US2022089716A1PendingUtilityA1
Transition analysis method for chromatography column qualification
Est. expiryApr 20, 2038(~11.7 yrs left)· nominal 20-yr term from priority
Inventors:Paul Randolph
G01N 30/56C07K 16/244G01N 2030/562C07K 2317/24G01N 2030/8831B01D 15/363C07K 1/22G01N 35/00623B01D 15/3809C07K 1/18B01D 15/206G01N 2030/889C07K 16/065C07K 16/241G01N 30/86B01D 15/166G01N 30/89G01N 30/8665A61K 39/39591G01N 30/88B01D 15/20C07K 2317/565C07K 2317/31B01D 15/362
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modified1 - 17 . (canceled)
18 . A system comprising a computing device, a chromatography column, a detector communicatively connected to the computing device, and at least one mobile phase;
wherein the detector is configured to collect a column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during a first operation of the chromatography column comprising column packing; and wherein the computing device comprises processor and a non-transitory computer-readable medium with instructions stored thereon, which, when executed by the processor, perform steps comprising: a) determining a model gamma cumulative distribution curve based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front using Formula Ia for a rising transition front or Formula Ib for a falling transition front,
C
=
1
-
1
Γ
(
k
)
γ
(
k
,
V
-
V
i
θ
)
or
Formula
Ia
C
=
1
Γ
(
k
)
γ
(
k
,
V
-
V
i
θ
)
Formula
Ib
wherein C is column outlet signal for a given V, V is the accumulated flow divided by the column volume, and k, θ, and Vi are the shape, scale and offset parameters used to define the curve;
b) calculating a height equivalent theoretical plate (HETP) value for the at least one mobile phase transition front using Formula II and the model gamma cumulative distribution curve parameters of k, θ, and Vi,
HETP
=
σ
2
μ
2
L
wherein
μ
=
k
θ
+
V
i
σ
=
k
θ
2
L
=
column
length
;
and
Formula
II
c) assessing quality of the chromatography column packing based on said calculated HETP value,
19 . The system of claim 18 , wherein the chromatography column is conditioned, replaced, or repacked based on said assessing.
20 . The system of claim 18 ,
wherein the detector is configured to collect column outlet signals and accumulated flow parameters at two or more intervals of a corresponding mobile phase transition front during one or more subsequent uses of the chromatography column packing; wherein the computing device comprises processor and a non-transitory computer-readable medium with instructions stored thereon, which, when executed by the processor, perform steps comprising: a) said determining and said calculating using the column outlet signal and accumulated flow parameters collected during each of the one or more subsequent uses of the chromatography column packing; b) determining an HETP value of the chromatography column packing during each of said one or more subsequent uses based on said performing; c) compiling a trend of the determined HETP values of the chromatography column packing of the two or more subsequent uses; and d) identifying a change in the quality of the chromatography column packing based on said compiled trend, wherein said conditioning, replacing or repacking the chromatography column is based on said identifying.
21 . The system of claim 20 , wherein an increase in the HETP value of the chromatography column packing in the one or more subsequent uses of said column packing as compared to the HETP value of the chromatography column packing in one or more earlier uses of said column packing identifies a decrease in quality of the chromatography column packing.
22 . The system of claim 18 , wherein the detector is configured to collect column outlet signals and accumulated flow parameters of two or more different mobile phase transition fronts during said first operation of the column packing, and
wherein the computing device comprises processor and a non-transitory computer-readable medium with instructions stored thereon, which, when executed by the processor, performs steps comprising: a) said determining and calculating using the column outlet signal and accumulated flow parameters collected for each of the two or more different mobile phase transition fronts independently to calculate an HETP value for each of the two of more different mobile phase transition fronts; and b) assessing the quality of the chromatography column packing based on the two or more calculated HETP values, whereby said conditioning, replacing or repacking the chromatography column is based on said assessing.
23 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from a mobile phase containing a denaturing agent to a mobile phase containing a non-denaturing agent.
24 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from a mobile phase containing a non-denaturing agent to a mobile phase containing a denaturing agent.
25 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from an alkaline mobile phase condition to a more acidic mobile phase condition.
26 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from an acidic mobile phase condition to a more alkaline mobile phase condition.
27 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from organic solvent containing mobile phase to an aqueous mobile phase.
28 . The system of claim 18 , wherein the mobile phase transition front is generated by a change from an aqueous mobile phase to an organic solvent containing mobile phase.
29 . The system of claim 18 , wherein the column outlet signal is conductivity.
30 . The system of claim 18 , wherein the step a) comprises:
normalizing said collected column outlet signal of the mobile phase transition front by setting the minimum signal value to 0 and the maximum conductivity value to 1.
31 . The system of claim 18 , wherein collecting the column outlet signal comprises:
adding a first mobile phase to the chromatography column containing said column packing; adding a second mobile phase to the chromatography column containing said column packing, wherein said first and second mobile phases have different detectable column outlet signals; and collecting said column outlet signal and accumulated flow parameters at two or more intervals of the mobile phase transition between the first and second mobile phases,
32 . The system of claim 31 , wherein the column outlet signal for the first and second mobile phases differ in signal by an amount exceeding the signal noise.
33 . The system of claim 18 , wherein the column outlet signal and accumulated flow parameters are collected at various intervals throughout the entirety of the mobile phase transition front.
34 . The system of claim 18 , wherein the chromatography column packing is selected from the group consisting of affinity chromatography packing material, ion exchange chromatography packing material, adsorption chromatography packing material, hydrophobic interaction chromatography packing material, metal chelate affinity chromatography packing material, size exclusion chromatography packing material, or molecular exclusion chromatography packing material.Join the waitlist — get patent alerts
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