High concentration protein formulations (>100g/L) are challenging to develop. Product concentrations are dictated by commercial needs (efficacious dose, frequency of dose, delivery volume/method etc) and are often constrained by molecule properties, facility constraints, and operational performance. In the drug commercialization lifecycle, often the final drug product concentration needs to be determined 2-3 years before the commercial manufacturing process is developed. Therefore, it is important to have tools that allow for the visualization of the high concentration operating space from formulation development to manufacture. In this talk we present the relations between (1) critical molecule parameters such as viscosity, (2) facility constraints such as hold up volumes, minimum tank working volumes, and (3) operational  parameters such as pressure and flowrate limitations, non-ideal loop wash out on overall design space. We will use process optimization tools, such as the recovery efficiency diagram that allows for process optimization, visualization of operational limitations, and process behavior.  We present case studies, which highlight the use of the engineering diagrams, the viscosity �concentration relationship and Cwall/Cgel (zero flux condition in TFF systems) on maximizing achievable protein concentrations. The case studies will highlight the inherent trade �off between step yield and maximum product concentration.

Evaluation of TFF operating space to enable manufacture of high protein concentration

245th National Meeting (2013)

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