Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development

Joshua D. Orchard, David Cetlin, Melanie Pallansch, Robert Barlow, Jon Borman, Arun Dhar, Luke Pallansch, Matthew Dickson

Research output: Contribution to journalArticle

Abstract

Viral contamination is an inherent risk during the manufacture of biopharmaceuticals. As such, biopharmaceutical companies must demonstrate the viral clearance efficacy of their downstream process steps prior to clinical trials and commercial approval. This is accomplished through expensive and logistically challenging spiking studies, which utilize live mammalian viruses. These hurdles deter companies from analyzing viral clearance during process development and characterization. We utilized a noninfectious minute virus of mice-mock virus particle (MVM-MVP) as a surrogate spiking agent during small scale viral filtration (VF) and anion exchange chromatography (AEX) studies. For VF experiments, in-process mAb material was spiked and processed through Asahi Kasei P15, P20, P35, and BioEX nanofilters. Across each filter type, flux decay profiles and log reduction values (LRVs) were nearly identical for either particle. For AEX experiments, loads were conditioned with various amounts of sodium chloride (9, 20, 23, and 41 mS/cm), spiked with either particle and processed through a Q-SFF packed column. LRV results met our expectations of predicting MVM removal.

Original languageEnglish (US)
Article numbere2921
JournalBiotechnology Progress
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Anions
Chromatography
Minute Virus of Mice
Sodium Chloride
Virion
Clinical Trials
Viruses

ASJC Scopus subject areas

  • Biotechnology

Cite this

Orchard, J. D., Cetlin, D., Pallansch, M., Barlow, R., Borman, J., Dhar, A., ... Dickson, M. (Accepted/In press). Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development. Biotechnology Progress, [e2921]. https://doi.org/10.1002/btpr.2921

Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development. / Orchard, Joshua D.; Cetlin, David; Pallansch, Melanie; Barlow, Robert; Borman, Jon; Dhar, Arun; Pallansch, Luke; Dickson, Matthew.

In: Biotechnology Progress, 01.01.2019.

Research output: Contribution to journalArticle

Orchard, Joshua D. ; Cetlin, David ; Pallansch, Melanie ; Barlow, Robert ; Borman, Jon ; Dhar, Arun ; Pallansch, Luke ; Dickson, Matthew. / Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development. In: Biotechnology Progress. 2019.
@article{0f22848224694893bf8dfd371a4db4ed,
title = "Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development",
abstract = "Viral contamination is an inherent risk during the manufacture of biopharmaceuticals. As such, biopharmaceutical companies must demonstrate the viral clearance efficacy of their downstream process steps prior to clinical trials and commercial approval. This is accomplished through expensive and logistically challenging spiking studies, which utilize live mammalian viruses. These hurdles deter companies from analyzing viral clearance during process development and characterization. We utilized a noninfectious minute virus of mice-mock virus particle (MVM-MVP) as a surrogate spiking agent during small scale viral filtration (VF) and anion exchange chromatography (AEX) studies. For VF experiments, in-process mAb material was spiked and processed through Asahi Kasei P15, P20, P35, and BioEX nanofilters. Across each filter type, flux decay profiles and log reduction values (LRVs) were nearly identical for either particle. For AEX experiments, loads were conditioned with various amounts of sodium chloride (9, 20, 23, and 41 mS/cm), spiked with either particle and processed through a Q-SFF packed column. LRV results met our expectations of predicting MVM removal.",
author = "Orchard, {Joshua D.} and David Cetlin and Melanie Pallansch and Robert Barlow and Jon Borman and Arun Dhar and Luke Pallansch and Matthew Dickson",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/btpr.2921",
language = "English (US)",
journal = "Biotechnology Progress",
issn = "8756-7938",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Using a noninfectious MVM surrogate for assessing viral clearance during downstream process development

AU - Orchard, Joshua D.

AU - Cetlin, David

AU - Pallansch, Melanie

AU - Barlow, Robert

AU - Borman, Jon

AU - Dhar, Arun

AU - Pallansch, Luke

AU - Dickson, Matthew

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Viral contamination is an inherent risk during the manufacture of biopharmaceuticals. As such, biopharmaceutical companies must demonstrate the viral clearance efficacy of their downstream process steps prior to clinical trials and commercial approval. This is accomplished through expensive and logistically challenging spiking studies, which utilize live mammalian viruses. These hurdles deter companies from analyzing viral clearance during process development and characterization. We utilized a noninfectious minute virus of mice-mock virus particle (MVM-MVP) as a surrogate spiking agent during small scale viral filtration (VF) and anion exchange chromatography (AEX) studies. For VF experiments, in-process mAb material was spiked and processed through Asahi Kasei P15, P20, P35, and BioEX nanofilters. Across each filter type, flux decay profiles and log reduction values (LRVs) were nearly identical for either particle. For AEX experiments, loads were conditioned with various amounts of sodium chloride (9, 20, 23, and 41 mS/cm), spiked with either particle and processed through a Q-SFF packed column. LRV results met our expectations of predicting MVM removal.

AB - Viral contamination is an inherent risk during the manufacture of biopharmaceuticals. As such, biopharmaceutical companies must demonstrate the viral clearance efficacy of their downstream process steps prior to clinical trials and commercial approval. This is accomplished through expensive and logistically challenging spiking studies, which utilize live mammalian viruses. These hurdles deter companies from analyzing viral clearance during process development and characterization. We utilized a noninfectious minute virus of mice-mock virus particle (MVM-MVP) as a surrogate spiking agent during small scale viral filtration (VF) and anion exchange chromatography (AEX) studies. For VF experiments, in-process mAb material was spiked and processed through Asahi Kasei P15, P20, P35, and BioEX nanofilters. Across each filter type, flux decay profiles and log reduction values (LRVs) were nearly identical for either particle. For AEX experiments, loads were conditioned with various amounts of sodium chloride (9, 20, 23, and 41 mS/cm), spiked with either particle and processed through a Q-SFF packed column. LRV results met our expectations of predicting MVM removal.

UR - http://www.scopus.com/inward/record.url?scp=85074276579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074276579&partnerID=8YFLogxK

U2 - 10.1002/btpr.2921

DO - 10.1002/btpr.2921

M3 - Article

AN - SCOPUS:85074276579

JO - Biotechnology Progress

JF - Biotechnology Progress

SN - 8756-7938

M1 - e2921

ER -