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@ARTICLE{Kumar:276293,
      author       = {Kumar, Vijesh and Leweke, Samuel and von Lieres, Eric and
                      Rathore, Anurag S.},
      title        = {{M}echanistic {M}odeling of {I}on-{E}xchange {P}rocess
                      {C}hromatography of {C}harge {V}ariants of {M}onoclonal
                      {A}ntibody {P}roducts},
      journal      = {Journal of chromatography / A},
      volume       = {1426},
      issn         = {0021-9673},
      address      = {New York, NY [u.a.]},
      publisher    = {Science Direct},
      reportid     = {FZJ-2015-06754},
      pages        = {140–153},
      year         = {2015},
      abstract     = {Ion-exchange chromatography (IEX) is universally accepted
                      as the optimal method for achieving process scale separation
                      of charge variants of a monoclonal antibody (mAb)
                      therapeutic. These variants are closely related to the
                      product and a baseline separation is rarely achieved. The
                      general practice is to fractionate the eluate from the IEX
                      column, analyze the fractions and then pool the desired
                      fractions to obtain the targeted composition of variants.
                      This is, however, a very cumbersome and time consuming
                      exercise. A mechanistic model that is capable of simulating
                      the peak profile will be a much more elegant and effective
                      way to make a decision on the pooling strategy. This paper
                      proposes a mechanistic model, based on the general rate
                      model, to predict elution peak profile for separation of the
                      main product from its variants. The proposed approach uses
                      inverse fit of process scale chromatogram for estimation of
                      model parameters using the initial values that are obtained
                      from theoretical correlations. The packed bed column has
                      been modeled along with the chromatographic system
                      consisting of the mixer, tubing and detectors as a series of
                      dispersed plug flow and continuous stirred tank reactors.
                      The model uses loading ranges starting at $25\%$ to a
                      maximum of $70\%$ of the loading capacity and hence is
                      applicable to process scale separations. Langmuir model has
                      been extended to include the effects of salt concentration
                      and temperature on the model parameters. The extended
                      Langmuir model that has been proposed uses one less
                      parameter than the SMA model and this results in a
                      significant ease of estimating the model parameters from
                      inverse fitting. The proposed model has been validated with
                      experimental data and has been shown to successfully predict
                      peak profile for a range of load capacities (15–28 mg/mL),
                      gradient lengths (10–30 CV), bed heights (6–20 cm), and
                      for three different resins with good accuracy (as measured
                      by estimation of residuals). The model has been also
                      validated for a two component mixture consisting of the main
                      mAb product and one of its basic charge variants. The
                      proposed model can be used for optimization and control of
                      preparative scale chromatography for separation of charge
                      variants.},
      cin          = {IBG-1},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {581 - Biotechnology (POF3-581)},
      pid          = {G:(DE-HGF)POF3-581},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000367276100016},
      doi          = {10.1016/j.chroma.2015.11.062},
      url          = {https://juser.fz-juelich.de/record/276293},
}