Downstream Process Optimization

As a specialized fermentation CDMO company, we are committed to providing end-to-end downstream process optimization services, from fermentation broth pretreatment to the purification of target products. With our advanced technology platform, extensive industry experience, and customized solutions, we significantly enhance product quality, reduce production costs, shorten production cycles, and ensure green and intelligent processing. Our goal is to help clients achieve efficient and sustainable production while strengthening their market competitiveness.

What is Downstream Process (DSP)?

The downstream process (DSP) refers to separating and refining the product of interest from the reaction broth, culture broth, or fermentation broth during the mass cultivation of microbial fermentation strains. The DSP involves multi-step procedures for the recovery and purification of target products, which is also the most costly process in the pharmaceutical industry. Therefore, optimization of microbial fermentation DSP is critical. DSP optimization involves a variety of techniques such as chromatography, membrane technology, crystallization, and distillation. For example, proteins expressed by microbial strains can be recovered and purified using size-exclusion chromatography or membrane separation techniques. As a result, the goal of DSP optimization is to achieve low cost, efficient yield, and high purity production of the target product through the most straightforward process, as well as easy disposal of process waste.

Importance of Downstream Process Optimization

Downstream process optimization plays a crucial role in the bioprocessing industry, directly impacting product quality, cost, production efficiency, and market competitiveness. The key benefits include:

1. Improving Product Quality

Purity Enhancement: Optimizing separation and purification steps to remove impurities and increase target product purity to meet the quality standards of pharmaceuticals, food, and chemical products.

Stability Improvement: Refining drying and packaging processes to ensure product stability during storage and transportation, thereby extending shelf life.

Removal of Harmful Substances: Eliminating pyrogens, toxins, pigments, and other impurities in the pretreatment phase to guarantee product safety.

2. Reducing Production Costs

Increasing Yield: Enhancing separation and purification efficiency to minimize product loss and improve recovery rates, reducing per-unit production costs.

Energy and Resource Efficiency: Implementing high-efficiency separation technologies (e.g., membrane separation, crystallization) and optimizing process parameters to lower energy consumption and raw material waste.

Reducing Waste Treatment Costs: Optimizing processes to minimize waste generation and enable resource recycling, reducing environmental protection costs.

3. Enhancing Production Efficiency

Shortening Production Cycles: Streamlining processes to eliminate unnecessary steps, boosting efficiency, and reducing the time required to produce final products from fermentation broth.

Automation and Intelligence: Leveraging real-time monitoring and automated control technologies to improve process stability and reproducibility while minimizing human errors.

4. Strengthening Market Competitiveness

Regulatory Compliance: Ensuring optimized processes meet international and domestic regulatory standards, facilitating market entry.

Adaptability to Diverse Needs: Enabling quick response to market changes by flexibly adjusting process parameters to meet different purity, formulation, and packaging requirements.

Brand Enhancement: Delivering high-quality products and efficient production processes to build customer trust and enhance corporate reputation.

5. Promoting Green Production

Environmental Impact Reduction: Optimized processes help minimize wastewater, gas emissions, and solid waste, reducing environmental impact.

Resource Recycling: Implementing waste recovery and reuse strategies to minimize resource waste and support sustainable development.

Application of DSP Optimization

Pharmaceutical relevant agents productions include small molecules and biomolecules, such as antibodies, enzymes, hormones, growth factors and recombinant protein vaccines. The development and optimization of fermentation DSP expand the production of these valuable molecules, particularly, fulfill the requirements stated by authorities, including the Food and Drug Administration. In biological drugs manufacturing, product quality highly depends on the production process. Therefore, optimization and establishment of generic fermentation DSP can be served as a practical approach to achieve large-scale production under safe and compliant conditions.

Our Services

1. Fermentation Broth Pretreatment

Impurity Removal: Eliminating proteins, inorganic ions, pigments, pyrogens, and toxins from the fermentation broth.

Processing Performance Enhancement: Adjusting pH, temperature, and adding flocculants or filter aids to reduce viscosity and improve filtration efficiency.

Solid-Liquid Separation: Using centrifugation, filtration, or membrane separation to remove cells and suspended solids.

2. Initial Product Separation and Enrichment

Extraction: Employing organic solvents or supercritical fluid extraction for hydrophobic product enrichment.

Adsorption: Utilizing ion-exchange resins or activated carbon to remove impurities or concentrate the target product.

Membrane Separation: Applying microfiltration or ultrafiltration techniques to separate substances of different molecular weights.

3. High-Purity Product Refinement

Chromatographic Techniques: Using high-performance liquid chromatography (HPLC), ion-exchange chromatography, and other methods for further purification.

Crystallization: Controlling crystallization conditions to isolate the target product in a high-purity crystalline form.

4. Final Product Processing

Drying: Utilizing spray drying, freeze drying, or other techniques to convert products into powder or solid forms.

Packaging: Providing standardized packaging solutions based on customer requirements to ensure product quality and stability.

Our Methods

Technologies for product separation and purification from fermentation broth including:

• The solid-liquid separation technologies, including centrifugation, filtration separation, sedimentation separation, etc.
• Cell breaking technologies, including high temperatures, ultrasound, osmotic pressure, surfactant and wall lysing enzymes, etc.
• Membrane separation technologies, including microfiltration (MF), ultrafiltration (UF), reverse osmosis (RO), dialysis, electrodialysis (ED), gas separation (GS), permeate vaporization (PV), emulsion membrane (ELM).
• Protein purification technology, such as precipitation, chromatographic separation and ultrafiltration, etc.
• Product packaging, such as vacuum drying and freeze-drying, etc.

Concepts of Quality by Design (QbD) provides complete guidance for the fermentation process to maximize the product's efficacy and safety.

Our Advantages

• Personalized downstream process solutions based on different target products' requirements and fermentation scales
• Advanced processing and production facilities, including fermenters of different sizes, continuous sterilization, multiple aseptic feed lines, separation and purification equipment.
• High efficiency and competitive costs.
• Experienced in microbial fermentation from laboratory scale to large-scale production.
• Equipped with fully automated fermenters and capable of industrial manufacturing.
• Effective separation and purification technologies.
• Comprehensive capability to perform complex molecules extraction and production.

Our Capability

DSP Capability

Screening, development and preparation of Ion Exchange Resins, Microporous Adsorption Resins with high adsorption capacity, good exchange efficiency and stabled chemical properties.

Adoption of high-efficiency green separation technology with membrane and chromatography technology.

Design and implementation of complex product separation and purification process.

Preparation of reference standards for the target compound and the related impurities.

Advanced Equipment

Centrifuge: Disc/Decanter; Various membrane systems; Chromatography; Drying equipment: Spray & freeze-drying

Seamless One-Stop Service

Integrated development and manufacturing through lab scale to filing.

Expertise in microbial fermentation process and chemical synthesis.

Fast and Cost Effective

Super fast delivery of service and products; High efficiency; Competitive cost

Excellent Quality

Top quality service; Continuous improvement

We have a good track record in supporting the needs of microbial fermentation technology for biotransformation by pharmaceutical and supplement companies.

Service Workflow

1. Project Initiation

Understanding client requirements, including target product, fermentation system, and quality expectations.

Signing cooperation agreements and defining project timelines and milestones.

2. Fermentation Broth Pretreatment

Analyzing broth composition and selecting appropriate pretreatment methods (e.g., flocculation, heating, pH adjustment).

Conducting experiments to optimize pretreatment conditions, ensuring reduced viscosity and effective impurity removal.

3. Solid-Liquid Separation

Choosing centrifugation, filtration, or membrane separation based on broth characteristics.

Optimizing separation parameters to ensure efficient removal of cells and suspended solids.

4. Initial Product Separation and Enrichment

Applying extraction, adsorption, or membrane separation for product enrichment.

Conducting validation experiments to assess separation efficiency and refine process parameters.

5. High-Purity Product Refinement

Selecting appropriate chromatography or crystallization methods based on product properties.

Conducting small-scale tests and optimizing purification conditions.

6. Final Product Processing

Choosing suitable drying and packaging methods to maintain product integrity.

Conducting pilot-scale trials to validate product stability.

7. Process Optimization and Scale-Up

Utilizing laboratory and pilot-scale data to establish mathematical models and refine process parameters.

Scaling up from laboratory to industrial production while ensuring process stability and reproducibility.

8. Delivery and After-Sales Support

Providing comprehensive process reports and quality analysis documentation.

Offering technical support to assist clients in resolving production challenges.