Microbial Manufacturing

GMP production of recombinant proteins, enzymes, probiotic strains, plasmid DNA, single-domain antibodies, recombinant vaccines, nucleic acid drug ingredients, etc.

Featured Production Lines

Creative Biogene is a biotech CDMO for microbial production of commercial substances. Our microbial production services include GMP production of recombinant proteins, plasmid DNA, single-domain antibodies, recombinant vaccines, nucleic acid drug ingredients, etc. Our microbial GMP-manufacturing unit is equipped with state-of-the-art fermenters, harvesting equipment, and a choice of downstream purification capabilities.

Recombinant PROTEIN PRODUCTION
PROBIOTIC STRAIN PRODUCTION
RECOMBINANT ENZYME PRODUCTION
RECOMBINANT PLASMID PRODUCTION
RECOMBINANT VACCINE PRODUCTION
POLYSACCHARIDE PRODUCTION

End-to-End Development & Production Capability

Cell Banking
Strain Development
Cell Banking
Cell Characterization
Upstream Process
USP Development
DSP Development
Downstream Process
Analytical Methods
Analytics Development
Up-Scaling & Manufacturing
Up-Scaling
Manufacturing
QC & Batch Release
PCV Studies
Process Validation
Commercial GMP
GMP Manufacturing

Strain Development

 Chassis Strain Selection

Effective strategies have been developed for selecting and constructing chassis strains, thus to obtain a diverse range of products in a widely used cell factory.

Microbial Expression Optimization

Our services range from codon optimization to gene synthesis, clonal selection and purify. It's entirely customizable and flexible to fit how you run projects.

Microbial Strain Optimization

We utilize homologous recombination, site-specific recombination and CRISPR technology to generate custom genome-editing strains.

Cell Banking and Characterization

 Microbial Cell Bank Generation

Our cell line development laboratories enable unrivaled GMP-grade cell line generation, resulting in research cell banks (RCBs) master cell bank (MCBs), and working cell bank (WCBs), ammenable to IND and BLA filings.

Microbial Cell Bank Characterization

We have extensive experience in the characterization of microbial cell bank for pharmaceutical products, pesticides, veterinary medicines and industrial enzymes.

Upstream Process Development

 Fermentation Medium Optimization

Medium optimization services have been applied in the chemical, food, and pharmaceutical industries, with respect to increase the yield and activity of the desired product.

Process Parameter Optimization

Optimize conditions such as temperature, pH, oxygen levels, nutrient concentration, and agitation speed, to achieve the ideal balance between growth, metabolism, and product formation.

Bioreactor Selection and Optimization

Ensure optimal conditions for biological processes, maintaining an environment conducive to cell or microorganism growth and product formation.

Downstream Process Development

 Purification Processing

Our expertise ensures that you achieve the highest purity levels, maximize yield, and reduce operational costs, thereby enhancing the overall efficiency and quality of your bioproducts.

Freeze Drying

Freeze-drying is suitable for thermolabile materials and able to produce dry products with high-quality attributes.

Spray Drying

Spraying a liquid feed into a hot gas stream, causing the liquid to evaporate rapidly, leaving behind a dry powder, widely used in various industries.

Analytical Method Development

 Method Design and Optimization

Selection of analytical technique (e.g., HPLC, UPLC, GC, SDS-PAGE, Western blot, ELISA, qPCR)
Definition of critical quality attributes (CQAs)
Feasibility assessment and protocol drafting
Adjustment of parameters for sensitivity, specificity, and robustness
Troubleshooting interference from matrix components
Statistical design of experiments (DoE) for method fine-tuning

Method Validation

Accuracy, Precision, Specificity, Linearity, Range, Detection Limit (LOD), Quantitation Limit (LOQ), Robustness

Up-Scaling & Manufacturing

 R&D Scale Fermentation

Our lab-scale fermentation volume ranges from 0.5L to 100L and the conduction mimics the large-scale manufacturing as close as possible to meet different demands.

Pilot-Scale Fermentation

We offer a variety of pilot-scale fermenters (typically ranging from 10L to 500L) equipped with advanced control systems, allowing precise monitoring and optimization of parameters.

Industrial Fermentation

Full-scale services and management through equipment selection to products formulation and packaging, with a wide range of fermenter volumes from 1,000 liters to 10,000 liters.

QC & Batch Release

 Fermentation Quality Control

Integrated solutions can be offered with the professional equipment to help back up the whole development process of new products.

Batch Release Testing

Before the product is released for distribution, it undergoes final batch release testing, including confirming the product's identity, potency, sterility, endotoxin levels, and purity. The product must meet all specifications set out in the approved filing.

Process Characterization & Validation

 Process Characterization

Risk assessment (FMEA, Ishikawa)
Design of Experiments (DoE)
Identification of Critical Process Parameters (CPPs)
Data modeling and statistical analysis

Process Validation (PV)

Process Design
Process Qualification
Continued Process Verification (CPV)

Commercial GMP Manufacturing

 GMP-Compliant Fermentation

Production in ISO-certified cleanrooms
Fully validated stainless steel or single-use bioreactors
Real-time monitoring and automated control systems (PAT tools)

Deliverables

GMP-grade microbial biomass, cell lysates, secreted products, or purified intermediates
Batch Production Records (BPRs)
Certificate of Analysis (CoA)
Stability study data if requested

GMP BIOMANUFACTURING PLATFORMS

Advanced production systems designed to manufacture biopharmaceuticals in compliance with Good Manufacturing Practice (GMP) standards. Our platforms ensure consistent quality and minimize risks in the production process, meeting regulatory requirements for industrial use.

E. coli
E. coli

E. coli Platform

E. coli has been chosen as a highly promising and robust cell factory for its versatile advantages including easy cultivation, genetic manipulation and scalable fermentation. Heterologous production of natural products in E. coli has emerged as an attractive strategy to obtain molecules of interest. We possess a mature E. coli fermentation platform consisting of large fermentation tanks, bioreactors, and large-scale purification systems which enables us to provide high-purity and kilogram level products, at any scale from 5 to 10000L for both fed-batch and continuous cultivation.

High Cell Density Fermentation High Yield
Saccharommyces cerevisiae
Saccharommyces cerevisiae

Saccharommyces cerevisiae Platform

Yeast offers an eukaryotic expression system with many advantages for protein production. As a eukaryotic organism, yeast can perform many post-translational modifications similar to higher organisms. It combines the simplicity of bacterial culture with the protein processing capabilities of eukaryotic cells. Saccharomyces cerevisiae can produce high yields of recombinant proteins. Yeast expression systems are particularly valuable for proteins that require glycosylation or disulfide bond formation.

High Cell Density Fermentation High Yield Post-translational Modifications
Pichia pastoris
Pichia pastoris

Pichia pastoris Platform

Yeast offers an eukaryotic expression system with many advantages for protein production. As a eukaryotic organism, yeast can perform many post-translational modifications similar to higher organisms. It combines the simplicity of bacterial culture with the protein processing capabilities of eukaryotic cells. Pichia pastoris can produce high yields of recombinant proteins. Yeast expression systems are particularly valuable for proteins that require glycosylation or disulfide bond formation.

High Cell Density Fermentation High Yield Post-translational Modification
Bacillus Subtilis
Bacillus Subtilis

Bacillus subtilis Platform

Bacillus subtilis is a Gram-positive bacterium widely used for industrial protein production. Unlike E. coli, B. subtilis directly secretes proteins into the culture medium, which simplifies downstream processing. It has GRAS (Generally Recognized As Safe) status, making it suitable for food and pharmaceutical applications. B. subtilis has a natural capacity for high-level protein secretion and lacks endotoxins present in Gram-negative bacteria. These characteristics make it an excellent choice for the production of enzymes, antibiotics, and other industrial proteins.

High Cell Density Fermentation High Yield
Corynebacterium spp.
Corynebacterium spp.

Corynebacterium Platform

Corynebacterium species, particularly C. glutamicum, are important industrial microorganisms used primarily for the production of amino acids like L-glutamate and L-lysine. These Gram-positive bacteria have been engineered for heterologous protein expression with several advantages. They lack endotoxins, have minimal protease activity, and can secrete proteins into the culture medium. Corynebacterium expression systems are particularly useful for the production of membrane proteins and enzymes requiring specific cofactors.

Aspergillus spp.
Aspergillus spp.

Aspergillus Platform

Filamentous fungi are well-established expression hosts often used to produce extracellular proteins of use in the food and pharmaceutical industries. Aspergilli have been widely used in the production of organic acids, enzymes, and secondary metabolites. Several GRAS (generally recognized as safe) Aspergillus species hold a central role in the field of industrial biotechnology with multiple profitable applications. The expression systems presently used in Aspergillus species rely on either strong constitutive promoters, e.g., that for glyceraldehyde-3-phosphate dehydrogenase, or inducible systems derived from metabolic pathways, e.g., glaA (glucoamylase) or alc (alcohol dehydrogenase).

Trichoderma spp.
Trichoderma spp.

Trichoderma Platform

Trichoderma-Based Biocontrol Agents (BCAs) possess better ability to promote plant growth and soil remediation activity compared to their counterparts (virus, bacteria, nematodes and protozoa. Their capability to synthesize antagonistic compounds (proteins, enzymes and antibiotics) and micro-nutrients (vitamins, hormones and minerals) enhance their biocontrol activity. There has been an increasing research interest in applying microbial fermentations to manage plant parasitic nematodes worldwide. A growing number of studies have been devoted to analyze the potential of extracellular hydrolytic enzymes and secondary metabolites produced by some bio-control microorganisms.

Pseudomonas Fluorescens
Pseudomonas Fluorescens

Pseudomonas Fluorescens Platform

Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. Optimal temperatures for growth of P. fluorescens are 25–30°C. It tests positive for the oxidase test. It is also a nonsaccharolytic bacterial species. Heat-stable lipases and proteases are produced by P. fluorescens and other similar pseudomonads. Notable P. fluorescens strains have been sequenced for industrial applications.

Rhizopus spp.
Rhizopus spp.

Rhizopus spp. Platform

Rhizopus is a genus of common saprophytic fungi on plants and specialized parasites on animals. Rhizopus species grow as filamentous, branching hyphae that generally lack cross-walls (i.e., they are coenocytic). Rhizopus fermentation offers a sustainable and cost-effective method for producing various products with commercial and industrial value, making it an important process in the biotechnology and food industries.

Clostridium butyricum
Clostridium butyricum

Clostridium butyricum Platform

C. butyricum is a typical butyric acid bacterium found in soil and intestines of healthy animals and humans. An increasing number of reports on the probiotic potential of C. butyricum have been published. C. butyricum also plays a considerable role in soil mineralization processes and conversion of organic matter. A well-known property of C. butyricum is their ability to produce butyric acid and hydrogen, as well as effectively convert glycerol to 1,3-propanediol. We have characterized potent features of C. butyricum specific isolates in terms of their phylogenetic affiliation, fermentation capacity and antibacterial properties.

Lactic Acid Bacteria
Lactic Acid Bacteria

Lactic Acid Bacteria Platform

Lactic acid bacteria (LAB), including Lactococcus and Lactobacillus species, have emerged as important hosts for heterologous protein expression, particularly for food and pharmaceutical applications. These Gram-positive bacteria have GRAS status and are naturally present in many fermented foods. LAB expression systems offer advantages for the production of proteins requiring specific environments, such as those benefiting from the reducing conditions in these bacteria. They are particularly valuable for the development of live delivery vehicles for vaccines and therapeutic proteins targeting mucosal surfaces.

Customer Reviews

DR. DAVID CHEN

Head of Biologics R&D

"Your expertise in microbial fermentation and production has allowed us to bring our product to market faster than we anticipated. The attention to detail in every step of the process, from strain development to final product, has been outstanding."

LINDA NOVAK

Manufacturing Operations Manager

"Your team has been an invaluable partner in our product development. From the strain selection process to the final product manufacturing, your expertise and attention to detail have consistently exceeded our expectations."

SOPHIA KIM

Process Development Specialist

"We've been impressed by the consistency and quality of the microbial-based products you've produced for us. Your ability to meet both our technical requirements and regulatory standards gives us confidence in the success of our products."

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