Fermentation Process Development

Creative Biogene provide support for your microbial fermentation projects to optimize your existing fermentation and purification processes, and improve manufacturability and process economy irrespective of your development stage or expression platform. Process optimization is key to reducing potential pitfalls, such as formation of product related impurities or improper folding, leading to insoluble aggregates. Our experience with upstream optimization techniques and materials allows us to produce a functional protein across a variety of molecule types. We have equipped upstream development laboratory to develop, optimize and scale a process. Downstream purification and refolding are conducted following fermentation. We have developed the unit operations of downstream processing sequence, speeding up development while maintaining the highest standard of quality. Process validation support activities increase the process understanding, identify critical process parameters and define operating ranges.

Fermentation Process Development

Strain Selection

Select a suitable microbial strain for the desired fermentation application. Consider factors such as product yield, metabolic capabilities, environmental requirements, and genetic stability.

Medium Formulation

Develop a growth medium that provides the necessary nutrients for microbial growth and product formation. The composition of the medium should support optimal cell growth and productivity. Factors such as carbon source, nitrogen source, minerals, vitamins, and growth factors need to be optimized for the specific strain and product.

Inoculum Development

Establish an efficient and consistent inoculum development process. This involves selecting appropriate pre-culture conditions, such as inoculum size, growth phase, and incubation conditions, to generate a robust and viable inoculum for large-scale fermentation.

Process Parameter Optimization

Identify and optimize critical process parameters such as temperature, pH, dissolved oxygen, agitation, and aeration. These parameters significantly influence microbial growth, metabolism, and product formation. Using statistical experimental design methods, such as Design of Experiments (DoE), can help efficiently screen and optimize process parameters.

Fermentation Kinetics

Characterize the growth kinetics and metabolic behavior of the selected strain under different process conditions. Monitor key parameters such as biomass concentration, substrate consumption, product formation, and byproduct formation over time. This data helps understand the fermentation kinetics and guides process optimization.

Scale-up and Bioreactor Selection

Transition the fermentation process from laboratory-scale to larger production scales. Consider factors such as bioreactor design, vessel size, agitation and aeration mechanisms, and control systems. Ensure that the chosen bioreactor can support the specific requirements of the microbial strain and the production process.

Process Monitoring and Control

Implement appropriate monitoring and control systems to maintain optimal process conditions during fermentation. This may include real-time monitoring of temperature, pH, dissolved oxygen, and online analytics for measuring key process parameters. Use feedback control strategies to maintain stability and consistency throughout the fermentation process.

Downstream Processing Considerations

Consider downstream processing requirements during fermentation process development. Understand the characteristics of the desired product and plan for its extraction, purification, and formulation after fermentation. Integration of downstream processes with fermentation can help optimize the overall process efficiency.

Process Optimization and Scale-up

Continuously optimize the fermentation process based on experimental data and process modeling. Conduct iterative experiments to fine-tune the process parameters, medium composition, and culture conditions. Scale up the fermentation process incrementally to larger production volumes while maintaining consistent product quality and yield.

Process Validation and Quality Assurance

Validate the optimized fermentation process and establish robust quality assurance systems. Develop protocols for process validation, in-process testing, and product analysis to ensure that the final product meets the required specifications and regulatory standards.

Fermentation Development Purification and Refolding Process Validation
Fermentation development Filtration and chromatography development Scale-down modeling
Feed strategy optimization High throughput resin screening Process characterization
Media optimization Tangential flow filtration Critical process parameter studies
Induction kinetics optimization Impurity removal studies (endotoxin, residual DNA) Range finding studies
Recovery and separation development High throughput refolding development and optimization Analytical method validation
Inclusion body expression and recovery optimization PEGylation Development and Optimization Media & buffer stability
High cell-density fermentation Buffer characterization In-process hold studies
Alternatives to chromatography Resin and membrane re-use studies

Creative Biogene provides customers efficient and flexible fermentation process development services. Every fermentation development program Creative Biogene takes on is unique, depending on the starting point, objectives and degree of difficulty in achieving the objectives. Whereas some are long-term fermentation process development programs, requiring years for completion, others can be completed within mere months in a highly cost-effective manner.

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