Live From AAPS Biotech

AAPS Biotech is holding its annual meeting this year in San Diego, CA, the city with arguably the best weather in the world.

Tuesday sessions opened with a symposium on the challenges associated with high concentration protein formulations. Dr Vinay Radhakrishnan of Pfizer began with an overview of high concentration protein formulation, showing that the concentrations required of monoclonal antibody therapies have increased from a few mgs/mL for the first approved therapies, to more than 100 mgs/mL for therapies now entering the field. The increase is driven sometimes by therapeutic necessity, and sometimes by the desire to simplify dosing. Whatever the reason, to produce such high concentration protein formulations requires overcoming problems of aggregation and viscosity. Dr. James Colandene of HGS presented a case study of high variability in a fill line caused by the high viscosity of the product and clogging of the fill needles if a pause occurred in the fill line. Some of the variability could be reduced by shortening fill lines, increasing the needle size, and ensuring that the bulk product had equilibrated to room temperature before filling. Dr Rahul Rajan of Amgen presented data on formulations designed to increase stability after freeze-thaw. His group had found that alanine was effective at reducing aggregation of high concentration protein solutions, but was less effective after several freeze-thaw cycles because the alanine crystallized during freezing. He presented data showing that the addition of PEG200 in addition to alanine eliminated the problem, and hypothesized that the PEG did not prevent crystallization of alanine during freezing, but stabilized the protein when alanine was unavailable. Rajan concluded by introducing a pilot plant facility being brought on line at Amgen, where process controls to effectively manage high concentration formulations could be designed, tested, and scaled up in advance of Phase III material production.
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