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Toward QbD Process Understanding on DNA Vaccine Purification Using Design of Experiment
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Document Title
Toward QbD Process Understanding on DNA Vaccine Purification Using Design of Experiment
Author
Hocharoen L., Noppiboon S., Kitsubun P.
Name from Authors Collection
Affiliations
Bioprocess Research and Innovation Centre (BRIC), National Biopharmaceutical Facility (NBF), King Mongkut’s University of Technology Thonburi (KMUTT), Bangkok, Thailand; Biochemical Engineering and System Biology Research Group (IBEG), National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok, Thailand
Type
Article
Source Title
Frontiers in Bioengineering and Biotechnology
ISSN
22964185
Year
2021
Volume
9
Open Access
All Open Access, Gold, Green
Publisher
Frontiers Media S.A.
DOI
10.3389/fbioe.2021.657201
Format
Abstract
DNA vaccines, the third generation of vaccines, are a promising therapeutic option for many diseases as they offer the customization of their ability on protection and treatment with high stability. The production of DNA vaccines is considered rapid and less complicated compared to others such as mRNA vaccines, viral vaccines, or subunit protein vaccines. However, the main issue for DNA vaccines is how to produce the active DNA, a supercoiled isoform, to comply with the regulations. Our work therefore focuses on gaining a process understanding of the purification step which processes parameters that have impacts on the critical quality attribute (CQA), supercoiled DNA and performance attribute (PA), and step yield. Herein, pVax1/lacZ was used as a model. The process parameters of interest were sample application flow rates and salt concentration at washing step and at elution step in the hydrophobic interaction chromatography (HIC). Using a Design of Experiment (DoE) with central composite face centered (CCF) approach, 14 experiments plus four additional runs at the center points were created. The response data was used to establish regression predictive models and simulation was conducted in 10,000 runs to provide tolerance intervals of these CQA and PA. The approach of this process understanding can be applied for Quality by Design (QbD) on other DNA vaccines and on a larger production scale as well. © Copyright © 2021 Hocharoen, Noppiboon and Kitsubun.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Institute for the Promotion of Teaching Science and Technology
License
N/A
Rights
N/A
Publication Source
Scopus