Systematic Investigation of the Effect of Lyophilizate Collapse on Pharmaceutically Relevant Proteins, Part 2: Stability During Storage at Elevated Temperatures

Characterization of the Physical Stability of a Lyophilized IgG1 mAb after Accelerated Shipping-Like Stress

“…Solution turbidity and subvisible particle concentration increased with increasing storage ( T = 0 < T = 1 month < T = 3 months), especially for the samples stored at 40°C and 55°C. Similar to Schersch et al, we also noticed a color change during storage of the lyophilized protein at higher temperatures in this formulation, which Schersch et al reasonably attributed to the well‐known non‐enzymatic browning (Malliard‐type) reaction between reducing end sugars (potentially due to degraded sucrose) and lysine residues in the protein. The turbidity levels and subvisible particle concentrations are highest for the 24 h shaken samples compared with the intact and 2.5 min shaken samples (Intact ∼ 2.5 min shaking < 24 h shaking).…”

“…However, a bell‐shaped relationship between moisture content and physical stability (aggregation) has also been observed, for example, lyophilized recombinant human albumin displayed maximum aggregation at ∼50% moisture content . In terms of the effect of the physical integrity of a freeze‐dried cake on protein stability, it has been shown that when a lyophilized cake of an IgG1 mAb is physically collapsed to different extents by using different amounts of stabilizers and bulking agents during the freeze‐drying process, the mAb can still remain stable in the different preparations . The method of cake collapse, however, either during the freeze‐drying cycle or during storage at elevated temperatures, has been shown to potentially be an important factor in determining protein stability during subsequent storage …”

Assessment of Crystallinity in Processed Sucrose by Near‐Infrared Spectroscopy and Application to Lyophiles

“…However, once the initial NIR calibration is conducted on a calibration set using processed material, NIR can then be applied to rapidly and nondestructively measure crystallinity and could potentially be used on‐line within lyophilization equipment . The findings presented here demonstrate a valuable additional methodology for applying NIR to crystallinity determination of lyophiles that is significant because of the increased importance of monitoring‐controlled crystallization to augment stability in lyophiles and the critical role the solid‐state behavior of excipients plays in the stabilization of lyophilized biopharmaceuticals …”

Stability of collapse lyophilized influenza vaccine formulations

“…Collapse lyophilization is characterized by freeze-drying above the glass transition temperature (T g 0 ). Higher temperatures are exerted on the product while the time period which is necessary to dry the vaccine is shortened distinctively compared to conventional lyophilization (Schersch et al, 2012). Not only can the primary drying time be drastically shortened but also can a relaxation of the amorphous sugar matrix be achieved by exposure to the higher temperature in the end phase of the drying cycle.…”