Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells

Almeida, Aline G. and Pinto, Rodrigo C. V. and Smales, C. Mark and Castilho, Leda R. (2017) Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells. Biotechnology Letters, 39 (8). pp. 1109-1120. ISSN 0141-5492. E-ISSN 1573-6776. (doi:https://doi.org/10.1007/s10529-017-2353-y) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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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 °C. 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 °C, though this was not the case with samples stored at 40 °C. 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.

Item Type: Article
Uncontrolled keywords: Excipients Formulation Freeze-drying Lyophilization Recombinant factor IX Stability study
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Mark Smales
Date Deposited: 11 May 2017 08:21 UTC
Last Modified: 16 Aug 2017 14:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61688 (The current URI for this page, for reference purposes)
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