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Bioengineering 2014, 1(4), 213-230; doi:10.3390/bioengineering1040213

An Integrated Downstream Process Development Strategy along QbD Principles

Research Center of Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria
Institute of Biochemical Engineering, Vienna University of Technology, Gumpendorferstrasse 1A/166-4, 1060 Vienna, Austria
BIRD-C GmbH & CoKEG, Erne-Seder-Gasse 4, 1030 Vienna, Austria
Author to whom correspondence should be addressed.
Received: 31 July 2014 / Revised: 18 September 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
(This article belongs to the Special Issue Biopharmaceutical Process Development)
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The development, optimization, and analysis of downstream processes are challenged by a high number of potentially critical process parameters that need to be investigated using lab-scale experiments. These process parameters are spread across multiple unit operations and potentially show interactions across unit operations. In this contribution, we present a novel strategy for bioprocess development that considers the risk of parameter interactions across unit operations for efficient experimental design. A novel risk assessment tool (interaction matrix) is introduced to the Quality by Design (QbD) workflow. Using this tool, the risk of interaction across unit operations is rated. Subsequently, a design of experiments (DoE) across unit operations is conducted that has the power to reveal multivariate interdependencies. The power of the presented strategy is demonstrated for protein isolation steps of an inclusion body process, focusing on the quality attribute inclusion body purity. The concentration of Triton X-100 in the course of inclusion body (IB) purification was shown to interact with the g-number of the subsequent centrifugation step. The presented strategy targets a holistic view on the process and allows handling of a high number of experimental parameters across unit operations using minimal experimental effort. It is generically applicable for process development along QbD principles. View Full-Text
Keywords: quality by design; process development; interaction across unit operations; design of experiments; risk assessment; inclusion body purity quality by design; process development; interaction across unit operations; design of experiments; risk assessment; inclusion body purity

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Meitz, A.; Sagmeister, P.; Langemann, T.; Herwig, C. An Integrated Downstream Process Development Strategy along QbD Principles. Bioengineering 2014, 1, 213-230.

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