Related Experiment Video
Updated: Jun 4, 2026
06:24
Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
Published on: December 15, 2017
A review of advanced small-scale parallel bioreactor technology for accelerated process development: current state
Rachel Bareither1, David Pollard
1Biologics New & Enabling Technologies, Biologics Development, Merck Research Laboratories, Merck & Co. Inc., Rahway, NJ 07065, USA.
Biotechnology Progress
|February 12, 2011
Summary
High-throughput process development in pharma requires advanced small-scale systems for parallel reactions and automated sampling. Current technologies are insufficient, necessitating further innovation to accelerate drug development timelines and reduce costs.
Area of Science:
- Biotechnology
- Pharmaceutical Sciences
- Process Development
Background:
- The pharmaceutical and biotech industries are under pressure to reduce costs and speed up process development.
- There is a growing need for increased upstream experimentation to support Quality by Design (QbD) and systems biology predictive models.
Purpose of the Study:
- To evaluate the potential of small-scale, parallel reaction systems for accelerating pharmaceutical process development.
- To compare the limitations of current high-throughput process development technologies against desired criteria for mimicking large-scale commercial processes.
Main Methods:
- Review and comparison of state-of-the-art high-throughput process development systems, including shake flasks, microfluidic reactors, microtiter plates, and small-scale stirred reactors.
- Assessment of system capabilities for enabling multiple reactions in parallel (n ≥ 20), automated sampling, and integrated purification.
Main Results:
- A significant improvement (four to fivefold) in development timelines could be achieved with a suitable small-scale system.
- Existing technologies like shake flasks and microtiter plates have limitations in mimicking large-scale commercial processes.
- Current automated solutions are insufficient to fully accelerate upstream process development.
Conclusions:
- Further technological advancements are crucial for developing automated small-scale systems.
- Such systems are needed to meet the demands for faster, more efficient pharmaceutical process development.
- Innovation in high-throughput process development is essential for the biotech and pharmaceutical sectors.
Related Concept Videos
01:27Upstream Processing
Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
01:29Bioreactor Design and Operational System
Bioreactors are engineered vessels designed to cultivate microorganisms under controlled conditions for industrial bioprocessing. They maintain sterility and allow precise regulation of pH, temperature, oxygen, and nutrient levels to optimize microbial growth and metabolite production. Bioreactors range from small laboratory units of 1 liter to industrial systems holding up to 500,000 liters, though only about 75% of their volume is actively used for fermentation. The remaining headspace...
01:14Scale-Up Processes
The scale-up of microbial fermentation processes is essential in industrial biotechnology, allowing the transition from laboratory-scale experiments to commercial-scale production while aiming to maintain product yield and quality. This process requires meticulous adjustment of equipment design, process parameters, and contamination control strategies to accommodate increasing culture volumes.At the laboratory scale, cultures are typically maintained in 1 to 10-liter glass or autoclavable...
01:18Bioreactor Controls-II
In aerobic fermentations, oxygen is vital for microbial growth and metabolite production. Since air comprises only about 20% oxygen and the gas is poorly soluble in water—just 9 ppm at 20°C—supplying sufficient oxygen becomes a critical challenge, especially in high-demand processes like yeast growth or citric acid production. Even a fully saturated broth may offer only a few seconds of oxygen availability.To address this, sterile or scrubbed air is introduced into the fermentor via a sparger...
01:22Bioreactor Controls-III
Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
01:30Designing Growth Media for Bioreactors
Growth media provide essential nutrients that support cell growth and metabolism, thereby enhancing the yield of valuable products such as enzymes, antibiotics, and biomass. Designing an effective growth medium involves balancing all components to prevent nutrient limitations or toxic excesses, both of which can impair growth and reduce product yields.Composition of a Typical Growth MediumA typical growth medium contains carbon and nitrogen sources, salts, vitamins, trace elements, and...