Quality by Design in process development and scale-up for lyophilized parenteral products

In the last decade FDA invited pharmaceutical industry to modernize their manufacturing, applying the most recent Process Analytical Technologies and the Quality by Design paradigm. The final goal is the promotion of more efficient and cost-effective processes, building drug product quality within the process rather than testing it off-line at the end of the process (1). This article shows how this goal can be achieved in the case of freeze-drying of parenteral products. In particular, the problem of design and scale-up is shown for a real case in industry, i.e., the freeze-drying of an antiviral drug. Examples are given of cycles designed varying either freezing conditions or scale of equipment.