Assessing the impact of fast-track drug registration by Anvisa in Brazil: A descriptive study of new drug registrations from 2017 to 2022
Prompt release of novel pharmaceuticals is very much sought after during critical circumstances to aid patients and society in need. Nonetheless, the expeditious availability of these medications may jeopardize the well-structured investigations and observations. To tackle this concern, regulatory agencies globally have implemented expedited registration procedures. In Brazil, the National Health Surveillance Agency (Anvisa) has likewise implemented an expedited registration process to cater to patients who cannot afford to wait. The objective of this study is to evaluate the impact of Anvisa’s accelerated drug registration on the challenging regulatory environment in Brazil. Data pertaining to medications registered by Anvisa from 2017 to 2022 through the expedited process were procured from the Federal Government’s transparency portal and the medication consultation portal. The registration of novel drugs by Anvisa through both standard and expedited processes during this timeframe was analyzed. The introduction of the accelerated registration regulation by Anvisa in 2017 led to a substantial rise in registration requests utilizing this regulatory modality. Furthermore, the data concerning drug registration through all channels unveiled a noteworthy reduction in average response time. Despite concerns pertaining to the effectiveness and safety of drugs registered through the expedited process, often reliant on Phase II studies, the utilization of this process is on the rise worldwide, including in Brazil. To ensure the sustainability of health-care systems, it may be advantageous to implement provisional registration in conjunction with subsequent evaluation through real-world studies and financing based on risk-sharing agreements. In conclusion, the accelerated drug registration process implemented by Anvisa in Brazil has exhibited promising results in terms of reduced response times. Nevertheless, the effectiveness and safety of drugs registered through this process necessitate meticulous evaluation. The implementation of provisional registration and the integration of real-world studies, alongside managed entry agreements, could offer a sustainable alternative for health-care systems.
Amini, L., Silbert, S.K., Maude, S.L., Nastoupil, L.J., Ramos, C.A., Brentjens, R.J., et al. (2022). Preparing for CAR T cell therapy: Patient selection, bridging therapies and lymphodepletion. Nature Reviews Clinical Oncology, 19:342-355. https://doi.org/10.1038/s41571-022-00607-3
ANVISA. (2022a). Autorizada Pesquisa Nacional Com Células CAR-T Para Tratar Câncer. Agência Nacional de Vigilância Sanitária-anvisa. Available from: https://www.gov.br/anvisa/ pt-br/assuntos/noticias-anvisa/2022/autorizada-pesquisa-nacional-com-celulas-car-t-para-tratar-cancer-1 [Last accessed on 2022 Dec 12].
ANVISA. (2022b). Institucional. Agência Nacional de Vigilância Sanitária-anvisa. Available from: https://www.gov.br/anvisa/ pt-br/acessoainformacao/institucional/capa-institucional [Last accessed on 2022 Dec 12].
Archanjo, E. (2022). Kymriah®. Bulas de Medicamentos. Available from: https://portal.novartis.com.br/medicamentos/ kymriah [Last accessed on 2022 Dec 12].
Bootes, A., Maundu, J., Golding, S., McDonald, M., & Lombard, J. (2019). Fast-track pathways for drug approvals: The Australian experience so far. Australian Prescriber, 42:118-119. https://doi.org/10.18773/austprescr.2019.044
Brasil. (2016). Lei No 13.411.
Brasil. (2017a). Resolução RDC n° 204, de 27 de Dezembro de 2017. Brazil: Agência Nacional de Vigilância Sanitária (Anvisa). Available from: http://antigo.anvisa.gov.br/ documents/10181/2718376/RDC_204_2017_.pdf/ b2d4ae64-2d91-44e9-ad67-b883c752c094 [Last accessed on 2023 Apr 20].
Brasil. (2017b). Resolução RDC n° 205, de 28 de Dezembro de 2017. Brazil: Agência Nacional de Vigilância Sanitária (Anvisa). Available from: https://bvsms.saude.gov.br/bvs/ saudelegis/anvisa/2017/rdc0205_28_12_2017.pdf [Last accessed on 2023 Apr 20].
Canada, H. (2002). Priority Review of Drug Submissions (Therapeutic Products). Available from: https://www. canada.ca/en/health-canada/services/drugs-health-products/drug-products/fact-sheets/priority-review-drug-submissions-therapeutic-products.html [Last accessed on 2022 Dec 12].
EMA. (2018). Accelerated Assessment. European Medicines Agency. Available from: https://www.ema.europa.eu/en/ human-regulatory/marketing-authorisation/accelerated-assessment [Last accessed on 2022 Dec 12].
FDA. (2018). Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review: What Do These Terms Mean? Washington, DC: U.S. Food and Drug Administration. Available from: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track [Last accessed on 2023 Apr 25].
Fogel, D.B. (2018). Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemporary Clinical Trials Communications, 11:156-164. https://doi.org/10.1016/j.conctc.2018.08.001
Gagnon, M.A. (2015). New drug pricing: Does it make any sense? Prescrire International, 24:192-195.
Gammie, T., Lu, C.Y., & Babar, Z.U.D. (2015). Access to orphan drugs: A comprehensive review of legislations, regulations and policies in 35 countries. PLoS One, 10:e0140002. https://doi.org/10.1371/journal.pone.0140002
Hwang, T.J., Ross, J.S., Vokinger, K.N., & Kesselheim, A.S. (2020). Association between FDA and EMA expedited approval programs and therapeutic value of new medicines: Retrospective cohort study. BMJ, 371:m3434. https://doi.org/10.1136/bmj.m3434
INCA. (2022). INCA Estima 704 Mil Casos de Câncer Por Ano no Brasil Até 2025. Instituto Nacional de Câncer-INCA. Available from: https://www.gov.br/inca/pt-br/assuntos/ noticias/2022/inca-estima-704-mil-casos-de-cancer-por-ano-no-brasil-ate-2025 [Last accessed on 2023 Apr 25].
Kubler, P. (2018). Fast-tracking of new drugs: Getting the balance right. Australian Prescriber, 41:98-99. https://doi.org/10.18773/austprescr.2018.032
Lexchin, J. (2015a). Post-market safety warnings for drugs approved in Canada under the Notice of Compliance with conditions policy. British Journal of Clinical Pharmacology, 79:847-859. https://doi.org/10.1111/bcp.12552
Lexchin, J. (2015b). Health Canada’s use of its priority review process for new drugs: A cohort study. BMJ Open, 5:e006816. https://doi.org/10.1136/bmjopen-2014-006816
Line, N. (2021). Anvisa Acelera Registro de Medicamentos de Especialidades. Available from: https:// panoramafarmaceutico.com.br/fast-track-da-anvisa-acelera-registro-de-medicamentos-de-especialidades [Last accessed on 2023 May 05].
Linger, M., & Martin, J. (2018). Pharmacovigilance and expedited drug approvals. Australian Prescriber, 41:50-53. https://doi.org/10.18773/austprescr.2018.010
Martin, J., & Shenfield, G. (2016). The hazards of rapid approval of new drugs. Australian Prescriber, 39:2-3. https://doi.org/10.18773/austprescr.2016.005
Mayer-Hamblett, N., & VanDevanter, D.R. (2020). Accelerated approval or risk reduction? How response biomarkers advance therapeutics through clinical trials in cystic fibrosis. Trends in Molecular Medicine, 26:1068-1077. https://doi.org/10.1016/j.molmed.2020.08.002
Ministério da Saúde. (2022). Portaria Sctie/MS No 172. Brazil: Ministério da Saúde.
Mostaghim, S.R., Gagne, J.J., & Kesselheim, A.S. (2017). Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: Retrospective cohort study. BMJ, 358:j3837. https://doi.org/10.1136/bmj.j3837
Nash, L. (2016). Fast-track approval of medicines in Australia. Lancet Oncology, 17:1487. https://doi.org/10.1016/S1470-2045(16)30492-2
Nguengang Wakap, S., Lambert, D.M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., et al. (2020). Estimating cumulative point prevalence of rare diseases: Analysis of the orphanet database. European Journal of Human Genetics, 28:165-173. https://doi.org/10.1038/s41431-019-0508-0
OECD. (2023). Exchange Rates (Indicator). Available from: http://data.oecd.org/conversion/exchange-rates.htm [Last accessed on 2023 Feb 02]. https://doi.org/10.1787/037ed317-en
Shahryari, A., Jazi, M.S., Mohammadi, S., Nikoo, H.R., Nazari, Z., Hosseini, E.S., et al. (2019). Development and clinical translation of approved gene therapy products for genetic disorders. Frontiers in Genetics, 10:868. https://doi.org/10.3389/fgene.2019.00868
Wong, C.H., Siah, K.W., & Lo, A.W. (2019). Estimation of clinical trial success rates and related parameters. Biostatistics, 20:273-286. https://doi.org/10.1093/biostatistics/kxx069
Zampirolli Dias, C., Godman, B., Gargano, L.P., Azevedo, P.S., Garcia, M.M., Cazarim, M.S., et al. (2020). Integrative review of managed entry agreements: Chances and limitations. Pharmacoeconomics, 38:1165-1185. https://doi.org/10.1007/s40273-020-00943-1
Zeng, X., Zhang, Y., Kwong, J.S.W., Zhang, C., Li, S., Sun, F., et al. (2015). The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: A systematic review. Journal of Evidence-based Medicine, 8:2-10. https://doi.org/10.1111/jebm.12141