Characterization of murine monoclonal antibody to tumor necrosis factor (TNF-MAb) formulation for freeze-drying cycle development

Purpose. This study was designed to characterize the formulation of protein pharmaceuticals for freeze-drying cycle development. Thermal properties of a protein formulation in a freezing temperature range are important in the development of freezing and primary drying phases. Moisture sorption prope rties and the relationship between moisture and stability are the bases for the design of the secondary drying phase. Methods. We have characterized the formulation of TNF-MAb for the purpose o f freeze-drying cycle development. The methods include: DTA. with ER probes , freeze-drying microscopy, isothermal water adsorption, and moisture optim ization. Results. The DTA/ER work demonstrated the tendency to "noneutectic" freezin g for the TNF-MAb formulation at cooling rates of -1 to -3 degreesC/min. Th e probability of glycine crystallization during freezing was quite low. A s pecial treatment, either a high subzero temperature holding or annealing co uld promote the maximum crystallization of glycine, which could dramaticall y increase the T-g' of the remaining solution. The freeze-drying microscopy further indicated that, after the product was annealed, the cake structure was fully maintained at a T-p below -25 degreesC during primary drying. Th e moisture optimization study demonstrated that a drier TNF-MAb product had better stability. Conclusions. An annealing treatment should be implemented in the freezing p hase in order for TNF-MAb to be dried at a higher product temperature durin g primary drying. A secondary drying phase at an elevated temperature was n ecessary in order to achieve optimum moisture content in the final product.