Method of filling degassed drug product into containers and drug product filling device

Patent metadata

Field	Value
Publication number	US-12448160-B2
Application number	US-202117157594-A
Country	US
Kind code	B2
Filing date	Jan 25, 2021
Priority date	Jul 27, 2018
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

An inventive drug product filling device for filling a liquid drug product into containers is disclosed. The drug filling device includes a drug product preparer configured for preparing the liquid drug product and a filling station configured for filling the liquid drug product into the containers. The filling station is fluidly coupled to the drug product preparer. A degasser is fluidly interposed between the drug product preparer and the filling station. The degasser has a membrane configured for at least partially separating off gas from the liquid drug product. Methods of (i) filling a liquid drug product into containers, (ii) increasing the accuracy of the filling weight of a liquid drug product in a container, (iii) increasing the stability oxygen-sensitive active pharmaceutical ingredient in a liquid drug product, and (iv) reducing polysorbate aggregate formation in a liquid drug product are also disclosed.

First claim

What is claimed is:

1. A drug product filling device for filling a liquid drug product into containers, comprising:
a) a drug product preparer configured for preparing the liquid drug product;
b) a filling station configured for filling the liquid drug product into the containers, the filling station being fluidly coupled to the drug product preparer;
c) a degasser fluidly interposed between the drug product preparer and the filling station, the degasser comprising a degasser membrane configured for at least partially separating off at least one gas from the liquid drug product, wherein the degasser comprises at least one hollow fiber membrane module including a plurality of hollow fibers having a first side and an opposing second side, the first side defining an interior lumen receiving the liquid drug product, wherein the hollow fibers of the at least one hollow fiber membrane module are at least partially formed by the degasser membrane and are sterilizable, wherein the hollow fibers form fiber bundles having opposing ends embedded in opposed sealings; and
d) at least one in-line filtering device fluidically interposed between the drug product preparer and the filling station, wherein the in-line filtering device comprises a sterile filter.

2. The drug product filling device according to claim 1 , wherein the degasser is configured for applying a pressure difference over the degasser membrane, with the liquid drug product being in contact with the degasser membrane on the first side and with the opposing second side of the degasser membrane being exposed to a lower pressure than the first side.

3. The drug product filling device according to claim 2 , wherein the degasser comprises at least one of a vacuum source or a vacuum port configured for applying a vacuum to the second side.

4. The drug product filling device according to claim 1 , wherein the opposing ends of the fiber bundles are connected to connection ports.

5. The drug product filling device according to claim 1 , wherein the hollow fiber membrane module comprises a housing having the hollow fibers disposed therein.

6. The drug product filling device according to claim 5 , wherein the hollow fiber membrane module comprises a fiber entry port connected to a first end of the hollow fibers, a fiber exit port connected to a second end of the hollow fibers, and a housing entry port and a housing exit port, both the housing entry port and the housing exit port being connected to an inner space inside the housing between the hollow fibers and a wall of the housing.

7. The drug product filling device according to claim 6 , wherein the hollow fiber membrane module is fluidly interposed between the drug product preparer and the filling station in a manner selected from the group consisting of the following options:
i) the fiber entry port is fluidly connected to the drug product preparer, and the fiber exit port is fluidly connected to the filling station;
ii) the housing entry port is fluidly connected to the drug product preparer, and the housing exit port is fluidly connected to the filling station.

8. The drug product filling device according to claim 7 , comprising option i), wherein one or both of the housing entry port and the housing exit port are connected to a suction device.

9. The drug product filling device according to claim 7 , comprising option ii), wherein one or both of the fiber entry port and the fiber exit port are connected to a suction device.

10. The drug product filling device according to claim 1 , wherein the degasser has at least one entry port connected to the drug product preparer and at least one exit port connected to the filling station.

11. The drug product filling device according to claim 1 , wherein the filling station further comprises at least one inspection device for optically inspecting the containers after filling with the liquid drug product.

12. A method of filling at least one liquid drug product into containers, comprising:
A) providing at least one drug product filling device configured for filling at least one liquid drug product into containers, wherein step A) further comprises:
i) providing a drug product preparer configured for preparing the liquid drug product;
ii) providing a filling station configured for filling the liquid drug product into the containers, the filling station being fluidically coupled to the drug product preparer;
iii) providing a degasser fluidly interposed between the drug product preparer and the filling station and the degasser comprising at least one degasser membrane for separating off at least one gas from the liquid drug product, wherein the degasser comprises at least one hollow fiber membrane module including a plurality of hollow fibers at least partially formed by the degasser membrane, the plurality of hollow fibers having a first side and an opposing second side, the first side defining an interior lumen receiving the liquid drug product, wherein the hollow fibers are at least partially formed by the degasser membrane and are sterilizable, wherein the hollow fibers form fiber bundles having opposing ends embedded in opposed sealings;
iv) providing at least one in-line filtering device fluidically interposed between the drug product preparer and the filling station, wherein the in-line filtering device comprises a sterile filter;

B) conducting the liquid drug product from the drug product preparer to the filling station, wherein the liquid drug product is at least partially degassed upon passing through the degasser; and
C) filling the at least partially degassed liquid drug product into the containers using the filling station.

13. The method of claim 12 , wherein the filling station further comprises at least one inspection device for optically inspecting the containers after filling with the liquid drug product.

14. The method of claim 12 , wherein the degasser is configured for applying a pressure difference over the degasser membrane, with the liquid drug product being in contact with the degasser membrane on the first side and with the opposing second side of the membrane being exposed to a lower pressure than the first side.

15. A method of increasing the accuracy of the filling weight of a liquid drug product in a container, the method comprising:
I. preparing the liquid drug product via a drug product preparer;
II. degassing the liquid drug product by at least partially separating off at least one gas from the liquid drug product by using a degasser, the degasser comprising at least one degasser membrane, wherein the degasser comprises at least one hollow fiber membrane module including a plurality of hollow fibers at least partially formed by the degasser membrane, the plurality of hollow fibers having a first side and an opposing second side, the first side defining an interior lumen receiving the liquid drug product, wherein the hollow fibers are at least partially formed by the degasser membrane and are sterilizable, wherein the hollow fibers form fiber bundles having opposing ends embedded in opposed sealings;
III. providing at least one in-line filtering device fluidically interposed between the drug product preparer and a filling station, wherein the in-line filtering device comprises a sterile filter;
IV. filling the degassed liquid drug product into the container via the filling station.

16. The method of claim 15 , wherein the filling station further comprises at least one inspection device for optically inspecting the containers after filling with the liquid drug product.

17. The method of claim 15 , wherein

Assignees

• Hoffmann La Roche
• Hoffmann La Roche

Inventors

• Boeuf Julien
• Keehnen Vincent
• Rakel Natalie
• Ulmer Alexander
• Zieres Gerald

Classifications

• B01D63/031

  Two or more types of hollow fibres within one bundle or within one potting or tube-sheet · CPC title

• B65B63/00

  Auxiliary devices, not otherwise provided for, for operating on articles or materials to be packaged · CPC title

• B65B3/003 Primary

  Filling medical containers such as ampoules, vials, syringes or the like · CPC title

• B01D2313/24

  Specific pressurizing or depressurizing means · CPC title

• B01D2313/13

  Specific connectors · CPC title