Quality by Design characterization of the perfusion culture process for recombinant FVIII

Yong Jae Kim; Sang Hoon Paik; Sang Kyul Han; Sunggeun Lee; Yoomin Jeong; Ji youn Kim; Chan Wha Kim

doi:10.1016/j.biologicals.2019.03.004

Quality by Design characterization of the perfusion culture process for recombinant FVIII

Yong Jae Kim
, Sang Hoon Paik
, Sang Kyul Han
, Sunggeun Lee
, Yoomin Jeong
, Ji youn Kim
, Chan Wha Kim^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.

Original language	English
Pages (from-to)	37-46
Number of pages	10
Journal	Biologicals
Volume	59
DOIs	https://doi.org/10.1016/j.biologicals.2019.03.004
Publication status	Published - 2019 May

Bibliographical note

Funding Information:
This work was supported by funding the GC Pharma . The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2019

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

Design space
Perfusion culture
Process characterization
Quality by Design (QbD)
Recombinant Factor FVIII

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
General Immunology and Microbiology
Pharmacology

Access to Document

10.1016/j.biologicals.2019.03.004

Cite this

@article{69187633866e4e558ca6f9aa3432a8e8,

title = "Quality by Design characterization of the perfusion culture process for recombinant FVIII",

abstract = "A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.",

keywords = "Design space, Perfusion culture, Process characterization, Quality by Design (QbD), Recombinant Factor FVIII",

author = "Kim, \{Yong Jae\} and Paik, \{Sang Hoon\} and Han, \{Sang Kyul\} and Sunggeun Lee and Yoomin Jeong and Kim, \{Ji youn\} and Kim, \{Chan Wha\}",

note = "Funding Information: This work was supported by funding the GC Pharma . The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2019 Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = may,

doi = "10.1016/j.biologicals.2019.03.004",

language = "English",

volume = "59",

pages = "37--46",

journal = "Biologicals",

issn = "1045-1056",

publisher = "Academic Press",

}

TY - JOUR

T1 - Quality by Design characterization of the perfusion culture process for recombinant FVIII

AU - Kim, Yong Jae

AU - Paik, Sang Hoon

AU - Han, Sang Kyul

AU - Lee, Sunggeun

AU - Jeong, Yoomin

AU - Kim, Ji youn

AU - Kim, Chan Wha

N1 - Funding Information: This work was supported by funding the GC Pharma . The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Publisher Copyright: © 2019 Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/5

Y1 - 2019/5

N2 - A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.

AB - A Quality by Design (QbD) concept was applied to characterize a cell culture process for production of the recombinant Factor VIII (rFVIII). We characterized the production bioreactor process and defined the design space by applying risk assessment to determine potential critical process parameters (CPPs) impacting critical quality attributes (CQAs). Characterization studies were subsequently performed using a qualified scaled-down model (SDM) and a multi-factorial design of experiment (DOE) approach to determine both the individual and combined impacts of the potential CPPs on CQAs. Among the operating parameters characterized, production temperature, production pH and a shift in the timing of production affected rFVIII activity and tyrosine sulfation level. Finally, we identified CPPs and established a design space for the cell culture process to identify appropriate conditions for routine manufacturing.

KW - Design space

KW - Perfusion culture

KW - Process characterization

KW - Quality by Design (QbD)

KW - Recombinant Factor FVIII

UR - https://www.scopus.com/pages/publications/85063352781

UR - https://www.scopus.com/pages/publications/85063352781#tab=citedBy

U2 - 10.1016/j.biologicals.2019.03.004

DO - 10.1016/j.biologicals.2019.03.004

M3 - Article

C2 - 30926289

AN - SCOPUS:85063352781

SN - 1045-1056

VL - 59

SP - 37

EP - 46

JO - Biologicals

JF - Biologicals

ER -

Quality by Design characterization of the perfusion culture process for recombinant FVIII

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this