Single-use technology for solvent/detergent virus inactivation of industrial plasma products

Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Elizabeth Goodrich, Jessica Shea, Eric Youssef, Thierry Burnouf

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture. CONCLUSION Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.

Original languageEnglish
Pages (from-to)1384-1393
Number of pages10
JournalTransfusion
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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Virus Inactivation
Detergents
Technology
Bovine Viral Diarrhea Viruses
Murine Leukemia Viruses
Polysorbates
Octoxynol
Immunoglobulins
Stainless Steel
Polyethylene
Thrombin
Glass
Blood Proteins
Proteins
Peptide Hydrolases
Phosphates
Economics
Viruses
Costs and Cost Analysis

ASJC Scopus subject areas

  • Hematology
  • Immunology
  • Immunology and Allergy

Cite this

Hsieh, Y. T., Mullin, L., Greenhalgh, P., Cunningham, M., Goodrich, E., Shea, J., ... Burnouf, T. (2016). Single-use technology for solvent/detergent virus inactivation of industrial plasma products. Transfusion, 56(6), 1384-1393. https://doi.org/10.1111/trf.13619

Single-use technology for solvent/detergent virus inactivation of industrial plasma products. / Hsieh, Yao Ting; Mullin, Lori; Greenhalgh, Patricia; Cunningham, Michael; Goodrich, Elizabeth; Shea, Jessica; Youssef, Eric; Burnouf, Thierry.

In: Transfusion, Vol. 56, No. 6, 01.06.2016, p. 1384-1393.

Research output: Contribution to journalArticle

Hsieh, YT, Mullin, L, Greenhalgh, P, Cunningham, M, Goodrich, E, Shea, J, Youssef, E & Burnouf, T 2016, 'Single-use technology for solvent/detergent virus inactivation of industrial plasma products', Transfusion, vol. 56, no. 6, pp. 1384-1393. https://doi.org/10.1111/trf.13619
Hsieh YT, Mullin L, Greenhalgh P, Cunningham M, Goodrich E, Shea J et al. Single-use technology for solvent/detergent virus inactivation of industrial plasma products. Transfusion. 2016 Jun 1;56(6):1384-1393. https://doi.org/10.1111/trf.13619
Hsieh, Yao Ting ; Mullin, Lori ; Greenhalgh, Patricia ; Cunningham, Michael ; Goodrich, Elizabeth ; Shea, Jessica ; Youssef, Eric ; Burnouf, Thierry. / Single-use technology for solvent/detergent virus inactivation of industrial plasma products. In: Transfusion. 2016 ; Vol. 56, No. 6. pp. 1384-1393.
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abstract = "BACKGROUND Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1{\%} tri-n-butyl phosphate (TnBP) with 1{\%} Triton X-100 or 1{\%} Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3{\%} TnBP combined with 1{\%} Tween 80 or 1{\%} Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture. CONCLUSION Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.",
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AU - Greenhalgh, Patricia

AU - Cunningham, Michael

AU - Goodrich, Elizabeth

AU - Shea, Jessica

AU - Youssef, Eric

AU - Burnouf, Thierry

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N2 - BACKGROUND Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture. CONCLUSION Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.

AB - BACKGROUND Virus inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) virus inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus inactivation studies were performed with xenotropic murine leukemia virus (XMuLV) and bovine viral diarrhea virus (BVDV) to determine the kinetics of virus inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient inactivation of both XMuLV and BVDV was observed, with differences in the rate of inactivation dependent on both virus and S/D mixture. CONCLUSION Effective S/D virus inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.

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