Manufacture of prefilled syringes

• US 6,189,195 B1
• Filed: 08/22/1995
• Issued: 02/20/2001
• Est. Priority Date: 08/22/1995
• Status: Expired due to Fees

• Current Assignee: Medrad Incorporated (Bayer AG)
• Original Assignee: Medrad Incorporated (Bayer AG)
• Inventors: Robinson, Michelle, Rhinehart, Edward J., Reilly, David M., Hitchins, Mark W., Gelblum, Eugene A.
• Primary Examiner(s): HUGHES, SAMUEL T
• Application Number:
  US08/517,645
• Time in Patent Office: 2,009 Days
• Field of Search: 297/22, 294/29, 294/34, 294/69, 531/22, 534/28
• US Class Current: 29/434
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: Y10T 29/49808 Shaping container end to encapsulate material
• CPC Class Codes: Y10T 29/4984 Retaining clearance for motion between assembled parts

Abstract

This invention relates to a process for manufacturing prefilled syringes where at least one of the syringe components is manufactured in at least a class 100 environment. The process includes the steps of manufacturing syringe components, such as the barrel and plunger substrate, within at least a class 100 and MCB-3 environment; manufacturing syringe components, such as the plunger cover and tip seal in an environment less clean than a class 100 environment; decontaminating the plunger cover and tip seal; lubricating at least one of the barrel, plunger substrate, plunger cover and tip seal; assembling the barrel and tip seal to form a barrel/tip seal combination; assembling the plunger cover and plunger substrate to form a plunger; filling the barrel/tip seal combination with a predetermined amount of fluid; and final assembling of the prefilled syringe by inserting the plunger into the barrel/tip seal combination. When the syringe components are manufactured at different locations, each component is tripled-bagged to maintain the component substantially free from contaminants, and transported to an assembly site where the components are unpackaged and assembled into the barrel/tip seal combination and plunger. When filling and final assembly of the barrel/tip seal combination takes place at a location separate from its assembly site, the barrel/tip seal combination is tripled-bagged to maintain it substantially free from contaminants, and transported to a filling and final assembling site for filling and final assembling into a prefilled syringe.

Claims

1. A process of manufacturing a syringe, the process comprising:

molding a barrel and a plunger substrate within at least a class 100 environment, without subsequently washing the barrel and the plunger substrate;

packaging the barrel and plunger substrate within at least a class 100 environment, thereby maintaining the barrel and the plunger substrate substantially free of contaminants;

molding a plunger cover and a tip seal within an environment less clean than a class 100 environment;

packaging the plunger cover and the tip seal within at least a class 100 environment, thereby maintaining the plunger cover and the tip seal substantially free of contaminants;

transporting the packaged barrel and the packaged tip seal to a first assembly site having at least a class 100 environment;

unpackaging the barrel and the tip seal within the at least class 100 environment at the first assembly site;

assembling the unpackaged tip seal to the unpackaged barrel within the at least class 100 environment at the first assembly site, thereby providing a barrel/tip seal combination;

transporting the packaged plunger substrate and the packaged plunger cover to a second assembly site having at least a class 100 environment;

unpackaging the plunger substrate and the plunger cover within the at least class 100 environment at the second assembly site;

assembling the unpackaged plunger cover to the unpackaged plunger substrate within the at least class 100 environment at the second assembly site, thereby providing a plunger assembly;

packaging the barrel/tip seal combination within at least a class 100 environment, thereby maintaining the barrel/tip seal combination substantially free of contaminants;

packaging the plunger assembly within at least a class 100 environment, thereby maintaining the plunger assembly substantially free of contaminants;

transporting the packaged barrel/tip seal combination and the packaged plunger assembly to a final assembly site having least a class 100 environment;

unpackaging the barrel/tip seal combination and the plunger assembly within the at least class 100 environment at the final assembly site; and

assembling the unpackaged plunger assembly to the unpackaged barrel/tip seal combination within the at least class 100 environment at the final assembly site.

4. The process of claim 1 wherein the barrel and plunger substrate are molded within at least a MCB-3 environment.

5. The process of claim 1 wherein the first assembly site is at least a MCB-3 environment.

6. The process of claim 1, further comprising the steps of:

prior to packaging the plunger cover and tip seal;

decontaminating and lubricating the plunger cover and tip seal.

7. The process of claim 1 wherein each packaging step comprises the steps of:

inserting each of the barrel, plunger substrate, plunger cover and tip seal into respective first containers;

sealing the respective first containers;

inserting the respective sealed first containers into respective second containers;

sealing the respective second containers;

transporting the respective sealed second containers to an environment less clean than a class 100 environment;

inserting the respective sealed second containers into respective third containers; and

sealing the respective third containers.

8. The process of claim 7, further comprising the steps of:

prior to transporting the packaged barrel and packaged tip seal to the first assembly site, transporting the packaged barrel and packaged tip seal to a receiving site being less clean than a class 100 environment;

removing each of the packaged barrel and packaged tip seal from the respective sealed third containers;

transporting the packaged barrel and packaged tip seal to a feedthrough area; and

removing each of the packaged barrel and packaged tip seal from the respective sealed second containers.

9. The process of claim 8, further comprising the steps of:

after transporting each of the packaged barrel and packaged tip seal to the first assembly site, removing each of the packaged barrel and packaged tip seal from the respective sealed first containers.

10. The process of claim 7, further comprising the steps of:

prior to transporting the packaged plunger substrate and packaged plunger cover to the second assembly site, transporting the packaged plunger substrate and packaged plunger cover to a receiving site being less clean than a class 100 environment;

removing each of the packaged plunger substrate and packaged plunger cover from the respective sealed third containers;

transporting the packaged plunger substrate and packaged plunger cover to a feedthrough area; and

removing each of the packaged plunger substrate and packaged plunger cover from the respective sealed second containers.

11. The process of claim 10, further comprising the step of:

after transporting each of the packaged plunger substrate and packaged plunger cover to the second assembly site, removing each of the packaged plunger substrate and packaged plunger cover from the respective sealed first containers.

12. The process of claim 1, further comprising the steps of:

after forming the barrel/tip seal combination, packaging the barrel/tip seal combination to maintain it substantially free from contaminants;

after forming the plunger, packaging the plunger to maintain it substantially free from contaminants;

transporting the packaged barrel/tip seal combination and packaged plunger to a final assembly site which is at least a class 100 environment; and

finally assembling the syringe by inserting the plunger into the barrel/tip seal combination to form a prefilled syringe.

13. The process of claim 1 wherein the final assembly site is at least a MCB-3 environment.

14. The process of claim 1 wherein the steps of packaging the barrel/tip seal combination and packaging the plunger comprise the steps of:

inserting each of the barrel/tip seal combination and plunger into a respective first container;

sealing the respective first containers;

inserting the respective sealed first containers into respective second containers;

sealing the respective second containers;

transporting the respective sealed second containers to an environment less clean than a class 100 environment;

inserting the respective sealed second containers into respective third containers; and

sealing the respective third containers.

15. The process of claim 14, further comprising the steps of:

prior to final assembly of the syringe, transporting the packaged barrel/tip seal combination and packaged plunger to a receiving site being less clean than a class 100 environment;

removing each of the packaged barrel/tip seal combination and packaged plunger from the respective sealed third containers;

transporting each of the packaged barrel/tip seal combination and packaged plunger to a feedthrough area; and

removing each of packaged barrel/tip seal combination and packaged plunger from the respective sealed second containers.

16. The process of claim 15, further comprising the step of:

after transporting each of the packaged barrel/tip seal combination and packaged plunger to the final assembly site, removing each of the packaged barrel/tip seal combination and packaged plunger from the respective sealed first containers.

17. The process of claim 1, further comprising the step of:

after final assembly of the syringe, sterilizing the prefilled syringe.

22. The process of claim 1, further comprising the step of filling the assembled barrel/tip seal combination at the final assembly site with a contrast fluid.

2. A process of manufacturing a syringe, the process comprising:

molding a barrel and a plunger substrate within at least a class 100 environment;

packaging the barrel and the plunger substrate within at least a class 100 environment, thereby maintaining the barrel and the plunger substrate substantially free of contaminants;

molding a plunger cover and a tip seal within an environment less clean than a class 100 environment;

packaging the plunger cover and the tip seal within at least a class 100 environment, thereby maintaining the plunger cover and the tip seal substantially free of contaminants;

transporting the packaged barrel and the packaged tip seal to a first assembly site having at least a class 100 environment;

unpackaging the barrel and the tip seal within the at least class 100 environment at the first assembly site;

assembling the unpackaged tip seal to the unpackaged barrel within the at least class 100 environment at the first assembly site, thereby providing a barrel/tip seal combination;

transporting the packaged plunger substrate and the packaged plunger cover to a second assembly site having at least a class 100 environment;

unpackaging the plunger substrate and the plunger cover within the at least class 100 environment at the second assembly site;

assembling the unpackaged plunger cover to the unpackaged plunger substrate within the at least class 100 environment at the second assembly site, thereby providing a plunger assembly;

inserting each of the barrel/tip seal combination and the plunger assembly into a respective first container within at least a class 100 environment, thereby maintaining the barrel/tip seat combination and the plunger assembly substantially free of contaminants;

sealing the respective first containers;

inserting the respective sealed first containers into respective second containers;

sealing the respective second containers;

inserting the respective sealed second containers into respective third containers;

sealing the respective third containers;

transporting the packaged barrel/tip seal combination and the packaged plunger assembly to a final assembly site having least a class 100 environment;

unpackaging the barrel/tip seal combination and the plunger assembly within the at least class 100 environment at the final assembly site; and

assembling the unpackaged plunger assembly to the unpackaged barrel/tip seal combination within the at least class 100 environment at the final assembly site.

18. The process of claim 2 wherein the final assembly site is at least a MCB-3 environment.

19. The process of claim 2, further comprising:

prior to final assembly of the syringe, transporting the packaged barrel/tip seal combination and packaged plunger to a receiving site being less clean than a class 100 environment;

removing each of the packaged barrel/tip seal combination and packaged plunger from the respective sealed third containers;

transporting each of the packaged barrel/tip seal combination and packaged plunger to a feedthrough area; and

removing each of packaged barrel/tip seal combination and packaged plunger from the respective sealed second containers.

3. A process of manufacturing a syringe, the process comprising:

molding a barrel and a plunger substrate within at least a class 100 environment, without subsequently washing the barrel and the plunger substrate;

molding a plunger cover and a tip seal within an environment less clean than a class 100 environment;

inserting each of the barrel, the plunger substrate, the plunger cover and the tip seal into respective first containers within at least a class 100 environment, thereby maintaining the barrel, the plunger substrate, the plunger cover and the tip seal substantially free of contaminants;

sealing the respective first containers;

inserting the respective sealed first containers into respective second containers;

sealing the respective second containers;

inserting the respective sealed second containers into respective third containers;

sealing the respective third containers;

transporting the packaged barrel and the packaged tip seal to a first assembly site having at least a class 100 environment;

unpackaging the barrel and the tip seal within the at least class 100 environment at the first assembly site;

assembling the unpackaged tip seal to the unpackaged barrel within the at least class 100 environment at the first assembly site, thereby providing a barrel/tip seal combination;

transporting the packaged plunger substrate and the packaged plunger cover to a second assembly site having at least a class 100 environment;

unpackaging the plunger substrate and the plunger cover within the at least class 100 environment at the second assembly site;

assembling the unpackaged plunger cover to the unpackaged plunger substrate within the at least class 100 environment at the second assembly site, thereby providing a plunger assembly;

packaging the barrel/tip seal combination within at least a class 100 environment, thereby maintaining the barrel/tip seal combination substantially free of contaminants;

packaging the plunger assembly within at least a class 100 environment, thereby maintaining the plunger assembly substantially free of contaminants;

transporting the packaged barrel/tip seal combination and the packaged plunger assembly to a final assembly site having least a class 100 environment;

unpackaging the barrel/tip seal combination and the plunger assembly within the at least class 100 environment at the final assembly site; and

assembling the unpackaged plunger assembly to the unpackaged barrel/tip seal combination within the at least class 100 environment at the final assembly site.

20. The process of claim 3, further comprising:

prior to transporting the packaged barrel and packaged tip seal to the first assembly site, transporting the packaged barrel and packaged tip seal to a receiving site being less clean than a class 100 environment;

removing each of the packaged barrel and packaged tip seal from the respective sealed third containers;

transporting the packaged barrel and packaged tip seal to a feedthrough area; and

removing each of the packaged barrel and packaged tip seal from the respective sealed second containers.

21. The process of claim 3, further comprising:

prior to transporting the packaged plunger substrate and packaged plunger cover to the second assembly site, transporting the packaged plunger substrate and packaged plunger cover to a receiving site being less clean than a class 100 environment;

removing each of the packaged plunger substrate and packaged plunger cover from the respective sealed third containers;

transporting the packaged plunger substrate and packaged plunger cover to a feedthrough area; and

removing each of the packaged plunger substrate and packaged plunger cover from the respective sealed second containers.