Comparator product issues for biowaiver implementation: the case of Fluconazole
DOI:
https://doi.org/10.1590/s2175-97902022e19504%20Keywords:
Nontuberculous mycobacteria, Tuberculosis, Diagnosis, Microscopy, Molecular diagnosisAbstract
The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria.
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Aljaberi A, Chatterji A, Dong Z, Shah NH, Malick W, Singhal D, et al. Understanding and optimizing the dual excipient functionality of sodium lauryl sulfate in tablet formulation of poorly water soluble drug: wetting and lubrication. Pharm Dev Technol. 2012;18(2):490-503.
Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12(3):413-20.
Bergström CAS, Andersson SBE, Fagerberg JH, Ragnarsson G, Lindahl A. Is the full potential of the biopharmaceutics classification system reached? Eur J Pharm Sci. 2014;57:224-31.
Brasil. Agencia Nacional de Vigilância Sanitária (ANVISA). Instrução Normativa N˚ 10, de 29 de setembro de 2016, Determina a publicação da “Lista de fármacos candidatos à bioisenção baseada no Sistema de Classificação Biofarmacêutica (SCB)”. (cited 1 January 2018). Available from: Available from: http://portal.anvisa.gov.br/documents/10181/2718376/ IN_10_2016_.pdf/5c6384cd-4743-4a96-a4c7-5ef5626c0a80
» http://portal.anvisa.gov.br/documents/10181/2718376/ IN_10_2016_.pdf/5c6384cd-4743-4a96-a4c7-5ef5626c0a80
Brasil. Agencia Nacional de Vigilância Sanitária (ANVISA). Resolução, RDC N˚333, dispõe sobre: Dispõe sobre rotulagem de medicamentos e outras providências. 2003. (cited 20 November 2019). Available from: Available from: http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2003/rdc0333_19_11_2003.html
» http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2003/rdc0333_19_11_2003.html
Brasil. Agencia Nacional de Vigilância Sanitária (ANVISA). Resolução, RDC N˚60, dispõe sobre: Os critérios para a concessão e renovação do registro de medicamentos com princípios ativos sintéticos e semissintéticos, classificados como novos, genéricos e similares, e dá outras providências. 2014. (cited 16 January 2018). Available from: Available from: http://portal.anvisa.gov.br/documents/10181/2867994/%281%29RDC_60_2014_ COMP.pdf/e25c9c39-d035-44cb-821e-d0cbafd8668f
» http://portal.anvisa.gov.br/documents/10181/2867994/%281%29RDC_60_2014_ COMP.pdf/e25c9c39-d035-44cb-821e-d0cbafd8668f
Brasil. Agencia Nacional de Vigilância Sanitária (ANVISA). Resolução, RDC N˚ 37, dispõe sobre: O guia para isenção e substituição de estudos de biodisponibilidade relativa/bioequivalência e dá outras providências. 2011. (cited 16 February 2018). Available from: Available from: https://www20.anvisa.gov.br/coifa/pdf/rdc37.pdf
» https://www20.anvisa.gov.br/coifa/pdf/rdc37.pdf
Brasil. Agencia Nacional de Vigilância Sanitária (ANVISA). Resolução, RDC N˚ 31, dispõe sobre: A realização dos Estudos de Equivalência Farmacêutica e de Perfil de Dissolução Comparativo. 2010. (cited 1 June 2018). Available from: Available from: http://portal.anvisa.gov.br/documents/33880/2568070/res0031_11_08_2010.pdf/5e157d%0A15-d3d5-4bb9-98db- 5667e4d9e0c8
» http://portal.anvisa.gov.br/documents/33880/2568070/res0031_11_08_2010.pdf/5e157d%0A15-d3d5-4bb9-98db- 5667e4d9e0c8
Brasil. Lei federal 9787: Altera a Lei no 6.360, de 23 de setembro de 1976, que dispõe sobre a vigilância sanitária, estabelece o medicamento genérico, dispõe sobre a utilização de nomes genéricos em produtos farmacêuticos e dá outras providências. 1999. (cited 20 November 2019). Available from: Available from: http://www.planalto.gov.br/ccivil_03/leis/L9787.htm
» http://www.planalto.gov.br/ccivil_03/leis/L9787.htm
Camenisch Gian P. Drug disposition classification systems in discovery and development: a comparative review of the BDDCS, ECCS and ECCCS concepts. Pharm Res . 2016;33(11):2583-2593.
Cardot J-M, Garcia Arieta A, Paixao P, Tasevska I, Davit B. Implementing the biopharmaceutics classification system in drug development: reconciling similarities, differences, and shared challenges in the ema and us-fda-recommended approaches. AAPS J. 2016;18(4):1039-46.
Charoo N, Cristofoletti R, Graham A, Lartey P, Abrahamsson B, Groot DW, et al. Biowaiver monograph for immediate- release solid oral dosage forms: fluconazole. J Pharm Sci. 2014;103(12):3843-58.
Davit BM, Kanfer I, Tsang YC, Cardot J-M. BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements. AAPS J . 2016;18(3):612-8.
Duque MD, Silva DA, Issa MG, Porta V, Löbenberg R, Ferraz HG. In silico prediction of plasma concentrations of fluconazole capsules with different dissolution profiles and bioequivalence study using population simulation. Pharmaceutics. 2019;11(5):215.
Elder DP, Kuentz M, Holm R. Pharmaceutical excipients - quality, regulatory and biopharmaceutical considerations. Eur J Pharm Sci . 2016;87:88-99.
Fekete P, Virgula J, Furdyga E, Leventiszne M, Klebovich H, Baloghne K. et al. Fluconazole capsules with improved release. Patent No. WO2005/002553A2. 2005
Food and Drug Administration (FDA). Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system - 2017. (cited 8 Janeiro 2018). Available from: Available from: https://www.fda.gov/downloads/Drugs/Guidances/ucm070246.pdf
» https://www.fda.gov/downloads/Drugs/Guidances/ucm070246.pdf
García-Arieta A. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence. Eur J Pharm Sci . 2014;65:89-97.
Grande-Ortiz M, Taipe-Cadenillas S, Villodas-Saldaña C, Rodríguez-Calzado J, Moreno-Exebio L. Equivalencia terapéutica evaluada mediante estudios in vitro de medicamentos multifuentes: Estudio de casos de amoxicilina, doxiciclina y fluconazol en Lima, Perú. Rev Peru Med Exp Salud Publica. 2019;36(1):74.
International Pharmaceutical Federation (FIP). Biowaiver Monographs - 2014. (cited 16 August 2018). Available from: Available from: https://www.fip.org/bcs_monographs
» https://www.fip.org/bcs_monographs
Kubbinga M, Langguth P, Barends D. Risk analysis in bioequivalence and biowaiver decisions. Biopharm Drug Dispos. 2013;34(5):254-61.
Kubbinga M, Moghani L, Langguth P. Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: Lactose in solid oral dosage forms. Eur J Pharm Sci . 2014;61:27-31.
Larregieu CA, Benet LZ. Distinguishing between the permeability relationships with absorption and metabolism to improve BCS and BDDCS predictions in early drug discovery. Mol Pharm. 2014;11(4):1335-44.
Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm. 2004;58(2):265-78.
Löbenberg R, Chacra NB, Stippler ES, Shah VP, DeStefano AJ, Hauck WW, et al. Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas. AAPS J . 2012;14(3):462-72.
Niazi SK, Swarbrick J. Handbook of Bioequivalence Testing. Second ed. Chicago, Illinois: 2007.
Ono A, Sugano K. Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations. Eur J Pharm Sci . 2014;64:37-43.
Parr A, Hidalgo IJ, Bode C, Brown W, Yazdanian M, Gonzalez MA, et al. The Effect of excipients on the permeability of BCS Class III compounds and implications for biowaivers. Pharm Res . 2016;33(1):167-76.
Polli JE. In Vitro studies are sometimes better than conventional human pharmacokinetic in vivo studies in assessing bioequivalence of immediate-release solid oral dosage forms. AAPS J . 2008;10(2):289-99.
Ramirez E, Laosa O, Guerra P, Duque B, Mosquera B, Borobia AM, et al. Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System. Br J Clin Pharmacol. 2010;70(5):694-702.
Reddy NHS, Patnala S, Kanfer I. Investigation of Biowaivers for immediate release formulations containing BCS III drugs, acyclovir, atenolol, and ciprofloxacin hydrochloride, using dissolution testing. AAPS PharmSciTech. 2017;18(2):424-31.
Rowe R, Sheskey P, Quinn M. Handbook of Pharmaceutical Excipients. Sixth ed. North Yorkshire: 2009.
Suarez-Sharp S, Delvadia PR, Dorantes A, Duan J, Externbrink A, Gao Z, et al. Regulatory perspectives on strength-dependent dissolution profiles and biowaiver approaches for Immediate Release (IR) oral tablets in new drug applications. AAPS J . 2016;18(3):578-88.
Teleginski LK, Maciel AB, Mendes C, Silva MAS, Bernardi LS, de Oliveira PR. Fluconazole - excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver. J Therm Anal Calorim. 2015;120(1):771-81.
Vaithianathan S, Haidar SH, Zhang X, Jiang W, Avon C, Dowling TC, et al. Effect of common excipients on the oral drug absorption of biopharmaceutics classification system class 3 drugs cimetidine and acyclovir. J Pharm Sci . 2016;105(2):996-1005.
Varma M, El-Kattan A, Feng B, Steyn S, Maurer T, Scott D, et al. Extended Clearance Classification System (ECCS) informed approach for evaluating investigational drugs as substrates of drug transporters. Clin Pharmacol Ther. 2017;102(1):33-6.
World Health Organization (WHO). Recommended comparator products : Medicines for HIV/AIDS and related diseases 2018:1-7. (cited 1 October 2018). Available from: Available from: https://extranet.who.int/prequal/sites/default/files/documents/Comparator2018-HIV_14May_0.pdf
» https://extranet.who.int/prequal/sites/default/files/documents/Comparator2018-HIV_14May_0.pdf
World Health Organization (WHO). Promoting access, quality and innovation to save and improve lives 2016:15. (cited 5 April 2018). Available from: Available from: http://apps.who.int/iris/bitstream/10665/204469/1/WHO_EMP_2016.01_eng. pdf?ua=1
» http://apps.who.int/iris/bitstream/10665/204469/1/WHO_EMP_2016.01_eng. pdf?ua=1
Wu C-Y, Benet LZ. Predicting drug disposition via application of bcs: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res . 2005;22(1):11-23.
Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, et al. Biopharmaceutics classification system: the scientific basis for biowaiver extensions. Pharm Res . 2002;19(7):921-5.
Zervos M, Meunier F. Fluconazole (Diflucan®): a review. Int J Antimicrob Agents. 1993;3(3):147-70.
Zhang W, Li Y, Zou P, Wu M, Zhang Z, Zhang T. The Effects of pharmaceutical excipients on gastrointestinal tract metabolic enzymes and transporters-an update. AAPS J . 2016;18(4):830-43.
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