Spray-dried human plasma

Abstract

The technology relates to spray dried plasma and methods of making the same. The method includes providing plasma to a spray drying apparatus, spray drying the plasma, at the spray drying apparatus, to form physiologically active plasma powder, the spray drying apparatus configured utilizing one or more parameters, and storing the physiologically active plasma powder.

1 . A method for spray drying plasma, the method comprising:
 providing plasma to a spray drying apparatus;   spray drying the plasma, at the spray drying apparatus, to form physiologically active plasma powder; and   storing the physiologically active plasma powder.   
     
     
         2 . The method of  claim 1 , comprising, during the providing, spray drying, and storing steps, maintaining the plasma and plasma powder in an isolated sterile environment. 
     
     
         3 . The method of  claim 1 , comprising processing plasma in a closed sterile process to produce physiologically active plasma powder suitable for reconstitution and transfusion to a human subject. 
     
     
         4 . The method of  claim 1 , further comprising, during the spray drying, maintaining the plasma at a temperature below a threshold temperature to prevent denaturing of proteins in the plasma. 
     
     
         5 . The method of  claim 4 , wherein the threshold temperature is 44° C. or less. 
     
     
         6 . The method of  claim 4 , wherein the threshold temperature is 48° C. or less. 
     
     
         7 . The method of  claim 4 , further comprising, during the spray drying, maintaining the plasma at a temperature within a selected temperature range 
     
     
         8 . The method of  claim 7 , comprising, during the spray drying, maintaining the plasma at a temperature within a selected temperature range of 41-43° C. 
     
     
         9 . The method of  claim 7 , comprising, during the spray drying, maintaining the plasma at a temperature within a selected temperature range of 37-48° C. 
     
     
         10 . The method of  claim 2 , wherein spray drying the plasma comprises:
 directing plasma to a spray nozzle at a plasma flow rate;   directing a heated drying gas to a drying chamber at an inlet temperature and a drying gas flow rate;   directing a non reactive spray gas to the nozzle at a spray gas flow rate;   combining the plasma and spray gas at the nozzle to atomize the plasma; and   combining the atomized plasma and drying gas to dry the atomized plasma.   
     
     
         11 . The method of  claim 10 , wherein the inlet temperature is in the range of 85-120° C. 
     
     
         12 . The method of  claim 10 , wherein the inlet temperature is in the range of 92-117° C. 
     
     
         13 . The method of  claim 10 , wherein the plasma flow rate is in the range of 2-20 mL/minute, the drying gas flow rate is in the range of 20-80 m 3 /hour, and the spray gas flow rate is in the range of 300-500 L/hr. 
     
     
         14 . The method of  claim 10 , wherein the plasma flow rate is in the range of 8-12 mL/minute, the drying gas flow rate is in the range of 30-40 m 3 /hour, and the spray gas flow rate is in the range of 350-450 L/hr. 
     
     
         15 . The method of  claim 10 , further comprising:
 determining an outlet temperature of the plasma powder; and   adjusting at least one of: the plasma flow rate, the inlet temperature, the spray gas flow rate, and the drying gas flow rate based on the outlet temperature.   
     
     
         16 . The method of  claim 1 , further comprising reconstituting the physiologically active plasma powder utilizing a reconstitution fluid to form physiologically active reconstituted plasma. 
     
     
         17 . The method of  claim 16 , further comprising applying the physiologically active reconstituted plasma to a human. 
     
     
         18 . The method of  claim 16 , wherein the reconstitution fluid comprises at least one selected from the list consisting of: distilled water, saline solution, and glycine. 
     
     
         19 . The method of  claim 18 , wherein the reconstitution fluid is a buffered solution. 
     
     
         20 . The method of  claim 1 , wherein the powder, when reconstituted, exhibits physiological activity substantially equivalent to Thawed Plasma. 
     
     
         21 . The method of  claim 1 , wherein the powder, when reconstituted, exhibits physiological activity substantially equivalent to FP24. 
     
     
         22 . The method of  claim 1 , wherein the powder, when reconstituted, exhibits physiological activity substantially equivalent to FFP. 
     
     
         23 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by an aPTT of about 65 seconds or less, a PT of about 31 seconds or less, and a Fibrinogen level of at least about 100 mg/dL. 
     
     
         24 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by an aPTT of about 35 seconds or less, a PT of about 15 seconds or less, and a Fibrinogen level of at least about 223 mg/dL. 
     
     
         25 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by an aPTT in the range of 28-66 seconds, a PT in the range of 14-31 seconds, and a Fibrinogen level in the range of 100-300 mg/dL. 
     
     
         26 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by an aPTT in the range of 30-35 seconds, a PT in the range of 10-15 seconds, and a Fibrinogen level in the range of 223-500 mg/dL. 
     
     
         27 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 10 IU/dL, a Factor IX level of at least about 10 IU/dL, a Protein C level of at least about 10 IU/dL, and a Protein S level of at least about 10 IU/dL. 
     
     
         28 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 30 IU/dL, a Factor IX level of at least about 25 IU/dL, a Protein C level of at least about 55 IU/dL, and a Protein S level of at least about 54 IU/dL 
     
     
         29 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 54 IU/dL, a Factor IX level of at least about 70 IU/dL, a Protein C level of at least about 74 IU/dL, and a Protein S level of at least about 61 IU/dL. 
     
     
         30 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level in the range of 30-110 IU/dL, a Factor IX level in the range of 25-135 IU/dL, a Protein C level in the range of 55-130 IU/dL, and a Protein S level of in the range of 55-110 IU/dL. 
     
     
         31 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level in the range of 34-172 IU/dL, a Factor IX level in the range of 70-141 IU/dL, a Protein C level in the range of 74-154 IU/dL, and a Protein S level of in the range of 61-138 IU/dL. 
     
     
         32 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 10 IU/dL, and a Factor VIII level of at least about 10 IU/dL. 
     
     
         33 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 30 IU/dL, and a Factor VIII level of at least about 25 IU/dL. 
     
     
         34 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 63 IU/dL, and a Factor VIII level of at least about 47 IU/dL. 
     
     
         35 . The method of  claim 1 , wherein the dried plasma, when reconstituted, is characterized by at least one of a Factor V level in the range of 63-135 IU/dL, a Factor VIII level in the range of 47-195 IU/dL. 
     
     
         36 . The method of  claim 1 , wherein the powder has an average particle size of about 30 microns or less. 
     
     
         37 . The method of  claim 1 , wherein the powder has a maximum particle size of about 100 microns or less. 
     
     
         38 . The method of  claim 1 , wherein the powder comprises at least 30% dried protein by weight. 
     
     
         39 . The method of  claim 1 , wherein, when reconstituted with 1 mL of fluid per 0.09 grams of powder, the reconstituted plasma has a protein concentration in the range of 35 mg/mL to 60 mg/mL. 
     
     
         40 . A product comprising:
 a physiologically active dried plasma in the form of a powder.   
     
     
         41 . The product of  claim 40 , wherein the physiologically active dried plasma is sterile. 
     
     
         42 . The product of  claim 41 , wherein the dried plasma, when reconstituted, exhibits physiological activity substantially equivalent to Thawed Plasma. 
     
     
         43 . The product of  claim 41 , wherein the dried plasma, when reconstituted, exhibits physiological activity substantially equivalent to FP24. 
     
     
         44 . The product of  claim 41 , wherein the dried plasma, when reconstituted, exhibits physiological activity substantially equivalent to FFP. 
     
     
         45 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by an aPTT of about 65 seconds or less, a PT of about 31 seconds or less, and a Fibrinogen level of at least about 100 mg/dL. 
     
     
         46 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by an aPTT of about 35 seconds or less, a PT of about 15 seconds or less, and a Fibrinogen level of at least about 223 mg/dL. 
     
     
         47 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by an aPTT in the range of 28-66 seconds, a PT in the range of 14-31 seconds, and a Fibrinogen level in the range of 100-300 mg/dL. 
     
     
         48 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by an aPTT in the range of 30-35 seconds, a PT in the range of 10-15 seconds, and a Fibrinogen level in the range of 223-500 mg/dL. 
     
     
         49 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 10 IU/dL, a Factor IX level of at least about 10 IU/dL, a Protein C level of at least about 10 IU/dL, and a Protein S level of at least about 10 IU/dL. 
     
     
         50 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 30 IU/dL, a Factor IX level of at least about 25 IU/dL, a Protein C level of at least about 55 IU/dL, and a Protein S level of at least about 54 IU/dL. 
     
     
         51 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level of at least about 54 IU/dL, a Factor IX level of at least about 70 IU/dL, a Protein C level of at least about 74 IU/dL, and a Protein S level of at least about 61 IU/dL. 
     
     
         52 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level in the range of 30-110 IU/dL, a Factor IX level in the range of 25-135 IU/dL, a Protein C level in the range of 55-130 IU/dL, and a Protein S level of in the range of 55-110 IU/dL. 
     
     
         53 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor VII level in the range of 34-172 IU/dL, a Factor IX level in the range of 70-141 IU/dL, a Protein C level in the range of 74-154 IU/dL, and a Protein S level of in the range of 61-138 IU/dL. 
     
     
         54 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 10 IU/dL, and a Factor VIII level of at least about 10 IU/dL. 
     
     
         55 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 30 IU/dL, and a Factor VIII level of at least about 25 IU/dL. 
     
     
         56 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of: a Factor V level of at least about 63 IU/dL, and a Factor VIII level of at least about 47 IU/dL. 
     
     
         57 . The product of  claim 41 , wherein the dried plasma, when reconstituted, is characterized by at least one of a Factor V level in the range of 63-135 IU/dL, a Factor VIII level in the range of 47-195 IU/dL. 
     
     
         58 . The product of  claim 41 , wherein the powder has an average particle size of about 30 microns or less. 
     
     
         59 . The product of  claim 41 , wherein the powder has a maximum particle size of about 100 microns or less. 
     
     
         60 . The product of  claim 41 , wherein the powder comprises at least 30% dried protein by weight. 
     
     
         61 . The product of  claim 41 , wherein, when reconstituted with 1 mL of fluid per 0.09 grams of powder, the reconstituted plasma has a protein concentration in the range of 35 mg/mL to 60 mg/mL. 
     
     
         62 . An apparatus for spray drying plasma comprising:
 a plasma source;   a pressurized spray gas source;   a drying gas source;   a spray dry nozzle in sterile fluid communication with the plasma and spray gas sources;   a drying chamber in sterile fluid communication with the spray dry nozzle and the drying gas source to receive a spray of plasma from the nozzle for drying;   a particle collection device configured to collect spray dried plasma from an outlet of the drying chamber; and   a collection device gas outlet port in fluid communication with the collection device, the gas outlet port comprising a sterile outlet port;
 wherein the spray nozzle, drying chamber, and collection device define a sterile isolated interior volume. 
   
     
     
         63 . The apparatus of  claim 62 , wherein the gas outlet port comprises a sterile filter. 
     
     
         64 . The apparatus of  claim 62 , wherein the nozzle is in sterile fluid communication with each of the spray gas source and the drying gas source through a respective sterile filter. 
     
     
         65 . The apparatus of  claim 62 , wherein the gas outlet port is in fluid communication with an external volume through the sterile outlet filter. 
     
     
         66 . The apparatus of  claim 62 , wherein the gas outlet port is in fluid communication with the drying gas source to provide closed recirculation of the drying gas. 
     
     
         67 . The apparatus of  claim 62 , wherein the plasma source comprises a peristaltic pump configured to deliver a flow of plasma to an inlet of the nozzle at a plasma flow rate. 
     
     
         68 . The apparatus of  claim 67 , wherein the spray gas source comprises a source of pressurized non reactive gas, and is configured to deliver the non reactive gas to the nozzle at a spray gas flow rate. 
     
     
         69 . The apparatus of  claim 68 , wherein the drying gas source comprises a source of drying gas, and is configured to deliver heated drying gas to the nozzle at a drying gas flow rate and an inlet temperature. 
     
     
         70 . The apparatus of  claim 69 , further comprising a controller configured to control at least one selected from the list consisting of: the plasma flow rate, the spray gas flow rate, the drying gas flow rate, and the inlet temperature. 
     
     
         71 . The apparatus of  claim 69 , further comprising at least one sensor for measuring outlet temperature information indicative of an outlet temperature the spray dried plasma, the sensor in communication with the controller; and
 wherein the controller comprises a servo loop that controls the outlet temperature to a selected value by adjusting, based on the outlet temperature information, at least one selected from the list consisting of: the plasma flow rate, the spray gas flow rate, the drying gas flow rate, and the inlet temperature.   
     
     
         72 . The apparatus of  claim 68 , wherein the controller comprises a servo loop that controls the outlet temperature to a selected value by adjusting, based on the outlet temperature information, the plasma flow rate. 
     
     
         73 . An attachment for a plasma spray drying apparatus comprising:
 a plasma inlet port for sterile attachment to a plasma source;   a spray gas inlet port for removable sterile attachment to a pressurized gas source;   at least one drying gas inlet port for removable sterile attachment to a drying gas source;   a spray dry nozzle in fluid communication with the plasma and spray gas inlets;   a drying chamber in fluid communication with the attached spray nozzle and drying gas inlet to receive a spray of plasma for drying;   a particle collection device configured to collect spray dried plasma from an outlet of the drying chamber; and   a collection device gas outlet port in sterile fluid communication with the collection device;   wherein the spray nozzle, drying chamber, and collection device define a sterile isolated interior volume.   
     
     
         74 . The attachment of  claim 73 , wherein at least one of the inlet and outlet ports comprises a sterile filter. 
     
     
         75 . The attachment of  claim 73 , wherein the drying chamber is at least partially collapsible. 
     
     
         76 . The attachment of  claim 73 , wherein the attachment comprises a plastic or polymer material. 
     
     
         77 . The attachment of  claim 73 , wherein the particle collection device comprises a cyclone chamber. 
     
     
         78 . The attachment of  claim 73 , wherein the particle collection device comprises a detachable storage portion configured to receive collected spray dried plasma. 
     
     
         79 . A product comprising:
 a physiologically active spray dried plasma powder made using the method of any of  claims 1 - 39 .