More than 15 years of continuous processing using chemostat cultures. A Shire niche?

The poster summarizes Shire´s almost unique approach using continuous chemostat cultures for routine commercial production of blood clotting factors. It describes the process, the technology and background on the reasons for applying this approach. In addition the poster covers obstacles and challenges Shire was facing over the last years using continuous culture including transfer and scale up. Finally it elaborates on the different control strategies, Chemostat (D=constant;μ=D) versus Turbidostat (Cell density is constant), and how Shire improved these microbial concepts for animal cells by inventing the concept of the Cell specific Dilution Rate: (DCell Density=constant)

Optimization of an Antibody Light Chain Framework Enhances Expression, Biophysical Properties and Pharmacokinetics

Efficacy, safety, and manufacturability of therapeutic antibodies are influenced by their biopharmaceutical and biophysical properties. These properties can be optimized by library approaches or rationale protein design. Here, we employed a protein engineering approach to modify the variable domain of the light chain (VL) framework of an oxidized macrophage migration inhibitory factor (oxMIF)-specific antibody. The amendment of the antibody sequence was based on homology to human germline VL genes. Three regions or positions were identified in the VL domain—L1-4, L66, L79—and mutated independently or in combination to match the closest germline V gene. None of the mutations altered oxMIF specificity or affinity, but some variants improved thermal stability, aggregation propensity, and resulted in up to five-fold higher expression. Importantly, the improved biopharmaceutical properties translated into a superior pharmacokinetic profile of the antibody. Thus, optimization of the V domain framework can ameliorate the biophysical qualities of a therapeutic antibody candidate, and as result its manufacturability, and also has the potential to improve pharmacokinetics