Abstract

This article examines pharmaceutical services and access to essential medicines in Brazil during the 30 years since the advent of Brazil’s Unified Health System from a comprehensiveness perspective. The following topics are addressed: the “realignment” of pharmaceutical services; human resources in pharmaceutical services; the essential medicines concept; the rational use of medicines; technological advances and drug manufacturing; and ethical regulation. With a strong regulatory focus and a structural framework centered on the National Medicines Policy, the past three decades represent a mixture of progress and setbacks, considering the national complexities of the healthcare system and the political, economic and social changes that have influenced policy and access to medicines, which is a key concern even in the world’s richest countries, as the forums of discussion on global health have demonstrated. We show that major steps forward have been taken, highlighting that the recent fiscal austerity measures imposed by the government threaten to seriously undermine social progress.

Pharmaceutical services; National medicines policy; Essential medicines; Comprehensiveness in healthcare; Unified Health System

Introduction

As we contemplate present-day Brazil, with the current political situation threatening to undermine the impressive social progress made by the country, it is important to look back to 1988 and remember what the 30 years that have passed since the creation of the Citizens’ Constitution mean for the Unified Health System (Sistema Único de Saúde – SUS) and the right to health with universal access to healthcare. The transition from 20 years of military rule to the return to democracy gave rise to the progressive, supra-party health reform movement, which envisaged a fair and equitable country with social justice¹1. Escorel S. Reviravolta na saúde: origem e articulação do movimento sanitário. Rio de Janeiro: Editora Fiocruz; 1999..

This movement included pharmaceutical services, which has undergone major changes during the 30-year period covered by this article (Chart 1). It is within this context that we discuss the main milestones in pharmaceutical services and access to medicines in Brazil focusing on the key guidelines and priorities laid out in the National Medicines Policy (NMP) and one of the guiding principles of the SUS, comprehensiveness.

With regard to World Health Organization (WHO) guidelines, in previous works we highlighted the importance of discussions for influencing and guiding different countries in the implementation of actions directed at ensuring access to essential medicines²2. Bermudez J. Acesso a medicamentos: direito ou utopia? Rio de Janeiro: E-papers; 2014.,³3. Bermudez J. Contemporary challenges on access to medicines: beyond the UNSG High-Level Panel. Cien Saude Colet 2017; 22(8):2435-2439.. Recently, based on an extensive review of literature, the WHO highlighted a number of challenges to ensuring access to safe health technologies, various of which are discussed in this article⁴4. World Health Organization (WHO). Addressing the global shortage of, and access to, medicines and vaccines. Geneva: WHO; 2013. Report No: EB142/13..

Commissions of inquiry, decrees and laws, the reorientation of public policies, and technological proposals have failed to echo the idea of a state pharmaceutical industry widely discussed during the military regime. Nonetheless, a series of proposals and initiatives have had a definite impact on pharmaceutical services in the SUS over the last three decades.

Realignment of pharmaceutical services – the comprehensiveness paradigm

This guideline brought together key structural elements for the consolidation of the SUS. The fact that it was entitled “reorientation”(realignment) was innovative in itself, “giving a new orientation or new meaning” to a process that had already begun and was evolving.

Up to that point, the term “pharmaceutical services” was coined from a medicine supply perspective. Although the decree⁵5. Brasil. Presidência da República. Decreto no 68.806, de 25 de Junho de 1971. Institui a Central de Medicamentos (CEME). Diário Oficial da União 1971; 26 jun. that created the state pharmaceutical company Central de Medicamentos (CEME)contained the term pharmaceutical services, a clear definition of its scope, objectives, and activities would only be provided with the creation of the NMP. Thus, the reorientation of pharmaceutical services set out in the NMP represented a proposal for the effective integration of pharmaceutical services into the SUS, paving the way for the promotion of citizenship in line with the constitutional right to health.

The reorientation of pharmaceutical services proposed by the NMP was cross-cutting, producing direct impacts in the field of public health⁶6. Vasconcelos DMM, Chaves GC, Azeredo TB, Silva RM. Política Nacional de Medicamentos em retrospectiva: um balanço de (quase) 20 anos de implementação. Cien Saude Colet 2017; 22(8):2609-2614.. The priorities set forth in the guideline are built around three key elements: decentralization, funding, and logistical actions⁷7. Brasil. Portaria MS/GM No 3916, de 30 de outubro de 1998. Aprova a Política Nacional de Medicamentos. Brasília, DF. Diário Oficial da União 1998; 31 out.. Moreover, it guided and reinforced commitment to the constituent elements of pharmaceutical services within each of the three management levels of the SUS.

The inherent characteristics of this guideline reflect the social and political context in Brazil, reproducing the developments in the field of health witnessed during each 10-year period (Chart 2).

During the first 10 years of the SUS, pharmaceutical services were characterized by the transition between the abolishment of the CEME and the coming into force of the NMP. During this initial period, the Basic Pharmacy Program was reintroduced, marked by the supply of medicine kits to small municipalities, reflecting the centralized nature of pharmaceutical services and similar problems and criticisms to those observed in the CEME period⁸8. Cosendey MAE, Bermudez JAZ, Reis ALA, Silva HF, Oliveira MA, Luiza VL. Assistência farmacêutica na atenção básica de saúde: a experiência de três estados brasileiros. Cad Saude Publica 2000; 16(1):171-182..

Between 1998 and 2007, principles consistent with those of the SUS can be observed, with a focus on the organization of pharmaceutical services based on decentralization and the search for funding to provide access to medicines. Changes were made to tendering methods and more efficient and effective procurement procedures were introduced, which meant that state and local government faced the challenge of strengthening their planning and management capacity.

Two other important events can also be highlighted during this 10-year period. The first involved the restructuring of SUS funding, which was divided into blocks, improving the status of pharmaceutical services which was allocated its own specific block. However, this did not lead to a large increase in resources for pharmaceutical services. Federal government spending figures for the period 2010 to 2016 show an average growth of 21% across the three dispensing components of the block⁹9. Vieira FS. Integralidade da assistência terapêutica e farmacêutica: um debate necessário. Rev Saude Publica 2017; 51:126., where the basic component was the only to suffer a fall.

Another aspect was the fragmentation of care resulting from the organization of pharmaceutical services according to three medicine dispensing components. Models of organization and management of services that focus on the product rather than service delivery hamper patient care and certainly jeopardize comprehensive care in the SUS¹⁰10. Rover MRM, Vargas-Peláez CM, Farias MR, Leite SN. Da organização do sistema à fragmentação do cuidado: a percepção de usuários, médicos e farmacêuticos sobre o Componente Especializado da Assistência Farmacêutica. Physis 2016; 26(2):691-711..

The second event was the introduction of the “Popular Pharmacy Program” (the Popular Pharmacy Program do Brazil- PFPB), which underwent various changes throughout its lifetime, relying heavily on the pharmaceutical industry for its consolidation and expansion. This program represented a return to a centralized approach to the provision of medicines. Questions were also raised as to the interface between this program and the public model in the SUS, raising doubts about its complementary or competitive action and its higher costs compared with studied public scenarios¹¹11. Silva RM, Caetano R. “Farmácia Popular do Brasil” Program: characterization and evolution between 2004 and 2012. Cien Saude Colet 2015; 20(10):2943-2956.. Furthermore, we can question to what extent this model, which emphasizes consumption as a central element of the promotion of access to medicines, is consistent with the principle of comprehensiveness, bearing in mind that the PFPB does not set out actions for promoting the appropriate use of medicines, therapeutic drug monitoring, etc.¹¹11. Silva RM, Caetano R. “Farmácia Popular do Brasil” Program: characterization and evolution between 2004 and 2012. Cien Saude Colet 2015; 20(10):2943-2956..

Finally, the last 10-year period, from 2008 to the present day, has brought old and new challenges. The strengthening of the primary care model through the expansion of the Family Health Strategy introduced actions directed at organizing pharmaceutical services via family health support centers. This permitted integration between pharmacists and other health professionals, enabling actions to promote the appropriate use of medicines, an example of comprehensive care and one of the underlying principles of the SUS.

Other recent events jeopardize the future of the SUS, such as the constitutional amendment that freezes government spending, which certainly undermines the right to health¹²12. Vieira FS, Benevides RPS. Os impactos do novo regime fiscal para o financiamento do Sistema Único de Saúde e para a efetivação do direito à saúde no Brasil. Rio de Janeiro: IPEA; 2016..

The abolishment of funding blocks without increasing resources is likely to weaken internal areas of the public health system, such as pharmaceutical services, as they are forced to compete with each other for resources. Although it is still too early to assess the full impact, we propose the following questions: (1) what will be the role of the Ministry of Health in inducing, formulating and regulating policy? (2) what will be management capacity and funding implications for local government? (3) to what extent will installed capacity with hard technology drain resources from other sectors? (4) how should striking regional disparities be addressed?

During the 30 years since the creation of the SUS and 20 years since the advent of the NMP, the primary focus of pharmaceutical services has been supply and logistics oriented towards supporting health actions and services, with limited focus on the social practices of care and provision of pharmaceutical services directed at the correct use of medicines. This challenges us to think of reorientation as a continuous and living movement that brings about a positive transformation of reality rather than an end in itself.

The breadth of activities and actions involved means that, in likeness to comprehensiveness, ‘pharmaceutical services’ has become a polysemous term. That is why it is necessary to incorporate concrete actions into the care practices of professionals and into the organization of pharmaceutical services and government responses that are sensitive to health needs and the perspective that defends this doctrinal value⁹9. Vieira FS. Integralidade da assistência terapêutica e farmacêutica: um debate necessário. Rev Saude Publica 2017; 51:126.,¹³13. Pinheiro R, Mattos RA, editores. Os Sentidos da Integralidade na atenção e no cuidado à saúde Rio de Janeiro. Rio de Janeiro: CEPESC/IMS/UERJ, Abrasco; 2006..

Human resources in pharmaceutical services

Human resources are a critical element of health systems and services. Appropriate human resources in terms of both quantity and quality are necessary to operate health policies. Both the WHO and Pan American Health Organization consider human resources to be one of the key components of a NMP¹⁴14. World Health Organization (WHO). How to develop and implement a national drug policy. Geneva: WHO; 2003. Vol. 6.,¹⁵15. Organización Panamericana de la Salud (OPS). Conceptos, estrategias y herramientas para una política farmacéutica nacional en las Américas. Washigton: OPS; 2016..

One of the guidelines of Brazil’s NMP deals with human resources development, providing that the three levels of government (federal, state and local) are responsible for ensuring that there are enough trained personnel available to implement the policy (Chart 2) and stating that there is a need for capacity-building in specific areas, such as the promotion of the rational use of medicines, technological development, pharmaceutical services, and health surveillance¹⁶16. Azeredo T. Política Nacional de Medicamentos no Brasil: da estrutura normativa à reflexão dos agentes sobre o processo de implementação [tese]. Rio de Janeiro: Fiouz; 2012..

With respect to the implementation of the NMP, Azeredo¹⁶16. Azeredo T. Política Nacional de Medicamentos no Brasil: da estrutura normativa à reflexão dos agentes sobre o processo de implementação [tese]. Rio de Janeiro: Fiouz; 2012. shows that the guideline in question has relatively few normative instruments. According to the author, possible explanations for this situation include the lack of importance given to this guideline and coordination difficulties with the Ministry of Education in proposing the necessary changes¹⁶16. Azeredo T. Política Nacional de Medicamentos no Brasil: da estrutura normativa à reflexão dos agentes sobre o processo de implementação [tese]. Rio de Janeiro: Fiouz; 2012.. The situation seems to have improved with the introduction of the following measures: the creation of the Department of Work and Education Management; the expansion of the programa Pró-Saúde (Pro Health program)to include pharmaceutical services; the publication of Ministerial Order Nº 2.981/2009¹⁷17. Brasil. Portaria No 2.981, de 26 de novembro de 2009. (Revogada pela PRT no 1554/GM/MS de 30.07.2013). Aprova o Componente Especializado da Assistência Farmacêutica. Diário Oficial da União 2009; 27 nov., which sets a specific percentage for the allocation of financial resources to the basic component of pharmaceutical services for structuring and activities linked to continuing education; and the creation of the programa Qualifar-SUS, which aims to promote continuing education by offering face-to-face and distance learning courses¹⁸18. Brasil. Portaria MS/GM 1.214, de 13 de junho de 2012. Institui o Programa Nacional de Qualificação da Assistência Farmacêutica no âmbito do Sistema Único de Saúde (QUALIFAR-SUS). Diário Oficial da União 2012; 14 jun..

Despite the above situation, it is important to recognize the importance of and the efforts made by the Ministry of Health over the last the 20 years since the publication of the NMP. Chart 2 shows the different initiatives taken by this body to strengthen pharmaceutical services through promoting staff capacity building, mainly pharmacists¹⁹19. Agência Nacional de Vigilância Sanitária (Anvisa). Rede Sentinela - Histórico. Brasília: Anvisa; 2003.,²⁰20. Emmerick IC, Chaves LA, Marin N, Luiza VL. Strengthening the capacity of managers in pharmaceutical services based on Primary Health Care (PHC) at different levels of the health system. Hum Resour Health 2014; 12(1):34., including the first national course on teaching the rational use of medicines directed at physicians in 2002, which focused on medicines prescribing, and local and regional capacity-building programs.

However, despite these efforts, a number of challenges remain, including the concentration of pharmacists in state capitals²¹21. Luiza VL, Oliveira MA, Chaves GC, Bermudez AZ, Flynn MB. Pharmaceutical Policies in Brazil. In: Zaheer-Ud-Din Babar, editor. Pharmaceutical policy in countries with developing healthcare systems. New York: Springer Berlin Heidelberg; 2017., inadequate structure of pharmaceutical services, and lack of trained personnel²²22. Lima-Dellamora EC, Caetano R, Osorio-de-Castro CGS. Dispensação de medicamentos do componente especializado em polos no Estado do Rio de Janeiro. Cien Saude Colet 2012; 17(9):2387-2396. and difficulties in prioritizing capacity building given the work demands of pharmacists²³23. Miai ET, Nogueira-Martins MCF. Farmacêuticos na Atenção Básica: um estudo qualitativo sobre necessidades e possibilidades de qualificação dos profissionais para a integralidade do cuidado aos usuários-cidadãos. Bol Inst Saúde 2014; 15(Supl.):71-79.. Furthermore, other barriers exist that cannot be overcome only with capacity building.

Essential medicines – efficacy, cost-effectiveness, quality, and safety

The path taken by essential medicines in Brazil between 1988 and 2018 is closely tied to that of the NMP (Chart 3).

The principle of comprehensiveness evolved during the lead-up to the creation of the SUS. In the 1980s and 1990s, comprehensiveness was viewed as the identification of and response to the health needs of the population²⁴24. Kalichman AO, Ayres JRCM. Integralidade e tecnologias de atenção à saúde: uma narrativa sobre contribuições conceituais à construção do princípio da integralidade no SUS. Cad Saude Publica 2016; 32(8):e00183415.. Under this umbrella, essential medicines were conceived as those which satisfy health needs²⁵25. World Health Organization (WHO). WHO Expert Committee on The Selection of Essential Drugs. The Selection of Essential Drugs: first report of the WHO Expert Committee. Geneva: WHO; 1977.. This concept predominated in the NMP, with the adoption and continuing review of the National List of Essential Medicines (Rename, acronym in Portuguese).

A national list of medicines and ingredients had existed since 1964. During the time of the CEME, the Rename served as a basis for the selection of medicines which were purchased and distributed in a centralized manner. In 1996, within the scope of the drafting of the NMP, the first evidence-based list of essential medicines was born, ushering in an intense process of consecutive reviews²⁶26. Osorio-de-Castro CGS, Azeredo TB, Pepe VLE, Lopes LC, Yamauti S, Godman B, Gustafsson LL. Policy Change and the National Essential Medicines List Development Process in Brazil between 2000 and 2014: Has the Essential Medicine Concept been Abandoned? Basic Clin Pharmacol Toxicol 2017; 122(4):402-412..

In 2002, the WHO defined essential medicines as those that satisfy the priority health care needs of the population²⁷27. World Health Organization (WHO). WHO Perspective: The Selection of Essential Medicines. Geneva: WHO; 2002., showing that the concepts of ‘essentiality’ and ‘priority’ were complementary. In Brazil, the responsibility for reviewing the list was transferred to the Multidisciplinary Commission for Updating the National List of Essential Medicines (COMARE, acronym in Portuguese), which had its own rules of procedure and explicit criteria for the inclusion and exclusion ofmedicines²⁸28. Brasil. Ministério da Saúde (MS). Relação Nacional de Medicamentos Essenciais, RENAME, 2010. Brasília: MS; 2010.. The concept of essential medicines as those that satisfy the priority health care needs was institutionalized at local and state level with the creation of municipal and state lists of essential medicines. Comprehensiveness therefore depended upon the effective implementation of a hierarchical system in which the local and state selection of essential medicines complemented the needs guided by the Rename. The notion of ‘essentiality’ – medicines selected on the basis of efficacy, safety, quality, and affordability – reflected comprehensiveness. Two reviews of the list were conducted up to 2006²⁶26. Osorio-de-Castro CGS, Azeredo TB, Pepe VLE, Lopes LC, Yamauti S, Godman B, Gustafsson LL. Policy Change and the National Essential Medicines List Development Process in Brazil between 2000 and 2014: Has the Essential Medicine Concept been Abandoned? Basic Clin Pharmacol Toxicol 2017; 122(4):402-412..

In the 2000s, divergences began to appear between the above concept of essential medicines and that which governed the national list. Pressure to innovate within the SUS intensified. With the supply and adoption of new technologies, the objective was to guide service users through levels of care in a ‘regulated’ manner. Needs should be met, but within lines of care that determined supply within the system¹⁷17. Brasil. Portaria No 2.981, de 26 de novembro de 2009. (Revogada pela PRT no 1554/GM/MS de 30.07.2013). Aprova o Componente Especializado da Assistência Farmacêutica. Diário Oficial da União 2009; 27 nov.. At the same time, the funding for organization of pharmaceutical services began to determine provision of essential medicines, placing pressure on selection. The Rename became vulnerable to the supply capacity of municipal governments. Weaknesses of in local government management began to be felt after the decentralization of pharmaceutical services²⁹29. Brasil. Ministério da Saúde (MS). Gabinete do Ministro. Portaria no 176, de 08 de março de 1999. Estabelece critérios e requisitos para a qualificação dos municípios e estados ao incentivo à Assistência Farmacêutica Básica e define valores a serem transferidos. Diário Oficial da União 1999; 9 mar.. Although ministerial orders that tied funding of essential medicines to their presence on the Rename³⁰30. Conselho Nacional de Secretários de Saúde (CONASS). Assistência farmacêutica no SUS. Brasília: CONASS; 2011. were unable to prevent the application of evidence-based selection, they weakened the hierarchical process that integrated local and national lists²⁷27. World Health Organization (WHO). WHO Perspective: The Selection of Essential Medicines. Geneva: WHO; 2002.,³¹31. Hogerzeil HV. The concept of essential medicines: lessons for rich countries. BMJ 2004; 329(7475):1169-1172., leading to serious gaps and fragmented provision of essential medicines in the SUS.

Difficulties in ensuring comprehensiveness became evident with an increase in the health litigation for access to essential medicines since 2007. The litigation for access represents an important milestone in the attainment of the right to health as a fundamental human right³²32. Ventura M, Simas L, Pepe VLE, Schramm FR. Judicialization of the right to health, access to justice and the effectiveness of the right to health. Physis 2010; 20(1):77-100.. However, fragmented funding has had an enormous impact on the provision of essential medicines and ‘grey’ areas not covered by funding have grown, impelling users to seek access through the courts.

Between 2008 and 2010, two editions of the National Formulary (Formulário Terapêutico Nacional – FTN) were produced – one referring to the 2006 Rename and the other to the 2008 RENAME. The FTN is an important complement to the list of essential medicines since it contains a wide spectrum of information and advice on prescribing.

The adoption of the concept of essential medicines also implies regulatory actions, such as ‘cleaning up’ the market by restricting the registration of medicines of doubtful therapeutic value³¹31. Hogerzeil HV. The concept of essential medicines: lessons for rich countries. BMJ 2004; 329(7475):1169-1172.,³³33. Wannmacher L. Importância dos Medicamentos Essenciais em Prescrição e Gestão Racionais. Uso Racional de medicamentos: temas selecionados 2012; 2(2):15-20.,³⁴34. Wannmacher L. Seleção de Medicamento. In: Osorio-de-astro CGS, Luiza VL, Castilho SR, Oliveira MA, Marin N, editors. Assistência Farmacêutica: gestão e prática para profissionais de saúde. Rio de Janeiro: Fiocruz; 2014. p. 79-88., training of prescribers in the rational use of medicines, and monitoring medicines introduced onto the market to curb abuse and misuse and to assess their effectiveness and safety in the real world. However, Brazil has not taken the restriction and monitoring path. Clinical protocol and therapeutic guidelines were introduced in 1997 and their development has been notable since 2002³³33. Wannmacher L. Importância dos Medicamentos Essenciais em Prescrição e Gestão Racionais. Uso Racional de medicamentos: temas selecionados 2012; 2(2):15-20.. Protocols are a crucial strategy for the establishment of acceptable use standards, since they are based on best evidence. However, their implementation has been relaxed and their application in the SUS has been feebler than expected³⁵35. Camargo IA, Almeida Barros BC, Nascimento Silveira MS, Osorio-de-Castro CGS, Guyatt G, Lopes LC. Gap Between Official Guidelines and Clinical Practice for the Treatment of Rheumatoid Arthritis in São Paulo, Brazil. Clin Ther 2016; 38(5):1122-1133..

Six updated versions of the Rename were produced up to 2012 (of which only the first five were published). However, Law 12.401³⁶36. Brasil. Presidência da República. Lei n. 12.401, de 28 de abril de 2011. Altera a Lei no 8.080, de 19 de setembro de 1990, para dispor sobre a assistência terapêutica e a incorporação de tecnologia em saúde no âmbito do Sistema Único de Saúde - SUS. Diário Oficial da União 2011; 29 abr. had negative consequences, transferring the responsibility to incorporate new technologies into the SUS and to review and update the Rename to the newly created National Commission for the Incorporation of Technologies (Conitec, acronym in Portuguese). The list published in 2012, compiled by the Ministry of Health based on all the lists and supply of medicines in the SUS was recognized as a list of all SUS-funded medicine products³⁷37. Brasil. Presidência da República. Casa Civil. Decreto no 7.508, de 28 de junho de 2011. Regulamenta a Lei no 8.080, de 19 de setembro de 1990, para dispor sobre a organização do Sistema Único de Saúde - SUS, o planejamento da saúde, a assistência à saúde e a articulação interfederativa, e dá outras providências. Diário Oficial da União 2011; 29 jun., rather than a list of essential medicines. Paradoxically, all cancer and ophthalmology medicines were excluded from the list. Through the lens of the national list, comprehensiveness came to be understood as ‘everything’³⁸38. Santos-Pinto CDB, Ventura M, Pepe VLE, Osorio-de-Castro CGS. Novos delineamentos da Assistência Farmacêutica frente à regulamentação da Lei Orgânica da Saúde. Cad Saude Publica 2013; 29(6):1056-1058.,³⁹39. Yamauti SM, Bonfim JRA, Barberato-Filho S, Lopes LC. Essencialidade e racionalidade da relação nacional de medicamentos essenciais do Brasil. Cien Saude Colet 2017; 22(3):975-986. provided through the funding components, except those products funded by the APAC. It thus became a positive list for the system, relegating the concept of essential medicines and comprehensiveness based on need.

In 2013, the rules and regulations governing the registration⁴⁰40. Brasil. Presidência da República. Decreto No 8.077, de 14 de agosto de 2013. Regulamenta as condições para o funcionamento de empresas sujeitas ao licenciamento sanitário, e o registro, controle e monitoramento, no âmbito da vigilância sanitária, dos produtos de que trata a Lei no 6.360, de 23 de setembro de 1976, e dá outras providências. Diário Oficial da União 2013; 15 ago. of medicines and expanded access and compassionate use of drugs⁴¹41. Brasil. Agência Nacional de Vigilância Sanitária. Diretoria Colegiada. Resolução - RDC No 38, de 12 de agosto de 2013. Aprova o regulamento para os programas de acesso expandido, uso compassivo e fornecimento de medicamento pós-estudo. Diário Oficial da União 2013; 13 ago. were relaxed, shortening the time it takes for a product to access the Brazilian market. This is an international trend resulting from pressure for innovation and funding⁴²42. Osorio-de-Castro CGS, Caetano R, Pepe VLE. The 21st Century Cures Act: can the regulatory framework survive the “cures”? Cad Saude Publica 2015; 31(9):1807-1810., leading to an unprecedented growth in health litigation and jeopardizing the public provision of medicines. In this respect, in 2016, spending on the provision of medicines across the three levels of care of the SUS amounted to R$13 billion, while spending on medicines provided as a result of judicial decisions was R$8 billion⁴³43. Brasil. Ministério da Saúde (MS). 300 Dias de Gestão. R$ 2,9 bilhões de eficiência. Mais serviços para a população. Brasília: MS; 2017..

Uneven progress has been made in the public provision of medicines over the 20 years since the NMP came into force: excellent access to particular medicines in certain primary healthcare niches can be seen⁴⁴44. Brasil. Ministério da Saúde (MS). Componente populacional: resultados. Brasília: MS; 2016., while enormous difficulties are faced by patients who need specialtydrugs⁹9. Vieira FS. Integralidade da assistência terapêutica e farmacêutica: um debate necessário. Rev Saude Publica 2017; 51:126.,⁴⁵45. Chieffi AL, Barradas RDCB, Golbaum M. Legal access to medications: a threat to Brazil’s public health system? BMC Health Serv Res 2017; 17(1):499.. However, the regular review of the Rename and the adoption of the concept of essential medicines, regarded as core elements of the policy that guide provision and all pharmaceutical services activities, have been jeopardized over time. The adoption of the idea of essentiality is a key factor for the successful implementation of the SUS and is in full consonance with the principle of comprehensiveness. It makes sense within the idea of care networks as a strategy to overcome fragmented care⁴⁶46. Brasil. Ministério da Saúde, Gabinete do Ministro. Portaria MS/GM No 4.279, de 30 de dezembro de 2010. Estabelece diretrizes para a organização da Rede de Atenção à Saúde no âmbito do Sistema Único de Saúde (SUS). Diário Oficial da União 2010; 30 dez..

Rational use of medicines

Together with access to quality medicines, the rational use of medicines is seen as a central goal of any national medicines policy. Since the landmark Nairobi Conference on the Rational Use of Drugs⁴⁷47. World Health Organization (WHO). The Rational use of drugs: report of the conference of experts, Nairobi, 25-29 November 1985. Geneva, Albany: WHO; WHO Publications Center USA; 1987., it has been widely recognized that the benefits of access are not concretized, and may even be lost, if medicines are not used properly.

There is a current trend to use the term “the appropriate use of medicines” instead of the “rational use”, since misuse may be supported by spurious rationalities.

Strategies to promote the appropriate use of medicines have been classified as regulatory, management-based, and educational⁴⁸48. Marin N, Luiza VL, Osorio-de-Castro CGS, Machado-dos-Santos S. Assistência Farmacêutica para gerentes municipais. Rio de Janeiro: OPAS/OMS; 2003..The main milestones in the promotion of the appropriate use of medicines in Brazil are summarized in Chart 3.

Few actions directed at the promotion of the appropriate use of medicines were developed in Brazil up to the end of the 1980s. One of the few national actions was the publication of the therapeutic mementos of the CEME, which provided advice and information on the characteristics, use and care that should be taken with medicines contained in the Rename. The last memento was published in 1989⁴⁹49. Brasil. Ministério da Saúde (MS). Central de Medicamentos. Memento terapêutico CEME 89/90: relação de medicamentos essenciais - RENAME e relação de medicamentos básicos - RMB. Brasília: MS; 1989..

At the end of the 1990s,a number of independent professional and user associations emerged whose prime aim was to promote the appropriate use of medicines. Also at that time, partnerships were established with international organizations representing different continents. Although the Pharmaceutical Services Center at the Oswaldo Cruz Foundation, created in 1998, and the PAHO/WHO Collaborating Center state that the main focus of their work is pharmaceutical policy, these centers have worked on various themes related to the appropriate use of medicines.

Given that regulatory measures are a core component of the promotion of the appropriate use of medicines, Brazil’s regulatory body has always played an important role in this area. In this respect, it is important to highlight the development of good dispensing practices -which have a direct impact on the appropriate use of medicines - byBrazil’s National Health Surveillance Agency (Anvisa, acronym in Portuguese)in the period 1988 to 1997⁵⁰50. Brasil. Agência Nacional de Vigilância Sanitária. Resolução no 328, de 22 de julho de 1999. Dispõe sobre requisitos exigidos para a dispensação de produtos de interesse à saúde em farmácias e drogarias. Diário Oficial da União 1999; 23 jul..

One of the highlights of the period 1998to 2007 was the creation of the National Committee for the Promotion of the Rational Use of Medicines⁵¹51. Brasil. Ministério da Saúde. Gabinete do Ministro. Portaria No 1.555, de 27 de junho de 2007. Institui o Comitê Nacional para a Promoção do Uso Racional de Medicamentos. Diário Oficial da União 2007; 28 jun., which was redefined in 2013⁵²52. Brasil. Ministério da Saúde. Gabinete do Ministro. Portaria No 834, de 14 de maio de 2013. Redefine o Comitê Nacional para a Promoção do Uso Racional de Medicamentos no âmbito do Ministério da Saúde. Diário Oficial da União 2013; 15 maio.. This committee is comprised of various organizations and has developed a number of actions, including the organization of events – the most notable of which was the Brazilian Congress on the Rational Use of Medicines – and the production of educational material, recommendations on regulatory actions, and the promotion of campaigns. During the same period, Brazil created the National Pharmaco vigilance System within ANVISA, strongly induced by the PAHO and national groups that advocated for the appropriate use of medicines⁵³53. Mendes MCP, Pinheiro RO, Avelar KES, Teixeira JL, Silva GMS. História da farmacovigilância no Brasil. Rev Bras Farm 2008; 89(3):246-251.. Brazil gained important recognition when it was included as the 62^nd member of the International Drug Monitoring Program Brazil⁵³53. Mendes MCP, Pinheiro RO, Avelar KES, Teixeira JL, Silva GMS. História da farmacovigilância no Brasil. Rev Bras Farm 2008; 89(3):246-251..

Finally, the period 2008 to 2018 has witnessed a larger number of initiatives, such as the updating of drug marketing and advertising regulations in 2008⁵⁴54. Brasil. Agência Nacional de Vigilância Sanitária. Resolução RDC No 96, de 17 de dezembro de 2008. Dispõe sobre a propaganda, publicidade, informação e outras práticas cujo objetivo seja a divulgação ou promoção comercial de medicamentos. Diário Oficial da União 2008; 18 dez., the development of good pharmacy practices, including the provision of pharmaceutical services in pharmacies and drugstores⁵⁵55. Brasil. Agência Nacional de Vigilância Sanitária. Resolução-RDC no 44, de 17 de agosto de 2009. Dispõe sobre Boas Práticas Farmacêuticas para o controle sanitário do funcionamento, da dispensação e da comercialização de produtos e da prestação de serviços farmacêuticos em farmácias e drogarias e dá outras providências. Diário Oficial da União 2009; 18 ago.,the definition of uniform standards for the content of patient information leaflets⁵⁶56. Brasil, Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada. RDC No 47, de 8 de setembro de 2009. Estabelece regras para elaboração, harmonização, atualização, publicação e disponibilização de bulas de medicamentos para pacientes e para profissionais de saúde. Diário Oficial da União 2009; 9 set., and the establishment of regulations for prescribing and selling antimicrobial drugs⁵⁷57. Brasil. Agência Nacional de Vigilância Sanitária. Resolução RDC No 20, de 5 de maio de 2011. Dispõe sobre o controle de medicamentos à base de substâncias classificadas como antimicrobianos, de uso sob prescrição, isoladas ou em associação. Diário Oficial da União 2011; 6 maio..

The progress made by these initiatives involves controversies. With respect to drug marketing and advertising, during the time of the public hearing which resulted in the regulatory instrument, a large group of researchers, professionals, and activists made an emphatic pronouncement criticizing the document, particularly the failure to adopt prior inspection. The group argued that in the case of subsequent detection of an infringement, the small size of the fine does not act as a deterrent because risks are more than compensated by the sales during the period in which marketing piece are broadcast. Indeed, studies have shown a low level of compliance with the legislation governing marketing pieces directed at both professionals and users⁵⁸58. Abdalla MCE, Castilho SR. Análise da propaganda de medicamentos dirigida a profissionais de saúde. Rev Direito Sanitário 2017 9; 18(1):101.,⁵⁹59. Soares JCRS. Quando o anúncio é bom, todo mundo compra: o Projeto Monitoração e a propaganda de medicamentos no Brasil. Cien Saude Colet 2008; 13(Supl.):641-649..

With respect to pharmaceutical services, the Federal Pharmacy Council established regulations for prescribing drugs⁶⁰60. Brasil. Conselho Federal de Farmácia. Prescrição farmacêutica e atribuições clínicas do farmacêutico: recompilação de documentos. CFF; 2015., a topic that lacks consensus even among pharmacy professionals⁶¹61. Folha de São Paulo. Disputas de médicos com biomédicos e farmacêuticos vão para a Justiça - 15/11/2016 - Cotidiano . Folha de S.Paulo. 2016. Disponível em: http://www1.folha.uol.com.br/cotidiano/2016/11/1832292-disputas-de-medicos-com-biomedicos-e-farmaceuticos-vao-para-a-justica.shtml
http://www1.folha.uol.com.br/cotidiano/2... . Anvisa made efforts to strengthen actions related to patient information leaflets, such as the bulário eletrônico⁶²62. Fujita PL, Machado CJS, Teixeira MO. A bula de medicamentos e a regulação de suas configurações em termos de forma e conteúdo no Brasil. Saúde Soc 2014; 23(1):277-292., an online system providing information about medicines to the public and professionals alike.

Finally, with respect to antimicrobial drugs, the regulations have led to an initial decrease in consumption⁶³63. Wirtz VJ, Hogerzeil HV, Gray AL, Bigdeli M, de Joncheere CP, Ewen MA, Gyansa-Lutterodt M, Jing S, Luiza VL, Mbindyo RM, Möller H, Moucheraud C, Pécoul B, Rägo L, Rashidian A, Ross-Degnan D, Stephens PN, Teerawattananon Y, ‘t Hoen EF, Wagner AK, Yadav P, Reich MR. Essential medicines for universal health coverage. Lancet 2016; 389(10067):403-476..

The promotion of the appropriate use of medicines is firmly situated in the field of health promotion and disease prevention, be it primary, secondary, tertiary or quaternary care, and is therefore intertwined with the healthcare process. It could be said, therefore, that actions in this area satisfy the principle of comprehensiveness. The promotion of the appropriate use of medicines involves numerous challenges, given that it has a significant impact on the consumption of medicines, and therefore sales, requiring changes in the behavior of professionals, managers, and consumers.

Technological development and manufacturing

The technological dependence of Brazil within the pharmaceutical industry was evident throughout the twentieth century and the government responded to this situation in various moments. Brazil was considered a “peripheral” country within an industry consolidated mainly in European countries and the United States and whose base depended on launching new innovations onto the market and sales growth⁶⁴64. Achilladelis B, Antonakis N. The dynamics of technological innovation: the case of the pharmaceutical industry. Res Policy 2001; 30(4):535-588..

At the beginning of the 1970s, the domestic production of medicines was related to pharmaceutical services. With the creation of a public market, which ensured constant demand, the CEME adopted other instruments to stimulate public sector production and the development of active pharmaceutical ingredients (APIs)⁶⁵65. Bermudez JAZ. Remédio: Saúde ou Indústria? A Produção de Medicamentos no Brasil. Vol. 1. Rio de Janeiro: Relume Dumará; 1992.. The CEME was abolished in 1997 amidst claims of irregularities because it did not meet any of its initial goals (Chart 4 )⁸8. Cosendey MAE, Bermudez JAZ, Reis ALA, Silva HF, Oliveira MA, Luiza VL. Assistência farmacêutica na atenção básica de saúde: a experiência de três estados brasileiros. Cad Saude Publica 2000; 16(1):171-182..

The first ten years of existence of the SUS therefore came to end with a long-term perspective stemming from the publication of the NMP in 1998. Aspects related to industrial policy were recognized, with the inclusion of specific guidelines for scientific and technological development and the promotion of pharmaceutical production¹⁶16. Azeredo T. Política Nacional de Medicamentos no Brasil: da estrutura normativa à reflexão dos agentes sobre o processo de implementação [tese]. Rio de Janeiro: Fiouz; 2012..

These guidelines led to the development of concrete initiatives directed at the national pharmaceutical industry, including Brazil’s Generic Medicines Policy (Law 9.787/99), which, using financing provided by the National Bank for Economic and Social Development, stimulated the growth of the private national pharmaceutical industry⁶⁶66. Quental C, Abreu JC de, Bomtempo JV, Gadelha CAG. Medicamentos genéricos no Brasil: impactos das políticas públicas sobre a indústria nacional. Cien Saude Colet 2008; 13(Supl.):619-628., and the Projeto Guarda Chuva (the Umbrella Project), which ensured financing for government pharmaceutical manufacturers (LFOs, acronym in Portuguese), focusing on the production of antiretroviral drugs in the context of the HIV/AIDS epidemic⁶⁷67. Fischer-Pühler P. O Acesso ao Medicamentos - a gestão da política pública entre 1997 e 2002. Rio de Janeiro: Livrotab; 2003.. Lessons learned from these experiences show that LFOs play an important role in production cost estimation and in the strategic development of products under monopoly, contributing to government efforts in the negotiation of prices with transnational companies.

The 1^st National Medicines and Pharmaceutical Services Conference sought to align pharmaceutical services with other policies related to manufacturing and science and technology recognized by the National Pharmaceutical Services Policy (PNAF, acronym in Portuguese).

With respect to health science and technology, one of the main milestones is the National Science, Technology and Innovation Policy (PNCTI, acronym in Portuguese), approved in 2004 during the 2^ndNational Health Science and Technology Conference and published in 2008, which incorporates the principles of scientific merit and social relevance⁶⁸68. Brasil. Ministério da Saúde (MS). Política nacional de ciência, tecnologia e inovação em saúde. Brasília: MS; 2008..

In the second ten years of existence of the SUS, the scope of pharmaceutical industry development extended beyond the health sector with the approval of the Industrial, Technological and Foreign Trade Policy (PITCE, acronym in Portuguese), which encompassed the pharmaceutical industry, aiming to reduce national vulnerability caused by external dependence in technology-intensive areas.

In 2007, with the compulsory licensing of patents of the antiretroviral drug efavirenz, local production became an option once again for the implementation of the measure, resulting in the creation of a consortium for the production of the active pharmaceutical ingredient, meaning that a domestically produced generic drug became available in 2009,generating considerable public spending savings.

In 2008, during the third 10-year period since the creation of the SUS, the Industrial Health Complex (Complexo Industrial da Saúde- CIS) was created as one of the key areas of the federal government’s strategic plan for the health sector⁶⁹69. Brasil. Ministério da Saúde (MS). Mais saúde: direito de todos: 2008 - 2011. Brasília: MS; 2008., resulting in the approval of a series of regulatory instruments that changed the face of pharmaceutical industry policy, emphasizing the revival of the national industry and strengthening of LFOs⁷⁰70. Chaves GC, Azeredo TB, Vasconcelos DMM de, Ruiz AM, Scopel CT, Oliveira MA, Hasenclever L. Estudo da produção pública de medicamentos no Brasil: capacitação tecnológica e acesso a medicamentos. Rio de Janeiro: E-papers; No prelo.. In 2009, Production Development Partnerships were established as technology transfer arrangements to strengthen these two segments, considering that the purchase of products by the SUS provided the prospect of sustained demand without competition.

A recent assessment of LFOs shows that little progress has been made in relation to technological capacity and capacity to contribute to improved access to medicines⁷⁰70. Chaves GC, Azeredo TB, Vasconcelos DMM de, Ruiz AM, Scopel CT, Oliveira MA, Hasenclever L. Estudo da produção pública de medicamentos no Brasil: capacitação tecnológica e acesso a medicamentos. Rio de Janeiro: E-papers; No prelo., suggesting that the government has limited ability to address pharmaceutical services deficiencies in the SUS. The selection of appropriate technologies for domestic production and industry development should be considered in the light of comprehensiveness, which in this case would require an analysis of market dynamics to prioritize those areas where there is a risk of shortage, treatment gaps, and high-cost products with a view to subsidizing and regulating prices.

Ethical regulations, research and medicines

The regulation of ethics in pharmaceutical research is governed by the National Health Council (NHC), which involves the Ministry of Health in some of its functions⁷¹71. Brasil. Conselho Nacional de Saúde. Resolução no 446, de 11 de agosto de 2011. qualifica o processo de análise ética das pesquisas, sendo o ser humano considerado em sua individualidade, como foco essencial do processo de produção da ciência e garante o monitoramento das pesquisas com seres humanos em andamento no Brasil. Diário Oficial da União 2011; 12 ago..

The first resolution regulating health research in Brazil was the NHC Resolution 01/88. Low levels of adherence to these regulations among the scientific community resulted in the need for a new resolution that was more comprehensive in relation to ethical considerations in research. In 1995, headed by the NHC, a commission was created to elaborate a new resolution. Published in 1996⁷²72. Oliveira MA, Santos EM, Mello JMC. AIDS, ativismo e regulação de ensaios clínicos no Brasil: o Protocolo 028. Cad Saude Publica 2001; 17(4):863-875.,⁷³73. Novaes MRCG, Guilhem D, Lolas F. Dez anos de experiência do comitê de ética em pesquisa da secretaria de saúde do Distrito Federal, Brasil. Acta Bioethica 2008; 14(2):185-192., Resolution 196/96 updated guidelines and provided for the creation of a centralized ethical review system comprised of the National Research Ethics Commission (CONEP, acronym in Portuguese) “an independent advisory, deliberative, regulatory, and educational collegial body attached to the NHC” and research ethics committees (RECs), defined as “interdisciplinary and independent advisory, deliberative, and educational collegial bodies, with ‘public munus’, created to defend the interests of research participants in their integrity and dignity and to contribute to the development of research in accordance with ethical standards”⁷⁴74. Brasil. Conselho Nacional de Saúde. Resolução No 196, de 10 de outubro 1996. Diário Oficial da União 1996; 11 out.. This resolution was revoked in 2012 with the publication of NHC Resolution 466/12,which brought a number of advances, including instructions on the use of placebos and the requirement that sponsors provide participants free indefinite access to the best provenly effective prophylactic, diagnostic and therapeutic methods at the end of the study⁷⁵75. Brasil. Conselho Nacional de Saúde. Resolução No 466, de 12 de dezembro de 2012. Aprova as diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União 2012; 13 dez..

The following resolutions are important instruments in the ethical review process in Brazil: NHC Resolution 506/16 “establishes criteria for the accreditation of RECs in the CEP/CONEP system in public and private institutions” to promote the decentralization of the system and strengthening the autonomy of research to act on a regionalized basis; and Resolution 510/16, which establishes rules and regulations for research in the field of human and social sciences and other fields that use methods specific to these areas, seeking to promote an analysis that is more suited to the specificities of this type of research. This instrument also creates a new area in the Plataforma Brazil for the submission of projects and establishes new flows for the assessment of studies in accordance with the risks involved⁷⁶76. Brasil. Conselho Nacional de Saúde. Resolução Nº 510, de 7 de abril de 2016. Dispõe sobe as normas aplicáveis a pesquisas em Ciências Humanas e Sociais cujos procedimentos metodológicos envolvam a utilização de dados diretamente obtidos com os participantes ou de informações identificáveis ou que possa acarretar riscos maiores do que os existentes na vida cotidiana, na forma definida nesta Resolução. Diário Oficial da União 2016; 8 abr..

Bill 7082/17, which has already been approved by the Senate (Bill 200/15) and is currently under consideration by the Chamber of Representatives seeks to provide greater judicial legitimacy and swiftness to clinical trials and proposes limits to the mandatory provision of post-study medicines guaranteed by Resolution 466/12. The bill also proposes the creation of a new ethical regulation system for clinical trials connected to the Ministry of Health. In our view, this proposal is inconsistent considering the primary function of the NHC, which is a participatory and deliberative body attached to the Ministry of Health that plays an important role in formulating and overseeing the implementation of the country’s health policy and has taken important steps in guaranteeing the protection of research participants in Brazil.

Final considerations

Thirty years is a long time. The country is huge, unequal and complex and has gone through various political, economic and social changes throughout the period. The theme of essential medicines and pharmaceutical services is broad, central and cross-cutting. Thus, to tell this story it is necessary to break it down into parts and make choices.

Selecting the events was no easy task. We focused principally, but not exclusively, on regulatory instruments, which express an implementation effort. However, this does not necessarily guarantee that they have been fully or successfully implemented, given that this paper is not intended to be an evaluation of achievements. On the other hand, we consider it necessary to warn of the consequences of current policies and the dismantling of solid structures that represent significant social advances. Let’s defend the SUS!

References

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History