초록 ▼

A facility (1) for producing a container loaded with a biopharmaceutical fluid, includes: a container (2) wherein a biopharmaceutical fluid is placed (B); a control module (9) for controlling the filling of gas into the container (2); and an analysis module (10) for estimating a parameter for contro

A facility (1) for producing a container loaded with a biopharmaceutical fluid, includes: a container (2) wherein a biopharmaceutical fluid is placed (B); a control module (9) for controlling the filling of gas into the container (2); and an analysis module (10) for estimating a parameter for controlling the gas filling; and a pumping device (40) for generating a depression in the inner filling space (Vg).

대표청구항 ▼

1. Facility for the preparation of a container loaded with a biopharmaceutical fluid, wherein the facility comprises: a fluidtight container in which is placed a biopharmaceutical fluid and a gas which occupies an inner filling space, the container comprising a gas passage opening and being adapted

1. Facility for the preparation of a container loaded with a biopharmaceutical fluid, wherein the facility comprises: a fluidtight container in which is placed a biopharmaceutical fluid and a gas which occupies an inner filling space, the container comprising a gas passage opening and being adapted to be filled with gas to an initial level of positive pressure in the inner filling space;a control module for controlling the filling of the container with gas;an analysis module for estimating a gas filling control parameter; anda pumping means for generating a negative pressure in the inner filling space by forcing the gas to flow out of the container via the gas passage opening, the control module and the pumping means being coordinated to adjust the duration of the forced flow on the basis of the control parameter determined by the analysis module. 2. Facility according to claim 1, wherein the control module is adapted to selectively control a flow of released gas through the gas passage opening of the container, so as to reduce the pressure level in the inner filling space, and the gas filling control parameter is representative of said inner filling space, the analysis module being configured to estimate said control parameter by monitoring the flow of released gas between a first level of positive pressure OP1 and a second level of positive pressure OP2 in the inner filling space. 3. Facility according to claim 2, wherein the analysis module comprises or is connected to a timer adapted to determine the duration of the gas release Δt required to drop from the first level of positive pressure OP1 to the second level of positive pressure OP2. 4. Facility according to claim 2, wherein the analysis module determines, as the control parameter, the inner filling space using the following correlation: Vg=Q/k+Vc where: Vg is the inner filling space occupied by the gas;Q is a volumetric flow rate constant;Vc is a volume constant;k is a decay constant;knowing that the decay constant is calculated using the equation: k=−ln(OP2/OP1)/Δt with OP1 being the first level of positive pressure inside the container;OP2 the second level of positive pressure inside the container;Δt being the duration of the gas release required to drop from the first level of positive pressure OP1 to the second level of positive pressure OP2;ln representing the natural logarithm function. 5. Facility according to claim 1, further comprising a plurality of valves comprising valves selectively controlled by the control module and having: a first configuration permitting the flow of gas in an incoming direction into the container; anda second configuration permitting the flow of gas in an outgoing direction from the container;the control module being adapted to successively configure the first configuration to enable the container to be filled with gas to a state of positive pressure within said inner filling space, and the second configuration to enable gas to escape from the container via its gas passage opening at most until a state of pressure equilibrium is reached in said inner filling space. 6. Facility according to claim 5, wherein said plurality of valves comprises a first gas inlet valve selectively opened by the control module in the first configuration and a second gas release valve selectively opened by the control module in the second configuration, the gas inlet valve and the gas release valve being in fluid communication with said gas passage opening. 7. Facility according to claim 5, wherein the pumping means comprises a vacuum pump and a third gas removal valve that is one among said plurality of valves, the control module being configured for selectively opening the gas removal valve and closing the gas inlet valve and the gas release valve when the vacuum pump is actuated. 8. Facility according to claim 1, wherein the analysis module comprises or is connected to a pressure sensor in fluid communication with the gas passage opening and adapted for measuring a level of positive pressure inside the container. 9. Facility according to claim 1, comprising a gas injection device adapted to inject gas, into the container by said gas passage opening prior to the control parameter determination. 10. Facility according to claim 9, wherein the gas injection device, the pumping means, and a control unit comprising the control module and the analysis module are incorporated into a device for preparing the interior of the container. 11. Facility according to claim 9, wherein the gas is pressurized gas. 12. Facility according to claim 1, wherein the container is flexible and sealed closed, the container comprising gas-impermeable plastic walls. 13. Method for preparing a sealed container loaded with a biopharmaceutical fluid, a gas occupying an inner filling space inside the container at an initial level of positive pressure, wherein the gas filling level within the container is controlled, the method comprising the steps of: b) estimating a gas filling control parameter which is representative of said inner filling space,c) generating a negative pressure in the inner filling space by forcing gas to flow out of the container, the duration of the forced flow being adjusted according to said control parameter. 14. Method according to claim 13, wherein the forced flow is achieved by pumping at a constant flow rate, the forced flow being stopped after a first time limit corresponding to the time required to discharge an amount of gas equal to 30% of the initial amount of gas contained in the inner filling space determined in step b) and before a second time limit corresponding to the time required to evacuate an amount of gas equal to 50% of the initial amount of gas contained in the inner filling space determined in step b). 15. Method according to claim 13, further comprising the following step before step b): a) selectively controlling a flow of released gas through a gas passage opening of the container, so as to lower the positive pressure inside the container; and wherein the estimating in b) includes monitoring the flow of released gas between a first level of positive pressure OP1 and a second level of positive pressure OP2 in the inner filling space. 16. Method according to claim 15, wherein said control parameter is estimated by determining the duration of the gas release Δt required to drop from the first level of positive pressure OP1 to the second level of positive pressure OP2. 17. Method according to claim 13, comprising, prior to step a), the steps of: injecting a gas into the container until a positive pressure is reached in the inner filling space of between 10 and 50 mbar; andfreezing the biopharmaceutical fluid. 18. Method according to claim 17, wherein the gas is air or nitrogen. 19. Method according to claim 13, wherein step b) is performed when a gas release valve in fluid communication with the gas passage opening is selectively opened, said gas release valve remaining open until the pressure between the inner filling space and the environment is equalized, several measurements of a parameter of the gas representative of a level of positive pressure in the inner filling space being performed during step b).