Monitoring of the freezing state of a biopharmaceutical fluid found in a container

• US 10,031,033 B2
• Filed: 03/20/2014
• Issued: 07/24/2018
• Est. Priority Date: 03/22/2013
• Status: Active Grant

• Current Assignee: Sartorius Stedim North America Inc. (Sartorius AG)
• Original Assignee: Sartorius Stedim North America Inc. (Sartorius AG)
• Inventors: Cutting, Jonathan
• Primary Examiner(s): LaBalle, Clayton E
• Assistant Examiner(s): Rhodes, Jr., Leon W
• Application Number:
  US14/779,193
• Publication Number:
  US 20160047764A1
• Time in Patent Office: 1,587 Days
• Field of Search: 374 24
• CPC Class Codes: A01N 1/0252 Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
• CPC Class Codes: A01N 1/0263 Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
• CPC Class Codes: F25D 19/00 Arrangement or mounting of refrigeration units with respect to devices or objects to be refrigerated, e.g. infrared detectors
• CPC Class Codes: F25D 29/008 Alarm devices
• CPC Class Codes: G01K 11/06 using melting, freezing, or softening
• CPC Class Codes: G01K 11/28 using measurements of density measuring density in general G01N9/00

Abstract

A device for monitoring the freezing state of a biopharmaceutical fluid in a container intended to receive a biopharmaceutical fluid that must pass between the liquid state and the frozen state, includes a peripheral envelope (25) made of plastic, to be connected to a heat treatment receptacle (5), a sensor (19) suitable for detecting a control parameter which is a macroscopic parameter of the container, and an analysis system (62) suitable for determining a freezing state of the biopharmaceutical fluid on the basis of the macroscopic parameter of the container.

Claims

1. Monitoring device for monitoring the freezing state of a biopharmaceutical fluid in a container intended to receive a biopharmaceutical fluid that is to transition between the liquid state and the frozen state, wherein the device comprises a peripheral envelope made of plastic, intended and suitable for association with a thermal treatment receptacle,

wherein the device further comprises a sensor suitable for non-intrusively detecting a control parameter which is a macroscopic parameter of the container, and an analysis system suitable for determining a freezing state of the biopharmaceutical fluid on the basis of the macroscopic parameter of the container, the macroscopic parameter being derived directly or indirectly from an average density of a non-gaseous portion of contents of the container.

2. Monitoring device according to claim 1, wherein the sensor is adapted to detect a value of the control parameter repeatedly over time during the thermal treatment process.

3. Monitoring device according to claim 2, wherein the parameter values over time show an abrupt change when there is a change in the freezing state of the biopharmaceutical fluid, and wherein the analysis system is adapted to detect this abrupt change.

4. Monitoring device according to claim 3, wherein the parameter values over time show an abrupt change when transitioning between a state where a portion of the biopharmaceutical fluid is not frozen and a state where the entire biopharmaceutical fluid is frozen.

5. Monitoring device according to claim 3, wherein the parameter values over time show an abrupt change when transitioning between a state where the entire biopharmaceutical fluid is not frozen and a state where a portion of the biopharmaceutical fluid is frozen.

6. Monitoring device according to claim 1, wherein the analysis system is adapted to determine a frozen state of the biopharmaceutical fluid on the basis of an absolute value of the control parameter.

7. Monitoring device according to claim 6, wherein the analysis system is adapted to determine the frozen state of the biopharmaceutical fluid on the basis of an initial value of the control parameter, and of a change over time in the absolute value of the control parameter determined from the sensor.

8. Monitoring device according to claim 1, wherein the non-gaseous portion comprise one and/or the other among a liquid phase and a solid phase, the container possibly further containing a gaseous phase.

9. Monitoring device according to claim 1, wherein the control parameter is the gas pressure in an upper portion of the container arranged above the biopharmaceutical fluid in an end head portion of the container, said portion being filled with a gas.

10. Monitoring device according to claim 1, comprising a gas entry/exit line adapted to be associated in a fluidtight communication with a gas entry/exit port of the container, said port being located in an upper portion of the container arranged above the biopharmaceutical fluid in an end head portion of the container, said portion being filled with a gas, the sensor being suitable for determining a parameter of the headspace.

11. Monitoring device according to claim 10, the control parameter being the amount of gas in the headspace, the volume of gas in the head space, or the volume of biopharmaceutical fluid in the container.

12. Monitoring device according to claim 10, further comprising an opening/closing valve associated with the gas entry/exit port.

13. Monitoring device according to claim 10, wherein the sensor comprises a pressure sensor intended and suitable for measuring or monitoring the gas pressure in the upper portion or in the gas entry/exit line, and a regulation system intended and suitable for controlling the entry/release of gas into/from the upper portion via the gas entry/exit port and the gas entry/exit line, according to a desired pressure profile in the headspace.

14. Monitoring device according to claim 13, further comprising a means intended and suitable for allowing the entry/release of gas into/from the headspace, via the gas entry/exit port and the gas entry/exit line.

15. Monitoring device according to claim 14, wherein the regulation system intended and suitable for controlling the entry/release of gas into/from the upper portion, via the gas entry/exit port and the gas entry/exit line, operates so as to allow the entry of gas when the gas pressure in the upper portion decreases and to release gas when the gas pressure in the upper portion increases.

16. Monitoring device according to claim 1, further comprising a control system suitable for thermally controlling the freezing receptacle according to the freezing state determined by the analysis system.

17. Thermal treatment system for a biopharmaceutical fluid, comprising a thermal treatment receptacle intended and suitable for receiving a container of biopharmaceutical fluid, and a monitoring device according to claim 1.

18. Thermal treatment system according to claim 17, comprising a plurality of thermal applicators in the receptacle, independently controllable, and wherein the control system independently controls said thermal applicators.

19. System according to claim 17, comprising a plurality of thermal treatment receptacles each intended and suitable for receiving a respective container of biopharmaceutical fluid, each receptacle being independently controllable by the control system, wherein the control system is adapted to control each thermal treatment receptacle independently according to the freezing state determined for each container.

20. Method for monitoring the freezing state of a biopharmaceutical fluid in a container intended to receive a biopharmaceutical fluid that is to transition between the liquid state and the frozen state, comprising a peripheral envelope of plastic, intended and suitable for association with a thermal treatment receptacle, wherein a sensor non-intrusively detects a control parameter which is a macroscopic parameter of the container, and an analysis system determines a freezing state of the biopharmaceutical fluid on the basis of the macroscopic parameter of the container, the macroscopic parameter being derived directly or indirectly from an average density of a non-gaseous portion of contents of the container.