Zak Yusoff, pharmaceutical freeze-drying applications manager at SP Scientific discusses why a quality by design (QbD) approach is key to achieving optimal lyophilisation of limited and expensive biopharmaceutical drugs.
Snowflakes
Historically, scale-up has been accomplished largely empirically, relying on multiple runs and prior experience. Although this approach can result in quicker regulatory approval, it also increases the risk of vial rejection within and between batches leading to increased costs. Difficulties also arise when scaling up the development and manufacturing process. As the demand for better yields and higher quality of biopharmaceuticals intensifies, optimising the lyophilisation process throughout the product’s life cycle plays an important role in providing a quality, successful biological product.
The US Food and Drugs Administration (FDA) strongly recommends a QbD approach to drug manufacturing, suggesting quality should not be inspected solely at the end of production but must be designed into the entire manufacturing process. Although implementation of this idea may appear a daunting task, and futile at the earlier stages of product development, controlled lyophilisation in the laboratory that can be transferred to full commercialisation will avoid the need for repeated optimisation of the lyophilisation conditions at each stage. As part of a QbD approach, Process Analytical Technology (PAT) tools can be used to improve the freeze-drying process by defining critical parameters and a range within which an acceptable product is obtained.