Abstract

BACKGROUND: Since 2015 Zika virus (ZIKV) has spread within the Americas and even before in other regions. In 2016, the World Health Organisation (WHO) declared the ZIKV as a "Public Health Emergency of International Concern" (PHEIC). Therefore, it is very important to confirm the pathogen safety of blood plasma products. These products generally demand an effective donor selection as well as robust pathogen elimination/reduction steps within the manufacturing processes. Here, we provide experimental evidence that both solvent/detergent (S/D) treatment and pasteurization effectively inactivate ZIKV.

STUDY DESIGN AND METHODS: The ZIKV inactivation capacity of the pasteurization step and the S/D treatment for different products and process conditions were investigated. Therefore, in-process material from commercial batches was collected and spiked with ZIKV in a ratio of approximately 1:10. Viral loads were determined prior to the safety steps and at pre-defined intervals during the individual processes to investigate the inactivation kinetics. Each process was investigated in duplicate runs.

RESULTS: Sixty minutes after S/D treatment the viral titer was below detection limit during manufacturing of human plasma resulting in mean ZIKV reduction factor (LRF) of ≥ 6.78 log10. For immunoglobulin (IgG) after 240 min of S/D treatment the LRF was determined to be ≥ 7.00 log10. ZIKV was inactivated ≥ 6.18 log10 after 480 min by S/D treatment during the manufacture of factor VIII.

During pasteurization of human albumin ZIKV infectivity was already below the detection limit after the heat-up phase. This finding was confirmed by subsequent test samples up to 2 hours. A LRF of ≥ 7.48 log10 was demonstrated.

CONCLUSION: We showed that different S/D treatment procedures inactivate the ZIKV to below the detection limit. This effect was seen independently of various product matrices or the choice of S/D reagent at various concentrations and temperatures, while taking product-specific treatment times into consideration. We also showed that pasteurization is a very efficient inactivation step for the ZIKV. These results demonstrate the effectiveness of S/D treatment against even newly emerging lipid-enveloped viruses like ZIKV in the manufacturing of human plasma and derivatives thereof, such as IgG or factor VIII.

Disclosures

Schmidt:Octapharma: Employment. Kuehnel:Octapharma: Employment. Mueller:Octapharma: Employment. Pichotta:Octapharma: Employment. Radomski:Octapharma: Employment. Volk:Octapharma: Employment. Knaub:Octapharma: Employment.

Author notes

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Asterisk with author names denotes non-ASH members.

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