Method for external sterilization of drug delivery device

Patent metadata

Field	Value
Publication number	US-12233177-B2
Application number	US-202017022695-A
Country	US
Kind code	B2
Filing date	Sep 16, 2020
Priority date	Sep 16, 2019
Publication date	Feb 25, 2025
Grant date	Feb 25, 2025

Abstract

A method of externally sterilizing a drug delivery device utilizing Nitrogen Dioxide (NO2) is provided, including placing the drug delivery device in a sterilization chamber, introducing into the chamber a dose of NO2 having a concentration of between about 2 and 20 milligrams per Liter by applying a vacuum level of between about 10 and 600 Torr and holding the vacuum level for a dwell time of between about 2 and 20 minutes, repeating the step of introducing into the chamber a dose of NO2 for a number of pulses between about 1 and 24, purging the sterilization chamber of at least substantially all of the NO2, and aerating the sterilization chamber.

First claim

What is claimed is:

1. A method of externally sterilizing a drug delivery device utilizing Nitrogen Dioxide (NO2), comprising:
placing the drug delivery device in a sterilization chamber, wherein the drug delivery device is a syringe comprising a barrel, a flange portion, and a backstop coupled with the flange portion;
introducing into the sterilization chamber a dose of NO2 having a concentration of between about 2 and 20 milligrams per Liter by applying a vacuum level of between about 10 and 600 Torr and holding the vacuum level for a dwell time of between about 2 and 20 minutes, wherein the backstop is configured to permit or promote the NO2 to flow through a space between the backstop and the syringe when the backstop is coupled with the syringe;
repeating the step of introducing into the sterilization chamber the dose of NO2 for a number of pulses between about 1 and 24;
purging the sterilization chamber of at least substantially all of the NO2; and
aerating the sterilization chamber.

2. A method as in claim 1 , wherein the syringe is a pre-filled syringe further comprising a stopper and a plunger rod, and wherein the barrel contains a medicament.

3. A method as in claim 2 , wherein the medicament is a VEGF antagonist.

4. A method as in claim 1 , wherein the barrel is a plastic barrel.

5. A method as in claim 1 , wherein the vacuum level is between about 100 and 500 Torr.

6. A method as in claim 1 , wherein the vacuum level is between about 150 and 400 Torr.

7. A method as in claim 1 , wherein the vacuum level is between about 150 and 300 Torr.

8. A method as in claim 1 , wherein the concentration of the dose of NO2 is between about 2 and 10 milligrams per Liter.

9. A method as in claim 1 , wherein the concentration of the dose of NO2 is between about 2 and 7 milligrams per Liter.

10. A method as in claim 1 , wherein the chamber has a relative humidity is between about 70 and 90 percent.

11. A method as in claim 1 , wherein the dwell time is between about 2 and 12 minutes.

12. A method as in claim 1 , wherein the dwell time is between about 2 and 7 minutes.

13. A method as in claim 1 , wherein the number of pulses is between about 1 and 12.

14. A method as in claim 1 , wherein the number of pulses is between about 1 and 8.

15. A method as in claim 1 , wherein the number of pulses is between about 1 and 4.

16. A method as in claim 1 , wherein the number of pulses is between about 1 and 2.

17. A method as in claim 1 , wherein the step of aerating the sterilization chamber includes aerating the sterilization chamber a number of cycles between about 12 and 70 cycles to at least substantially prevent discoloration of the drug delivery device.

18. A method as in claim 1 , wherein the method of externally sterilizing the drug delivery device achieves at least a 2 logs microbial reduction.

19. A method as in claim 1 , wherein the method of externally sterilizing the drug delivery device achieves at least a 3 logs microbial reduction.

20. A method as in claim 1 , wherein the method of externally sterilizing the drug delivery device achieves at least a 4 logs microbial reduction.

21. A method as in claim 1 , wherein the method of externally sterilizing the drug delivery device achieves at least a 5 logs microbial reduction.

22. A method as in claim 1 , wherein the method of externally sterilizing the drug delivery device achieves at least a 6 logs microbial reduction.

23. A method of externally sterilizing a drug delivery device utilizing Nitrogen Dioxide (NO2), comprising:
placing the drug delivery device in a sterilization chamber, wherein the drug delivery device is a syringe comprising a barrel, a flange portion, and a backstop coupled with the flange portion;
introducing into the sterilization chamber a dose of NO2 having a concentration of between about 5 and 20 milligrams per Liter by applying a vacuum level of between about 150 and 500 Torr and holding the vacuum level for a dwell time of between about 5 and 10 minutes, wherein the backstop is configured to permit or promote the NO2 to flow through a space between the backstop and the syringe when the backstop is coupled with the syringe;
repeating the step of introducing into the sterilization chamber the dose of NO2 for a number of pulses between about 1 and 24;
purging the sterilization chamber of at least substantially all of the NO2; and
aerating the sterilization chamber a number of cycles between about 20 and 90.

24. A method of externally sterilizing a pre-filled syringe having a drug container and a medicament contained in the drug container, the method of externally sterilizing comprising the following steps:
placing the pre-filled syringe in a sterilization chamber, the pre-filled syringe comprising a flange portion and a backstop coupled with the flange portion;
introducing into the sterilization chamber a dose of Nitrogen Dioxide (NO2) having a predetermined concentration by applying a predetermined vacuum level and holding the vacuum level for a predetermined dwell time, wherein the backstop is configured to permit or promote the NO2 to flow through a space between the backstop and the pre-filled syringe when the backstop is coupled with the pre-filled syringe;
repeating the step of e introducing into the sterilization chamber the dose of NO2 for a number of pulses between about 1 and 24;
purging the sterilization chamber of at least substantially all of the NO2; and
aerating the sterilization chamber a predetermined number of cycles,
wherein the method of externally sterilizing the pre-filled syringe achieves at least a log 6 lethality target for the pre-filled syringe while realizing an ingress of NO2 gas into the drug container of less than 3.0 parts per million, as measured 30 days after externally sterilizing the pre-filled syringe.

Assignees

• Amgen Inc

Inventors

• Mismar Wael
• Liu Jessica Hai
• Wu Chia-Jung
• Abbas Shermeen A
• Devitt Shaun
• Schalhoub Kenneth G
• Bitong Anthony
• Due Mads Schjoth
• Guirguis Malak
• Saifan Rami

Classifications

• A61L2103/15

  Laboratory, medical or dentistry appliances, e.g. catheters or sharps · CPC title

• A61L2103/05

  Living organisms or biological materials · CPC title

• A61L2202/122

  Chambers for sterilisation · CPC title

• A61L2/26

  Accessories · CPC title

• A61M5/3137

  Specially designed finger grip means, e.g. for easy manipulation of the syringe rod · CPC title