Scale-up and predictability in process development with suspension cultures of mammalian cells for recombinant protein manufacture: comments on a trend reversal

2013 ◽  
Vol 1 (4) ◽  
pp. 333-335 ◽  
Author(s):  
Maria Joao De Jesus ◽  
Florian Maria Wurm
2018 ◽  
Vol 17 (2) ◽  
Author(s):  
Neng Herawati ◽  
Arizah Kusumawati ◽  
Adi Santoso

Pichia pastoris is a group of methylotropic yeast known as a host of expression and protein production which is widely used for biopharmaceutical-based drug production. This yeast can grow fast with a high cell density. Its genetic stability, high cell density, and stress resistance make the development process and scale-up of P. pastoris can increase to a scale of 200,000 liters of culture. In contrast to the expensive and complex development of recombinant protein production in mammalian cells, the development of production in P. pastoris is relatively simple and cheaper. The advantage of P. pastoris as an expression system is that it is able to use methanol as a carbon source by inducing the expression of alcohol oxidase oxidase (AOX) enzyme. Promoter used by this enzyme is also used as a strong promoter for the expression of proteins that we want. Unlike in bacterial and mammalian systems, recombinant protein production in Pichia cells is not contaminated with endotoxins or viruses so it is safer and simplifies the downstream processes in bioproduction. The level of endogenous protein in the low supernatant allows Pichia to cultivate with a high volumetric productivity, therefore the process of protein production becomes very economical. This review provides an overview of several things that must be considered in utilizing P. pastoris as an expression system including the selection of vectors, strains, vector integration mechanisms into the genome, glycosylation processes, and applications in industry.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Seedhabadee Ganeshan ◽  
Seon Hwa Kim ◽  
Vladimir Vujanovic

AbstractThe benefit of microorganisms to humans, animals, insects and plants is increasingly recognized, with intensified microbial endophytes research indicative of this realization. In the agriculture industry, the benefits are tremendous to move towards sustainable crop production and minimize or circumvent the use of chemical fertilizers and pesticides. The research leading to the identification of potential plant endophytes is long and arduous and for many researchers the challenge is ultimately in scale-up production. While many of the larger agriculture and food industries have their own scale-up and manufacturing facilities, for many in academia and start-up companies the next steps towards production have been a stumbling block due to lack of information and understanding of the processes involved in scale-up fermentation. This review provides an overview of the fermentation process from shake flask cultures to scale-up and the manufacturing steps involved such as process development optimization (PDO), process hazard analysis (PHA), pre-, in- and post-production (PIP) challenges and finally the preparation of a technology transfer package (TTP) to transition the PDO to manufacturing. The focus is on submerged liquid fermentation (SLF) and plant endophytes production by providing original examples of fungal and bacterial endophytes, plant growth promoting Penicillium sp. and Streptomyces sp. bioinoculants, respectively. We also discuss the concepts, challenges and future perspectives of the scale-up microbial endophyte process technology based on the industrial and biosafety research platform for advancing a massive production of next-generation biologicals in bioreactors.


Author(s):  
Deepak B. Thimiri Govinda Raj ◽  
Niamat Ali Khan ◽  
Srisaran Venkatachalam ◽  
Sivakumar Arumugam

2014 ◽  
Vol 18 (10) ◽  
pp. 1175-1180 ◽  
Author(s):  
Luciano Lattuada ◽  
Maria Argese ◽  
Valeria Boi ◽  
Laura Galimberti ◽  
Sonia Gazzetto

2011 ◽  
Vol 12 (1) ◽  
pp. 372-378 ◽  
Author(s):  
Sajal Manubhai Patel ◽  
Michael J. Pikal

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