Cryoconcentration and 3D Temperature Profiles During Freezing of mAb Solutions in Large-Scale PET Bottles and a Novel Scale-Down Device

Bluemel, Oliver; Buecheler, Jakob W.; Rodrigues, Miguel A.; Hoelzl, Georg; Bechtold-Peters, Karoline; Frieß, Wolfgang

doi:10.1007/s11095-020-02886-w

Cited by 11 publications

(30 citation statements)

References 21 publications

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“…SmartFreeZ (Porto Salvo, Portugal) provided the SDDs used in this study. A detailed description of the development assisted by CFD can be found elsewhere [ 26 ]. The specific SDD was designed to predict thawing in a rectangular 2 L PharmaTainer™ bottle.…”

Section: Methodsmentioning

confidence: 99%

“…The temperature measurements were performed as previously described [ 26 ]. Briefly, five type T thermocouples (TCs) connected to an HH520 handheld data logger thermometer (OMEGA Engineering GmbH, Deckenpfronn, Germany) were positioned at half liquid height in the edges and the centre of the 125 mL bottle using stainless steel capillaries (Acufirm Ernst Kratz GmbH, Berlin, Germany) for reproducible placement (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we characterised the performance of this innovative SDD during freezing, revealing a good agreement between the SDD and large-scale 2 L bottles [ 26 ]. It still needs to be evaluated whether this SDD also reflects thawing at large-scale.…”

Section: Introductionmentioning

confidence: 97%

“…While our previous study focused on the validation of the SDD during freezing [ 26 ], this study aims to validate the SDD in respect of thawing. Therefore, we compared temperature profiles at several locations in the SDD to a 125 mL and a 2 L bottle.…”

Section: Introductionmentioning

confidence: 99%

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Scaling Down Large-Scale Thawing of Monoclonal Antibody Solutions: 3D Temperature Profiles, Changes in Concentration, and Density Gradients

Bluemel

Buecheler

Hauptmann³

et al. 2021

Pharm Res

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Purpose Scale-down devices (SDD) are designed to simulate large-scale thawing of protein drug substance, but require only a fraction of the material. To evaluate the performance of a new SDD that aims to predict thawing in large-scale 2 L bottles, we characterised 3D temperature profiles and changes in concentration and density in comparison to 125 mL and 2 L bottles. Differences in diffusion between a monoclonal antibody (mAb) and histidine buffer after thawing were examined. Methods Temperature profiles at six distinct positions were recorded with type T thermocouples. Size-exclusion chromatography allowed quantification of mAb and histidine. Polysorbate 80 was quantified using a fluorescent dye assay. In addition, the solution’s density at different locations in bottles and the SDD was identified. Results The temperature profiles in the SDD and the large-scale 2 L bottle during thawing were similar. Significant concentration gradients were detected in the 2 L bottle leading to marked density gradients. The SDD slightly overestimated the dilution in the top region and the maximum concentrations at the bottom. Fast diffusion resulted in rapid equilibration of histidine. Conclusion The innovative SDD allows a realistic characterisation and helps to understand thawing processes of mAb solutions in large-scale 2 L bottles. Only a fraction of material is needed to gain insights into the thawing behaviour that is associated with several possible detrimental limitations.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Scaling Down Large-Scale Thawing of Monoclonal Antibody Solutions: 3D Temperature Profiles, Changes in Concentration, and Density Gradients

Bluemel

Buecheler

Hauptmann³

et al. 2021

Pharm Res

Self Cite

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“…Developing reliable downscale models for cost-effective simulation of this process has been elusive over the years due to technical challenges. In their publication, Bluemel et al describe an ingenious scale down device (SDD) that succeeded in simulating the temperature profile and cryo-concentration behavior of protein solutions in a 2 L bottle using a 125 mL bottle only (both at 80% fill volume) (17). The device greatly improves the capabilities of the process development scientist in generating reliable data while saving a lot on material needs.…”

mentioning

confidence: 99%