Scientific Approaches for the Application of QbD Principles in Lyophilization Process Development

Lyophilization (or freeze drying) is an important manufacturing capability for delivering high-quality parenteral drug products. Significant lyophilization process knowledge based on established scientific fundamentals and understanding of the good freeze drying practice principles exists within the pharmaceutical industry. This cumulative scientific knowledge should be leveraged across the portfolio of both small and large molecules and serves as the basis to gain process and product understanding. By using the scientific principles of lyophilization, good freeze drying practices and existing product knowledge, a risk-based approach to process development will facilitate focused efforts to increase product and process understanding to decrease those risks and identify which parameters are critical for product quality. Ultimately, this approach driven by scientific principles results in the development of a robust control strategy for a given product. The process whereby this occurs is based on principles of Quality by Design (QbD) as defined in ICH Q8 (R2) Pharmaceutical Development. This chapter brings together the technical knowledge of the lyophilization process, well-established scientific lyophilization principles and elements of QbD to provide guidance on approaches to develop a robust manufacturing process and support a regulatory filing strategy for drug products, while maximizing the freedom to operate. While it incorporates QbD elements that align with ICH Q8 (R2), Q9, Q10, and Q11, the goal is to define a knowledge space based on robust scientific evidence and principles. Having this knowledge and data will provide the basis to justify the control strategy and lyophilization process description in the dossier that presents the critical product quality attributes and a process control strategy that is defined by the critical process parameters to ensure consistent product quality.