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Table 2 Unique issues for large versus small molecules

From: Analytical approaches to ensure product quality -- AAPS Joint Face-to-Face Meeting of the Stability, the Pharmaceutical Impurities, and the CMC Statistics Focus Groups, April 6th, 2016 in Gaithersburg, MD

• Applicability of Arrhenius equation for large molecules
• Perceived need to start with first principles
• Variability for biologics may make it more difficult to precisely model
• Fundamental model selection for biologics
• Lack of trust of non-linear models
• Temperature and/or Humidity is too high thus modeling is not predictive.
• Physical changes/polymorph changes–modeling in solids
• Modeling is difficult for proteins in solution–reversible step vs irreversible steps
• Label condition for Biologic drug substances is -20C – > what is accelerated?
• Extrapolation can be risky