Introduction

The discussion on interchangeability and automatic substitution of biological drugs with biosimilars has divided opinions among experts, patients, and health policymakers in Brazil and elsewhere in the world. Biosimilars are biological products that contain a similar bioactive component to that of an approved reference biological, for which biosimilarity can be proven through an exercise of complete comparability (quality, preclinical, and clinical) to guarantee similar safety and efficacy ¹1. World Health Organization. Guidelines on evaluation of similar biotherapeutic products. Geneva: World Health Organization; 2009.^,22. Agência Nacional de Vigilância Sanitária. RDC nº 55, de 16 de dezembro de 2010. Dispõe sobre o registro de produtos biológicos novos e produtos biológicos e dá outras providências. Diário Oficial da União 2010; 17 dez.. However, the confirmation of biosimilarity does not mean that the biosimilars are interchangeable. This requires clinical studies that analyze whether there is an additional safety risk or reduction in efficacy during the switch or treatment transition from a biological to a biosimilar or vice-versa ³3. Azevedo VF, Babini A, Caballero-Uribe CV, Castañeda-Hernández G, Borlenghi C, Jones HE. Practical guidance on biosimilars, with a focus on Latin America: what do rheumatologists need to know? J Clin Rheumatol 2019; 25:91-100.^,44. O'Callaghan J, Barry SP, Bermingham M, Morris JM, Griffin BT. Regulation of biosimilar medicines and current perspectives on interchangeability and policy. Eur J Clin Pharmacol 2019; 75:1-11.. Box 1 presents the main questions concerning the discussion on the substitution/interchangeability of biosimilars.

Three public hearings were held in Brazil in 2018 to discuss the process of procurement ⁵5. BioredBrasil. Conheça o posicionamento e questionamentos da Biored Brasil ao Departamento de Logísticas do Ministério da Saúde. https://www.bioredbrasil.com.br/wp-content/uploads/2018/01/Biored-Brasil-questionamentos-DLOG-SE-MS-16-01-2018.pdf (acessado em 25/Jan/2018).
https://www.bioredbrasil.com.br/wp-conte... ^,66. BioredBrasil. Ministério da Saúde debate compra de trastuzumabe mesmo sem saber como será realizada a dispensação. https://www.bioredbrasil.com.br/ministerio-da-saude-discuti-compra-de-trastuzumabe-mesmo-sem-saber-como-sera-realizada-dispensacao/ (acessado em 25/Jan/2019).
https://www.bioredbrasil.com.br/minister... ^,77. Torres P. Ministério da Saúde manifesta a intenção de troca automática de medicamento biológico originador por biossimilar. Blog Artrite Reumatóide 2018; 17 jan. https://artritereumatoide.blog.br/ministerio-da-saude-manifesta-a-intencao-de-troca-automatica-de-medicamento-biologico-originador-por-biossimilar/.
https://artritereumatoide.blog.br/minist... and substitution and interchangeability ⁸8. Câmara dos Deputados. Debater sobre a Resolução da Diretoria Colegiada da ANVISA na regulação da intercambialidade entre o produto originador e o produto biossimilar. https://edemocracia.camara.leg.br/audiencias/sala/807 (acessado em 02/Dez/2018).
https://edemocracia.camara.leg.br/audien... of reference biological drugs with their biosimilars in the Brazilian Unified National Health System (SUS) ⁵5. BioredBrasil. Conheça o posicionamento e questionamentos da Biored Brasil ao Departamento de Logísticas do Ministério da Saúde. https://www.bioredbrasil.com.br/wp-content/uploads/2018/01/Biored-Brasil-questionamentos-DLOG-SE-MS-16-01-2018.pdf (acessado em 25/Jan/2018).
https://www.bioredbrasil.com.br/wp-conte... ^,66. BioredBrasil. Ministério da Saúde debate compra de trastuzumabe mesmo sem saber como será realizada a dispensação. https://www.bioredbrasil.com.br/ministerio-da-saude-discuti-compra-de-trastuzumabe-mesmo-sem-saber-como-sera-realizada-dispensacao/ (acessado em 25/Jan/2019).
https://www.bioredbrasil.com.br/minister... ^,77. Torres P. Ministério da Saúde manifesta a intenção de troca automática de medicamento biológico originador por biossimilar. Blog Artrite Reumatóide 2018; 17 jan. https://artritereumatoide.blog.br/ministerio-da-saude-manifesta-a-intencao-de-troca-automatica-de-medicamento-biologico-originador-por-biossimilar/.
https://artritereumatoide.blog.br/minist... . The Department of Health Logistics under the Brazilian Ministry of Health assessed the possibility of automatically substituting reference biological drugs with their biosimilar versions ⁵5. BioredBrasil. Conheça o posicionamento e questionamentos da Biored Brasil ao Departamento de Logísticas do Ministério da Saúde. https://www.bioredbrasil.com.br/wp-content/uploads/2018/01/Biored-Brasil-questionamentos-DLOG-SE-MS-16-01-2018.pdf (acessado em 25/Jan/2018).
https://www.bioredbrasil.com.br/wp-conte... ^,66. BioredBrasil. Ministério da Saúde debate compra de trastuzumabe mesmo sem saber como será realizada a dispensação. https://www.bioredbrasil.com.br/ministerio-da-saude-discuti-compra-de-trastuzumabe-mesmo-sem-saber-como-sera-realizada-dispensacao/ (acessado em 25/Jan/2019).
https://www.bioredbrasil.com.br/minister... ^,77. Torres P. Ministério da Saúde manifesta a intenção de troca automática de medicamento biológico originador por biossimilar. Blog Artrite Reumatóide 2018; 17 jan. https://artritereumatoide.blog.br/ministerio-da-saude-manifesta-a-intencao-de-troca-automatica-de-medicamento-biologico-originador-por-biossimilar/.
https://artritereumatoide.blog.br/minist... . No health technology assessment (HTA) studies were presented, and what prevailed were discussions on economic issues. In the hearing on the regulation of substitution/interchangeability ⁸8. Câmara dos Deputados. Debater sobre a Resolução da Diretoria Colegiada da ANVISA na regulação da intercambialidade entre o produto originador e o produto biossimilar. https://edemocracia.camara.leg.br/audiencias/sala/807 (acessado em 02/Dez/2018).
https://edemocracia.camara.leg.br/audien... , even when the issue was raised on the need for medical consent at the moment of switch in dispensing the medication, no decision was made on regulation of the substitution/interchangeability in the SUS. Therefore, to date there is no regulatory policy in Brazil that ensures absence of loss of efficacy or safety in the treatment transition ⁵5. BioredBrasil. Conheça o posicionamento e questionamentos da Biored Brasil ao Departamento de Logísticas do Ministério da Saúde. https://www.bioredbrasil.com.br/wp-content/uploads/2018/01/Biored-Brasil-questionamentos-DLOG-SE-MS-16-01-2018.pdf (acessado em 25/Jan/2018).
https://www.bioredbrasil.com.br/wp-conte... ^,66. BioredBrasil. Ministério da Saúde debate compra de trastuzumabe mesmo sem saber como será realizada a dispensação. https://www.bioredbrasil.com.br/ministerio-da-saude-discuti-compra-de-trastuzumabe-mesmo-sem-saber-como-sera-realizada-dispensacao/ (acessado em 25/Jan/2019).
https://www.bioredbrasil.com.br/minister... ^,77. Torres P. Ministério da Saúde manifesta a intenção de troca automática de medicamento biológico originador por biossimilar. Blog Artrite Reumatóide 2018; 17 jan. https://artritereumatoide.blog.br/ministerio-da-saude-manifesta-a-intencao-de-troca-automatica-de-medicamento-biologico-originador-por-biossimilar/.
https://artritereumatoide.blog.br/minist... ^,88. Câmara dos Deputados. Debater sobre a Resolução da Diretoria Colegiada da ANVISA na regulação da intercambialidade entre o produto originador e o produto biossimilar. https://edemocracia.camara.leg.br/audiencias/sala/807 (acessado em 02/Dez/2018).
https://edemocracia.camara.leg.br/audien... . This situation notwithstanding, in two years there were 39 public purchases of approved biosimilars for infliximab, etanercept, and trastuzumab ⁹9. Banco de Preços em Saúde. Compras públicas (SIASG) de infliximabe, etarnecepte e trastuzumabe no período de 07/05/2017 a 07/05/2019. http://bps.saude.gov.br/ (acessado em 07/Mai/2019).
http://bps.saude.gov.br/... .

Various measures by Brazilian society and the Ministry of Health triggered a strong movement to draft a National Policy on Biological Drugs in the scope of the SUS. This policy aims to address issues in research and development, production, regulation, access, and monitoring in the use of biologicals supplied by the SUS ⁵5. BioredBrasil. Conheça o posicionamento e questionamentos da Biored Brasil ao Departamento de Logísticas do Ministério da Saúde. https://www.bioredbrasil.com.br/wp-content/uploads/2018/01/Biored-Brasil-questionamentos-DLOG-SE-MS-16-01-2018.pdf (acessado em 25/Jan/2018).
https://www.bioredbrasil.com.br/wp-conte... ^,77. Torres P. Ministério da Saúde manifesta a intenção de troca automática de medicamento biológico originador por biossimilar. Blog Artrite Reumatóide 2018; 17 jan. https://artritereumatoide.blog.br/ministerio-da-saude-manifesta-a-intencao-de-troca-automatica-de-medicamento-biologico-originador-por-biossimilar/.
https://artritereumatoide.blog.br/minist... ^,1010. Oliveira P. Troca de medicamentos biológicos por biossimilares divide opiniões na saúde. Senado Notícias 2017; 15 ago. https://www12.senado.leg.br/noticias/materias/2017/08/15/troca-de-medicamentos-biologicos-por-biossimilares-divide-opinioes-na-saude.
https://www12.senado.leg.br/noticias/mat... ^,1111. Ministério da Saúde. 9º Fórum Latino-Americano de Biossimilares: Portal do Ministério da Saúde. http://portalms.saude.gov.br/sctie/boletim-decit-em-acao/43953-mural-news-9-forum-latino-americano-de-biossimilares (acessado em 25/Ago/2018).
http://portalms.saude.gov.br/sctie/bolet... . The current context of design and implementation of national policies for the incorporation of these drugs is thus of the utmost importance for identifying which actors and institutions will participate in the decisions at the federal level concerning the HTA process for biosimilars.

This article aims to contextualize the Brazilian situation in the international debate on the incorporation of biosimilars by health systems, highlighting perspectives in the use of HTA studies, especially regarding challenges related to interchangeability and substitution of biosimilars.

Interchangeability and substitution of biologicals and biosimilars

Patients that use biologicals and biosimilars may experience various situations during treatment. Sometimes patients do not only replace the reference biological with a biosimilar, but also one biosimilar with another biosimilar, or a biosimilar with another biological from a different class ¹²12. Faccin F, Tebbey P, Alexander E, Wang X, Cui L, Albuquerque T. The design of clinical trials to support the switching and alternation of biosimilars. Expert Opin Biol Ther 2016; 16:1445-53.. This substitution can occur for medical reasons (for example, to minimize adverse reactions), or for nonmedical reasons (for example, cost reduction), also known as automatic substitution, in which there is no consent to the decision by either the prescribing physician or the patient ¹³13. Moots R, Azevedo V, Coindreau JL, Dörner T, Mahgoub E, Mysler E, et al. Switching between reference biologics and biosimilars for the treatment of rheumatology, gastroenterology, and dermatology inflammatory conditions: considerations for the clinician. Curr Rheumatol Rep 2017; 19:37.. There is also interchangeability, when the reference biological can be substituted with the biosimilar without consulting the prescriber, since there is proof that repeated switching between the drugs does not pose an additional safety risk or reduction in efficacy ¹⁴14. Food and Drug Administration. Biosimilar and interchangeable products. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products (acessado em 02/Dez/2018).
https://www.fda.gov/drugs/biosimilars/bi... ^,1515. Garcia R. Intercambiabilidade entre medicamentos biológicos. J Bras Econ Saúde 2016; 8:61-4..

Demonstration of interchangeability is not a requirement for registering the drug, which is up to each regulatory agency. The definitions differ from one country to another ¹⁵15. Garcia R. Intercambiabilidade entre medicamentos biológicos. J Bras Econ Saúde 2016; 8:61-4.^,1616. The Canadian Agency for Drugs and Technologies in Health. Biosimilars - regulatory, health technology assessment, reimbursement trends, and market outlook. Ottawa: The Canadian Agency for Drugs and Technologies in Health; 2018.. In Brazil, the Brazilian Health Regulatory Agency (Anvisa) published a note of clarification on interchangeability and substitution of biosimilars and reference biologicals, emphasizing that interchangeability relates more directly to clinical practice than to regulatory status ¹⁷17. Agência Nacional de Vigilância Sanitária. Nota de Esclarecimento nº 003/2017/GPBIO/GGMED/ANVISA-REVISADA. http://portal.anvisa.gov.br/documents/33836/4095801/Nota+de+esclarecimento+003+de+2017+-+Medicamentos+Biol%C3%B3gicos/0774f2d7-5c83-45b7-832d-37efdf21790c (acessado em 02/Nov/2018).
http://portal.anvisa.gov.br/documents/33... , thus involving broader aspects such as specific studies, data from the literature, case-by-case medical assessment, and issues of traceability and pharmacovigilance. Anvisa thus assumes its role as the regulatory body responsible for certifying the registration of new biosimilars in Brazil, but as for interchangeability, the agency reported that it is the responsibility of the Ministry of Health and the prescribing physician ¹⁷17. Agência Nacional de Vigilância Sanitária. Nota de Esclarecimento nº 003/2017/GPBIO/GGMED/ANVISA-REVISADA. http://portal.anvisa.gov.br/documents/33836/4095801/Nota+de+esclarecimento+003+de+2017+-+Medicamentos+Biol%C3%B3gicos/0774f2d7-5c83-45b7-832d-37efdf21790c (acessado em 02/Nov/2018).
http://portal.anvisa.gov.br/documents/33... . Nevertheless, we emphasize that numerous biosimilars have been registered with regulatory agencies for marketing purposes ¹⁸18. GABI online. Biosimilars approved in Europe. http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe (acessado em 02/Jun/2019).
http://www.gabionline.net/Biosimilars/Ge... ^,1919. GABI online. Biosimilars approved in the US. http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US (acessado em 02/Jun/2019).
http://www.gabionline.net/Biosimilars/Ge... ^,2020. Agência Nacional de Vigilância Sanitária. Primeiro medicamento biológico por comparabilidade é registrado pela Anvisa. http://portal.anvisa.gov.br/noticias (acessado em 02/Dez/2018).
http://portal.anvisa.gov.br/noticias... , no regulatory agency in the world has ever certified a biosimilar as interchangeable ¹⁴14. Food and Drug Administration. Biosimilar and interchangeable products. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products (acessado em 02/Dez/2018).
https://www.fda.gov/drugs/biosimilars/bi... ^,1515. Garcia R. Intercambiabilidade entre medicamentos biológicos. J Bras Econ Saúde 2016; 8:61-4.^,2121. Garcia R, Araujo DV. The regulation of biosimilars in Latin America. Curr Rheumatol Rep 2016; 18:16..

Although regulatory agencies have the role of authorizing the marketing of these drugs, registration does not guarantee their incorporation, coverage, and/or reimbursement by health plans. This mechanism is essential for guaranteeing access to effective and safe drugs for the population and that are cost-effective for health systems. There are HTA agencies or organizations responsible for conducting and assessing HTA studies, primarily to inform health decision-making ²²22. International Network of Agencies for Health Technology Assessment. Glossary HTA 2018. http://htaglossary.net (acessado em 15/Dez/2018).
http://htaglossary.net... .

HTA organizations like Brazil’s National Commission for the Incorporation of Technologies in the SUS (CONITEC), the U.K. National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH) use HTA studies (rapid reviews, mini-HTA, and full HTA ²³23. Merlin T, Tamblyn D, Ellery B. What's in a name? Developing definitions for common health technology assessment product types of the International Network of Agencies for Health Technology Assessment (INAHTA). Int J Technol Assess Health Care 2014; 30:430-7.) in decision-making processes. HTA involves a systematic assessment of the properties and effects of a health technology, aimed at informing decision-making in order to rationalize the incorporation of technologies in health systems in a safe, efficacious, and cost-effective way, aimed mainly at the systems’ sustainability ²²22. International Network of Agencies for Health Technology Assessment. Glossary HTA 2018. http://htaglossary.net (acessado em 15/Dez/2018).
http://htaglossary.net... . Besides assessing equivalence or non-inferiority and safety/immunogenicity, HTA studies of biosimilars can also assess whether there is any risk in the treatment transition, by summarizing evidence from substitution/interchangeability studies and cost-effectiveness analyses of treatment transition between biologicals and biosimilars ¹³13. Moots R, Azevedo V, Coindreau JL, Dörner T, Mahgoub E, Mysler E, et al. Switching between reference biologics and biosimilars for the treatment of rheumatology, gastroenterology, and dermatology inflammatory conditions: considerations for the clinician. Curr Rheumatol Rep 2017; 19:37.^,2424. Feagan BG, Lam G, Ma C, Lichtenstein GR. Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab. Aliment Pharmacol Ther 2019; 49:31-40..

HTA agencies have adopted different strategies to develop HTA studies of biosimilars ¹⁶16. The Canadian Agency for Drugs and Technologies in Health. Biosimilars - regulatory, health technology assessment, reimbursement trends, and market outlook. Ottawa: The Canadian Agency for Drugs and Technologies in Health; 2018.. For example, agencies in New Zealand and France use the same process for assessing a new drug’s clinical and economic benefit, while other agencies like the one in the United Kingdom adopt a customized assessment. Agencies in Canada and Australia use both approaches. Other agencies only conduct HTA studies if the reference biological has not been assessed or if it has been assessed but is not reimbursable. Agencies in Germany and the Netherlands do not conduct HTA studies of biosimilars ¹⁶16. The Canadian Agency for Drugs and Technologies in Health. Biosimilars - regulatory, health technology assessment, reimbursement trends, and market outlook. Ottawa: The Canadian Agency for Drugs and Technologies in Health; 2018..

The CADTH has a well-established policy with guidelines for the submission of assessment of biosimilars, in the form of a mini-HTA, including risk assessment of the treatment transition ²⁵25. Canadian Agency for Drugs and Technologies in Health. pan-Canadian oncology drug review submission guidelines for biosimilars. https://www.cadth.ca/sites/default/files/pcodr/pCODR%27s%20Drug%20Review%20Process/pcodr-submission-guidelines-biosimilars.pdf (acessado em 02/Dez/2018).
https://www.cadth.ca/sites/default/files... . In the United Kingdom, representatives from the public regulatory and HTA agencies, the pharmaceutical industry association, and HTA experts met to discuss the role of HTA for biosimilars. The majority shared the view that the organizations should adopt greater flexibility in the choice of processes and methods to determine whether biosimilars should be assessed from the perspective of health economics ²⁶26. Mestre-Ferrandiz J, Towse A. What is the role of HTA for biosimilars? London: Office of Health Economics; 2014. (Briefing, 54).. Although HTA is consolidated as a scientific and technological practice and its influence is expanding among decisionmakers, there is still no hegemonic position on its role for biosimilars. In a survey of national associations of pharmaceutical companies from 32 European countries, 24 countries (75%) stated that the HTA process does not apply to biosimilars ²⁷27. Reiland J, Freischem B, Roediger A. What pricing and reimbursement policies to use for off-patent biologicals in Europe? Results from the second EBE biological medicines policy survey. GaBi J 2017; 6:61-78.. According to these associations, the evidence furnished for marketing registration and issues related to the drug’s cost can be sufficient for the incorporation of biosimilars ¹⁶16. The Canadian Agency for Drugs and Technologies in Health. Biosimilars - regulatory, health technology assessment, reimbursement trends, and market outlook. Ottawa: The Canadian Agency for Drugs and Technologies in Health; 2018.^,2626. Mestre-Ferrandiz J, Towse A. What is the role of HTA for biosimilars? London: Office of Health Economics; 2014. (Briefing, 54).^,2828. Stewart A, Aubrey P, Belsey J. Addressing the health technology assessment of biosimilar pharmaceuticals. Curr Med Res Opin 2010; 26:2119-26..

Application of HTA to biosimilars in the Brazilian context

Medical societies and patients’ associations have positioned themselves in favor of introducing biosimilars in Brazil, as long as the scientific parameters are adequate ²⁹29. Fernandes GS, Sternberg C, Lopes G, Chammas R, Gifoni MAC, Gil RA, et al. The use of biosimilar medicines in oncology - position statement of the Brazilian Society of Clinical Oncology (SBOC). Braz J Med Biol Res 2018; 51:e7214.^,3030. Torres P, Kos IA, Isaac A, Oliveira NR, Silva MI, Oliveira AP, et al. Consenso brasileiro multi-institucional de pacientes sobre medicamentos biossimilares. J Bras Econ Saúde 2017; 9:39-43.. They also emphasize the need for CONITEC to update the Clinical Protocols and Therapeutic Guidelines in relation to the biosimilars provided by the SUS and the supply of proof of biosimilars’ efficacy and safety, especially in the case of monoclonal antibodies and fusion proteins, through studies with adequate equivalence margins capable of detecting significant clinical differences ³¹31. Azevedo VF, Meirelles ES, Kochen JA, Medeiros AC, Miszputen SJ, Teixeira FV, et al. Recommendations on the use of biosimilars by the Brazilian Society of Rheumatology, Brazilian Society of Dermatology, Brazilian Federation of Gastroenterology and Brazilian Study Group on Inflammatory Bowel Disease - focus on clinical evaluation of monoclonal antibodies and fusion proteins used in the treatment of autoimmune diseases. Autoimmun Rev 2015; 14:769-73..

There is no regulation to date by Anvisa on substitution/interchangeability of any biological or biosimilar drugs, just as there are no HTA studies in Brazil to support interchangeability/substitution with any biosimilars approved in the country. Law n. 12,401 of 2011 ³²32. Brasil. Lei nº 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. provides that HTA of technologies submitted to CONITEC must consider the scientific evidence on the efficacy, accuracy, effectiveness, and safety as well as comparative economic analyses of the costs and benefits in relation to technologies already incorporated in the SUS ³³33. Departamento de Ciência e Tecnologia, Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Ministério da Saúde. Diretrizes metodológicas: diretriz de avaliação econômica. 2ª Ed. Brasília: Ministério da Saúde; 2014..

A search in the Information System of the Brazilian Network of Health Technology Assessment (SISREBRATS) and reports with recommendations by CONITEC showed clearly that the topic of biosimilar products is recent in CONITEC, and that there is no standard understanding on definitions and decision-making processes involving biosimilars. CONITEC is represented in the Working Group that is participating in the National Policy on Biological Drugs in the context of the SUS, but it has still not reported officially whether it will apply the HTA process to assessments of biosimilars ³⁴34. Ministério da Saúde. Enquete pública: medicamentos biológicos. http://portalms.saude.gov.br/gt-de-biologicos/participe-das-consultas (acessado em 02/Set/2018).
http://portalms.saude.gov.br/gt-de-biolo... . In 2018, the Department of Science and Technology of the Science, Technology, and Strategic Inputs Secretariat of the Ministry of Health participated in four meetings, including a deliberative dialogue. However, no product resulting from the discussions has been made available to the public so far ³⁵35. Departamento de Ciência e Tecnologia, Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Ministério da Saúde. Medicamentos biológicos. Revista Ciências SUS 2018; (2). http://portalarquivos2.saude.gov.br/images/pdf/2018/dezembro/26/Revista-cienciaSUS-Edicao2.pdf.
http://portalarquivos2.saude.gov.br/imag... .

The aspects discussed above call attention to the need for an official position by CONITEC concerning HTA for biosimilars. The commission should indicate the type of HTA study to be performed for biosimilars or whether their incorporation can be backed only by the evidence required at the time of registration of the biosimilar, which does not include risk assessment of substitution/interchangeability.

Conclusions

In the international scenario, HTA studies of biosimilars have still not been standardized, and policies for their regulation and incorporation are in the design and implementation phase to address issues of interchangeability and substitution of biosimilars ²⁸28. Stewart A, Aubrey P, Belsey J. Addressing the health technology assessment of biosimilar pharmaceuticals. Curr Med Res Opin 2010; 26:2119-26.. The drafting is under way in Brazil on a National Policy on Biological Drugs in the context of the SUS, which can contribute to a transparent process of incorporation of biosimilars. However, with the growing supply of biosimilar drugs on markets, it is essential for HTA agencies to take a more consolidated position on the assessment of biosimilars. This theme relights the debate on evidence-based regulation of biological therapies and biosimilars in contemporary health systems, capable of preserving treatment efficacy and safety while promoting more efficient and sustainable health systems.

Publication Dates

History