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Characterization of the Physical Stability of a Lyophilized IgG1 mAb After Accelerated Shipping-like Stress
Telikepalli, Srivalli Kumru, Ozan S. Kim, Jae Hyun Joshi, Sangeeta B. O'Berry, Kristin B. Blake-Haskins, Angela W. Perkins, Melissa D. Middaugh, C. Russell Volkin, David B.
Telikepalli, Srivalli
Kumru, Ozan S.
Kim, Jae Hyun
Joshi, Sangeeta B.
O'Berry, Kristin B.
Blake-Haskins, Angela W.
Perkins, Melissa D.
Middaugh, C. Russell
Volkin, David B.
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Abstract
Upon exposure to shaking stress, an IgG1 mAb formulation in both liquid and lyophilized state formed subvisible particles. Since freeze-drying is expected to minimize protein physical instability under these conditions, the extent and nature of aggregate formation in the lyophilized preparation was examined using a variety of particle characterization techniques. The effect of formulation variables such as residual moisture content, reconstitution rate, and reconstitution medium were examined. Upon reconstitution of shake-stressed lyophilized mAb, differences in protein particle size and number were observed by Microflow Digital Imaging (MFI), with the reconstitution medium having the largest impact. Shake-stress had minor effects on the structure of protein within the particles as shown by SDS-PAGE and FTIR analysis. The lyophilized mAb was shake-stressed to different extents and stored for 3 months at different temperatures. Both extent of cake collapse and storage temperature affected the physical stability of the shake-stressed lyophilized mAb upon subsequent storage. These findings demonstrate that physical degradation upon shaking of a lyophilized IgG1 mAb formulation includes not only cake breakage, but also results in an increase in subvisible particles and turbidity upon reconstitution. The shaking-induced cake breakage of the lyophilized IgG1 mAb formulation also resulted in decreased physical stability upon storage.
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Date
2015-02
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Publisher
Elsevier
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Keywords
Proteins, Protein aggregation, Particles, Monoclonal antibody, IgG, Stability, Particle size, Freeze drying/lyophilizaton
Citation
Telikepalli, S., Kumru, O. S., Kim, J. H., Joshi, S. B., O’Berry, K. B., Blake-Haskins, A. W., … Volkin, D. B. (2015). Characterization of the Physical Stability of a Lyophilized IgG1 mAb After Accelerated Shipping-like Stress. Journal of Pharmaceutical Sciences, 104(2), 495–507. http://doi.org/10.1002/jps.24242