Abstract
This chapter explores the design of an original generic medicine formulation technology in Brazil, which consists in producing heat-stable capsules of a molecule used in AIDS tritherapy to increase its effectiveness. As Abbott had originally developed and patented this technology to prevent competition from generics, Brazil decided to form a national consortium to develop a competing technology. The Brazilian consortium benefited from an international cooperation network on HIV/AIDS involving Brazil and seven developing countries. The Chinese partner provided raw material for R&D. The author of this chapter participated in the consortium supervised by the Ministry of Health, which, in the mid-2000s, was comprised of public and private pharmaceutical laboratories and the National Technological Institute, which specialized in the polymer industry. She was thus able to gather detailed observations of technological exchanges and R&D operations. The chapter documents the local production of a hybrid technology, between pharmaceutical chemistry and polymer chemistry, using the concepts and methods of the knowledge economy to describe the know-how of laboratories, and the sources and appropriation of information (codified and uncodified) by the various actors, both public and private. It envisages international technological cooperation between developing countries.
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- 1.
In Pavitt’s supplier-dominated model, “most innovations come from suppliers of equipment and materials, although in some cases large customers and government-financed research and extension services also make a contribution. Technical choices resemble more closely those de- scribed in Salter’s vintage model, the main criteria being the level of wages, and the price and performance of exogenously developed capital goods” (Pavitt 1984).
- 2.
Conversely to other protease inhibitors, Ritonavir plays a strategic role in the composition of antiretroviral therapeutic regimens thanks to its activity as a “booster”. In other words, this molecule figures in absolutely all antiretroviral therapies comprising protease inhibitors, regardless the patients’ status, whereas they are “naive”, experienced or treatment-resistant individuals. This particular condition grants Ritonavir with a very attractive position within the antiretroviral market, therefore pushing local governments of developing countries, as well as generic pharmaceutical manufacturers to find alternative means to promote scaled-up access.
- 3.
Traditional pharmaceutical model: constituted solely of pharmochemical synthesis and pharmaceutical formulation.
- 4.
In 2005 the Brazilian government, after having threatened Abbott with a compulsory license, reached an agreement with the multinational company: Abbott agreed to reduce its price and avoided the issuing of a compulsory license.
- 5.
Adverse effects include abdominal pain, headache, anorexia and diarrhoea.
- 6.
Namely, generic manufacturers, such as Cipla, Okasa Ltd. and Matrix Lab Ltd.
- 7.
Abbott’s patent applications BRPI 0609173–3 and WO 8067164.
- 8.
Indeed, the unitary prices for Ritonavir greatly vary between the USA (USD10.70/pill), developed countries (Denmark, USD2.63; Austria, USD2.04; France, USD1.61; Canada, USD1.42) and developing countries (an average of USD0.114), according to MSF’s annual survey on ARV prices (MSF 2010).
- 9.
Pediatric formulations are made solely by Aurobindo and Matrix (Dionisio et al. 2010).
- 10.
Zidovudine, Lamivudine, Stavudine, Nevirapine, Didanosine, Indinavir, Efavirenz, Saquinavir and Tenofovir.
- 11.
Comprised within the National Technological System (SIBRATEC).
- 12.
Interview with the coordinator of HS Ritonavir project, September 2011.
- 13.
Personal interview with the technical coordinator of INT , in August 2011.
- 14.
- 15.
Available at: http://www.usp.org/
- 16.
High-performance liquid chromatography.
- 17.
Impurities generates very close spikes in the HPLC spectrum, therefore impeding the acquisition of consistent results.
- 18.
Extrudate is the material being delivered from an extruder.
- 19.
Donato, E.M. Perfil de Dissolução in vitro baseado nos dados in vivo, estudos de estabilidade térmica e metodologia analítica. Tese de Doutorado – Porto Alegre: UFRGS, 2008.
- 20.
Please refer to Table 2.1 for a list of all codified information deployed in the technological development of heat-stable Ritonavir.
- 21.
For instance, temperature, pressure, rotation and reaction times.
- 22.
The Brazilian experiences concerning the national strategies addressed to promote intellectual property (IP) flexibilization of essential medicines exceeds the scope of the article and will not be discussed here. Nevertheless, it is relevant to underline Farmanguinhos’ successful experiences in the promotion of IP flexibilization strategies both at the national and international levels, including Pre-Grant Oppositions (Tenofovir) and the granting of Compulsory License (Efavirenz). For further information, see d’Almeida et al. (2008).
- 23.
UFRGS stands for Universidade Federal do Rio Grande do Sul.
- 24.
As stated in the previous sections, Cristalia was the only Brazilian company that holds both the pharmochemical (API) and the pharmaceutical (final product) technical competences in the execution of the full pharmaceutical process.
- 25.
Please refer to Table 2.4 for a list of all non-codified information deployed in the technological development of heat-stable Ritonavir.
- 26.
Differential scanning calorimetry.
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d’Almeida, C.M.R. (2019). Knowledge Generation and Laboratory Capacity Building in the Fight Against HIV/AIDS in Brazil: Experiences on the Development of a Heat-Stable Formulation Comprising Ritonavir. In: Cassier, M., Correa, M. (eds) Health Innovation and Social Justice in Brazil. Palgrave Macmillan, Cham. https://doi.org/10.1007/978-3-319-76834-2_2
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