CASE STUDY CAPABILITY
Pre-Clinical to Phase III API Development
Table of contents
Sai Life Sciences partnered with a leading U.S. Big Pharma company to optimize and scale a highly sensitive C‑terminal peptide containing six stereocenters. The objective was to enhance stage-wise yields, eliminate chromatography in the final step, and ensure high-purity API supply through late-stage clinical development.
Overview & Objective
The project focused on developing a robust, scalable process for a complex peptide API with six stereocenters. The goals included:
- Achieving ~80% yield at each stage
- Delivering >98% purity
- Eliminating column chromatography in the final API stage
- Enabling smooth progression from pre-clinical to Phase III supply
Approach
To address the complexity and sensitivity of the molecule—particularly given that the final API required lyophilization—Sai Life Sciences implemented a series of targeted process innovations:
- Developed an alternative purification strategy to eliminate column chromatography
- Screened protecting groups that improved hydrophobicity and supported acid/base workups for better impurity removal
- Achieved >80% yield in all stages with final purity >99%
- Synthesized and characterized 27 process impurities and established comprehensive purge studies
- Defined process controls and specification limits for all critical impurities
- Developed and validated robust, specific HPLC methods to support scale-up and regulatory filings
Outcome / Results / Evidence
The optimized process delivered strong technical and operational gains:
- Consistently achieved >80% yield across stages
- Final API purity exceeded 99%
- Successfully demonstrated the process at 20 kg scale
- Supported Big Pharma’s progression to Phase III with a highly controlled, regulatory-ready process
Key Takeaways / Impact
- RMC reduced by 44% through process optimization and chromatography elimination
- High scalability validated, delivering >99.5% purity at 20 kg scale
- Registration campaign underway, backed by well-characterized impurities and validated analytical methods
- Strong customer confidence reinforced through scientific rigor and reliable large-scale execution