Linearly scalable single use bioreactor system

Abstract

Disclosed is a single-use bioreactor bag design providing substantially equivalent maximum shear rate at the impeller tip and average or bulk shear rate over a range of power per unit working volume and rpm needed for bio culture processing. The uniformity in shear profile of the bag design providing a unique advantage when used as a scale-down or scale-up platform. Also disclosed is a linearly scalable, single-use, bioreactor system for use in carrying out a scalable biomanufacturing process, the system comprising two single-use bioreactor bags of different volumes, wherein the ratio H/D of the height of the working volume H to the diameter D of the tank, or of the bag is equal to about 1.5, and the bulk shear in each of the bags is substantially constant.

What is claimed is: 
     
         1 . A linearly scalable bioreactor system for use in carrying out a scalable biomanufacturing process, the system comprising:
 a bioprocessing bag having a flexible wall, a working volume of from about 2 liters to about 10 liters, and a height to diameter ratio at maximum working volume of about 1.5; and   an impeller operatively connected to an inside bottom surface of the flexible wall, the ratio of the diameter of the impeller, Di, to the diameter of the bioprocessing bag, Dt, equal to a value of from about 0.6 to about 0.7, the bioprocessing bag capable of exhibiting substantially the same impeller shear rate and bulk shear rate over a range of values of power per unit volume; and   a sparging surface positioned beneath the impeller.   
     
     
         2 . The linearly scalable bioreactor system of  claim 1 , wherein the distance from the impeller to the sparging surface is maintained at less than the diameter of the impeller. 
     
     
         3 . The linearly scalable bioreactor system of  claim 1 , wherein the impeller is maintained at from about 3 mm to about 200 mm from the sparging surface. 
     
     
         4 . The linearly scalable bioreactor system of  claim 1 , wherein the impeller is maintained at from about 6 mm to about 100 mm from the sparging surface. 
     
     
         5 . The linearly scalable bioreactor system of  claim 1 , wherein the impeller is maintained at about 6.25 mm from the sparging surface. 
     
     
         6 . The linearly scalable bioreactor system of  claim 1 , wherein the impeller is mounted on an impeller plate attached to the inside bottom surface of the flexible wall. 
     
     
         7 . The linearly scalable bioreactor system of  claim 6 , wherein the impeller is a pitch blade impeller mounted on a center of the impeller plate. 
     
     
         8 . The linearly scalable bioreactor system of  claim 1 , wherein the maximum working volume is about 10 liters. 
     
     
         9 . A linearly scalable bioreactor system for use in carrying out a scalable biomanufacturing process, the system comprising:
 a first bioprocessing bag having a first volume, a first flexible wall, and an aspect ratio of first bag height at the first bag maximum working volume to first bag diameter equal to a first H/D;   a first impeller operatively connected to a first inside surface of the first flexible wall, the ratio of the first impeller, Di, to the diameter of the first bioprocessing bag, Dt, equal to a of the diameter value of from about 0.6 to about 0.7;   a second single-use bioprocessing bag having a second volume that is larger than the first volume of the first bioprocessing bag, a second flexible wall, and an aspect ratio and an aspect ratio of second bag height at the second bag maximum working volume to second bag diameter equal to a second H/D, wherein the first and the second H/D are substantially equal to one another,   a second impeller operatively connected to a second inside surface of the second flexible wall, the ratio of the diameter of the second impeller, D 2   i , to the diameter of the second bioprocessing bag, D 2   t , is not equal to a value of from about 0.6 to about 0.7; and wherein the first and the second impeller are of the same type, and are each positioned over substantially the same gas sparging/aeration components and positioned similarly relative to the impeller, and are each configured to operate within the first and second bag, respectively, such that, in a bioprocessing operation utilizing the same fluid within the first and the second bioprocessing bags, under similar conditions, and at the same power per unit volume, the average or bulk shear rate value of the fluid in the first bioprocessing bag is within +/−25 percent of the average or bulk shear rate value of the fluid in the second bioprocessing bag.   
     
     
         10 . The linearly scalable bioreactor system of  claim 9 , wherein the distance of the first and second impellers from the gas sparging/aeration components is maintained at less than a diameter of at least one of the first and second impellers. 
     
     
         11 . The linearly scalable bioreactor system of  claim 9 , wherein the first and second impellers are maintained at from about 3 mm to about 200 mm from the gas sparging/aeration components. 
     
     
         12 . The linearly scalable bioreactor system of  claim 9 , wherein the first and second impellers are maintained at from about 6 mm to about 100 mm from the gas sparging/aeration components. 
     
     
         13 . The linearly scalable bioreactor system of  claim 9 , wherein the first and second impellers are maintained at about 6.25 mm from the gas sparging/aeration components. 
     
     
         14 . The linearly scalable bioreactor system of  claim 9 , wherein the first and second impellers are mounted on first and second impeller plates, which are in turn attached to the first and second inside surfaces, respectively. 
     
     
         15 . The linearly scalable bioreactor system of  claim 14 , wherein at least one of the first and second impellers is a pitch blade impeller mounted on a center of its respective impeller plate. 
     
     
         16 . The linearly scalable bioreactor system of  claim 9 , wherein the maximum working volume is about 10 liters. 
     
     
         17 . A linearly scalable 10 liter bioprocessing system which substantially simulates the shear and power/unit volume characteristics of any one of a 50 liter to a 5000 liter bioprocessing system comprising a flexible-walled bioreactor bag, the 10 liter bioprocessing system comprising:
 a bioprocessing bag having a working volume of from about 2 liters to about 10 liters;   
       a flexible wall; and
 an impeller mounted operatively connected to an inside bottom surface of the flexible wall, the ratio of the diameter of the impeller, Di, to the diameter of the bioprocessing bag, Dt, equal to a value of from about 0.6 to about 0.7, the bioprocessing bag capable of exhibiting substantially the same impeller shear rate and bulk shear rate over a range of values of power per unit volume; 
 a process measuring system; 
 a system of field actuating devices or field actuators; 
 a local processing unit and associated software logic configured to convert a measuring system input and pass the measuring system input to a supervisory controller or human machine input device for data manipulation and storage and to transform the measuring system input from the supervisory controller or human machine input device to a manipulation of the field actuating device or the field actuator, and 
 a sparging surface positioned beneath the impeller. 
 
     
     
         18 . The linearly scalable 10 liter bioprocessing system of  claim 17  comprising:
 a human machine interface and associated software programming comprising at least one of a computer mouse, a keyboard and a touch-screen; and 
 a supervisory controller and software programming capable of acting on a specific configurable parameter chosen from a process input, a setpoint, an alarm, and combinations thereof. 
 
     
     
         19 . A linearly scalable 10 liter bioprocessing system which substantially simulates the polymer chemistry characteristics of each of the components of any one of a 50 liter to a 5000 liter bioprocessing system comprising a flexible-walled bioreactor bag, the 10 liter bioprocessing system comprising:
 a bioprocessing bag having a working volume of from about 2 liters to about 10 liters;   a flexible wall;   an impeller operatively connected to an inside bottom surface of the flexible wall, the ratio of the diameter of the impeller, Di, to the diameter of the bioprocessing bag, Dt, equal to a value of from about 0.6 to about 0.7, the bioprocessing bag capable of exhibiting substantially the same impeller shear rate and bulk shear rate over a range of values of power per unit volume; and   a sparging surface positioned beneath the impeller.   
     
     
         20 . The linearly scalable 10 liter bioprocessing system of  claim 19 , wherein the bioprocessing bag comprises polyethylene in the form of a film. 
     
     
         21 . The linearly scalable 10 liter bioprocessing system of  claim 19 , wherein the bioprocessing bag and the impeller are comprised of the same class of polymers, respectively, as that of the bioprocessing bag and impeller of one of the 50 liter to the 5000 liter bioprocessing systems. 
     
     
         22 . The linearly scalable 10 liter bioprocessing system of  claim 19 , wherein the impeller comprises a material chosen from PEEK™, polycarbonate, and stainless steel.