ProBio provides the developability anlaysis report comprises three parts: the immunogenicity analysis, post-translational modification (PTM)and antibody aggregation analysis. If high-risk issues are identified, our experts have an extensive antibody engineering capabilities to improve your antibody sequences.
Some antibody drugs that have progressed into CMC or clinical stages encounter problems with non-specific binding or self-interaction. These issues often result in side effects such as immunogenicity and reduced drug efficacy, leading to substantial economic losses. In vitro developability assays should be conducted before costly in vivo animal study to reduce those developability risk.
Non-specific binding | Antibody self-interaction | Plasma stability | ||
---|---|---|---|---|
Assay type | BVP ELISA | DNA ELISA | Affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) | Plasma stability |
Application | mAb/bsAb/naked Ab in ADC | mAb/bsAb/naked Ab in ADC | mAb-Fc/bsAb/naked Ab in ADC | mAb/bsAb/ADC/AOC |
Timeline | 1-2 weeks | 1-2 weeks | 1-2 weeks | 2-3 weeks |
Manufacturability assessment is one of the most important evaluation in the development of biologics, which is bridging the drug discovery and CMC. The benefits of manufacturability assessment include:
Seivice | Service content | Deliverables | Timeline | |||||
---|---|---|---|---|---|---|---|---|
Basic Developability Assessment | Quality attributes | Test item | Stressed conditions |
Report:
|
6-8 weeks | |||
None | 40℃ | Low pH 3.5 | ||||||
Tagg | DLS | ✔ | - | - | ||||
Conc. | UV280 | ✔ | ✔ | ✔ | ||||
Purity | SEC-HPLC | ✔ | ✔ | ✔ | ||||
Purity | CE-SDS-NR | ✔ | ✔ | ✔ | ||||
Premium Developability Assessment | Quality attributes | Test item | Stressed conditions |
Report:
|
6-8 weeks | |||
None | 40℃ | Low pH 3.5 | Freeze-thaw | |||||
Tagg | DLS | ✔ | - | - | - | |||
Tm | DSC | ✔ | - | - | - | |||
Conc. | UV280 | ✔ | ✔ | ✔ | ✔ | |||
Purity | SEC-HPLC | ✔ | ✔ | ✔ | ✔ | |||
Purity | CE-SDS-NR | ✔ | ✔ | ✔ | ✔ | |||
Charge variants | icIEF | ✔ | ✔ | ✔ | ✔ |
Developability assessment help to identify the potential developability risk and help to select the CMC candidates. Candidate C was chosen and finally succeed in CMC.
Stability | Analytical methods | Changes from Tday0 and Tend | ||
---|---|---|---|---|
Candidate A | Candidate B | Candidate C | ||
Free-thaw | Appearance | Remain the same | Remain the same | Remain the same |
Stressful (40oC & 2 weeks) | Appearance | Remain the same | Remain the same | Remain the same |
CE-SDS-NR | Decrease ca.10% | Remain the same | Remain the same | |
SEC-HPLC | Remain the same | Remain the same | Remain the same | |
PTM by MS | ~ 10% deamidation (not CDR) | ~ 10% deamidation (not CDR) | ~ 5% Oxidation (not CDR) | |
cIEF | Acidic and basic increased | Main peak changed | Acidic and basic increased | |
Bioactivity | Remain the same | Remain the same | Remain the same | |
Acidic condtion (pH3.5 & 25°C & 4h) | Appearance | Remain the same | slight suspension | slight suspension |
SEC-HPLC | Decreased ca. 70% | Decrease ca.40% | Decrease ca.5% | |
PTM by MS | ~ 10% deamidation (not CDR) | ~ 20% Oxidation ( CDR) | Remain the same | |
cIEF | Remain the same | Main peak changed | Remain the same | |
Bioactivity | Remain the same | Decreased | Remain the same |