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Elements of Quality by Design in Development and Scale-Up of Freeze-Dried Parenterals
ABSTRACT:
A key concept in the Quality by Design paradigm is design space—a multidimensional space that encompasses combinations of product design and processing variables that provide assurance of suitable product performance. This article discusses design space in the context of developing, scaling up, and transferring freeze-dried products to a manufacturing setting. Smooth technology transfer starts with a robust formulation and an appropriate container and closure system. The design space is developed as an envelope in a graph of sublimation rate, shelf temperature, and chamber pressure. One boundary of the design space is established by failure of the formulation under aggressive cycle conditions. Other boundaries of the design space are determined by equipment performance, including refrigeration capacity, condenser capability, heating capacity, or limitations of the dynamics of water vapor flow within the system. Definition of this design space assures a thorough understanding of both the product and the process, and it minimizes the probability of unpleasant surprises in the technology transfer process.
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