DESIGN SPACE DEVELOPMENT: A CASE STUDY
Thermal Characterization and Initial Lyophilization Development
Table 1. Initial/target lyophilization cycle for monoclonal antibody X
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The MAb discussed in this case study was formulated in a solution containing a buffer, a sugar lyoprotectant, and a surfactant.
To understand the thermal characteristics of this formulation, we performed freeze-drying microscopy experiments.6 The collapse temperature was determined to be –14 °C (Figure 3), suggesting that product temperature during primary drying
must be maintained well below –14 °C.
Figure 4. Process inputs and outputs for lyophilization design space development
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During the early process development phase for this molecule, an initial lyophilization cycle (Table 1) was implemented based
on prior lyophilization experience with similar products and literature knowledge.7–9 Briefly, the approach consisted of experiments to accomplish primary drying in a reasonable duration while maintaining product
temperature well below the collapse temperature.
Risk Assessments for the Lyophilization Unit Operation
Figure 5. Risk ranking and filtering tool (CQA = critical quality attribute)
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The process inputs and outputs for lyophilization generally are well known and are shown in Figure 4.7–9 To identify the parameters that must be characterized, we used the risk ranking tool depicted in Figure 5.10 The main and interaction effect scores for each parameter were assigned based on a mechanistic understanding of the lyophilization
process and experience with products and equipment. The overall severity score was then used to decide the nature of characterization
for the parameter.
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