Optimisation of a freeze-drying process of high purity Factor VIII and Factor IX concentrates

Ronzi, Elena; Capolongo, Antonio; Rovero, Giorgio; Bucci, E; Mondini, Sara; Falbo, Anna

doi:10.1016/s0255-2701(02)00080-6

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Thus maintaining a low pressure and controlling the heat flux by the shelf temperature appears as a good policy (20,21). It should be noted, however, that in the considered pilot-scale freeze-dryer a significant fraction of the transferred heat (up to 50% at low shelf temperatures) comes from the chamber, mainly by radiation.…”

Section: Freeze-drying Cycle Optimisationmentioning

confidence: 99%

An Interactive Tool for the Optimization of Freeze-Drying Cycles Based on Quality Criteria

et al. 2007

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Section: Freeze-drying Cycle Optimisationmentioning

confidence: 99%

An Interactive Tool for the Optimization of Freeze-Drying Cycles Based on Quality Criteria

et al. 2007

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“…The protocol adapted from Tang and Pikal (2004) had an elegant cake appearance for Factor IX formulated in the Benefix® formulation, but not for Rixubis® formulation. The protocol adapted from Ronzi et al (2003) did not give a good cake appearance for either formulation, presenting a very fragile cake (Figure 1). The method adapted from…”

Section: Comparison Of Lyophilization Methodsmentioning

confidence: 99%

“…Two different lyophilization methods were compared, using the formulations of 5 commercial products Benefix® and Rixubis®: (i) a method adapted from Ronzi et al (2003), which was proposed for lyophilization of Factors FVIII and IX, and (ii) a method adapted from Tang and Pikal (2004), which was proposed for biopharmaceuticals in general. The freeze drying programs utilized in this study are described in Table 2 and Table 3.…”

Section: Comparison Of Lyophilization Methodsmentioning

confidence: 99%

“…For the Ronzi lyophilization method with the same starting material, approximately 73% and 80% of biological activity was recovered for the Benefix® and Rixubis® formulations, respectively. There was no significant difference in the activity between the two methods, however, even if the product is biologically active, a collapsed structure is not acceptable according to the quality standards of the industry (Ronzi et al, 2003). Therefore, based on the cake appearance further experiments were undertaken using the Tang and Pikal (2004) method and the proposed formulations were compared to the Benefix® formulation.…”

Section: Comparison Of Lyophilization Methodsmentioning

confidence: 99%

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

et al. 2017

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Objectives To develop a recombinant FIX (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 were able to maintain 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®). The stability study showed that 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 were found to show 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 a 0.234% (w/v) concentration appear suitable for use with a CHO cell derived recombinant FIX.

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Impact of residual moisture and formulation on Factor VIII and Factor V recovery in lyophilized plasma reference materials

2006

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Residual moisture content and formulation are important parameters when preparing lyophilized reference materials containing labile proteins. The protection of Factor VIII and Factor V activities were monitored in a lyophilized plasma preparation following formulation with either no additional excipient, 40 mM Hepes (4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid), 10 mg/mL glycine or a combination of 40 mM Hepes and 10 mg/mL glycine. The preservation of Factor VIII activity during freeze-drying was improved by the addition of either stabiliser and improved most, amongst the options studied, by the addition of both glycine and Hepes. The predicted stability at -20 degrees C and 20 degrees C was estimated using accelerated degradation studies. Although for plasma lyophilized alone there was some benefit from further desiccation over phosphorus pentoxide, resulting in very low moistures, for suitably formulated samples the predicted stability was as good for freeze-dried only samples as for those with further desiccation. This study emphasises the importance of optimum formulation on the stability of lyophilized proteins.

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Optimisation of a freeze-drying process of high purity Factor VIII and Factor IX concentrates

Cited by 5 publications

References 7 publications

An Interactive Tool for the Optimization of Freeze-Drying Cycles Based on Quality Criteria

An Interactive Tool for the Optimization of Freeze-Drying Cycles Based on Quality Criteria

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

Impact of residual moisture and formulation on Factor VIII and Factor V recovery in lyophilized plasma reference materials

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