Brazil has established a framework for provision of generic pharmaceuticals including for orally inhaled and nasal drug products (OINDP) to its populace. This includes the development of guidelines or “resolutions” and normative instructions describing the Brazilian medicines agency’s (Anvisa) expectations for demonstrating OINDP therapeutic equivalence. The Anvisa regulatory framework for OINDP therapeutic equivalence, challenges, and comparisons with the US Food and Drug Administration and European Medicines Agency approaches are assessed and discussed.
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Santos, GML. Review impact of emerging Anvisa guidelines and standards. 2016. http://ipacrs.org/news-events/events/2016ipacrssymposium. Accessed 16 Feb 2019.
Santos, GML. Considerations for generic OIPs in Brazil. IPAC-RS and University of Florida Orlando Inhalation Conference. 2014. http://ipacrs.org/assets/uploads/outputs/10-Day_1_OIC_2014_Santos.pdf Accessed 16 Feb 2019.
Portal da Saude, Ministério Da Saúde. Farmácia Popular. http://portalms.saude.gov.br/acoes-e-programas/farmacia-popular Accessed 16 Feb 2019.
Anvisa. Legislação. http://portal.Anvisa.gov.br/legislacao#/. Accessed 16 Feb 2019.
Lee SL, et al. Regulatory considerations for approval of generic inhalation drug products in the US, EU, Brazil, China, and India. AAPS J. 2015;17(5):1285–304.
Brazilian Health Surveillance Agency. Technical Note no. 001/2013, CEFAR/GTFAR/GGMED/Anvisa. Tests and procedures for conduct of pharmaceutical equivalence studies for nasal sprays, nasal aerosols, oral MDIs and oral DPIs, and on population bioequivalence statistical analysis applicable to selected tests. 25 Mar 2013.
A Resolution is a regulatory document containing mandatory requirements that usually undergoes a public consultation process. A Normative Instruction provides details associated with Resolution requirements such as testing procedures, acceptance criteria, etc, and is also subject to public consultation.
Brazilian Health Surveillance Agency (Anvisa). 2019. Resolution no. 278, 16 April 2019. Trials for evidence of therapeutic equivalence for OIDP and nasal sprays/aerosols.
Brazilian Health Surveillance Agency (Anvisa). 2019. Normative instruction no. 33, 16 April 2019. In vitro performance tests for OINDP.
International Pharmaceutical Aerosol Consortium on Regulation and Science. https://ipacrs.org/ Accessed 27 Dec 2018.
Brazilian Health Surveillance Agency (Anvisa). Technical and scientific basis for approval of the generic medicine registration for beclomethasone dipropionate Glenmark aerosol solution for oral inhalation. 2015.
Brazilian Health Surveillance Agency (Anvisa). 2014. Resolution no. 56, 08 October 2014. Certification of Good Practices for carrying out studies of bioavailability / bioequivalence of medicinal products.
Brazilian Health Surveillance Agency (Anvisa). 2016. Resolution no. 67, 23 March 2016. Qualification, Renewal of Qualification, Modifications post-qualification, Outsourcing of testing, Suspensions and Cancellations of Pharmaceutical Equivalence Centers.
Brazilian Health Surveillance Agency (Anvisa). 2010. Resolution no. 31, 11 August 2010. Pharmaceutical equivalence determination and dissolution profile comparisons. http://pesquisa.in.gov.br/imprensa/jsp/visualiza/index.jsp?jornal=1&pagina=36&data=12/08/2010. Accessed 16 Feb 2019.
Nardy, B. Pharmaceutical equivalence of inhalation products in Brazil. IPAC-RS Symposium, Scottsdale, AZ, 2016. https://ipacrs.org/news-events/events/2016ipacrssymposium. Accessed 16 Feb 2019.
Thakkar K, Suyog M, et al. Pharmacokinetic studies for proving bioequivalence of orally inhaled drug products—critical issues and concepts. Front Pharmacol. 2015;6:117.
Hochhaus G, Horhota S, et al. Pharmacokinetics of orally inhaled drug products. AAPS J. 2015;17(3):769–75.
Li, B. Bioequivalence of locally acting orally Inhaled and nasal drug product: regulatory histories and milestones. 3rd FDA PQRI Conference on Advancing Product Quality. 2017. http://pqri.org/3rd-fdapqri-conference-on-advancing-product-quality/ Accessed 25 August 2017.
European Medicines Agency. Committee for Medicinal Products for Human Use. Requirements for clinical documentation for orally inhaled products (OIP) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of asthma in children and adolescents. 2009 http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001151.jsp&mid=WC0b01ac0580034cf6 Accessed 16 Feb 2019.
Brazilian Health Surveillance Agency. 2016. Resolution no. 73, 07 April 2016. Post-registration changes, cancellation of registration of medicines with synthetic and semisynthetic APIs.
Newman SP, Chan HK. In vitro/In vivo comparisons in pulmonary drug delivery. J Aeorosl Med Pulm Drug Deliv. 2008;1(21):77–84.
FDA draft guidance on fluticasone propionate. Recommended October 2017.
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Discussion and analysis of the Anvisa (Brazil’s medicines agency) regulatory framework and emerging regulatory expectations for therapeutic equivalence of orally inhaled and nasal drug products
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Silva, M.C., Costa, H.S., Valadares, B.N. et al. Overview of Brazilian Requirements for Therapeutic Equivalence of Orally Inhaled and Nasal Drug Products. AAPS PharmSciTech 20, 235 (2019). https://doi.org/10.1208/s12249-019-1415-y
- orally inhaled drug products
- nasal drug products
- therapeutic equivalence