(513a) Integrated Model-Based Design and Scale-up for Peptide Chromatographic Purification

Chromatography is often an exclusive purification handle and needs to be well understood to articulate a quality control strategy. For peptide impurity rejections, the reverse-phase chromatography is the best option in comparison with other purification methods. Chromatography process modelling is well known in literature, and helps in accelerating the design, optimisation and scale-up. The objective here is to utilise “model-based approach integrated with experiments” methodology and applying it on a Lilly development asset with the objective of reduced experimentation and delivering an in-depth impurity control strategy. The methodology involves: (1) systematic experiments to determine peptide adsorption isotherm by inverse method (2) incorporating modifier effect into adsorption isotherm (3) characterisation of impurities by lumping them into pseudo-impurities (Journal of Chromatography A, 1284 (2013) 69– 79) (4) design of batch operating space using validated model (5) finally, optimising at scale with simulations for multi-column counter-current solvent gradient purification (MCSGP). The optimisation parameters selected for purification process are purity and productivity. This study helps in arriving at optimum operating space in an accelerated manner. The future work includes extending the methodology to other modalities such as oligomers and monoclonal antibodies as well as comparing various modes of continuous chromatography.