System and method for detecting a possible loss of integrity of a flexible bag for biopharmaceutical product

Patent metadata

Field	Value
Publication number	US-12018998-B2
Application number	US-202017621745-A
Country	US
Kind code	B2
Filing date	Jun 17, 2020
Priority date	Jun 26, 2019
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

Integrity of a flexible bag is verified by a testing system, using helium to detect existence of a possible hole. The bag is preliminary placed in vacuum chamber of a fluid-tightly isolated enclosure. After connecting a port of the bag to a helium feeding pipe and after pre-pressurizing the bag with nitrogen, a test is performed in a vacuum suction mode for a detection area outside the bag in the enclosure. Before starting the test phase, the bag is additionally filled with an amount of helium. A detection detects information representative of helium partial pressure in the internal volume, to allow detection of helium escaping from the bag, by analysis of a helium partial pressure drop. A small amount of nitrogen is sufficient to decrease leak rate mean value, so that uncertainty regarding integrity of some bags decreases.

First claim

The invention claimed is:

1. A testing system for verifying the integrity of a flexible bag, using a gas tracer, comprising:
an enclosure delimiting a vacuum chamber in which an internal volume is fluid-tightly isolated from outside of the enclosure;
a gas tracer supplying device provided with a feeding pipe for filling an inner volume of the flexible bag with the gas tracer, via an outlet of the feeding pipe when the flexible bag is placed in the vacuum chamber so as to be surrounded by the internal volume, the gas tracer supplying device comprising a gas tracer supply valve;
a vacuum suction assembly for performing vacuum suction and extracting gas from the internal volume outside the flexible bag, in a suction mode, the vacuum suction assembly comprising a vacuum suction assembly valve;
a vacuum suction line for performing vacuum suction and extracting gas from inside the flexible bag, in a suction mode, the vacuum suction line comprising a vacuum suction line valve;
at least one sensor associated with the vacuum chamber and capable of sensing the gas tracer external to the inner volume of the flexible bag, in a detection area of the internal volume, the detection area communicating with a suction inlet of the vacuum suction assembly;
a first valve arrangement comprising at least one first nitrogen source valve attached to a source of gaseous nitrogen so that gaseous nitrogen can be delivered inside the flexible bag, the first valve arrangement also comprising the gas tracer supply valve;
a second valve arrangement comprising second valves that include the vacuum suction assembly valve and the vacuum suction line valve;
an analysis module using information representative of evolution over time of a gas tracer partial pressure detected using the at least one sensor the analysis module being configured to detect a gas tracer leak reflecting a flexible bag integrity defect, on the basis of said information;

wherein the testing system further comprises:
a pressure controlling device connected to the first valve arrangement and to the second valve arrangement, the pressure controlling device being configured to inject and maintain a gaseous content of nitrogen inside the flexible bag at a predetermined pressure below a pressure threshold, after vacuum suction has been performed by the vacuum suction assembly and while the vacuum suction assembly is still operating in the suction mode, and after vacuum suction by the vacuum suction line has been performed, in order to keep the flexible bag in an inflated state in the vacuum chamber;

and wherein the pressure controlling device is configured to successively:
actuate vacuum suction inside the bag and in the internal volume, using the vacuum suction assembly and the vacuum suction line;
then trigger selective injection of the gaseous content of nitrogen in a closed or inactive state of the gas tracer supply valve;
and then trigger the gas tracer supplying device, by setting the gas tracer supply valve in an open or active state.

2. The system according to claim 1 , wherein the pressure controlling device is configured to inject nitrogen, so that a pressure in the flexible bag: remains between 10 mbar to 100 mbar after the injection of nitrogen, and is a positive pressure greater than pressure provided in the internal volume outside the flexible bag.

3. The system according to claim 2 , wherein the source of gaseous nitrogen is a source of pressurized nitrogen, the at least one first nitrogen source valve attached to the source of gaseous nitrogen being connected to the feeding pipe.

4. The system according to claim 2 , wherein the source of gaseous nitrogen is a source of pressurized nitrogen, the at least one first nitrogen source valve being connected to at least one auxiliary feeding pipe intended to be connected to a port of the flexible bag, the auxiliary feeding pipe being separate from the feeding pipe.

5. The system according to claim 1 , wherein the gas tracer supplying device is a first helium supplying device, the gas tracer being helium, and wherein the system further comprises a second helium supplying device for adding helium in the internal volume outside the flexible bag, the second helium supplying device comprising a feeding member that is:
distinct from the feeding pipe,
communicating with a helium source.

6. The system according to claim 1 , wherein the gas tracer supplying device is a helium supplying device, the gas tracer being helium, and wherein the system further comprises a second helium supplying device for adding helium in the internal volume outside the flexible bag, the second helium supplying device comprising a feeding member that is:
distinct from the feeding pipe,
communicating with a helium source.

7. The system according to claim 1 , wherein the gas tracer supplying device is a helium supplying device,
wherein the analysis module is adapted to use information representative of evolution over time of helium partial pressure detected by use of the at least one sensor, after the filling step, in order to obtain a test result representative of a helium partial pressure drop in the detection area, the analysis module being configured to:
use information representative of detected helium partial pressure detected after selective injection of the gaseous content of nitrogen inside the flexible bag, for a period that includes a period subsequent to the filling step, when the vacuum suction assembly is in the suction mode;
subtract a determined background value from raw measurement, after determining the determined background value on the basis of information representative of helium partial pressure detected by the at least one sensor before the filling step, when the vacuum suction assembly is in the suction mode; and
compare the test result to at least one reference result, so as to determine if the flexible bag filled with nitrogen and helium is considered to have or not to have passed the integrity verification.

8. The system according to claim 1 , comprising:
two plates that are in a spaced relationship;
a housing for receiving the flexible bag between the two plates, the plates forming constraining plates for constraining expansion of the flexible bag when filled with helium during the filling step.

9. The system according to claim 8 , wherein the two plates also form constraining plates for constraining expansion of the flexible bag before the filling step.

10. The system according to claim 9 , wherein the two plates are two vertical plates configured for restraining inflation of the bag before the filling step.

11. The system according to claim 9 , wherein the two plates are two horizontal plates configured for restraining inflation of the bag before the filling step.

12. A test method using a tracer gas for verifying integrity of a flexible bag in order to detect existence of a possible hole, the test method comprising:
in a preparation phase:
providing a testing system comprising an enclosure that delimits a vacuum chamber adapted to be fluid-tightly isolated from outside of the enclosure in an operating configuration of the enclosure;
placing the flexible bag in the vacuum chamber and connecting a port of the flexible bag to a feeding pipe in communication with a source of a tracer gas that is inert;
performing vacuum suction inside the flexible bag and outside the flexible bag in the vacuum chamber;
pre-pressurizing an inner volume of the flexible bag, using nitrogen, below a pressure threshold, in order to obtain vacuum outside the flexible bag in an internal volume of the vacuum chamber, while the flexible bag remains in an inflated state due to a g

Assignees

• Sartorius Stedim Fmt Sas

Inventors

• Thenard Laurent
• Cattaux Bastien
• Hogreve Marc
• Nachhattar Mandip
• Philippeau Delphine
• Urbaniak Tomasz

Classifications

• G01M3/3281

  removably mounted in a test cell · CPC title

• G01M3/3218

  for flexible or elastic containers · CPC title

• G01M3/3272

  for verifying the internal pressure of closed containers · CPC title

• G01M3/227

  for flexible or elastic containers · CPC title

• G01M3/229 Primary

  removably mounted in a test cell · CPC title