Project Grant R43TR003975

LABORATORY SCALE SYSTEM FOR CONTINUOUS PURIFICATION OF BIOPHARMACEUTICALS - PROJECT SUMMARY/ABSTRACT PAK BIOSOLUTIONS, INC. (PAK BIO) IS AN EARLY-STAGE COMPANY CREATING CONTINUOUS BIO-MANUFACTURING EQUIPMENT THAT SOLVES THE UNMET NEEDS OF PROCESS DEVELOPMENT SCIENTISTS AND MANUFACTURING PERSONNEL AIMING TO SHORTEN DRUG DEVELOPMENT TIMELINES AND MANUFACTURING COSTS. THERE ARE NO VENDOR SUPPLIED SYSTEMS THAT ENABLE A FULLY INTEGRATED CONTINUOUS PROCESS AT THE LABORATORY SCALE. WE ARE CURRENTLY FOCUSED ON THE DEVELOPMENT OF A LABORATORY SCALE VERSION OF OUR PILOT PAKTM PURIFICATION SYSTEM, THE FIRST COMMERCIAL FULLY CONTINUOUS SYSTEM ON THE MARKET THAT ENABLES UP TO 4 UNIT OPERATIONS TO BE RUN SIMULTANEOUSLY. THIS LABORATORY SCALE VERSION WILL ALLOW SCIENTISTS TO QUICKLY AND EFFICIENTLY DEVELOP A CONTINUOUS PROCESS USING A SINGLE SYSTEM CAPABLE OF RUNNING ALL UNIT OPERATIONS COMMONLY USED IN A BIO-MANUFACTURING PROCESS. BATCH MANUFACTURING IS THE INDUSTRY STANDARD AND HAS PROGRESSED LITTLE IN THE PAST FEW DECADES. THIS MANUFACTURING MODALITY REQUIRES CAPITAL-INTENSIVE STAINLESS-STEEL FACILITIES AND RESULTS IN LOW PRODUCTIVITY (DRUG/TIME/COST). AT BENCHTOP SCALE, SCIENTISTS MUST USE THE SAME BATCH TECHNIQUES WHICH SLOW DOWN PROCESS DEVELOPMENT TIME DUE TO THE SEGMENTED NATURE OF THIS MANUFACTURING STYLE. THESE STUDIES ARE NOT ONLY TIME INTENSIVE, BUT DO NOT ACCURATELY REFLECT THE COMPLEX PROCESS DYNAMICS FOUND IN A CONTINUOUS PROCESS. ADDITIONALLY, MANY CONTINUOUS UNIT OPERATIONS OPERATE IN A FUNDAMENTALLY DIFFERENT WAY THAN THEIR BATCH COUNTERPARTS (E.G., FLOW THROUGH VIRUS INACTIVATION AND SINGLE PASS DIAFILTRATION). THESE OPERATIONS REQUIRE A SCALED DOWN CONTINUOUS SYSTEM TO PROPERLY DEVELOP. OUR AIM THROUGH THIS FUNDING OPPORTUNITY IS TO DEVELOP A LABORATORY SCALE VERSION OF OUR EXISTING MANUFACTURING SCALE SYSTEM FOR USE IN CONTINUOUS PROCESS DEVELOPMENT. THE "MICRO PAK" SYSTEM WOULD PROVIDE PROCESS DEVELOPMENT SCIENTISTS WITH A UNIQUE TOOL TO DEVELOP A CONTINUOUS PROCESS WITH SCALED DOWN CONTINUOUS UNIT OPERATIONS. SCIENTISTS COULD CONFIDENTLY OPTIMIZE THE PROCESS AND QUICKLY SCALE UP TO MANUFACTURING SCALE WITH MINIMAL TO NO CHANGES IN THE PROCESSING MODALITY. TIME AND RESOURCES SAVED BY THE MICRO PAK WOULD TRANSLATE INTO CHEAPER $/GRAM MANUFACTURING COSTS AND INCREASE THE LIKELIHOOD OF SUCCESSFUL SCALE UP OF A CONTINUOUS PROCESS FROM DEVELOPMENT TO PRODUCTION. CONTINUOUS PROCESSING HAS BEEN OF INTEREST TO NEARLY ALL MAJOR BIOPHARMACEUTICAL ORGANIZATIONS. WITH A PROJECTED COST OF A MICRO PAK SYSTEM TO BE $325,000, WE ESTIMATE AN ANNUAL MARKET VALUE OF $91M/YEAR. TO SET US ON THE PATH TOWARDS COMMERCIALIZATION, WE PROPOSE TO FIRST DEVELOP A FUNCTIONAL PROTOTYPE CAPABLE OF RUNNING A CONTINUOUS PROCESS FROM INITIAL CAPTURE THROUGH FINAL DRUG SUBSTANCE ON A 1L CELL CULTURE/DAY SCALE. AFTER SUCCESSFUL COMPLETION OF THIS PHASE I FEASIBILITY STUDY PAK BIO WILL FURTHER OPTIMIZE AND VALIDATE THE SYSTEM. WE WILL THEN CONDUCT EXTENSIVE BETA TESTING THROUGH A SERIES OF DESIGN OF EXPERIMENTS STUDIES COMPARING CRITICAL QUALITY ATTRIBUTES OF SUBSTANCES PROCESSED WITH THE SMALL-SCALE SYSTEM COMPARED TO OUR PROCESS SCALE SYSTEM ON ALL UNIT OPERATIONS.