Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.

The invention provides a method for the continuous, microbe-reduced production and/or processing of a biopharmaceutical, biological macromolecular product from a heterogeneous cell culture-fluid mixture, comprising the steps of: (a) providing a particle-free fluid from a heterogeneous cell culture-fluid mixture containing the product, in the form of a product stream, (b) at least one filtration, providing a filtrate, (c) at least two chromatography steps for purifying the product, (d) at least one virus depletion, (e) at least one ultrafiltration and/or at least one diafiltration of the product stream of steps (b), (c) and/or (d), characterized in that the at least two chromatography steps from (c) comprise a purification via at least two chromatography columns and/or membrane adsorbers in each case and that the process is carried out in a closed and modular manner The invention further provides a corresponding modular system for carrying out said method.

The present invention refers to a method of purifying a glucagon-like peptide 1 analogs, the method comprising a two dimensional reversed phase high performance liquid chromatography protocol, wherein the first step is carried out at a pH value between 7.0 to 7.8 using a mobile phase comprising a phosphate buffer and acetonitrile, and the second step is carried out at a pH value below 3.0 using a mobile phase comprising trifluoroacetic acid and acetonitrile.

A method for preparing high-purity cannabidiol is characterized in that: the leaves of cannabis and top portions of the plant which account for about one-fifth of the whole plant are used as extraction sites; a technology of combined macroporous adsorption resin chromatography and polyamide chromatography is used for purification; and a mixed solvent system is used for crystallization purification so as to ensure that the yield is improved to the maximum extent under the premise of obtaining a high-purity product. The product obtained from this method contains high-purity CBD; the method has a high yield and is a simple process, and thus easy to industrialize.

A method of continuous separation of a plasmid from a process feed in an apparatus with at least three chromatography columns packed with separation matrix particles, wherein while one chromatography column is loaded with the process feed, another chromatography column is eluted with an eluent to recover the separated plasmid, and yet another chromatography column is eluted with a further eluent to remove contaminants.

Systems and methods for efficient, effective, and safe separation and isolation of multiple isotopes (e.g., Mo, Zr, Ba, Sr, Te, and lanthanide isotopes) from fission products includes use of a plurality of chromatography columns, each containing a chromatographic resin formulated to target one or more particular isotopes. The system is operable in a series configuration to load the multiple columns by a single pass of the sample. Then, the system may be transitioned (e.g., using valves) to a parallel configuration in which multiple columns of the system may be operated simultaneously to elute targeted isotopes. Additional parallel operations of the columns, using different eluent compositions, may be used to elute different targeted isotopes. The system may be reconditioned in preparation for a subsequent sample.

A method and an apparatus suitable for a continuous chromatography process which only needs three separation columns, and a two-step process containing two chromatographic steps, in which the first chromatographic step (capture) is performed alternating and sequentially on two separation columns, the second chromatographic step (polishing) is performed, also sequentially, on the third column.

A chromatography system includes a first chromatography column and a panel having a top face and an opposing bottom face, a first cavity being formed on the panel so as to pass through the top face and be encircled by an inner surface. The panel bounds an inlet fluid channel having an end terminating at an inlet opening formed on the inner surface encircling the first cavity so that the inlet fluid channel communicates with the first cavity. The panel also bounds a plurality of first outlet fluid channels each having an end terminating at an outlet opening formed on the inner surface encircling the first cavity so that each of the plurality of first outlet fluid channels communicate with the first cavity, a first one of the plurality of first outlet fluid channels being in fluid communication with the first chromatography column. A first valve is rotatably disposed within the first cavity.

The present invention relates to a method for determining operational status of a chromatography column (1; 39, 47, 59; 107, 109, 111, 113), comprising detecting a feed signal (21; 201) representative of the composition of a feed material provided to the inlet of the column; detecting the UV absorbance in the feed material, detecting an effluent signal (23; 203, 205, 207, 209) representative of the composition of the effluent from the column; and using the feed signal and the effluent signal to determine operational status of the column. The feed signal is generated using a first UV detector having a first UV cell pathlength operating at a first UV wavelength and in the effluent signal is generated using a second UV detector having a second UV cell pathlength operating at a second UV wavelength. The method further comprising determining a first threshold value based on the detected UV absorbance in the feed material, and selecting the first UV cell pathlength and/or first UV wavelength based on the first threshold value.

An alternating flow column chromatography apparatus comprising a U shaped or T shaped separation column including at least one loading port for loading of components for separation, a first purification column in fluid communication with one end of the separation column and a second purification column in fluid communication with another end of the separation column, at least one eluent input port, an eluate output port and an alternating flow valve in fluid communication with the primary eluent input port, the eluate output port, the first purification column and the second purification column wherein, when operated, the alternating flow valve reverses the flow of eluent through the purification columns and the separation column. Also a method of using the apparatus. A benefit of the apparatus and method is more efficient operation compared to existing direct flow column chromatography apparatuses.