ShilpaBio has innovated unique platforms positioned to provide business value to customers worldwide.
| Background | Receptor Fc Protein is used in treatment of neovascular (wet) age-related macular degeneration (AMD) 2mg/0.05ml is the dosage for therapy |
| Program Complexity | The molecule is highly sialylated, which affects absorption, serum half-life, and clearance from the serum, as well as the shelf-life of the product and the physical, chemical, and immunogenic properties of the glycoprotein. From a manufacturing perspective, the degree of sialylation is crucial since it alters the function of the product. In addition, insufficient or inconsistent sialylation is a major problem for product consistency. |
| Program Accomplishments | The innovator uses a fed-batch process for manufacturing the receptor-Fc Fusion protein. Shilpa Biologicals has developed a unique perfusion process using ATF (Alternative Tangential Flow). The ATF™ System was originally designed for perfusion processes in mammalian cell culture using hollow fiber filters to achieve efficient cell separation with low shear and allowing robust large-scale manufacturing. With ATF, we achieved high PCD (per cell density) and titers along with consistent sialylation. Our in-house developed ATF perfusion batch method resulted in higher yields and excellent quality. The process eliminated an extra step of depth filtration during downstream purification, which reduced the cost of manufacturing. By using this strategy, we were able to optimize the recovery of Fc protein as well as preserve the necessary biological properties. |
| Conclusions | We analyzed the structure of the Fc fusion molecule and created a glycan profile range with no impact on the bioactivity of the product. The unique perfusion strategy has been developed to achieve the highest PCD and titers along with necessary biological characteristics. |
Overlapping glycan range is observed in SBPL and Innovator product
Glycan Profiling by UPLC Analysis
We have developed an Fc fusion protein with high biosimilarity to the innovator. Our unique perfusion strategy has been developed to achieve the highest PCD and titers along with preservation of bioactivity
| Background | Time and cost are key considerations in the development and manufacturing of biologics for global supply The ability to achieve optimal titers and yields are critical to ensure productivity |
| Program Complexity | Biologics manufacturing demands high yield in fermentation which can be achieved by modifying feeding strategies based upon the media and culture being used Fed-batch culture is an operational technique in biotech processes where one or more nutrients are fed to the bioreactor during cultivation and in which the product(s) remain in the bioreactor until end of the run This technique shortens fermentation time, achieves high cell density, increases productivity |
| Program Accomplishments | By changing the feeding strategy using chemically defined media, it made possible to get higher titers and yields to meet the market demand Higher cell density gives higher titers in a single batch which reduces the time and cost consumption for multiple batches required for global supply We developed a receptor Fc fusion protein in fermentation with high PCD and titers by using fed batch technology where the cost and time requirement in minimal as compared to the other manufacturers |
| Conclusions | Achieved cumulative yield of 4-5g/L of Fc protein in 15 days in 2-10L fermenters Scale up is on-going for higher levels of production of the Fc protein for commercial manufacturing |
We have developed a receptor Fc fusion protein with high PCD and titers by using fed batch technology with highly optimized cost and time requirements as compared to other manufacturers
| Background | Development of Sputnik V vaccine in adenovirus platform to achieve ~2000 doses/L cGMP manufacturing of vaccine Timeline: 6 months |
| Program Complexity | Process was not developed; lack of technical support and ambiguity over manufacturing process and analytical methods We optimized the process to bring in consistency in yield and quality; developed analytical methods required for full validation |
| Program Accomplishments | Facility was modified to suite vaccine production and seamless scale up/validation was performed Entire process development and manufacturing was conducted successfully based on tech transfer documents Audit was conducted by India’s national regulatory body (The Central Drugs Standard Control Organisation for cosmetics, pharmaceuticals and medical devices/CDSCO) to ensure compliance to global standards |
| Conclusions | We delivered a high-quality product under full compliance to global standards |
We demonstrated the ability to modify our facilities and scale up our capacity with speed to meet the demands of a national public health emergency under full compliance to global regulatory standards
| Background | Hypovolemia is treated by protein based drug product. The natural source of protein is a potential source of contamination with adventitious viruses that can cause diseases in humans. Availability is limited as it depends on the availability of natural liquid source. To develop recombinant protein based drug product to replace the currently available one. Timeline: 12 months |
| Program Complexity | Protein is large of approximately 66 kDa molecular weight. It has multiple disulfide bonds and one unique disulfide that needs to be maintained free for ensuring activity. Glycosylation is absent in natural form and the recombinant source needs to match the same. |
| Program Accomplishments | Pichia pastoris is selected as the source for the expression of recombinant protein and clone is designed in such a way that the copy number of the construct is high in the clone. Product development is completed achieving titers in upstream process up to 6 to 8 gr per liter. Downstream process is designed in such a way to achieve high purity of >99% with all process related impurities controlled within limits. In vitro studies confirmed that structure, activity/binding and purity/impurity levels in drug product developed are either similar or better compared to the natural source. |
| Conclusions | High purity product meeting quality requirements is developed within the timeline. Currently at 1 kL and 3 kL upstream scales. Planning to scaleup to 30 kL and 55 kL to meet the supply demand of the product. |
We demonstrated the ability to modify our facilities and scale up our capacity with speed to meet the demands of a national public health emergency under full compliance to global regulatory standards
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Making high quality biopharmaceuticals affordable to patients globally. Write to us with your queries.
