Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/26401
Title: Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells
Authors: Almeida, Aline G.
Pinto, Rodrigo C. V.
Smales, C. Mark
Castilho, Leda R.
Affilliation: Universidade Federal do Rio de Janeiro. Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia. Programa de Engenharia Quimica. Laboratório de Engenharia de Cultivos Celulares. Rio de Janeiro, RJ, Brasil. / Universidade Federal do Rio de Janeiro. Programa de Bioquímica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.
University of Kent at Canterbury. Industrial Biotechnology Centre and School of Biosciences. Canterbury, NJ, United Kingdom.
Abstract: Objectives: To develop a recombinant human factor IX (rFIX) formulation equivalent to commercially available products in terms of cake appearance, residual moisture, proportion of soluble aggregates and activity maintenance for 3 months at 4–8 ºC. Results: NaCl and low bulking agent/cryoprotectant mass ratio had a negative impact on cake quality upon lyophilisation for a wide range of formulations tested. Particular devised formulations maintained rFIX activity after lyophilization with a similar performance when compared with the rFIX formulated using the excipients reported for a commercially available FIX formulation (Benefix). rFIX remained active after 3 months when stored at 4 ºC, though this was not the case with samples stored at 40 ºC. Interestingly, particular formulations had an increase in residual moisture after 3 months storage, but not above a 3% threshold. All four formulations tested were equivalent to the Benefix formulation in terms of particle size distribution and cake appearance. Conclusions: Three specific formulations, consisting of surfactant polysorbate-80, sucrose or trehalose as cryoprotectant, mannitol or glycine as bulking agent, L-histidine as buffering agent, and NaCl added in the reconstitution liquid at 0.234% (w/v) were suitable for use with a CHO cell-derived recombinant FIX.
Keywords: Excipients
Formulation
Freezedrying
Lyophilization
Recombinant factor IX
Stability study
keywords: Excipientes
Formulação
Congelamento
Liofilização
Fator IX recombinante
Estudo de estabilidade
DeCS: Excipientes
Composição de Medicamentos
Congelamento
Liofilização
Issue Date: 2017
Citation: ALMEIDA, A. G; PINTO, R. C. V.; SMALES, C. M.; CASTILHO, L. R. Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells. Biotechnology Letters, v. 39, n. 8, p. 1109-1120, aug. 2017.
ISSN: 0141-5492
Copyright: open access
Appears in Collections:Biomanguinhos - Artigos de Periódicos




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