Integrating QbD Tools for Flexible Scale-Up Batch Size Selection for Solid Dosage Forms

Abstract

The pilot scale batch size for solid oral dosage forms is currently defined by major regulatory agencies as one-tenth of the full production, or 100,000 units, whichever is larger. The current criterion is arbitrary and is not based on scientific and risk assessment principles. The approach does not consider geometric, kinematic, and dynamic changes that come into play on scale-up. Even if this criterion is met, impact of scale-up on critical quality attributes cannot be ruled out and also reproducibility cannot be assured simply by restricting the scale-up size. In keeping with the vision for the 21st Century Good Manufacturing Practice initiative to build quality into the product, it is imperative that the selection of scale-up batch size be based on science and risk assessment principles and be part of the product development program. Scale-up should never be seen as an isolated activity. This article will review various tools that can be integrated with quality by design for flexible batch size selection during scale-up.