LYOPHILIZATION METHOD AND DEVICE

• US 20100154245A1
• Filed: 08/03/2009
• Published: 06/24/2010
• Est. Priority Date: 04/28/2003
• Status: Active Grant

• Current Assignee: Dr Py Institute LLC
• Original Assignee: Daniel Py
• Inventors: Py, Daniel
• Granted Patent: US 8,272,411 B2
• Time in Patent Office: Days
• US Class Current: 34/287
• CPC Class Codes: A61J 1/1425 Snap-fit type
• CPC Class Codes: A61J 1/1431 Permanent type, e.g. welded or glued
• CPC Class Codes: A61J 1/1468 Containers characterised by specific material properties
• CPC Class Codes: A61J 1/1481 with connection retaining means, e.g. thread or snap-fit
• CPC Class Codes: A61J 1/1487 with friction fit, e.g. connecting tubes directly to a protruding port
• CPC Class Codes: A61J 1/18 Arrangements for indicating condition of container contents, e.g. sterile condition
• CPC Class Codes: A61J 1/2037 having valve means
• CPC Class Codes: A61J 1/2041 having removable plugs
• CPC Class Codes: A61J 1/2055 having gripping means
• CPC Class Codes: A61J 1/2096 Combination of a vial and a syringe for transferring or mixing their contents
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: B65B 55/08 by irradiation
• CPC Class Codes: B65D 47/248 the valve being opened or closed by imparting a motion to the valve stem B65D47/244, B65D47/245 take precedence

Abstract

A lyophilization device configured for use in a lyophilization process has a body defining a chamber for receiving a liquid to be lyophilized, and a stopper creating a liquid-tight seal between the chamber and ambient atmosphere to form a sealed, empty sterile chamber. The stopper is adapted so that the chamber may be sterile filled with the substance through the stopper. A fluid passageway is formed through the stopper, through which the chamber is evacuated. The substance is lyophilized, the fluid passageway is closed, and the lyophilized substance is hermetically sealed within the chamber.

Claims

1. A method comprising the following steps:

providing a sealed empty sterile device including a body defining a chamber, and a stopper forming a liquid-tight seal between the chamber and ambient atmosphere;

sterile filling a liquid substance to be lyophilized through the stopper and into the sealed, empty, sterile chamber;

forming a fluid passageway through the stopper and evacuating the chamber through the fluid passageway of the stopper;

lyophilizing the substance within the evacuated chamber; and

closing the fluid passageway through the stopper and hermetically sealing the lyophilized substance within the chamber.

2. A method as defined in claim 1, wherein the closing step occurs after the lyophilizing step.

3. A method as defined in claim 1, further comprising the step of sterilizing the sealed empty device.

4. A method as defined in claim 3, wherein the sterilizing step includes irradiating the sealed empty device.

5. A method as defined in claim 4, wherein the step of irradiating the sealed empty device includes subjecting the device to at least one of gamma, e-beam and laser radiation.

6. A method as defined in claim 1, wherein the device includes a valve assembly coupled in fluid communication with the chamber and defining (i) an open position permitting at least one of (a) passage of the substance through the valve assembly and into the chamber, and (b) passage of fluid out of the chamber;

and (ii) a closed position forming a fluid-tight seal between the chamber and ambient atmosphere, wherein the method comprises the following steps;

sterilizing the sealed empty device;

filling the sterilized empty device with the substance by moving at least one of the valve assembly and a filling member into engagement with the other;

introducing substance from the filling member through the valve assembly and into the chamber; and

moving at least one of the valve assembly and filling member relative to the other to disengage the valve assembly and filling member.

7. A method as defined in claim 6, wherein the valve assembly extends through the stopper.

8. A method as defined in claim 6, wherein the valve assembly includes a flexible valve member defining a spring that is approximately dome-shaped when the valve assembly is in the closed position.

9. A method as defined in claim 1, wherein the device includes a valve assembly including an axially-extending valve seat, and a flexible valve member overlying the valve seat and forming a normally closed interface defining a fluid-tight seal between the valve member and the valve seat, wherein the method further comprises the following steps:

filling the sterile empty chamber with the substance by moving at least one of the valve assembly and a filling member into fluid communication with the other;

introducing the substance from the filling member at sufficient pressure into the interface between the valve member and the valve seat to flex the valve member relative to the valve seat and flow through the interface between the valve member and the valve seat and into the chamber;

terminating the flow of the substance from the filling member into the interface between the valve member and the valve seat, allowing the flexible valve member to form the normally closed interface defining the fluid-tight seal between the valve member and the valve seat, and sealing the substance with the chamber; and

moving at least one of the valve assembly and the filling member relative to the other to disconnect the valve assembly and the filling member from fluid communication with each other.

10. A method as defined in claim 9, further comprising the step of providing a device including a valve assembly wherein the axially-extending valve seat and flexible valve member form an inlet valve for introducing the substance through the inlet valve and into the chamber, and the device further includes an outlet valve that is normally closed and forms a fluid-tight seal between the chamber and ambient atmosphere;

and dispensing substance from the chamber through the outlet valve.

11. A method as defined in claim 10, wherein the dispensing step includes dispensing multiple doses of the substance from the chamber through the outlet valve, and maintaining the substance remaining within the chamber after each dose sterile and sealed within the chamber with respect to the ambient atmosphere.

12. A method as defined in claim 11, further comprising the step of connecting the device to a syringe, injecting a diluent from the syringe into the chamber, and mixing the lyophilized substance with the diluent within the chamber.

13. A method as defined in claim 6, further comprising the step of connecting the device to a syringe, moving the valve member from the closed to the open position, injecting a diluent from the syringe into the chamber, and mixing the lyophilized substance with the diluent within the chamber.

14. A lyophilization device comprising a body defining a sealed, empty sterile chamber, and a stopper forming a liquid-tight seal between the chamber and ambient atmosphere, wherein the stopper is adapted for sterile filling a liquid substance to be lyophilized through the stopper and into the sealed, empty, sterile chamber, forming a fluid passageway through the stopper and evacuating the chamber through the fluid passageway of the stopper, lyophilizing the substance within the evacuated chamber, and closing the fluid passageway through the stopper and hermetically sealing the lyophilized substance within the chamber.

15. A lyophilization device as defined in claim 14, further comprising a one-way valve defining the fluid passageway.

16. A lyophilization device as defined in claim 15, wherein the one-way valve extends through the stopper.

17. A lyophilization device as defined in claim 14, wherein the device includes a vial defining the body and the chamber within the body.

18. A lyophilization device as defined in claim 15, wherein the one-way valve defines (i) an open position permitting at least one of (a) passage of the substance through the one-way valve and into the chamber, and (b) passage of fluid out of the chamber;

and (ii) a closed position forming a fluid-tight seal between the chamber and ambient atmosphere.

19. A lyophilization device as defined in claim 18, wherein the one-way valve includes a flexible valve member defining a spring that is approximately dome-shaped when the one-way valve is in the closed position.

20. A lyophilization device as defined in claim 15, wherein the one-way valve includes an axially-extending valve seat, and a flexible valve member overlying the valve seat and forming a normally closed interface defining a fluid-tight seal between the valve member and the valve seat.

21. A lyophilization device as defined in claim 20, wherein the axially-extending valve seat and flexible valve cover form an inlet valve for introducing the substance through the inlet valve and into the chamber, and the device further includes an outlet valve that is normally closed and forms a fluid-tight seal between the chamber and ambient atmosphere.