Evaluating the impact of media and feed combinations on CHO cell culture performance and monoclonal antibody (trastuzumab) production.

Unlabelled: The choice of media and feeds significantly influences the performance of Chinese Hamster Ovary (CHO) mammalian cell cultures in producing desired biologics like monoclonal antibodies (mAb). Sub-optimal nutrient feed/media composition can severely impact cell proliferation and the quality of the final mAb product. For instance, proper protein glycosylation, crucial for mAb stability, safety, and efficacy, heavily relies on cell culture conditions.

Real-time dissolved carbon dioxide monitoring I: Application of a novel in situ sensor for CO monitoring and control.

Dissolved carbon dioxide (dCO ) is a well-known critical parameter in bioprocesses due to its significant impact on cell metabolism and on product quality attributes. Processes run at small-scale faces many challenges due to limited options for modular sensors for online monitoring and control. Traditional sensors are bulky, costly, and invasive in nature and do not fit in small-scale systems.

Real-time dissolved carbon dioxide monitoring II: Surface aeration intensification for efficient CO removal in shake flasks and mini-bioreactors leads to superior growth and recombinant protein yields.

Mass transfer is known to play a critical role in bioprocess performance and henceforth monitoring dissolved O (DO) and dissolved CO (dCO ) is of paramount importance. At bioreactor level these parameters can be monitored online and can be controlled by sparging air/oxygen or stirrer speed. However, traditional small-scale systems such as shake flasks lack real time monitoring and also employ only surface aeration with additional diffusion limitations imposed by the culture plug.

Comparison and implementation of different control strategies for improving production of rHSA using Pichia pastoris.

Recombinant protein production by various host organisms is strictly regulated, which is determined mainly by host cell genetics and maintenance of process variables within desirable limits in a reactor. Since the process dynamics typically exhibit nonlinear interactions amongst the critical process variables, the commonly employed controllers are suboptimal for control of most bioprocesses. In this article, we present the implementation of an augmented controller for improving the production of recombinant human serum albumin (rHSA) using Pichia pastoris.

Fluorescence based real time monitoring of fouling in process chromatography.

A real time monitoring of fouling in liquid chromatography has been presented. The versatility of the approach has been proven by successful implementation in three case studies with an error <1%. The first application demonstrates the monitoring of protein A ligand density and foulant concentration for assessing performance of protein A chromatography resin during purification of monoclonal antibodies.

Enabler for process analytical technology implementation in fermentation: Fluorescence-based soft sensors for rapid quantitation of product titer.

Rapid quantitation of product titer is a critical input for control of any bioprocess. This measurement, however, is marred by the myriad components that are present in the fermentation broth, often requiring extensive sample pretreatment before analysis. Spectroscopy techniques such as fluorescence spectroscopy are widely recognized as potential monitoring tools.

Knowledge management in a waste based biorefinery in the QbD paradigm.

Shifting resource base from fossil feedstock to renewable raw materials for production of chemical products has opened up an area of novel applications of industrial biotechnology-based process tools. This review aims to provide a concise and focused discussion on recent advances in knowledge management to facilitate efficient and optimal operation of a biorefinery. Application of quality by design (QbD) and process analytical technology (PAT) as tools for knowledge creation and management at different levels has been highlighted.

Bridging the gap between PAT concepts and implementation: An integrated software platform for fermentation.

Bioreactor control significantly impacts both the amount and quality of the product being manufactured. The complexity of the control strategy that is implemented increases with reactor size, which may vary from thousands to tens of thousands of litres in commercial manufacturing. The Process Analytical Technology (PAT) initiative has highlighted the need for having robust monitoring tools and effective control schemes that are capable of taking real time information about the critical quality attributes (CQA) and the critical process parameters (CPP) and executing immediate response as soon as a deviation occurs.

Maximizing biomass concentration in baker's yeast process by using a decoupled geometric controller for substrate and dissolved oxygen.

Biomass production by baker's yeast in a fed-batch reactor depends on the metabolic regime determined by the concentration of glucose and dissolved oxygen in the reactor. Achieving high biomass concentration in turn is dependent on the dynamic interaction between the glucose and dissolved oxygen concentration. Taking this into account, we present in this paper the implementation of a decoupled input-output linearizing controller (DIOLC) for maximizing biomass in a fed-batch yeast process.