Project Grant R41TR004571

RAPID DEHYDRATION AND STABILIZATION OF BIOPHARMACEUTICAL FORMULATIONS AT ROOM TEMPERATURE - ABSTRACT INAEDIS PROPOSES TO DEVELOP A PLATFORM TECHNOLOGY FOR RAPID ROOM TEMPERATURE DEHYDRATION OF VACCINES AND BIOPHARMACEUTICAL FORMULATIONS USING ULTRA-FINE DROPLET AEROSOLS, ELIMINATING THE NEED FOR LOGISTICALLY CHALLENGING COLD CHAIN INFRASTRUCTURE. SOME 20% OF PHARMACEUTICALS AROUND $35B IN VALUE ARE ESTIMATED TO BE DAMAGED BY POOR TEMPERATURE CONTROL DURING TRANSPORT ALONE, AND THE CHALLENGES OF MAINTAINING COLD CHAIN DURING STORAGE AND HANDLING ONLY ADD TO WASTAGE AND REDUCED EFFICACY. ALARMINGLY, COLD CHAIN BREACH HAS BEEN IMPLICATED IN CASES OF VACCINE-PREVENTABLE DISEASE OR EVEN ADVERSE EVENTS FOLLOWING IMMUNIZATION. FOR EXAMPLE, ONE STUDY REPORTED ADVERSE EVENTS SUFFERED BY 7% OF PATIENTS ADMINISTERED WITH TEMPERATURE COMPROMISED VACCINES, 13% OF WHICH WERE CONSIDERED SERIOUS. FREEZE-DRYING OF BIOLOGICAL FORMULATIONS, WHICH IS TRADITIONAL IN THE PRODUCTION OF PHARMACEUTICALS, INTRODUCES TIME-CONSUMING (1-3 DAYS OF PROCESSING), POORLY SCALABLE, ENERGY INEFFICIENT, AND EXPENSIVE BATCH MANUFACTURING. ALTERNATIVE SPRAY DRYING METHODS HAVE BEEN EXPLORED, THOUGH THIS TECHNIQUE REMAINS INEFFICIENT (0.1-1 G OF INHALABLE PARTICULATE PRODUCT OUT OF 1 KG OF LIQUID FORMULATION), ENERGY INTENSE AND POSES RISK OF PRODUCT THERMAL DAMAGE DUE TO APPLIED HIGH DRYING TEMPERATURES (100-200 C). TO MITIGATE THE CONSEQUENCES OF POOR VACCINE ACCESS AND VACCINE FAILURE ON POPULATION IMMUNIZATION, THERE IS A CLEAR NEED FOR THERMAL STABILIZATION OF THE FORMULATIONS ENABLING ROBUST VACCINE TRANSPORT AND STORAGE SOLUTIONS. INAEDIS HAS DEVELOPED A METHOD OF RAPID ROOM TEMPERATURE AEROSOL DEHYDRATION (RTAD), A SCALABLE SYSTEM FOR CONTINUOUS DEHYDRATION OF LIQUID PHARMACEUTICAL AND BIOPHARMACEUTICAL FORMULATIONS THAT PROVIDES THERMAL STABILIZATION OF BIOLOGICAL DRUGS AND ELIMINATES THE NEED FOR A COLD SUPPLY CHAIN. INAEDIS'S PROCESS CAN GENERATE AEROSOLS WITH DROPLETS THAT ARE 100X SMALLER (0.2-10 MM) AND YIELD 100X MORE INHALABLE PARTICULATE PRODUCT (50- 300 G) FROM 1 KG OF LIQUID THAN EXISTING SPRAY DRYING TECHNOLOGIES, WITHOUT APPLYING HEAT FOR DRYING, WHICH MITIGATES THE RISK OF DAMAGE OF THERMOLABILE BIOLOGICALS AND PROVIDES A SIGNIFICANT REDUCTION IN ENERGY REQUIREMENTS. PRELIMINARY STUDIES CONDUCTED WITH A TOP 10 PHARMA COMPANY HAVE DEMONSTRATED SUPERIORITY OF THE SYSTEM OVER TRADITIONAL SPRAY DRYERS WITH RESPECT TO POWDER DISSOLUTION, PROTEIN AGGREGATION, PARTICLE SIZE AND SIZE UNIFORMITY, AND INHALABILITY OF BIOLOGIC FORMULATION. INTERNAL STUDIES HAVE ALSO EXHIBITED A 5-10X IMPROVEMENT IN BACTERIOPHAGE SURVIVAL RATE. FOR THIS PHASE I, INAEDIS SEEKS TO ESTABLISH THE EFFICACY, RELIABILITY, AND APPLICABILITY OF RTAD. SPECIFIC AIMS INCLUDE: 1) DEMONSTRATE PLATFORM CAPABILITIES OF THE LABORATORY-SCALE RTAD PROCESS FOR THREE MAJOR CLASSES OF BIOFORMULATIONS, 2) DEMONSTRATE POWDER PERFORMANCE AND SHELF-LIFE STABILITY OF PRODUCED DEHYDRATED FORMULATIONS, AND 3) IMPROVE YIELD AND SCALE UP PROCESSES TO ESTABLISH COMMERCIAL VIABILITY OF THE CURRENT LABORATORY SCALE, AND RAMP UP PRODUCTION CAPACITY TO A PILOT SCALE. THIS WILL POSITION INAEDIS FOR PHASE II, DURING WHICH THE PLATFORM WILL BE ADAPTED AND VALIDATED ON A BROADER SPECTRUM OF COMMERCIALLY RELEVANT BIOPHARMACEUTICALS AND FURTHER SCALED UP TO MEET THE NEEDS OF PILOT CUSTOMERS IN THE PHARMACEUTICAL INDUSTRY.