Research Project
9046702
? DESCRIPTION (provided by applicant): Rising rates of chronic conditions such as cancer and cardiovascular and rheumatoid diseases are driving the demand for biologics used to treat them. Half of the top 100 drugs in the US will be biologics by 2016, and new product commercialization will require significant expansions in production capacity and improvements in manufacturing flexibility to meet future demands. In addition, the emergence of biosimilar will apply economic pressure on bio manufacturers to innovate new purification technologies to lower production costs. Purilogics(tm), LLC long-term objective is to develop and bring to market new purification technologies to increase production capacity and manufacturing flexibility and simultaneously lower the manufacturing cost of biologic drugs. In Phase I, Purilogics proposes to develop a new class of adsorptive membranes for use in biopharmaceutical downstream processing. The products of the effort will be two types' multimodal anion- exchange membranes for polishing step purification of biologics. These membranes will be differentiated from existing products because of their unique advantages of industry-best dynamic binding capacities, high productivity, excellent salt tolerance, and high selectivity for aggregates removal. The single-use products emanating from the project will simplify the current process by obviating the need for desalting and aggregate removal steps, column packing, regeneration and validation. The disposable and modular features will enable (contract) bio manufacturers to adjust purification capacity without significant capital expenditures. In Phase I, Purilogics proposes to develop prototype adsorptive membrane modules and validate their performance in-house and externally through collaboration with CharlestonPharma, LLC. The specific aims are to (1) synthesize and characterize multimodal anion-exchange membrane adsorbers with unique ligands and (2) fabricate and evaluate prototype single-use adsorptive membrane modules for validation. The membranes will be synthesized by functionalizing macroporous membrane supports with a high density of multimodal polymer chains. Benchmark testing will evaluate key performance metrics: static and dynamic binding capacities and log reduction values of impurities (host cell proteins, DNA) over a commercially relevant range of ionic strengths. External validation by CharlestonPharma will determine recovery, purity, and activity of cancer antibody products produced by their patented antibody platform technology. Removal of antibody aggregates, host cell proteins, endotoxins, and DNA impurities will be determined. The innovative products that result from this research effort will help biopharmaceutical manufacturers and contract bio manufacturers overcome significant unmet needs by increasing production capacity and manufacturing flexibility, while decreasing purification cost by >40% relative to existing technologies. The impact from a public health perspective is great, as increasing production capacity and decreasing manufacturing cost are essential to the production of affordable therapeutic products for improved public health.
