The present disclosure is directed to a method of operating a chromatography column. This method involves collecting column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during operation of the chromatography column comprising column packing. A model gamma cumulative distribution curve is determined based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front. The height equivalent theoretical plate (HETP) value is calculated for the at least one mobile phase transition front using parameters of the model gamma cumulative distribution curve and the quality of the chromatography column packing is assessed based on the calculated HETP value. If during routine column monitoring, an adverse trend in HETP is observed or the control limits are exceeded, the eluate product quality, column process performance, and/or impurity removal data should be evaluated to ensure product quality for the identified batch. Should any of the product quality or column performance fail the criteria set, appropriate corrective action, such as conditioning, repacking or replacing the column, and qualification should be performed prior to release for further use.

The present disclosure is directed to methods of characterizing a system containing a chromatographic column. The methods can include introducing a sample comprising a positive control and a negative control to the system containing a chromatographic column, wherein the positive control is a sensitive probe that interacts with the system and the negative control is substantially non-interacting with the system; after passing the sample through the chromatographic column, detecting the positive control and the negative control; and determining system suitability by comparing the amount of detected positive control to negative control. In some embodiments, determining system suitability (e.g., inertness of sample to the system) is accomplished by determining a ratio of detected positive control to negative control.

The present disclosure is directed to methods for evaluating system inertness, such as the inertness of a LC or other fluidic system. Some methods are directed to tests wherein the column has been removed prior to injecting a sample including a positive (e.g., metal reacting moiety) control into the system. Some methods can include: (1) repeatedly injecting the sample into a system, the system comprising: fluidic paths wherein interior surfaces of the fluidic paths define wetted surfaces, and wherein at least a portion of the wetted surfaces of the fluidic flow path are coated with an inert coating, wherein the inert coating is inert to at least one analyte in the sample; (2) detecting a value associated with the positive control; and (3) analyzing values associated with the detected positive control to determine system inertness.

Determining optimum operating binding capacity for a MCC process using one column, the process including N number of columns, comprises loading target product on a first column at a first residence time and/or flow rate; loading the product on the column at a second residence time and/or flow rate, the first residence time and/or flow rate being different than the second residence time and/or flow rate; generating a first breakthrough curve for the first residence time and/or flow rate and a second breakthrough curve for the second residence time and/or flow rate, wherein the first curve represents product breakthrough for the first column and the second curve represents product breakthrough for an Nth column; and using the curves to determine product loading capacity of the first column before product breakthrough at the Nth column; the product loading capacity of the first column equaling optimum operating binding capacity for the process.

The present disclosure is directed to a method of operating a chromatography column in methods of manufacture for producing anti-IL-12/IL-23p40 antibodies, e.g., the anti-IL-12/IL-23p40 antibody STELARA® (ustekinumab), specific pharmaceutical compositions of the antibodies, and antigen binding fragments thereof. This method involves collecting column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during operation of the chromatography column comprising column packing. A model gamma cumulative distribution curve is determined based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front. The height equivalent theoretical plate (HETP) value is calculated for the at least one mobile phase transition front using parameters of the model gamma cumulative distribution curve and the quality of the chromatography column packing is assessed based on the calculated HETP value. If during routine column monitoring, an adverse trend in HETP is observed or the control limits are exceeded, the eluate product quality, column process performance, and/or impurity removal data should be evaluated to ensure product quality for the identified batch. Should any of the product quality or column performance fail the criteria set, appropriate corrective action, such as conditioning, repacking or replacing the column, and qualification should be performed prior to release for further use.

Disclosed are methods for monitoring column chromatography performance. The methods can include acquiring one or more chromatogram ultraviolet (UV) traces generated by a chromatography system during sample purification and/or separation; and analyzing the one or more acquired chromatogram UV traces with an orthogonal partial least squares (OPLS) model, thereby allowing detection of column deterioration prior to column failure and quantitative analysis of UV signal in the one or more chromatogram UV traces.

A chromatography system includes a gradient delay volume defined as an overall fluid volume between where gradient is proportioned until an inlet of a chromatography column, a pump pumping a flow of gradient; and at least one valve located downstream from the pump, the at least one valve having a plurality of ports including an inlet port that receives the flow of gradient from the pump and an outlet port through which the flow of gradient exits the at least one valve, the at least one valve having at least two positions. A first position of the at least two positions of the at least one valve increases the gradient delay volume of the chromatography system relative to when the at least one valve is in a second position.

A method of operating a chromatography column is described for use in methods of manufacture for producing anti-IL-12/IL-23p40 antibodies, e.g., the anti-IL-12/IL-23p40 antibody STELARA® (ustekinumab). This method involves collecting column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during operation of the chromatography column comprising column packing. A model gamma cumulative distribution curve is calculated based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front. A height equivalent theoretical plate (HETP) value is calculated for the at least one mobile phase transition front using parameters of the model gamma cumulative distribution curve and the quality of the chromatography column packing is assessed based on the calculated HETP value.

A gas analyzer includes a sample inlet, a sample outlet, a detector, a monitoring component, and a controller. The sample inlet is configured to receive a sample and is coupled to the sample outlet. The detector is operably disposed between the sample inlet and the sample outlet and is configured to provide an indication relative to the sample. The monitoring component is configured to provide a diagnostic indication regarding at least one component of the gas analyzer. The controller is configured to control flow through the gas analyzer and is operably coupled to the detector to analyze the sample, provide the analysis to the monitoring component, and provide the indication of health to an output.

A method of mass spectrometry is disclosed comprising repeatedly or continuously causing first analyte sample to be released or ejected from a first sample. A determination is made as to whether or not a quality threshold such as an intensity threshold has been met or exceeded, wherein if the quality threshold has been met or exceeded then the method further comprises repeatedly or continuously causing second analyte sample to be released or ejected from a second sample.