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Open AccessArticle

Forced Degradation Studies to Identify Critical Process Parameters for the Purification of Infectious Measles Virus

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Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Wiesenstraße 14, 35390 Giessen, Germany
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Faculty of Biology and Chemistry, University of Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany
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Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project group Bioresources, Winchesterstr. 3, 35394 Giessen, Germany
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(8), 725; https://doi.org/10.3390/v11080725
Received: 25 June 2019 / Revised: 31 July 2019 / Accepted: 3 August 2019 / Published: 7 August 2019
Oncolytic measles virus (MV) is a promising treatment for cancer but titers of up to 1011 infectious particles per dose are needed for therapeutic efficacy, which requires an efficient, robust, and scalable production process. MV is highly sensitive to process conditions, and a substantial fraction of the virus is lost during current purification processes. We therefore conducted forced degradation studies under thermal, pH, chemical, and mechanical stress to determine critical process parameters. We found that MV remained stable following up to five freeze–thaw cycles, but was inactivated during short-term incubation (< 2 h) at temperatures exceeding 35 °C. The infectivity of MV declined at pH < 7, but was not influenced by different buffer systems or the ionic strength/osmolality, except high concentrations of CaCl2 and MgSO4. We observed low shear sensitivity (dependent on the flow rate) caused by the use of a peristaltic pump. For tangential flow filtration, the highest recovery of MV was at a shear rate of ~5700 s−1. Our results confirm that the application of forced degradation studies is important to identify critical process parameters for MV purification. This will be helpful during the early stages of process development, ensuring the recovery of high titers of active MV particles after purification. View Full-Text
Keywords: temperature; pH; buffer; ionic strength; osmolality; isoelectric point; shear stress; Measles virus; stability temperature; pH; buffer; ionic strength; osmolality; isoelectric point; shear stress; Measles virus; stability
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Loewe, D.; Häussler, J.; Grein, T.A.; Dieken, H.; Weidner, T.; Salzig, D.; Czermak, P. Forced Degradation Studies to Identify Critical Process Parameters for the Purification of Infectious Measles Virus. Viruses 2019, 11, 725.

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