Linearly scalable single use bioreactor system

Patent metadata

Field	Value
Publication number	US-9969965-B2
Application number	US-201213978726-A
Country	US
Kind code	B2
Filing date	Jan 11, 2012
Priority date	Jan 11, 2011
Publication date	May 15, 2018
Grant date	May 15, 2018

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 bioculture 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. The disclosed small scale system models larger scale systems from both a shear/scalability/performance basis and also from a validation and regulatory basis. In summary, the 10L bioreactor system disclosed provides for “linear scalability” by using the same or substantially simulating the same vessel geometry, gas sparging system, impeller shape and type, polymer composition of the flexible bag/components, process control system, and shear rates as larger 50-5000 L systems.

First claim

What is claimed is:

1. A linearly scalable bioreactor system for use in carrying out a scalable biomanufacturing process, the system comprising:
a first bioprocessing bag having a flexible wall, a working volume of from about 2 liters to about 10 liters, a height to diameter ratio at maximum working volume of about 1.5, and an impeller mounted on an impeller plate attached to an inside bottom surface of the flexible wall, the ratio of the diameter of the impeller, Di, to the diameter of the first bioprocessing bag, Dt, equal to a value of from about 0.6 to about 0.7, the first bioprocessing bag being capable of exhibiting substantially the same impeller shear rate and bulk shear rate over a range of values of power per unit volume, wherein the range of values of power per unit volume is from about 2 Watts per cubic meter to about 36 Watts per cubic meter; and
a second bioprocessing bag having a second flexible wall, a second working volume of from about 50 liters to about 5000 liters, a height to diameter ratio at maximum working volume of about 1.5, and a second impeller mounted on a second impeller plate attached to an inside bottom 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 , not being equal to a value of from about 0.6 to about 0.7, the second bioprocessing bag being capable of exhibiting substantially the same impeller shear rate and bulk shear rate over a range of values of power per unit volume;
wherein the impeller of the first bioprocessing bag and the impeller of the second bioprocessing bag are of the same type;
wherein at a power per unit volume of about 6.6 Watts per cubic meter, the first bioprocessing bag exhibits a bulk shear rate of about 5.4 and the second bioprocessing bag exhibits a bulk shear rate within about +/−25 percent of the bulk shear rate exhibited by the first bioprocessing bag; and
wherein the first bioprocessing bag and the second bioprocessing bag provide for linear scalability of a biomanufacturing process from the first bioprocessing bag to the second bioprocessing bag.

2. The linearly scalable bioreactor system of claim 1 , wherein the maximum working volume of the first bioprocessing bag is about 10 liters.

3. The linearly scalable bioreactor system of claim 1 , wherein:
the first bioprocessing bag has a working volume of about 2 liters.

4. The linearly scalable bioreactor system of claim 1 , wherein the maximum shear rate or the impeller shear rate of the first bioprocessing bag in operation is less than the maximum shear rate or the impeller shear rate of any larger scale bioprocessing system operating at the same power per unit volume.

5. The linearly scalable bioreactor system of claim 1 , wherein the flexible wall of the first bioprocessing bag comprises polyethylene.

6. The linearly scalable bioreactor system of claim 1 , wherein the impeller of the first bioprocessing bag is a pitch blade impeller mounted on the center of the impeller plate.

7. The linearly scalable bioreactor system of claim 1 , comprising a sparging surface positioned beneath the impeller of the first bioprocessing bag.

8. The linearly scalable bioreactor system of claim 1 , comprising a sensor.

9. The linearly scalable bioreactor system of claim 1 , comprising a means for heating or cooling contents of the first bioprocessing bag.

10. The linearly scalable bioreactor system of claim 1 , comprising a means for collecting and condensing the exit air gas, followed by filtration of the gas.

11. The linearly scalable bioreactor system of claim 1 , comprising a measurement and control system including a configurable software platform, the control system capable of operating in real-time and capable of accepting measurement inputs and controlling at least one component of the bioreactor system.

12. The linearly scalable bioreactor system of claim 11 , comprising a means for human interaction with the system through a touch-screen based interface on a device chosen from a desk-top computer, a lap-top computer, a notebook computer, and a remote control device.

13. The linearly scalable bioreactor system of claim 12 , wherein the touch-screen based interface is configured for allowing a user to enter set-points, calibrate field devices, manage alarms, configure operator identity and access levels, and view process values graphically, over time.

Assignees

• Tuohey Colin
• Deloggio Ted
• Erdenberger Thomas
• Clapp Kenneth P
• Damren Richard
• Galliher Parrish M
• Guertin Patrick
• Lee Jiyoung
• Fisher Michael
• Ge Healthcare Bio Sciences Corp

Inventors

• Tuohey Colin
• Deloggio Ted
• Erdenberger Thomas
• Clapp Kenneth P
• Damren Richard
• Galliher Parrish M
• Guertin Patrick
• Lee Jiyoung
• Fisher Michael

Classifications

• C12M27/02

  Stirrer or mobile mixing elements · CPC title

• C12M23/02

  Form or structure of the vessel (large containers B65D88/00) · CPC title

• C12M23/26

  flexible (flexible containers for laboratory use B01L3/505) · CPC title

• C12M23/28 Primary

  disposable or single use · CPC title

• C12M23/14

  Bags · CPC title