Quality by Design-Driven Process Development of Cell Culture in Bioreactor for the Production of Foot-And-Mouth Veterinary Vaccine

2019 ◽  
Vol 108 (7) ◽  
pp. 2288-2295 ◽  
Author(s):  
Xinran Li ◽  
Xuerong Liu ◽  
Rongbin Wang ◽  
Fanglan An ◽  
Jianqi Nie ◽  
...  
Keyword(s):  
Cell Culture ◽  
Quality By Design ◽  
Process Development ◽  
Veterinary Vaccine ◽  
Foot And Mouth

Miniature Bioreactors for Rapid Bioprocess Development of Mammalian Cell Culture

2012 ◽  
Vol 59 (1) ◽  
Author(s):  
Mohd Helmi Sani ◽  
Frank Baganz
Keyword(s):  
Cell Culture ◽  
Mammalian Cell ◽  
Process Development ◽  
Mammalian Cell Culture ◽  
Small Scale ◽  
Cell Culture Process ◽  
Deep Wells ◽  
Working Volume ◽  
Culture Process ◽  
And Control

At present, there are a number of commercial small scale shaken systems available on the market with instrumented controllable microbioreactors such as Micro–24 Microreactor System (Pall Corporation, Port Washington, NY) and M2P Biolector, (M2P Labs GmbH, Aachen, Germany). The Micro–24 system is basically an orbital shaken 24–well plate that operates at working volume 3 – 7 mL with 24 independent reactors (deep wells, shaken and sparged) running simultaneously. Each reactor is designed as single use reactor that has the ability to continuously monitor and control the pH, DO and temperature. The reactor aeration is supplied by sparging air from gas feeds that can be controlled individually. Furthermore, pH can be controlled by gas sparging using either dilute ammonia or carbon dioxide directly into the culture medium through a membrane at the bottom of each reactor. Chen et al., (2009) evaluated the Micro–24 system for the mammalian cell culture process development and found the Micro–24 system is suitable as scaledown tool for cell culture application. The result showed that intra-well reproducibility, cell growth, metabolites profiles and protein titres were scalable with 2 L bioreactors.

scholarly journals Characterising Foot-and-Mouth Disease Virus in Clinical Samples Using Nanopore Sequencing

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma Brown ◽  
Graham Freimanis ◽  
Andrew E. Shaw ◽  
Daniel L. Horton ◽  
Simon Gubbins ◽  
...  
Keyword(s):  
Cell Culture ◽  
Sequence Data ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Cell Culture Supernatant ◽  
Strain Identification ◽  
Consensus Sequences ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Foot And Mouth

The sequencing of viral genomes provides important data for the prevention and control of foot-and-mouth disease (FMD) outbreaks. Sequence data can be used for strain identification, outbreak tracing, and aiding the selection of the most appropriate vaccine for the circulating strains. At present, sequencing of FMD virus (FMDV) relies upon the time-consuming transport of samples to well-resourced laboratories. The Oxford Nanopore Technologies' MinION portable sequencer has the potential to allow sequencing in remote, decentralised laboratories closer to the outbreak location. In this study, we investigated the utility of the MinION to generate sequence data of sufficient quantity and quality for the characterisation of FMDV serotypes O, A, Asia 1. Prior to sequencing, a universal two-step RT-PCR was used to amplify parts of the 5′UTR, as well as the leader, capsid and parts of the 2A encoding regions of FMDV RNA extracted from three sample matrices: cell culture supernatant, tongue epithelial suspension and oral swabs. The resulting consensus sequences were compared with reference sequences generated on the Illumina MiSeq platform. Consensus sequences with an accuracy of 100% were achieved within 10 and 30 min from the start of the sequencing run when using RNA extracted from cell culture supernatants and tongue epithelial suspensions, respectively. In contrast, sequencing from swabs required up to 2.5 h. Together these results demonstrated that the MinION sequencer can be used to accurately and rapidly characterise serotypes A, O, and Asia 1 of FMDV using amplicons amplified from a variety of different sample matrices.

scholarly journals Online Monitoring and Control of Upstream Cell Culture Process Using 1D & 2D-LC with SegFlow Interface

2021 ◽  
Author(s):  
Letha Chemmalil ◽  
Dhanuka Wasalthanthri ◽  
Xin Zhang ◽  
June Kuang ◽  
Chun Shao ◽  
...  
Keyword(s):  
Cell Culture ◽  
Capital Investment ◽  
Quality By Design ◽  
Integrated System ◽  
Cell Culture Process ◽  
Next Generation ◽  
Monitoring And Control ◽  
Batch Mode ◽  
Knowledge Based ◽  
Online Measurements

The biopharmaceutical industry is transitioning from currently deployed batch-mode bioprocessing to a highly efficient and agile next generation bioprocessing with the adaptation of continuous bioprocessing, which reduces the capital investment and operational costs. Continuous bioprocessing, aligned with FDA’s quality-by-design (QbD) platform, is designed to develop robust processes to deliver safe and effective drugs. With the deployment of knowledge based operations, product quality can be built into the process to achieve desired critical quality attributes (CQAs) with reduced variability. To facilitate next generation continuous bio-processing, it is essential to embrace a fundamental shift-in-paradigm from “quality-by-testing” to “quality-by-design”, which requires the deployment of process analytical technologies (PAT). With the adaptation of PAT, a systematic approach of process and product understanding and timely process control are feasible. Deployment of PAT tools for real-time monitoring of CQAs and feedback control is critical for continuous bioprocessing. Given the current deficiency in PAT tools to support continuous bioprocessing, we have integrated Agilent 2D-LC with a post-flow-splitter in conjunction with the SegFlow automated sampler to the bioreactors. With this integrated system, we have established a platform for online measurements of titer and CQAs of monoclonal antibodies (mAbs) as well as amino acid concentrations of bioreactor cell culture.

Process development in the Quality by Design paradigm: Modeling of Protein A chromatography resin fouling

2018 ◽  
Vol 1570 ◽  
pp. 56-66 ◽  
Author(s):  
Lalita Kanwar Shekhawat ◽  
Mili Pathak ◽  
Jayati Sakar ◽  
Anurag S. Rathore
Keyword(s):  
Quality By Design ◽  
Process Development ◽  
Protein A ◽  
Design Paradigm

scholarly journals Cell culture propagation of foot-and-mouth disease virus: adaptive amino acid substitutions in structural proteins and their functional implications

Virus Genes ◽  
2019 ◽  
Vol 56 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Veronika Dill ◽  
Michael Eschbaumer
Keyword(s):  
Cell Culture ◽  
Amino Acid ◽  
Field Isolate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Rational Approach ◽  
Effective Control ◽  
Adaptive Mutations ◽  
Mouth Disease Virus ◽  
Foot And Mouth

AbstractFoot-and-mouth disease is endemic in livestock in large parts of Africa and Asia, where it is an important driver of food insecurity and a major obstacle to agricultural development and the international trade in animal products. Virtually all commercially available vaccines are inactivated whole-virus vaccines produced in cell culture, but the adaptation of a field isolate of the virus to growth in culture is laborious and time-consuming. This is of particular concern for the development of vaccines to newly emerging virus lineages, where long lead times from virus isolate to vaccine can delay the implementation of effective control programs. High antigen yields in production cells are also necessary to make vaccines affordable for less developed countries in endemic areas. Therefore, a rational approach to cell culture adaptation that combines prior knowledge of common adaptive mutations and reverse genetics techniques is urgently required. This review provides an overview of amino acid exchanges in the viral capsid proteins in the context of adaptation to cell culture.

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