Methods and systems for removing pressure and air from chromatography columns

Inventors

Chan, Alan Kit Ho • Peyser, James Ronald

Assignees

Repligen Corp

Abstract

Methods and systems for removing gases and/or pressure formed during the sterilization, e.g., the gamma irradiation, of prepacked chromatography systems (column plus attached tube and valve set) are described. The methods include purging the gas and/or pressure through specially designed tube and valve sets without breaching the sterility of the prepacked sterile chromatography system. The systems include a sterile or aseptic pre-packed chromatography column including a column having an inlet and an outlet, a tubing and valve set attached to the inlet and the outlet, and a pump configured to pump sterile or aseptic liquid from the fluid source along the tubing and valve set, into the column tube inlet and out of the column tube outlet along a first flow path, thereby removing any entrapped gas and/or pressure from the chamber.

Core Innovation

The invention provides aseptic/sterile systems and methods for removing entrapped gas, pressure, or both gas and pressure from a pre-packed chromatography column having a chamber and a column tube with a column tube inlet and a column tube outlet. A sterile or aseptic tubing and valve set forms a closed system attached to the column tube inlet and the column tube outlet, and defines at least two different fluid paths, each fluidly connected to the column tube inlet and the column tube outlet.

The method includes obtaining a tubing and valve set configured to define at least two selectable fluid paths using first and second valves and third and fourth valves disposed in different tubing branches. The pre-packed chromatography column and the tubing and valve set are sterilized and/or attached in a manner that maintains sterility of both components, and sterile or aseptic liquid is pumped from a sterile or aseptic fluid source through the tubing and valve set into the column tube inlet and out from the column tube outlet along a selected fluid path.

The described approach further enables valve configurations that provide a first flow path and a second flow path through the column using different valve open/closed configurations, including flow from the tubing inlet to the column tube outlet to the column tube inlet to the tubing outlet for the first flow path, and the opposite order for the second flow path. Optional embodiments describe venting via hydrophobic vent filters, use of sterile or aseptic filters, and use of an expansion bag and a controller-controlled valve/pump sequencing to manage fluid paths during de-gassing/de-pressurization.

Claims Coverage

The document includes two independent claims that cover a sterile/aseptic method for removing entrapped gas and/or pressure from a pre-packed chromatography column using a tubing-and-valve set defining at least two different fluid paths, with valve configuration and pumping of sterile/aseptic liquid along a selected flow path while maintaining sterility. Dependent claims refine venting, alternate flow-path configurations, and quantitative or standard-based constraints for sterilization and liquid volume.

Across the independent claims, the coverage centers on a sterilized tubing-and-valve set that defines at least two selectable fluid paths connected to the column tube inlet and outlet, maintaining sterility of the column and tubing/valve set, configuring valve states to establish the desired flow path, and pumping sterile or aseptic liquid through the selected flow path to remove entrapped gas and/or pressure from the column chamber and associated tubing.

Stated Advantages

Documented Applications