: Determining Critical Quality Attributes (CQAs) —such as glycosylation, aggregation, and host cell protein (HCP) levels—that must be controlled to ensure drug performance.
Once the CQAs are identified, the next step is to develop a deep mechanistic understanding of how manufacturing process parameters affect these CQAs. This involves systematic experimentation, often using Design of Experiments (DoE) methodologies, to map the relationship between inputs (e.g., bioreactor pH, temperature, mixing speed) and outputs (e.g., cell growth, titer, glycosylation profile). A Mab A Case Study In Bioprocess Development
The goal of upstream development is to create a robust cell culture process that maximizes yield (titer) while maintaining CQAs. : Determining Critical Quality Attributes (CQAs) —such as
To see the proposed in the study. a-mab-case-study-version.pdf - ISPE The goal of upstream development is to create
Protein A affinity chromatography served as the primary capture step due to its high selectivity for the Fc region of IgG1.
A robust CMC strategy is not a final step but a thread woven through all stages of development. An early focus on CMC helps maintain the vital link in quality between the drug used in clinical trials and the final marketed product. This involves generating comprehensive data on the manufacturing process, confirming its consistency through process performance qualification (PPQ) runs, and establishing a system of continued process verification after commercialization to ensure the process remains under control.