Our Science

ShilpaBio has innovated unique platforms positioned to provide business value to customers worldwide

Case Study I – Process Development for a Sialylated Therapeutic Fc Fusion Protein

Process Development for a Sialylated Therapeutic Fc Fusion Protein

Background Program Complexity Program Accomplishments Conclusions

1. Receptor Fc Protein is used in treatment of neovascular (wet) age-related macular degeneration (AMD)

2. 2mg/0.05ml is the dosage for therapy 1. The molecule is highly sialylated which affects absorption, serum half-life, and clearance from the serum, as well as the shelf-life of product and physical, chemical and immunogenic properties of the glycoprotein

2. From a manufacturing perspective, the degree of sialylation is crucial since it alters function of the product. In addition, insufficient or inconsistent sialylation is also a major problem for product consistency 1. The innovator uses fed batch process for manufacturing the receptor-Fc Fusion protein

2. Shilpa Biologicals has developed a unique perfusion process using ATF (Alternative Tangential Flow)

3. 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.

4. With ATF, we achieved high PCD (per cell density) and titers along with consistent sialylation

5. Our in-house developed ATF perfusion batch method resulted in higher yields and excellent quality

6. The process eliminated an extra step of depth filtration during downstream purification which reduced cost of manufacturing

7. By using this strategy, we were able to optimize recovery of Fc protein as well as preserve the necessary biological properties 1. We analyzed the structure of the Fc fusion molecule and created a glycan profile range with no impact on the bioactivity of the product

2. The unique perfusion strategy has been developed to achieve the highest PCD and titers along with necessary biological characteristics

Background	Program Complexity	Program Accomplishments	Conclusions
1. Receptor Fc Protein is used in treatment of neovascular (wet) age-related macular degeneration (AMD) 2. 2mg/0.05ml is the dosage for therapy	1. The molecule is highly sialylated which affects absorption, serum half-life, and clearance from the serum, as well as the shelf-life of product and physical, chemical and immunogenic properties of the glycoprotein 2. From a manufacturing perspective, the degree of sialylation is crucial since it alters function of the product. In addition, insufficient or inconsistent sialylation is also a major problem for product consistency	1. The innovator uses fed batch process for manufacturing the receptor-Fc Fusion protein 2. Shilpa Biologicals has developed a unique perfusion process using ATF (Alternative Tangential Flow) 3. 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. 4. With ATF, we achieved high PCD (per cell density) and titers along with consistent sialylation 5. Our in-house developed ATF perfusion batch method resulted in higher yields and excellent quality 6. The process eliminated an extra step of depth filtration during downstream purification which reduced cost of manufacturing 7. By using this strategy, we were able to optimize recovery of Fc protein as well as preserve the necessary biological properties	1. We analyzed the structure of the Fc fusion molecule and created a glycan profile range with no impact on the bioactivity of the product 2. 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

Case Study II – Process Development for Enhancing Yields for an Fc Fusion Protein

Process Development for Enhancing Yields for an Fc Fusion Protein




	Background Program Complexity Program Accomplishments Conclusions




	1. Time and cost are key considerations in the development and manufacturing of biologics for global supply 

2. The ability to achieve optimal titers and yields are critical to ensure productivity 

1. Biologics manufacturing demands high yield in fermentation which can be achieved by modifying feeding strategies based upon the media and culture being used

2. 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

3. This technique shortens fermentation time, achieves high cell density, increases productivity

1. By changing the feeding strategy using chemically defined media, it made possible to get higher titers and yields to meet the market demand

2. Higher cell density gives higher titers in a single batch which reduces the time and cost consumption for multiple batches required for global supply

3. 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

1. Achieved cumulative yield of 4-5g/L of Fc protein in 15 days in 2-10L fermenters 

2. Scale up is on-going for higher levels of production of the Fc protein for commercial manufacturing

Background	Program Complexity	Program Accomplishments	Conclusions
1. Time and cost are key considerations in the development and manufacturing of biologics for global supply 2. The ability to achieve optimal titers and yields are critical to ensure productivity	1. Biologics manufacturing demands high yield in fermentation which can be achieved by modifying feeding strategies based upon the media and culture being used 2. 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 3. This technique shortens fermentation time, achieves high cell density, increases productivity	1. By changing the feeding strategy using chemically defined media, it made possible to get higher titers and yields to meet the market demand 2. Higher cell density gives higher titers in a single batch which reduces the time and cost consumption for multiple batches required for global supply 3. 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	1. Achieved cumulative yield of 4-5g/L of Fc protein in 15 days in 2-10L fermenters 2. Scale up is on-going for higher levels of production of the Fc protein for commercial manufacturing

We have developed an optimal fed batch process for the production of receptor-Fc Fusion protein
We adopted a modified feeding strategy for achieving high PCD (per cell density) and titres

Cumulative yield per batch – 8 g/L in 15 days

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

Case Study III: Covid-19 Sputnik Vaccine Development and Manufacturing

Covid-19 Sputnik Vaccine Development and Manufacturing




	Background Program Complexity Program Accomplishments Conclusions




	1. Development of Sputnik V vaccine in adenovirus platform to achieve ~2000 doses/L

2. cGMP manufacturing of vaccine

3. Timeline: 6 months

1. Process was not developed; lack of technical support and ambiguity over manufacturing process and analytical methods

2. We optimized the process to bring in consistency in yield and quality; developed analytical methods required for full validation

1. Facility was modified to suite vaccine production and seamless scale up/validation was performed

2. Entire process development and manufacturing was conducted successfully based on tech transfer documents

3. 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 

1. We delivered a high-quality product under full compliance to global standards

Background	Program Complexity	Program Accomplishments	Conclusions
1. Development of Sputnik V vaccine in adenovirus platform to achieve ~2000 doses/L 2. cGMP manufacturing of vaccine 3. Timeline: 6 months	1. Process was not developed; lack of technical support and ambiguity over manufacturing process and analytical methods 2. We optimized the process to bring in consistency in yield and quality; developed analytical methods required for full validation	1. Facility was modified to suite vaccine production and seamless scale up/validation was performed 2. Entire process development and manufacturing was conducted successfully based on tech transfer documents 3. 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	1. 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

Global pain-point

Small Volume manufacturing
High operation costs of cell culture media

Next Steps – Programs in development

ContiGly™ platform for Development of pathway engineered cells that enable tunable glycosylation

ContiSec™ platform for Development of pathway engineered cells that enhance longevity and secretion from cells

ShilpaBio’s solution

High density continuous bioprocess platform for production of biopharmaceuticals from small footprint facility - ContiMAb™ , ContiFuse™ & ContiVir™
Development of low-cost cell culture media and media kit to enable continuous processing

ShilpaBio’s Scientific Mission 2021-2025

Continuous bioprocess platform ContiMAb & ContiFuse platforms to enable penetration of biologics from 5% to 30% of the patient population. Our scientists leverage the platforms for biosimilars portfolio development.

We welcome partners who share the mutual goal of making high quality biopharmaceuticals affordable to patients globally.
Please write to [email protected] with your queries.

For current partnerships, check our Partnerships section