Semba Biosciences Inc — Department of Health and Human Services SBIR Phase II: 102

Description

DESCRIPTION provided by applicant Monoclonal antibodies mAbs have become the leading drug class for cancer treatment and over anti neoplastic mAbs are in the biopharmaceutical pipeline Most mAb therapies must be administered in doses of mg kg resulting in per patient costs of up to $ per year The high price of mAb therapy causes a significant financial burden for patients insurance companies and the health care system To be come practical for the health care industry the cost of developing and producing these drugs must be reduced Clinical manufacturing expenses directly contribute to the overall drug development costs Recent developments in protein expression cell culture and bioreactor technologies have led to substantial advancements in protein production and mAb titers The development of downstream purification processes has not kept pace and represents a bottleneck that impedes cost effective and robust manufacturing Currently downstream processing DSP accounts for up to of the total mAb production cost The andquot industry standardandquot Protein A capture PAC is the most expensive DSP step contributing up to of the total cost per gram of product The current PAC method still uses one large column in a sequential batch process Continuous SMB simulated moving bed chromatography offers significant advantages over standard batch methods including more efficient use of expensive adsorbent with smaller columns reduced buffer consumption and operation under steady state conditions allowing more robust process analytics In the Phase I SBIR project R CA we investigated the feasibility of developing a continuous PAC process for the purification of clinical grade mAbs using our lab scale Octave tm SMB System We obtained equivalent or better mAb purity when our continuous process was directly compared with the standard batch process How ever the current Octave System is not designed for cGMP compliance or the scale required for clinical manufacture In Phase II we propose to develop a large scale continuous chromatography device for economical purification of clinical grade antibodies based on the Octave valve design and our Phase I findings The Phase II device will support flow rates up to L min and processing of L culture fluid containing g L mAb in hours which matches the future demand for therapeutic mAbs in the range of kg yr The Phase II de vice and optimized PAC process will increase productivity at least fold relative to batch methods and will feature a single use flow path to eliminate the need for sanitation and revalidation between campaigns This Phase II project will develop at least one prototype device that will be placed at a Beta test site The device will be a customizable plug and play chromatography module compatible with future integrated continuous bioprocessing facilities This project fits with the FDA strategic plan which seeks development of improved product manufacturing technologies including continuous processes rather than batch approaches PUBLIC HEALTH RELEVANCE Recent developments in protein expression cell culture and bioreactor technologies have led to substantial improvements in protein production and increased antibody mAb titers The development of downstream purification processes has not kept pace and represents a bottleneck that impedes cost effective and robust manufacturing Currently downstream processing accounts for a significant percentage of the total mAb production cost Improvements in manufacturing technologies which increase capacity and productivity are highly desired for speeding up progress through clinical trials The device developed under this proposal will dramatically improve productivity and reduce cost of the most expensive purification step by up to Incorporation of this device into manufacturing processes will ultimately improve patient access to new anti cancer mAb therapies at lower cost