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Single-Column Chromatography with Recycle Lag Analog to Simulated Moving Bed Processes
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The chromatography steps dominate the Downstream Processing (DSP) costs of a new
biopharmaceutical, which has propelled the biopharmaceutical industry to invest a lot
of effort on their improvement in order to reduce the costs of the biopharmaceutical
production. Liquid chromatography (LC) is currently the core technique within the
DSP strategy for the purification of biopharmaceuticals. Although single-column batch
chromatography is simpler to operate than continuous (multicolumn) chromatography,
the latter has many advantages over the former, including improved purity, yield, and
productivity.
The main objective of this thesis is the development of a new chromatographic platform
based on a novel single-column device that mimics the operation of multicolumn
chromatography through ingenious management and recycling of the mixed fractions
exiting the chromatographic column. The platform shares the benefits of the Simulated-
Moving-Bed (SMB) technology. However, the newly developed process uses only a single
chromatographic column.
The conceptual design of the set-up and its mathematical model were successfully
established. The laboratory prototype was built focusing on a simple, compact, and
versatile design with small footprint. The binary separation of nucleosides by reversedphase
chromatography was experimentally realized as proof of concept of the new system.
An effort was made in 3D manufacturing of flow distributors and internals to ensure the
proper operation of the recycle device and the improvement of its efficiency. A second
case study—the capture step of monoclonal antibodies by affinity chromatography on
protein A—was successfully used as a demonstration of the applicability of the newly
developed process.
The new system offers a more compact, less expensive, and simpler-to-operate alternative
to multicolumn SMB chromatography. Depending on the efficiency of the recycle
device, the single-column process can achieve the same purities as the analogous SMB
unit while keeping the specific productivity constant. Moreover, the single-column chromatograph
can be easily integrated into the existing downstream processing platforms of
complex biopharmaceuticals.
Descrição
Palavras-chave
Biomolecules Separation/Purification Continuous Chromatography Simulated Moving Bed Single-column with Recycle Lag