Rich CMC experience with> 90 CMC projects
＞20 IND approvals
42% CMC projects are challenging molecules
Nowadays mAb CMC development is becoming more and more standardized. However, there is no standard CMC strategy for multispecific antibody and recombinant protein. Customized CMC strategy should be developed according to the molecular features. There are many challenges in the development of recombinant protein CMC, such as low titer, light and heavy chain mismatch, low stability, complex purification process and challenging analytical development, which raise high requirements for CDMOs.
GenScript ProBio has a complete antibody protein drug process development platform, and has undertaken > 90 CMC projects, 42% are proteins and multi-specific antibodies. The most advanced project has entered into the clinical phase III.
GenScript ProBio’s cell line development platform is based on the proprietary CHOK1-GenS system with high productivity and excellent stability. The average titer can reach 5.4 g/L. CHOK1-GenS system is compatible with different molecular types, such as bispecific antibody and recombinant protein. It only takes less than 3 months from DNA to PCB.
For recombinant protein, GenScript ProBio pays attention to product quality and purity, and increase cell pool and clone selection scale to improve final titer.
1. Through the use of high-throughput platforms such as Ambr15 for process development, GenScript ProBio can efficiently complete clone screening, media screening and parameter optimization (i.e. pH, temperature, feed strategy). ProBio optimizes product quality based on molecular features.
2. Suitable additives to improve product qualityIn a recombinant protein case, ion additives help improve monomer purity.
3. Define the best harvesting timeBy extending the cell culture time and analyzing the trend of activity and viability, ProBio can define the best harvesting time is D11.
1.Attention to filter adsorptionVariant filter adsorption in recombinant protein cases.C filter shows the lowest adsorption performance.
2. S/D substitutes low pHProtein will fully precipitate under low pH, while S/D inactivation method can act as the substitution. S/D can also help improve the purity due to the aggregate precipitation.
3. AC resin selectionMany recombinant proteins are not suitable for protein A affinity chromatography. Multimodal resin can fulfill the purity and yield requirements.
4. Polish resin selectionMultimodal resin is suitable for recombinant protein polish purification and can remove aggregates.
Recombinant protein has special molecular properties. Conventional analysis methods cannot meet the needs of the projects. So recombinant protein projects need strong analytical development platform, including structure, residuals and bioactivity. This table shows some challenges and solutions in the protein projects.
Entered into clinical phase Ⅱ
GenScript ProBio’s cell line development platform is based on the proprietary CHOK1-GenS system with high productivity and excellent stability. The average titer for mAb can reach 5.4 g/L and the average titer for bsAb is 3.2 g/L. It only takes less than 3 months from DNA to PCB.
1. Suitable additives to improve product qualityIn one bispecific antibody case, modified amino acids help improve titer to 150%
2. Process optimization to improve titerIn one bispecific antibody case, optimizing culture conditions such as pH and temperature to improve titer.
3. Process intensificationIn addition to the traditional fed-batch process, GenScript ProBio also provides process intensification solutions such as high density inoculation to help improve titer.
4. Perfusion culture helps improve product qualityPerfusion culture helps increase full length ratio and purity
1. High-throughput downstream process screening platform
2. S/D method in place of low pH can help improve purity
3. Aggregate removalMultimodal resin is suitable for multispecific antibody purification and can remove aggregates.
In one trispecific antibody case, through downstream process optimization, purity was improved from 84.7% to 98.6%.
Multispecific antibodies often have chain mismatches, so appropriate analysis methods need to be developed to monitor the occurrence of mismatches.
LC-MS method can sensitively monitor chain mismatch.
GenScript ProBio has strong analytical development capabilities, and can design suitable bioassay and functional activity methods based on molecule features and MOA