Details

Autor(en) / Beteiligte

• Ng, Candy K.S.
• Osuna-Sanchez, Hector
• Valéry, Eric
• Sørensen, Eva
• Bracewell, Daniel G.

Titel

Design of high productivity antibody capture by protein A chromatography using an integrated experimental and modeling approach

Ist Teil von

• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2012-06, Vol.899, p.116-126

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• ► A lumped parameter transport-dispersive model is used. ► An experimental strategy for critical parameter estimation is designed. ► The impact of process variables on productivity is studied via use of model. An integrated experimental and modeling approach for the design of high productivity protein A chromatography is presented to maximize productivity in bioproduct manufacture. The approach consists of four steps: (1) small-scale experimentation, (2) model parameter estimation, (3) productivity optimization and (4) model validation with process verification. The integrated use of process experimentation and modeling enables fewer experiments to be performed, and thus minimizes the time and materials required in order to gain process understanding, which is of key importance during process development. The application of the approach is demonstrated for the capture of antibody by a novel silica-based high performance protein A adsorbent named AbSolute. In the example, a series of pulse injections and breakthrough experiments were performed to develop a lumped parameter model, which was then used to find the best design that optimizes the productivity of a batch protein A chromatographic process for human IgG capture. An optimum productivity of 2.9kgL−1day−1 for a column of 5mm diameter and 8.5cm length was predicted, and subsequently verified experimentally, completing the whole process design approach in only 75 person-hours (or approximately 2 weeks).