In-line monitoring of downstream purification processes for vsv based sars-cov-2 vaccine using a novel technique

Arik Makovitzki, Avital Jayson, Ziv Oren, Elad Lerer, Yaron Kafri, Eyal Dor, Lilach Cherry, Hanan Tzadok, Lilach Levin, Ophir Hazan, Irit Simon, Arnon Tal, Meni Girshengorn, Osnat Rosen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases the need for a rapid development of efficient vaccines. Among other vaccines in clinical trials, a recombinant VSV-∆G-spike vaccine was developed by the Israel Institute for Biological Research (IIBR) and is being evaluated. The development of an efficient downstream purification process (DSP) enables the vaccine to be advanced to clinical trials. The DSP must eliminate impurities, either process-or product-related, to yield a sufficient product with high purity, potency and quality. To acquire critical information on process restrictions and qualities, the application of in-line monitoring is vital and should significantly impact the process yield, product quality and economy of the entire process. Here, we describe an in-line monitoring technique that was applied in the DSP of the VSV-∆G-spike vaccine. The technique is based on determining the concentrations of metabolites, nutrients and a host cell protein using the automatic chemistry analyzer, Cobas Integra 400 Plus. The analysis revealed critical information on process parameters and significantly impacted purification processes. The technique is rapid, easy and efficient. Adopting this technique during the purification process improves the process yield and the product quality and enhances the economy of the entire downstream process for biotechnology and bio pharmaceutical products.

Original languageEnglish
Article number25
Issue number4
StatePublished - 3 Nov 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cobas analyzer
  • Downstream purification process (DSP)
  • Host cell proteins (HCP)
  • Lactate dehydrogenase (LDH)
  • Metabolites
  • Nutrients


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