Identifying conditions that trigger denaturation or chemical modifications
- Identifying conditions that trigger protein degradation, including denaturation, aggregation, and chemical degradation
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The industry's general approaches in identifying the main stress conditions that lead to denaturation or chemical modifications, including pH, temperature, oxygen, mechanical stress, etc.
- What are the typical stress conditions?
- Is a DOE study typically executed to understand overlapping effects? Or is OFAT preferred?
- What are the current challenges in analytical methods?
- What are the formulation solutions?
- Any existing examples or knowledge during formulation development
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Bridge the knowledge on protein formation from low concentration formulation to high concentration formulation. At ≥100 mg/mL, protein–protein interactions and altered microenvironments can shift degradation pathways, complicating extrapolation from dilute stability data.
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What are the main differences in protein degradation under low concentration vs high concentration formulations?
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The challenge in understanding reversible unfolding and irreversible degradation
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The translation from accelerated studies or stressed studies to the degradation pathway and kinetics under target storage conditions.
