The quality of biological products relies heavily on the precise implementation of downstream purification processes
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- Issue Time
- Nov 6,2025
Summary
The safety and effectiveness of biological products depend on the precise implementation of downstream purification processes.
This process aims to separate and purify high-purity, pharmacopoeial compliant bioactive substances from complex fermentation broth.
Purification is the core link in the commercialization of microbial drugs, determining product quality and industrial production level.
1、 The core challenge of purification process is the complex composition of fermentation broth, including microbial cells, metabolites, and non consumed culture medium.
The concentration of target active substances is extremely low, such as vitamin B12, which is only 0.02 kg/m ³, while the proportion of impurities is high and some of them have similar physical and chemical properties to the target.
Bioactive substances have poor stability and are prone to deactivation and decomposition under the influence of heat and chemical reagents, especially proteins whose activity depends on their spatial structure, which increases the difficulty of process control.
Some products require full aseptic operation, further raising the threshold for process implementation.
2、 Cost proportion and industry value
Downstream purification is a "high cost" for the production of biological products.
The proportion of post-treatment costs varies significantly among different products: the investment in purification in antibiotic production is about 4 times that of fermentation, 1.5 times that of organic acid and amino acid production, and the purification cost of genetic engineering drugs is as high as 60% to 90% of the total production cost.
Therefore, optimizing purification technology and reducing costs are key breakthroughs in promoting the development of the biopharmaceutical industry.
3、 Standardized downstream purification process flow
1. Fermentation broth pretreatment improves the properties of the fermentation broth by adjusting pH value, salt concentration, heating or flocculation, laying the foundation for subsequent separation operations and reducing processing pressure in subsequent processes.
2. Cell separation uses techniques such as sedimentation, centrifugation, filtration, or cross flow filtration to separate microbial cells from fermentation broth. If the target substance is an extracellular product, it can directly enter the preliminary purification stage after this step.
3. Cell lysis (exclusive to intracellular products) targets intracellular active substances and requires methods such as homogenization, grinding, enzymatic dissolution, or ultrasonic wall breaking to break the cell structure and release the target product.
4. Cell fragment separation utilizes techniques such as centrifugation, extraction, filtration, or cross flow filtration to remove fragments produced after cell fragmentation and further purify the feed solution.
5. Preliminary purification
Concentrate the target substance through methods such as precipitation, adsorption, extraction, or ultrafiltration, significantly reducing impurity content and reducing subsequent processing volume.
6. For high purification, precision separation technologies such as gel filtration chromatography, ion exchange chromatography and affinity chromatography are used to achieve high purity enrichment of target substances and ensure that products meet quality standards.
7. Finished products are processed by aseptic filtration, ultrafiltration, crystallization, freeze drying or spray drying, and the purified substances are processed into final products to ensure product stability and ease of use.
