Abstract

Regulatory science involves articulating knowledge that can establish the scientific bases for the definition of adequate and efficient regulatory mechanisms and practices. The interfaces between systemic and sectoral health and technological development policies were studied based on documentary analysis, especially from the National Pharmaceutical Policy (PNAF), with impacts on health regulation and stimulating the production of medicines of interest to the Unified Health System (SUS). The initiatives for the nationalized production of ARV “Efavirenz”, which was the subject of a compulsory license in 2007, and the establishment of Partnerships for Productive Development (PDP), contributed to defining innovative regulatory frameworks and practices, emphasizing the Regulatory Technical Committees (CTR) for monitoring the internalization of technologies and health registration of the resulting products. The permeation capacity of the principles and strategic axes of the PNAF was identified in the sectoral policies that were analyzed. As of 2014, no macro or sectoral policies on expanding access to medicines in the SUS with impacts on regulations were identified.

Key words:
Pharmaceutical policy; Health surveillance; Medicines

Introduction

The Brazilian setting requires the consideration of health regulation and its permeation in the context of public policies in light of the process of construction of the right to health, the Unified Health System (SUS), and the formulation of the National Health Policy, which includes the National Pharmaceutical Policy (PNAF) as one of its components¹Brasil. Conselho Nacional de Saúde. Resolução n°. 338, de 6 de maio de 2004. Aprova a Política Nacional de Assistência Farmacêutica. Diário Oficial da União 2004; 20 maio., and other sectoral policies.

In the field of health, the relationships of production and consumption of goods, services, or technologies are marked by their comprehensive interfaces, especially in the sectors underpinning the so-called Health Economic-Industrial Complex (CEIS). This complex can be defined as a selected set of productive activities that maintain cross-sector relationships for the purchase and sale of goods, services, or knowledge and technology, with a clear sector interdependence relationship²2 Gadelha CAG. O complexo industrial da sau´de e a necessidade de um enfoque dinâmico na economia da sau´de. Cien Saude Colet 2003; 8(2):521-535.. These relationships are subject to the actions of the State as a promoter of possible interfaces and regulator in the relationships established in the context of the CEIS³3 Gadelha CAG, Costa LS, Maldonado J. O Complexo Econômico-Industrial da Sau´de e a dimensa~o social e econômica do desenvolvimento. Rev Saude Publica 2012; 46(Supl.):21-28.. This complex has a common institutionality, represented by the entities of health regulation, technological incorporation, and research ethics⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902..

The development of new technologies and their availability for global consumption requires regulatory definitions that transcend the limits of the countries of origin⁵5 Barbui C, Addis A, Amato L, Traversa G, Garattini S. Can systematic reviews contribute to regulatory decisions? Eur J Clin Pharmacol 2017; 73:507-509.

6 Spindler P, Bach KF, Schmiegelow M, Bedlington N, Eichler HG. Innovation of Medical Products: The Evolution of Regulatory Science, Research, and Education. Ther Innov Regul Sci 2016; 50(1):44-48.^-77 Tsukamoto K, Takenaka T. Role of Academia in Regulatory Science for Global Drug Development. Yakugaku Zasshi 2016; 136(4):543-547., generating constant challenges to the action of regulatory bodies and states⁸8 Baldwin R, Black J, O'leary G. Risk Regulation and Transnationality: Institutional Accountability as a Driver of Innovation. Transnational Environmental Law 2014; 3(2):373-390.

9 Lucchese G. Globalização e Regulação Sanitária: Os Rumos da Vigilância Sanitária no Brasil. [tese] Rio de Janeiro: Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz; 2001.^-1010 Silva APJ, Tagliari, POP. Iniciativas de convergência regulatória em saúde nas Américas: histórico, evolução e novos desafios. Rev Panam Salud Publica 2016; 39(5):281-287., which calls for the strengthening of regulatory systems, components of health systems¹¹11 Allchurch MH, Barbano DBA, Pinheiro MH, Lazdin-Helds J. Fifty years of the European medicines regulatory network: reflections for strengthening intra-regional cooperation in the Region of the Americas. Rev Panam Salud Publica 2016; 39(5):288-293.^,1212 World Health Organization (WHO). Member States. [acessado 2018 nov 16]. Disponível em: http://www.who.int/countries/en/.
http://www.who.int/countries/en... .

Although the term “Health Surveillance” is unique to Brazil, health regulation does not diverge from internationally accepted concepts¹³13 Mendonça CS, Reis AT, Moraes JC, organizadores. A política de regulação do Brasil. Brasília: Organização Pan-Americana da Saúde; 2006.^,1414 Silva JAA, Costa EA, Lucchese G. SUS 30 anos: Vigilância Sanitária. Cien Saude Colet 2018; 23(6):1953-1961.. The dynamics of health surveillance are linked to scientific and technological development and the political processes that permeate the State, the market, and societies.

In this context, regulatory science is a field of knowledge in which the articulation and interfaces between different types of knowledge enable the development of scientific bases that can be used to ensure the safety, quality, and effectiveness of products and services made available to societies, and of instruments and practices that contribute to the decision and implementation of regulatory mechanisms¹⁵15 Meyer RJ. The Role of Academic Medical Centers in Advancing Regulatory Science. Clin Pharmacol Ther 2014; 95(51):29-31.

16 Tominaga T, Asahina Y, Uyama Y, Kondo T. Regulatory Science as a bridge between Science and society. Clin Pharmacol Ther 2011; 90(1):29-31.^-1717 Jasanoff S. Procedural choices in regulatory science. Technol Soc 1995; 17(3):279-293.. This field of knowledge has been the focus of attention of regulatory agencies recognized globally¹⁸18 Food and Drug Administration (FDA). Advancing Regulatory Science at FDA. 2011. [cited 2018 Set 24]. Available from: https://www.fda.gov/downloads/ScienceResearch/SpecialTopics/RegulatoryScience/UCM268225.pdf.
https://www.fda.gov/downloads/ScienceRes... ^,1919 Kurz X. Translating regulatory science into better processes. Eight Stakeholders forum on the implementation of the Pharmacovigilance legislation: Building on two years of operation. London: European Medicines Agency; 2018..

This study aimed to identify and analyze interfaces between sectoral policies geared to technological development for the production of medicines of interest to the Brazilian Unified Health System (SUS) and health regulation, guided by the PNAF, to identify regulatory actions and practices that can contribute to reducing SUS vulnerabilities and achieve sustainable access to medicines.

Methods

This study was carried out by documentary research, adopting the model proposed by Walt and Gilson²⁰20 Walt G, Gilson L. Reforming the health sector in developing countries: the central role of policy analysis. Health Policy Plan 1994; 9(4):353-370. to analyze health policies (Health Policy Analysis, HPA). The analytical model is comprehensive and analyzes complex relationships, highlighting the interrelationship between the four constituent elements of the so-called “policy analysis triangle” and its categories, namely, context, content, and process, for which different stakeholders can contribute. Concerning the content analysis of the policies, the strategies defined in the Situational Strategic Planning method described by Matus²¹21 Matus C. Política, planejamento e governo. Brasília: Instituto de Pesquisa Econômica Aplicada; 1993. were used. The association of different analytical tools is supported by different authors²²22 Buse K. Addressing the theoretical, practical and ethical challenges inherent in prospective health policy analysis. Health Policy and Planning 2008; 23:351-360.^,2323 Walt G, Shiffman J, Schneider H, Murray S, Brugha R, Gilson L. Doing' health policy analysis: methodological and conceptual reflections and challenges. Health Policy Plan 2008; 23:308-317., which may contribute to the greater strength and scope of the analyses performed.

Given the polysemic nature of the term “policy”, the study adopted the understanding of “public policy” as a process in which public action programs are elaborated and implemented, considering political-administrative devices coordinated around the explicit objectives of the governmental action in a defined sector or geographic space²⁴24 Muller P, Surel Y. Análise das políticas públicas. Pelotas: EDUCAT; 2002..

The study covered the period from 2003 to 2019, referring to the formulation and 15 years of PNAF’s implementation. Documents were searched on the websites of the Ministries of Health, Economy and Science, Technology and Innovation, the National Health Council, the National Health Surveillance Agency (ANVISA), and the National Bank for Economic and Social Development (BNDES) and printed publications of these institutions.

The study included public actions related to the development and internalization of technologies to produce medicines of interest to the SUS, access to, and health regulation of medicines. Documents addressing only organizational aspects and administrative rules were excluded from the analysis. The search identified 212 documents, which were read in full. The inclusion and exclusion criteria shortlisted this number to 110 documents for analysis.

Results

Chart 1 presents the synthesis of the analysis regarding the typology and content of public policies with identified interfaces between technological development and health regulation during the study period. The contexts, processes, and stakeholders related to the policies mentioned above were analyzed from these data, the results of which are shown in Chart 2. References to health regulation or health surveillance held a prominent place in the analyses.

Discussion

In 2003, pharmaceutical care was defined as one of the priorities of the Brazilian Ministry of Health, reflected in the establishment of the Secretariat of Science, Technology and Strategic Supplies (SCTIE), its Department of Pharmaceutical Care and Strategic Supplies (DAF)²⁵25 Rech N. Acesso aos medicamentos e à assistência farmacêutica. Brasília: Ministério da Saúde, Secretaria de Ciência, Tecnologia e Insumos Estratégicos; 2005.^,2626 Rech N, Farias MR. Assistência Farmacêutica, intersetorialidade, pesquisa e inovação. Newsletter ABCF 2015; 1:7-9., and holding the First National Conference on Medicines and Pharmaceutical Policy²⁷27 Bermudez JAZ, Esher A, Osorio-de-Castro CGS, Vasconcelos DMM, Chaves GC, Oliveira MA, Silva, RM, Luiza VL. Assiste^ncia Farmace^utica nos 30 anos do SUS na perspectiva da integralidade. Cien Saude Colet 2018; 23(6):1937-1951.^,2828 Brasil. Ministério da Sau´de (MS). Conselho Nacional de Sau´de. 1ª Conferência Nacional de Medicamentos e Assistência Farmacêutica. Relatório Final: efetivando o acesso, a qualidade e a humanização na assistência farmacêutica, com controle social. Brasília: MS; 2005.. The National Pharmaceutical Policy (PNAF) was established in the National Health Council (CNS) by Resolution CNS No. 338/2004¹Brasil. Conselho Nacional de Saúde. Resolução n°. 338, de 6 de maio de 2004. Aprova a Política Nacional de Assistência Farmacêutica. Diário Oficial da União 2004; 20 maio., and ratified by the Minister of Health²⁹29 Brasil. Presidência da República. Decreto de 12 de novembro de 1991. Delega competência ao Ministro de Estado da Saúde para homologar as decisões do Conselho Nacional de Saúde. Diário Oficial da União 1991; 13 nov., consolidating the permeations between access and rational use of medicines with the intersectoral policies of scientific, technological and industrial, development in Brazil²⁶26 Rech N, Farias MR. Assistência Farmacêutica, intersetorialidade, pesquisa e inovação. Newsletter ABCF 2015; 1:7-9.^,2727 Bermudez JAZ, Esher A, Osorio-de-Castro CGS, Vasconcelos DMM, Chaves GC, Oliveira MA, Silva, RM, Luiza VL. Assiste^ncia Farmace^utica nos 30 anos do SUS na perspectiva da integralidade. Cien Saude Colet 2018; 23(6):1937-1951..

The PNAF was the first public policy formulated and established within the social control of the SUS³⁰30 Leite SN, Manzini F, Veiga A, Lima MEO, Pereira MA, Araujo, SQ, Santos RF, Bermudez JAZ. Ciência, Tecnologia e Assistência Farmacêutica em pauta: contribuições da sociedade para a 16a Conferência Nacional de Sau´de. Cien Saude Colet 2018; 23(12):4259-4268., assuming a strategic role beyond the health care process. Its principle is its guiding role in formulating other sectoral policies, emphasizing medicines, industrial development, and science and technology policies. Concerning health regulation, the PNAF defined the construction of a health surveillance policy to guarantee people’s access to safe, effective, and quality services and products¹Brasil. Conselho Nacional de Saúde. Resolução n°. 338, de 6 de maio de 2004. Aprova a Política Nacional de Assistência Farmacêutica. Diário Oficial da União 2004; 20 maio. as one of its priority axes. This construction is still underway since Brazil has not yet advanced in establishing a national health surveillance policy. Regarding medicines, the PNAF assumes the strategic role of systemic policy (macropolitics), while the SUS guides the demand to the productive pharmaceutical sectors, whose capillarity began to influence the formulation or decision-making within other systemic public policies and sectoral policies (micropolitics).

From 2003 to 2006, the Ministry of Health worked painstakingly in joint coordination with the Ministry of Development, Industry, and Foreign Trade of the Forum on Competitiveness of the Pharmaceutical Productive Chain³¹31 Brasil. Ministe´rio da Sau´de (MS). Ministe´rio do Desenvolvimento, Indústria e Comércio Exterior. Fórum de competitividade da cadeia produtiva farmacêutica 2003-2006: O desafio de prosseguir Brasília: MS; 2007., and the stakeholders involved advanced discussions on scientific, technological, and industrial development to meet the demands of the SUS. In a context marked by the search for consensus, the Forum identified the economic and strategic relevance of medicines for the SUS, characterizing the pharmaceutical industrial policy as a “government priority” and “State policy” and recommending the prioritization of public policies geared to modernization and training of public pharmaceutical laboratories to conduct research and development (R&D) activities, and the implementation of public-private partnerships as a mechanism for inducing industrial production in the sector³¹31 Brasil. Ministe´rio da Sau´de (MS). Ministe´rio do Desenvolvimento, Indústria e Comércio Exterior. Fórum de competitividade da cadeia produtiva farmacêutica 2003-2006: O desafio de prosseguir Brasília: MS; 2007.. These definitions were aligned with those indicated by the PNAF.

A relevant consequence of the Forum was the inclusion of the topic “pharmaceuticals and medicines” as one of the four priorities of the Industrial, Technological, and Foreign Trade Policy (PITCE), an important advance in the coordination of sectoral policies to support the development of productive health sectors³²32 Brasil. Casa Civil da Presidência da República. Diretrizes de politica industrial, tecnológica e de comércio exterior. Brasília: Casa Civil da Presidência da República; 2004.^,3333 Brasil. Agência Brasileira de Desenvolvimento Industrial (ABDI). Dez anos de política industrial: balanço e perspectivas 2004-2014. Brasília: ABDI; 2015.. A more immediate result of such prioritization, in April 2004, the National Bank for Economic and Social Development (BNDES) launched the Pharmaceutical Chain Support Program (PROFARMA), initially to enable investments to adapt the national pharmaceutical park to new regulatory requirements and induce innovative activity in the pharmaceutical chain³⁴34 Palmeira Filho PL, Pieroni JP, Antunes MAS, Martins JV. O desafio do financiamento a` inovac¸a~o farmace^utica no Brasil: a experie^ncia do BNDES Profarma. Revista do BNDES 2012; 37:67-90. [acessado 2019 maio 20]. Disponível em: http://www.bndes.gov.br/bibliotecadigital.
http://www.bndes.gov.br/bibliotecadigita... . Although the Forum’s recommendations indicated the need for the National Health Surveillance System (SNVS) to adopt mechanisms for internalizing the guidelines resulting from the consensus obtained³¹31 Brasil. Ministe´rio da Sau´de (MS). Ministe´rio do Desenvolvimento, Indústria e Comércio Exterior. Fórum de competitividade da cadeia produtiva farmacêutica 2003-2006: O desafio de prosseguir Brasília: MS; 2007., no concrete actions in this regard had been identified until late 2006.

In 2004, the challenge of formulating a National Policy on Science, Technology, and Innovation in Health (PNCTIS) found a political-institutional context favorable to the resumption of discussions emanating from the First Thematic Conference held in 1994³⁵35 Goldbaum M, Serruya SJ. O Ministério da Saúde na política de ciência, tecnologia e inovação em saúde. REVISTA USP 2007; 73:40-47., insofar as science and technology policy in health is a component of the National Health Policy³⁵35 Goldbaum M, Serruya SJ. O Ministério da Saúde na política de ciência, tecnologia e inovação em saúde. REVISTA USP 2007; 73:40-47.^,3636 Guimara~es R, Noronha J, Elias FTS, Gadelha CAG, Carvalheiro JR, Ribeiro A. Política de ciência, Tecnologia e Inovação em Saúde. Cien Saude Colet 2019; 24(3):881-886.. The establishment of the Secretariat of Science, Technology, and Strategic Supplies (SCTIE)/MS contributed to this positive setting. The Second National Conference on Science, Technology and Innovation in Health (CNCTIS) held in July 2004 resulted in the proposed consolidated text of the PNCTIS, which was submitted for deliberation by the CNS³⁷37 Brasil. Conselho Nacional de Saúde. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. 2a Conferência Nacional de Ciência, Tecnologia e Inovação em Saúde. Brasília: MS; 2005.. Many items defined by the PNCTIS had an unequivocal relationship with the definitions of the PNAF, and regarding health regulation, the PNCTIS highlighted the role of ANVISA regarding the prior consent for patenting of health supplies³⁷37 Brasil. Conselho Nacional de Saúde. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. 2a Conferência Nacional de Ciência, Tecnologia e Inovação em Saúde. Brasília: MS; 2005..

The instrument of prior consent by ANVISA in the requests to grant patents for pharmaceutical products and processes resulting from the introduction of art. 229-C to the Intellectual Property Law (Law No. 9,279/96) by Law No. 10.196, of February 14, 2001³⁸38 Tojal SBB, Pessôa PR. Anue^ncia pre´via na concessa~o de patentes de medicamentos e a regulac¸a~o econo^mica da indu´stria farmace^utica. Revista de Direito Sanitário 2008; 8(3):148-165.. The application of the provisions of art. 229-C was the object of Joint Ordinance No. 1, of April 2017, agreed upon by ANVISA and the National Institute of Industrial Property (INPI)³⁹39 Brasil. Agência Nacional de Vigilância Sanitária. Instituto Nacional de Propriedade Industrial. Portaria Conjunta n° 1, de 12 de abril de 2017. Regulamenta os procedimentos para a aplicação do artigo 229-C da Lei nº 9.279, de14 de maio de 1996, acrescido pela Lei nº10.196, de 14 de fevereiro de 2001, e dá outras providências. Diário Oficial da União 2017: 13 abr.. The definitions of this ordinance limit the application of the procedure of prior consent by ANVISA since it may submit subsidies to the INPI’s examination regarding the patentability criteria in applications of interest to drug policies or pharmaceutical care within the SUS, but no veto power over compliance with these criteria. This decision followed the opposite path to that indicated by the PNCTIS³⁷37 Brasil. Conselho Nacional de Saúde. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. 2a Conferência Nacional de Ciência, Tecnologia e Inovação em Saúde. Brasília: MS; 2005..

In April 2007, after fruitless negotiations with the company holding the patent, the Brazilian government declared the patent rights on Efavirenz a matter of public interest to grant a compulsory license for non-commercial use⁴⁰40 Brasil. Ministério da Saúde (MS). Portaria n° 886, de 24 de abril de 2007. Declara de interesse público os direitos de patente sobre o efavirenz, para fins de concessão de licença compulsória para uso não comercial. Diário Oficial da União 2007; 25 abril., which was followed by the enactment of the Presidential Decree Nº 6.108/2007, establishing the compulsory licensing of Efavirenz⁴¹41 Brasil. Presidência da República. Decreto n° 6.108 de 4 de maio de 2007. Concede licenciamento compulsório, por interesse público, de patentes referentes ao Efavirenz, para fins de uso público não-comercial. Diário Oficial da União 2007; 5 maio., government response to the context of high vulnerability of the National STD/AIDS Program (PN DST/AIDS), established in 1986⁴²42 Bermudez JAZ, Oliveira MA, Esher A. Acesso a Medicamentos: Derecho Fundamental, Papel del Estado. Rio de Janeiro: ENSP; 2004.

43 Granjeiro A, Laurindo da Silva L, Teixeira PR. Resposta a` aids no Brasil: contribuições dos movimentos sociais e da reforma sanitária. Rev Panam Salud Publica 2009; 26(1):87-94.<sup>-44</sup>44 Hoirisch C. Licença Compulsória para Medicamentos como Poli´tica Pu´blica: O Caso do Antirretroviral Efavirenz [dissertação]. Rio de Janeiro: Fundação Getúlio Vargas; 2010. and whose free access to medicines by people living with HIV was established by Law No. 9.313, of November 1996<sup>45</sup>45 Brasil. Lei n° 9.313 de 13 de novembro de 1996. Dispõe sobre a distribuição gratuita de medicamentos aos portadores do HIV e doentes de AIDS. Diário Oficial da União 1996; 14 nov.. The impacts of the Brazilian Patent Law<sup>46</sup>46 Brasil. Presidência da República. Lei n° 9.279, de 14 de maio de 1996. Regula direitos e obrigações relativos a` propriedade industrial. Diário Oficial da União 1996; 15 mai. and the constant price hike of ARVs started to affect the sustainability of the Brazilian program, with around 70% of the PN STD/AIDS budget in the 2006-2007 period committed to the acquisition of imported ARVs⁴⁷47 Greco DB. Desafios da Epidemia de Aids após 10 anos de terapia antirretroviral. Brasília: Ministério da Saúde; 2007.. After adopting the compulsory license, the national production of Efavirenz was taken over by the Farmanguinhos/Fiocruz⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.^,4848 Rodrigues WCV, Soler O. Licenc¸a compulso´ria do efavirenz no Brasil em 2007: contextualizac¸a~o. Rev Panam Salud Publica 2009; 26(6):553-559. Pharmaceutical Technology Institute, facilitated by partnerships with national pharmaceutical and pharmochemical companies.

This initiative was anchored in the Interministerial Ordinance No. 128/2008, which established the guidelines for contracting drugs and medicines by the bodies and entities that make up the Unified Health System⁴⁹49 Brasil. Ministério do Planejamento, Orçamento e Gestão, Ministério da Saúde, Ministério de Ciência, Tecnologia e Inovação. Portaria n° 128 de 29 de maio de 2008. Estabelece as diretrizes para a contratação de fármacos e medicamentos pelos órgãos e entidades integrantes do Sistema Único de Saúde. Diário Oficial da União 2008; 30 mai.^,5050 Viana ALD, Silva HP, Iban~ez N, Iozzi FL. A poli´tica de desenvolvimento produtivo da sau´de e a capacitação dos laboratórios públicos nacionais. Cad Saude Publica [periódico na Internet]. 2016 Nov [acessado 2019 maio 12]; 32(Supl. 2): [cerca de 14 p.]. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-311X2016001405003&lng=en&nrm=iso.
http://www.scielo.br/scielo.php?script=s... . This productive arrangement was one of the pioneering examples of the use of the strategy that would later shape the Partnerships for Productive Development (PDP)⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.. These actions were aligned with the principles and strategic axes of PNAF¹Brasil. Conselho Nacional de Saúde. Resolução n°. 338, de 6 de maio de 2004. Aprova a Política Nacional de Assistência Farmacêutica. Diário Oficial da União 2004; 20 maio..

In this scenario, ANVISA acted proactively and published Ordinance No. 583/2007, which established the Technical-Regulatory Committee (CTR) within ANVISA to monitor the development, production, and registration of the drug object of the Decree N° 6.108 in Brazil, dated May 4, 2007⁵¹51 Brasil. Agência Nacional de Vigilância Sanitária. Portaria n° 583 de 8 de agosto de 2007. Institui o Comitê Técnico-Regulatório no âmbito da Anvisa com a finalidade de acompanhar o processo de desenvolvimento, produção e registro no Brasil do medicamento objeto do Decreto n. 6.108, de 04 de maio de 2007. Diário Oficial da União 2007; 08 ago.. This definition was innovative in the Brazilian regulatory-health setting, enabling an early and collaborative interface between the regulatory authority and the productive entities responsible for technological development initiatives of national interest. In February 2009, Farmanguinhos/Fiocruz delivered to the Ministry of Health the first batches of nationalized production of ARV Efavirenz⁵²52 Brasil. Fundação Oswaldo Cruz (Fiocruz). Farmanguinhos entrega ao Ministério da Saúde o Efavirenz nacional. Rio de Janeiro: Fiocruz; 2009., facilitated by the reduced regulatory times promoted by the CTR.

The National Policy for Productive Development was established in May 2008 as one of the initiatives to confront the marked acceleration of the deficit in the Brazilian trade balance in the pharmaceutical and medicine segments since the 2000s⁵³53 Vargas M, Gadelha CAG, Costa LS, Maldonado J. Inovação na indústria química e biotecnológia em saúde: em busca de uma agenda virtuosa. Rev Saude Publica 2012; 46(Supl.):37-40.. It defined the Economic-Industrial Health Complex (CEIS) as one of its priorities, accompanied by the establishment of the Executive Group for the Health Industrial Complex (GECIS) through Decree/2008⁵⁴54 Brasil. Ministe´rio da Sau´de (MS). Mais Sau´de: direito de todos 2008-2011. Brasília: MS; 2008.^,5555 Brasil. Decreto de 12 de maio de 2008. Cria, no âmbito do Ministério da Saúde, o Grupo Executivo do Complexo Industrial da Saúde - GECIS e dá outras providências. Diário Oficial da União 2008; 13 mai.. As the national manager of the SUS, the Ministry of Health assumed the role of conducting intersectoral initiatives to regulate and improve the efficiency of the CEIS, involving the industrial, economic, and technological fields, and meet SUS demands⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.^,5656 Vargas MA, Almeida ACS, Guimarães ALC. Parcerias para desenvolvimento produtivo (PDPS-MS): contexto atual, impactos no sistema de sau´de e perspectivas para a poli´tica industrial. Rio de Janeiro: Fundação Oswaldo Cruz; 2017.. The development policy defined in 2008 resumed and expanded the breadth and depth of the PITCE established in 2004⁵⁷57 Departamento Intersindical de Estatística e Estudos Socioeconômicos (DIEESE). Política de desenvolvimento produtivo - nova política industrial do governo. São Paulo: DIEESE; 2008.. As provided for in the Decree of its establishment⁵⁵55 Brasil. Decreto de 12 de maio de 2008. Cria, no âmbito do Ministério da Saúde, o Grupo Executivo do Complexo Industrial da Saúde - GECIS e dá outras providências. Diário Oficial da União 2008; 13 mai., the setting of a permanent forum for articulation with civil society to provide advice to the GECIS was defined, which placed the premise for the different social stakeholders’ participation in proposing strategies actions for the development of the health sector⁵⁸58 Brasil. Ministério da Saúde (MS). Portaria n° 1.942 de 17 de setembro de 2008. Aprova o Regimento Interno do Grupo Executivo do Complexo Industrial da Sau´de - GECIS e institui o Fórum Permanente de Articulação com a Sociedade Civil. Diário Oficial da União 2008; 18 set.. Regarding health regulation, GECIS’ competencies included actions to guarantee isonomic health regulation and support the quality of national production, including the modernization of health surveillance actions and the establishment of a support network for the quality and competitiveness of local production and the simplification and streamlining of regulatory processes³⁶36 Guimara~es R, Noronha J, Elias FTS, Gadelha CAG, Carvalheiro JR, Ribeiro A. Política de ciência, Tecnologia e Inovação em Saúde. Cien Saude Colet 2019; 24(3):881-886.^,5353 Vargas M, Gadelha CAG, Costa LS, Maldonado J. Inovação na indústria química e biotecnológia em saúde: em busca de uma agenda virtuosa. Rev Saude Publica 2012; 46(Supl.):37-40.. These definitions reinforced ANVISA’s initiatives to adopt the CTRs as a regulatory practice, especially from the positive results observed in the process resulting from the compulsory license adopted in 2007.

In the setting where public health policies were directed towards a virtuous articulation between health care and industrial development⁵⁹59 Gomes R, Pimentel Vitor, Losada M, Pieroni JP. O novo cenário de concorrência na indústria farmacêutica brasileira. BNDES Setorial 2014; 39:97-134., public procurement has become a vital instrument for inducing technological training and development of the productive base to reduce the vulnerability of the SUS and generate investments, employment, and income⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.. These assumptions are aligned with the guidelines and strategic axes established in the PNAF. As of 2009, PDPs were defined as an instrument established within the health policy to stimulate the CEIS and meet SUS demands⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.^,3636 Guimara~es R, Noronha J, Elias FTS, Gadelha CAG, Carvalheiro JR, Ribeiro A. Política de ciência, Tecnologia e Inovação em Saúde. Cien Saude Colet 2019; 24(3):881-886.^,6060 Cassiolato JE, Szapiro M. Os dilemas da política industrial e de inovação: os problemas da região Sudeste são os problemas do Brasil. In: Leal CLCF, Linhares LRF, Lemos CR,Silva MML,Lastres HMM. Um olhar territorial sobre o desenvolvimento: Sudeste. Rio de Janeiro: BNDES; 2015.^,6161 Silva GO, Elias FTS. Parcerias para o desenvolvimento produtivo: um estudo de avaliabilidade. Com Cienc Saude 2017; 28(2):125-139.. They are, therefore, an industrial policy mechanism used in health to internalize production and transfer drug technology, active pharmaceutical ingredients, and products of interest to the SUS⁶²62 Varrichio PC. As parcerias para o desenvolvimento produtivo da sau´de. In: Rauen AT (organizador). Políticas de inovação pelo lado da demanda no Brasil. Brasília: Ipea; 2017. p.179-234.. This initiative occurs under the coordination of the Ministry of Health presented under the GECIS in 2009⁶¹61 Silva GO, Elias FTS. Parcerias para o desenvolvimento produtivo: um estudo de avaliabilidade. Com Cienc Saude 2017; 28(2):125-139., through the establishment of a partnership between the technology holding company and a public producer entity qualified to supply the product to the SUS during the period of technological absorption, with the centralized acquisition by the Ministry of Health⁴4 Gadelha CAG, Temporão JG. Desenvolvimento, Inovac¸a~o e Sau´de: a perspectiva teo´rica e poli´tica do Complexo Econo^mico-Industrial da Sau´de. Cien Saude Colet 2018; 23(6):1891-1902.^,6363 Silva GO, Rezende KS. Parcerias para o desenvolvimento produtivo: a constituição de redes sociotécnicas no Complexo Econômico-Industrial da Saúde. Vigil Sanit Debate 2017; 5(1):11-12.^,6464 Gadelha CAG, Braga PSC. Health and innovation: economic dynamics and Welfare State in Brazil. Cad Saude Publica 2016; 32(Supl. 2):e00150115.. This strategy was a practical consequence of the inclusion of CEIS among the strategic axes of national health planning, strengthening the national pharmacochemical industry and official pharmaceutical laboratories, based on the arrangement for the transfer of technologies demanded by the SUS²⁸28 Brasil. Ministério da Sau´de (MS). Conselho Nacional de Sau´de. 1ª Conferência Nacional de Medicamentos e Assistência Farmacêutica. Relatório Final: efetivando o acesso, a qualidade e a humanização na assistência farmacêutica, com controle social. Brasília: MS; 2005.. In building and implementing the PDPs, the Ministry of Health, primarily through the SCTIE, assumed a prominent role as an institutional actor, with significant results for the sustainability of access to medicines in the SUS. From 2011 to early 2017, the savings resulting from the centralized purchase of medicines covered by the PDP reached BRL 4.68 billion³⁶36 Guimara~es R, Noronha J, Elias FTS, Gadelha CAG, Carvalheiro JR, Ribeiro A. Política de ciência, Tecnologia e Inovação em Saúde. Cien Saude Colet 2019; 24(3):881-886.. In this context, ANVISA defined the establishment of Technical-Regulatory Committees (CTR) to follow up and monitor the different partnerships defined for each public pharmaceutical laboratory involved⁶¹61 Silva GO, Elias FTS. Parcerias para o desenvolvimento produtivo: um estudo de avaliabilidade. Com Cienc Saude 2017; 28(2):125-139.^,6363 Silva GO, Rezende KS. Parcerias para o desenvolvimento produtivo: a constituição de redes sociotécnicas no Complexo Econômico-Industrial da Saúde. Vigil Sanit Debate 2017; 5(1):11-12.. Such CTRs were formally anchored in the Resolution of the Collegiate Board of Directors (RDC) of ANVISA of 02/2011⁶⁵65 Brasil. Agência Nacional de Vigilância Sanitária. Resolução de Diretoria Colegiada - RDC - n° 2 de 2 de fevereiro de 2011. Dispõe sobre os procedimentos no âmbito da ANVISA para acompanhamento, instrução e ana´lise dos processos de registro e pós-registro, no Brasil, de medicamentos produzidos mediante parcerias público-público ou público- privado e transferência de tecnologia de interesse do Sistema Único de Sau´de. Diário Oficial da União 2011; 3 fev., building on the successful regulatory practice experience adopted when the compulsory license of Efavirenz was issued in 2007.

The actions to include the CEIS in the national development policy and its strengthening to meet the demands of the SUS were reinforced with the incorporation of the GECIS into the Brasil Maior Plan, established in 2011 by Decree No. 7.540⁶⁶66 Brasil. Presidência da República. Decreto n° 7.540 de e de agosto de 2011. Institui o Plano Brasil Maior - PBM e cria o seu sistema de gestão. Diário oficial da União 2011; 3 ago.^,6767 Bercovici G. Complexo industrial da sau´de, desenvolvimento e proteção constitucional ao mercado interno. Rev Dir Sanit 2013; 14(2):9-42.. In this new setting, the Ministry of Health established the Program for the Development of the Health Industrial Complex (PROCIS) through MS Ordinance No. 506/2012⁶⁸68 Brasil. Ministério da Saúde (MS). Portaria n° 506 de 21 de março de 2012. Institui o Programa para o Desenvolvimento do Complexo Industrial da Saúde (PROCIS) e seu Comitê Gestor. Diário Oficial da União 2012; 22 mar. to strengthen the infrastructure of production and innovation in health in the public sector. In this context, the guidelines for establishing PDPs were defined through the Ministry of Health’s Ordinance No. 837/2012⁶⁹69 Brasil. Ministério da Saúde (MS). Portaria n° 837 de 18 de abril de 2012. Define as diretrizes e os critérios para o estabelecimento as Parcerias Para o Desenvolvimento Produtivo (PDP). Diário Oficial da União 2012; 27 abr., which was based on the National Health Plan⁷⁰70 Brasil. Ministério da Saúde (MS). Plano Nacional de Saúde (PNS) 2012-2015. Brasília: MS; 2011..

The interfaces of PROCIS with health surveillance are shown by the inclusion of ANVISA in its management committee⁶⁸68 Brasil. Ministério da Saúde (MS). Portaria n° 506 de 21 de março de 2012. Institui o Programa para o Desenvolvimento do Complexo Industrial da Saúde (PROCIS) e seu Comitê Gestor. Diário Oficial da União 2012; 22 mar. and the actions of this agency geared to technological and industrial development, such as the edition of RDC No. 50/2012, which provided for the procedures for the registration of products in the process of developing or transferring technologies that are the object of public-public or public-private Productive Development Partnerships of interest to the Unified Health System⁷¹71 Brasília. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada RDC - n° 50 de 13 de setembro de 2012. Dispõe sobre os procedimentos no âmbito da Anvisa para registro de produtos em processo de desenvolvimento ou de transferência de tecnologias objetos de Parcerias de Desenvolvimento Produtivo público-público ou público-privado de interesse do Sistema Único de Saúde. Diário Oficial da União 2012; 14 set.. This regulatory-sanitary definition innovated by setting mechanisms for the systematic internalization of all information related to the development of drugs subject to PDP, resulting in the gradual and monitored composition of product dossiers, with the reduced regulatory time required for the analysis and definition of the respective records and acceleration of their availability in the SUS.

The revision of the legal framework supporting the PDPs was defined by the Ministry of Health’s Ordinance No. 2.531/2014⁷²72 Brasil. Ministério da Saúde (MS). Portaria GM/MS no 2.531 de 12 de novembro de 2014. Redefine as diretrizes e os critérios para a definição da lista de produtos estratégicos para o Sistema Único de Saúde (SUS) e o estabelecimento das Parcerias para o Desenvolvimento Produtivo (PDP) e disciplina os respectivos processos de submissão, instrução, decisão, transferência e absorção de tecnologia, aquisição de produtos estratégicos para o SUS no âmbito das PDP e o respectivo monitoramento e avaliação. Diário Oficial da União 2014; 13 nov.. This regulation is related to the macro-policy of use and rationalization of the State’s purchasing power, including the criteria for defining strategic products for the SUS and fostering the development of the CEIS⁷³73 Oliveira EJV, Vivan AL, Albuquerque FC, Silva GO, Rezende KS, Barbosa LP. A consolidação do marco regulatório das parcerias para o desenvolvimento produtivo. Revista Eletrônica Gestão em Saúde [periódico na Internet]. 2015 out [acessado 2016 mar 18]; 6(Supl. 4): [cerca 19 p.]. Disponível em: blob:https://periodicos.unb.br/7473880f-c9af-4da8-b0a1-3351a6ec1472
https://periodicos.unb.br/7473880f-c9af-... . The regulation of the use of the State’s purchasing power was the object of the National Policy for Technological Innovation in Health (PNITS), defined by Decree No. 9.245/2017⁷⁴74 Brasil. Presidência da República. Decreto n° 9.245 de 20 de dezembro de 2017. Institui a Politica Nacional de Inovação Tecnológica na Saúde. Diário Oficial da União 2017; 21 Dez., in a weakening Brazilian democracy promoted by the legal-parliamentary coup of 2016⁷⁵75 Souza LEPF, Paim JS, Teixeira CF, Bahia L, Guimara~es R, Machado CV, Campos GW, Azevedo-e-Silva G. Os desafios atuais da luta pelo direito universal a` sau´de no Brasil. Cien Saude Colet 2019; 24(8):2783-2792.. However, the PNITS did not add any advances regarding health regulation. The context in which the PDP regulation was revised was marked by the need for greater transparency in the processes for its definition and the search for greater legal certainty for decision-making within public management. The initiatives adopted were strongly influenced by the recommendations resulting from the audit carried out by the Federal Court of Accounts (TCU), which assessed the regularity of the PDP signed by the Ministry of Health⁷⁶76 Brasil. Tribunal de Contas da União. Sessão Extraordinária Reservada do Plenário - Ata 18, de 9 de agosto de 2017. Brasília: Secretaria da Sessões/TCU, 2017. Disponível em: http://www.tcu.gov.br/Consultas/Juris/Docs/CONSES/TCU_ATA_0_S_2017_18.PDF. The new legal framework was an evolution regarding the criteria for defining strategic products for the SUS established in 2008 by Ordinance MS No. 978⁷⁷77 Brasil. Ministério da Saúde (MS). Portaria nº 978 de 16 de maio de 2008. Dispõe sobre a lista de produtos estratégicos, no âmbito do Sistema Único de Saúde, com a finalidade de colaborar com o desenvolvimento do Complexo Industrial da Saúde e institui a Comissão para Revisão e Atualização da referida lista. Diário Oficial da União 2008; 17 mai.. However, a recent study indicates that the criteria adopted for constructing a strategic list of products for the SUS do not incorporate elements of health technology assessment and the use of evidence, and the process lacks interactions between researchers and decision-makers⁷⁸78 Rezende KS, Silva GO, Albuquerque FC. Parcerias para o Desenvolvimento Produtivo: um ensaio sobre a construção das listas de produtos estratégicos. Saude Debate 2019; 43(2):155-168.^,7979 Silva GO, Elias FTS. Parcerias para o Desenvolvimento Produtivo: diagnóstico situacional da implementação na perspectiva dos atores envolvidos. Com Cienc Saude 2017; 28(3/4):313-325.. Concerning health regulation, the revised legal guidelines of the PDP reaffirmed the role of the CTR and included ANVISA in the Technical Assessment Committees (CTA), responsible for analyzing and evaluating the PDP proposals. Such definitions reinforce ANVISA’s strategic role in the context of the CEIS incentive policy and understanding CTR as a practice model in the health-regulatory field.

Final considerations

The study identified essential interfaces between the evolution of regulatory frameworks and practices with initiatives to foster technological development for the national production of medicines of interest to the SUS, based on the guidelines of the National Pharmaceutical Care Policy (PNAF).

Establishing the PDPs was an essential strategy for reducing SUS vulnerabilities. It implemented the Technical Regulatory Committees (CTR) as an innovative practice in health surveillance, considering the successful experience carried out during the compulsory license for the national production of Efavirenz in 2007. The incentives to the CEIS also boosted the adoption of new milestones and new regulatory practices regarding the internalization and development of technologies, keeping interfaces with PNAF’s guiding capacity on sectorial policies aimed at people’s access to medicines, with a reduction in time for its availability in the SUS, cost reduction, and addressing SUS vulnerabilities. However, as of 2014, no significant developments were identified in this context.

Although the study period was capped at year 2019, it was essential to refer to the current situation of the COVID-19 pandemic, which shows that investments in scientific and technological development and the adoption of milestones and new regulatory practices are fundamental for the country. Likewise, Brazil must overcome the gaps generated in the sectoral policies with the resumption and enhancement of the advances achieved. To this end, it is crucial to observe the principles defined in the national health policy and its social control, the strengthening of the national system of science, technology, and innovation, and the preservation of state companies with impacts on the health sector, where the State is a regulator that can prioritize national development, as opposed to subordinating it to particular economic interests or institutional neglect.

References

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