Developing Chemically Defined Media Through DOE: Complete Optimization with Increased Protein Production in Less than 8 Months

Hammett, Kimesha; Kuchibhatla, Jagdish; Hunt, Cindy; Holdread, Stacy; Brooks, James W.

doi:10.1007/978-1-4020-5476-1_123

Cited by 6 publications

(3 citation statements)

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“…A combination of high-throughput cell culture scale-down systems with statistical design of experiment (DOE) approaches is commonly applied to shorten development time. 54,55 While optimization of cell culture media is often considered to be cell line dependent and best accomplished if based on the metabolism and nutrient consumption of specific cell lines, the aggressive timelines under which cell culture processes are developed requires development of a "platform" approach for optimization of cell culture processes. While the platform process might not provide the greatest volumetric productivity that could be achieved with specific cell lines, it will have wide applicability across multiple cell lines such that it can be implemented with minimal modifications for cell lines derived within the company.…”

Section: Clone Selectionmentioning

confidence: 99%

Cell culture processes for monoclonal antibody production

Vijayasankaran

Shen

et al. 2010

mAbs

630

409

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Animal cell culture technology has advanced significantly over the last few decades and is now generally considered a reliable, robust and relatively mature technology. A range of biotherapeutics are currently synthesized using cell culture methods in large scale manufacturing facilities that produce products for both commercial use and clinical studies. The robust implementation of this technology requires optimization of a number of variables, including 1) cell lines capable of synthesizing the required molecules at high productivities that ensure low operating cost; 2) culture media and bioreactor culture conditions that achieve both the requisite productivity and meet product quality specifications; 3) appropriate on-line and off-line sensors capable of providing information that enhances process knowledge; and 4) good understanding of culture performance at different scales to ensure smooth scale-up. Successful implementation also requires appropriate strategies for process development, scale-up and process characterization and validation that enable robust operation that is compliant with current regulations. This review provides an overview of the state-of-the art technology in key aspects of cell culture, e.g., engineering of highly productive cell lines and optimization of cell culture process conditions. We also summarize the current thinking on appropriate process development strategies and process advances that might affect process development.

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Section: Clone Selectionmentioning

confidence: 99%

Cell culture processes for monoclonal antibody production

Vijayasankaran

Shen

et al. 2010

mAbs

630

409

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“…By applying DoE, a small number of experiments is sufficient to determine the influence of several parameters and to identify the most significant ones. HTP methods and DoE are both applied in the development of upstream as well as downstream processing [21,[26][27][28][29][30][31][32].…”

Section: State Of the Art In Process Development And Optimizationmentioning

confidence: 99%

“…Traditionally, media were developed by changing one factor at a time [26,27]. In order to reduce experimental efforts, DoE and high-throughput methods are applied in industrial development processes [30][31][32]. As an example, a top down approach is described by Ma et al (2009) [62].…”

Section: Media Development and Optimizationmentioning

confidence: 99%

Trends in Upstream and Downstream Process Development for Antibody Manufacturing

2014

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A steady increase of product titers and the corresponding change in impurity composition represent a challenge for development and optimization of antibody production processes. Additionally, increasing demands on product quality result in higher complexity of processes and analytics, thereby increasing the costs for product work-up. Concentration and composition of impurities are critical for efficient process development. These impurities can show significant variations, which primarily depend on culture conditions. They have a major impact on the work-up strategy and costs. The resulting "bottleneck" in downstream processing requires new optimization, technology and development approaches. These include the optimization and adaptation of existing unit operations respective to the new separation task, the assessment of alternative separation technologies and the search for new methods in process development. This review presents an overview of existing methods for process optimization and integration and indicates new approaches for future developments.

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Animal Cell Culture Media

Vijayasankaran¹,

Li²,

Shawley³

et al. 2010

Encyclopedia of Industrial Biotechnology

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Fed‐batch cell culture processes are the standard platform technology for the synthesis of high value biopharmaceutical proteins. Recent advances in cell line development and in the optimization of culture medium have enabled the operation of fed‐batch processes at significantly higher volumetric productivities than previously realized. While a robust basal medium is essential to ensure high productivity, a well‐developed feed medium coupled with an appropriate feeding strategy are essential for sustaining it over the course of the culture duration. Furthermore, optimization of cell culture medium needs to be cognizant of specific goals for its use. Different optimization strategies are adapted for developing platform media applicable for multiple cell lines and customized media developed for specific cell lines. While volumetric productivity continues to be an important parameter for cell culture medium optimization, the developed medium should also be robust during implementation in biopharmaceutical manufacturing facilities. The developed medium should be easy to prepare and have a long shelf life to ensure ease of process implementation in multiple commercial and clinical‐scale manufacturing sites. Due care should be taken to ensure that optimization of media does not lead to unacceptable alterations in the quality of the expressed protein. This article will address all these aspects that ensure the efficient optimization and implementation of animal cell culture media.

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Developing Chemically Defined Media Through DOE: Complete Optimization with Increased Protein Production in Less than 8 Months

Cited by 6 publications

References 0 publications

Cell culture processes for monoclonal antibody production

Cell culture processes for monoclonal antibody production

Trends in Upstream and Downstream Process Development for Antibody Manufacturing

Animal Cell Culture Media

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