisation of generic versions link them. of a patented drug for marketing until the expiry of the patent. This would considerably delay the entry of generic drugs into the The matter was posted for further hearing on February 2009; the Counsel of Bayer has concluded his arguments and the other par- ties in the case will be heard in the upcoming hearings11.
Previously, certain groups have advocated with the Indian gov- ernment to introduce the patent linkage system. In early 2008, the Ramya Sheshadri, Lawyers Collective HIV/AIDS Unit, Bangalore, India media reported Dr. Surinder Singh, the Drug Controller General of India (DCGI) as stating that the DCGI was planning to intro- duce patent linkage system and was in the process of obtaining 9 data on drugs which have been granted patents from the patent of- fice.8 The Indian Pharmaceutical Alliance and civil society groups raised objections to the proposal and also questioned the lack of 10 php?autono=321993 Aktionsbündnis gegen AIDS Action against AIDS

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