VIAL PREPARATION METHOD AND SYSTEM

• US 20130205719A1
• Filed: 08/05/2011
• Published: 08/15/2013
• Est. Priority Date: 08/06/2010
• Status: Active Grant

• Current Assignee: Hospira Australia Pty Limited (Pfizer Inc.)
• Original Assignee: Hospira Australia Pty Limited (Pfizer Inc.)
• Inventors: Knill, Andrew Malcolm, Wensley, Emma J., Suendermann, John Frederic
• Granted Patent: US 10,364,053 B2
• Time in Patent Office: Days
• US Class Current: 53/408
• CPC Class Codes: B01L 3/5082 Test tubes per se
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: B65B 31/027 closed by a stopper
• CPC Class Codes: B65B 7/00 Closing containers or receptacles after filling
• CPC Class Codes: B65B 7/2821 applying plugs or threadless stoppers for bottles or jars B67B1/04
• CPC Class Codes: B65D 39/0023 Plastic cap-shaped hollow plugs
• CPC Class Codes: B65D 81/2076 in an at least partially rigid container
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

Embodiments generally relate to vial preparation methods and to vials prepared by such methods. Some embodiments relate to use of an apparatus, such as a lyophilisation apparatus, to perform the methods. An illustrative vial preparation method comprises:

housing a plurality of vials in a temperature-controlled environment, wherein the plurality of vials each have a volume of a substance therein and each defines an unfilled volume therein, each vial having a stopper partially inserted into an opening of the vial so that gas can transfer between the unfilled volume and an external volume;

applying a vacuum to the environment to reduce pressure in the environment and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the environment to raise the pressure in the environment and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the environment at the second pressure level for a predetermined period;

repeating the applying, venting and allowing at least once; and

fully inserting the stopper into each opening to seal each vial after the repeating.

Claims

1. A preparation method, comprising:

housing a plurality of vials in a temperature-controlled environment, wherein the plurality of vials each have a volume of a substance therein and each defines an unfilled volume therein, each vial having a stopper partially inserted into an opening of the vial so that gas can transfer between the unfilled volume and an external volume;

applying a vacuum to the environment to reduce pressure in the environment and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the environment to raise the pressure in the environment and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the environment at the second pressure level for a predetermined period;

repeating the applying, venting and allowing at least once; and

fully inserting the stopper into each opening to seal each vial after the repeating.

2. The method of claim 1, further comprising, prior to the fully inserting, once repeating only the applying and venting.

3. The method of claim 1, further comprising, after the fully inserting, capping each vial with a cap to retain the stopper in each vial.

4. The method of claim 1, wherein the housing comprises housing the vials in lyophilization apparatus.

5. The method of claim 1, further comprising, before the applying, controlling the temperature in the environment to be at or around a temperature set-point.

6. The method of claim 5, wherein the temperature set-point is a first temperature set-point and the method further comprises, after the venting, controlling the temperature in the environment to be at or around a second temperature set-point that is different from the first temperature set-point.

7. The method of claim 5, wherein the repeating comprises repeating the controlling,

8. The method of claim 6, wherein at least one of:

the first temperature set-point is less than about 10°

C., optionally less than about 8°

C., optionally about 5°

C.; and

the second temperature set-point is between about 17°

C. and about 26°

C.

9. The method of claim 8 wherein the first temperature set-point is at or below a freezing temperature of the substance.

10. The method of claim 9, wherein the first pressure level is between about 0.0001 mbar and about 10 mbar.

11. The method of claim 5, wherein the temperature set-point is above a freezing temperature of the substance and wherein the first pressure level is greater than about 10 mbar and less about 500 mbar, optionally between about 10 mbar and about 300 mbar.

12. The method of claim 6, further comprising allowing the vials to rest in the environment for another predetermined period at or around the second temperature set-point.

13. The method of claim 12, wherein the another period is between about 15 minutes and about 45 or 60 minutes, optionally between about 25 and about 35 minutes, optionally about 30 minutes.

14. The method of claim 1, wherein the second pressure level is between about 800 mbar and about 1000 mbar, optionally between about 900 mbar and 950 mbar.

15. The method of claim 1, wherein the housing is performed at ambient pressure.

16. The method of claim 1, wherein the repeating of the applying, venting and allowing is performed at least twice.

17. The method of claim 16, wherein the repeating of the applying, venting and allowing is performed at least eight times.

18. The method of claim 1, wherein the repeating is performed a number of times effective to reduce a dissolved oxygen content of the substance to about 0.4% or less.

19. The method of claim 1, wherein the repeating is performed a number of times effective to reduce an oxygen gas content in the unfilled volume to less than or equal to about one percent.

20. The method of claim 19, wherein the repeating is performed a number of times effective to reduce the oxygen gas content in the unfilled volume to between about 0.01% and about 0.6%.

21. The method of claim 1, wherein prior to the applying, the unfilled volume contains a substantially atmospheric level of oxygen gas and/or the substance contains a substantially atmospheric level of dissolved oxygen.

22. The method of claim 1, wherein the predetermined time period is between about 15 minutes and about 45 or 60 minutes, optionally between about 25 minutes and about 35 minutes.

23. The method of claim 1, wherein the substance in a liquid form comprises an oxygen-sensitive solution.

24. The method of claim 1, wherein the substance in a liquid form is an aqueous solution free of volatile constituents.

25. The method of claim 1, wherein the substance in a liquid form is stable at temperatures between about 1°

C. and about 26°

C. and pressures between about 10 mbar and 1000 mbar.

116. The method of claim 1, wherein a volume of the liquid or the substance in liquid form remains substantially the same between the housing and the fully inserting, apart from a slight amount of evaporation.

26. A preparation method, comprising:

filling a plurality of vials with a predetermined volume of liquid so that an unfilled volume remains in each vial;

partially inserting a stopper into an opening of each vial so that gas can transfer between the unfilled volume of the vial and an external volume;

housing the vials in a temperature-controlled environment;

applying a vacuum to the environment to reduce pressure in the environment and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the environment to raise the pressure in the environment and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the environment at the second pressure level for a predetermined period;

repeating the applying, venting and allowing at least once; and

fully inserting the stopper into each opening to seal each vial after the repeating.

27-49. -49. (canceled)

50. A preparation method, comprising:

filling a plurality of vials with a predetermined volume of liquid so that an unfilled volume remains in each vial;

partially inserting a stopper into an opening of each vial so that gas can transfer between the unfilled volume of the vial and an external volume;

housing the vials in an environment in which the temperature is fixed at a selected temperature;

applying a vacuum to the environment to reduce pressure in the environment and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the environment to raise the pressure in the environment and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the environment at the second pressure level for a predetermined period;

repeating the applying, venting and allowing at least once; and

fully inserting the stopper into each opening to seal each vial after the repeating.

51-71. -71. (canceled)

72. Use of lyophilization apparatus to prepare a plurality of stoppered vials containing a liquid by a method comprising:

housing the plurality of vials containing the liquid in a closed chamber of the lyophilization apparatus, the vials each arranged to have a stopper partially inserted into an opening of the vial so that gas can transfer between an unfilled internal volume of the vial and an external volume;

controlling the lyophilization apparatus to substantially maintain a selected temperature above freezing in the chamber;

applying a vacuum to the chamber to reduce pressure in the chamber and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the chamber to raise the pressure in the chamber and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the chamber at the second pressure level for a predetermined time period;

repeating the applying, venting and allowing at least once; and

fully inserting the partially inserted stopper into the opening of each vial to seal each vial after the repeating.

73. Use of lyophilization apparatus to prepare a plurality of stoppered vials containing a substance by a method comprising:

housing the plurality of vials containing the substance in a closed chamber of the lyophilization apparatus, the vials each arranged to have a stopper partially inserted into an opening of the vial so that gas can transfer between an unfilled internal volume of the vial and an external volume;

applying a vacuum to the chamber to reduce pressure in the chamber and in the unfilled volume of each vial to a first pressure level;

venting an inert gas into the chamber to raise the pressure in the chamber and in the unfilled volume of each vial to a second pressure level;

allowing the vials to rest in the chamber at the second pressure level for a predetermined time period;

repeating the applying, venting and allowing at least once; and

fully inserting the partially inserted stopper into the opening of each vial to seal each vial after the repeating.

74-97. -97. (canceled)

98. A vial comprising:

a body having a neck and a single opening defined by the neck;

a stopper partly received in and sealing the opening;

a liquid contained by the body and the stopper, the liquid comprising an oxygen-sensitive formulation; and

a headspace defined between the body, the liquid and the stopper;

wherein the stopper has at least one projection received in the opening, wherein the projection defines at least one gap or aperture which, when the projection is partially inserted into the opening, allows gas transfer between the headspace and a volume external of the vial.

99-105. -105. (canceled)

106. A vial comprising:

a body having a neck and a single opening defined by the neck;

a stopper partly received in and sealing the opening;

a substance contained by the body and the stopper, the substance comprising an oxygen-sensitive formulation; and

a headspace defined between the body, the substance and the stopper;

wherein the stopper has at least one projection received in the opening, wherein the projection defines at least one gap or aperture which, when the projection is partially inserted into the opening, allows gas transfer between the headspace and a volume external of the vial.

107. The vial of claim 106, wherein the substance is in a liquid state or a frozen state.

108. The vial of claim 107, wherein the substance in the liquid state is an aqueous solution free of volatile constituents.

109. The vial of claim 107, wherein the substance in the liquid state is stable at temperatures between about 1°

C. and about 26°

C. and pressures between about 10 mbar and 1000 mbar.

110. The vial of claim 106, wherein an oxygen gas content in the headspace is less than or equal to about one percent.

111. The vial of claim 110, wherein the oxygen gas content in the headspace is between about 0.01% and about 0.6%.

112. The vial of claim 106, wherein a dissolved oxygen content in the substance is about 0.4% or less.

113. The vial of claim 106, further comprising a cap to hold the stopper onto the neck.

114. The vial of claim 106, wherein the stopper and vial body are arranged so that, when the stopper is fully inserted into the opening, the disc-shaped top overlies a rim around the opening and the at least one gap is fully occluded by the rim, thereby sealing the vial from gas transfer between the unfilled volume and the external volume.

115. (canceled)

117-122. -122. (canceled)