Pre-filled syringe

Patent metadata

Field	Value
Publication number	US-11826322-B2
Application number	US-202016998559-A
Country	US
Kind code	B2
Filing date	Aug 20, 2020
Priority date	Jan 13, 2017
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

The invention relates to a pre-filled syringe, an auto-injector device comprising such pre-filled syringe, a method of administering a pharmaceutical composition with such auto-injector device, and a manufacturing method for such auto-injector device. The pre-filled syringe comprises a container and a needle. The container is filled with a pharmaceutical composition comprising epinephrine, a buffer, and water. The buffer is configured to buffer in a pH range between 3 and 4. The needle is adhered to the container by means of a urethane acrylate or urethane methacrylate acrylic light cure adhesive, which is configured to provide a pull out resistance of the needle relative to the container which is between 30 N to 100 N, preferably between 50 N to 70 N, more preferably greater than 60 N after 90 days exposure to the pharmaceutical composition at 40° C. and 75% relative humidity (RH). In an example, the pharmaceutical composition is for the treatment of an anaphylactic event.

First claim

The invention claimed is:

1. A manufacturing method for an auto-injector, the manufacturing method comprising:
manufacturing a pharmaceutical composition, the pharmaceutical composition comprising epinephrine, a buffer, and water, wherein the pharmaceutical composition has a pH ranging between 3 and 4;
sterilizing the pharmaceutical composition;
adhering a stainless steel needle to a glass container with an adhesive, wherein the adhesive comprises at least one of a urethane acrylate adhesive or a urethane methacrylate adhesive;
filling the glass container with at least 1 mL of the pharmaceutical composition to form a pre-filled container; and
assembling the pre-filled container into the auto-injector, wherein the auto-injector is for single use injection and comprises a firing mechanism, wherein the firing mechanism is configured to expel only a single injection of about 0.3 mL of the at least 1 mL of the pharmaceutical composition from the pre-filled container, and the firing mechanism is configured to expel the single injection in less than 0.5 seconds.

2. The manufacturing method of claim 1 , wherein the manufacturing of the pharmaceutical composition comprises:
preparing a solution comprising the buffer and an antioxidant;
adding a pH adjuster to adjust a pH of the solution to a range between 2.5 and 4.3;
adding the epinephrine; and
adding, after adding the epinephrine, the pH adjuster or another pH adjuster to adjust a pH of the solution comprising the epinephrine to a range between 3 and 4.

3. The manufacturing method of claim 2 , wherein the pH adjuster or the other pH adjuster is added to adjust the pH of the solution comprising the epinephrine to about 3.4.

4. The manufacturing method of claim 1 , wherein the sterilizing of the pharmaceutical composition comprises performing an aseptic filtration.

5. The manufacturing method of claim 4 , wherein performing the aseptic filtration occurs at room temperature with a polyvinylidenfluoride filter.

6. The manufacturing method of claim 5 , wherein the polyvinylidenfluoride filter has a pore size ranging between 0.1 [tm and 0.3 [tm.

7. The manufacturing method of claim 1 , wherein the glass container is filled with the pharmaceutical composition through an opening, and wherein the opening is closed after the filling by a stopper using a vacuum stoppering technique.

8. The manufacturing method of claim 1 , wherein the stainless steel needle comprises 15 to 20% Cr, 8 to 16% Ni, and 3 to 4% Mo.

9. The manufacturing method of claim 1 , wherein the stainless steel needle comprises 15 to 20% Cr, 20 to 30% Ni, and 3 to 6% Mo.

10. The manufacturing method of claim 1 , wherein the buffer comprises at least one of bicarboxylic acid, tartrate salt, or sodium tartrate dihydrate.

11. The manufacturing method of claim 1 , wherein the pharmaceutical composition further comprises an antioxidant.

12. The manufacturing method of claim 11 , wherein the antioxidant comprises sodium metabisulfite.

13. The manufacturing method of claim 1 , wherein the firing mechanism is configured to expel the pharmaceutical composition from the pre-filled container at a pressure ranging between 100 psi and 4000 psi.

14. The manufacturing method of claim 1 , wherein, after the adhesive is exposed to the pharmaceutical composition for 90 days at 40° C. and 75% relative humidity, the adhesive is configured to resist a pull out force of between 30 N and 100 N applied to at least one of the stainless steel needle or the glass container.

15. The manufacturing method of claim 1 , wherein the firing mechanism is configured such that at least about 0.7 mL of the at least 1 mL of the pharmaceutical composition remains in the auto-injector after the single injection.

16. The manufacturing method of claim 15 , wherein the auto-injector is configured to prevent the at least about 0.7 mL of the at least 1 mL of the pharmaceutical composition from being expelled from the pre-filled container.

17. The manufacturing method of claim 16 , wherein the firing mechanism comprises a ram configured to expel the pharmaceutical composition from the pre-filled container, and wherein, after the single injection, the ram is configured to rest against the pre-filled container to prevent another injection of the pharmaceutical composition from the pre-filled container.

18. A manufacturing method for an auto-injector, the manufacturing method comprising:
degassing water comprising:
subjecting the water to a vacuum to form vacuumed water, sparging the vacuumed water with nitrogen gas to form sparged water, and subjecting the sparged water to a vacuum to form degassed water;
manufacturing a pharmaceutical composition, the pharmaceutical composition comprising epinephrine, a buffer, and the degassed water, wherein the pharmaceutical composition has a pH ranging between 3 and 4;
sterilizing the pharmaceutical composition;
adhering a stainless steel needle to a glass container with an adhesive, wherein the adhesive comprises at least one of a urethane acrylate adhesive or a urethane methacrylate adhesive;
filling the glass container with at least 1 mL of the pharmaceutical composition to form a pre-filled container; and
assembling the pre-filled container into the auto-injector, wherein the auto-injector comprises comprising a firing mechanism, wherein the firing mechanism is configured to expel the pharmaceutical composition from the pre-filled container.

19. The manufacturing method of claim 18 , wherein the water is subjected to the vacuum for about 45 minutes.

20. The manufacturing method of claim 18 , wherein the vacuumed water is sparged with the nitrogen gas at a minimum of 4 L/min for about 120 minutes.

21. The manufacturing method of claim 18 , wherein, after the adhesive is exposed to the pharmaceutical composition for 90 days at 40° C. and 75% relative humidity, the adhesive is configured to resist a pull out force of between 30 N and 100 N applied to at least one of the stainless steel needle or the glass container.

22. The manufacturing method of claim 18 , wherein the firing mechanism is configured to expel about 0.3 mL of the pharmaceutical composition from the pre-filled container in less than 0.5 seconds-during a single injection.

23. The manufacturing method of claim 18 , wherein the sterilizing of the pharmaceutical composition comprises performing an aseptic filtration.

24. The manufacturing method of claim 18 , wherein the glass container is filled with the pharmaceutical composition through an opening, and wherein the opening is closed after the filling by a stopper using a vacuum stoppering technique.

25. The manufacturing method of claim 18 , wherein the firing mechanism is configured to expel the pharmaceutical composition from the pre-filled container at a pressure ranging between 100 psi and 4000 psi.

26. The manufacturing method of claim 18 , wherein the buffer comprises at least one of bicarboxylic acid, tartrate salt, or sodium tartrate dihydrate.

27. The manufacturing method of claim 18 , wherein the pharmaceutical composition further comprises an antioxidant.

Assignees

• Teva Pharma

Inventors

• Joguparthi Vijay
• Lobrutto Rosario

Classifications

• B65B7/2821

  applying plugs or threadless stoppers (for bottles or jars B67B1/04) · CPC title

• B65B55/16

  by irradiation · CPC title

• A61K31/137 Primary

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61L31/022

  Metals or alloys · CPC title