Quality Control Workflow — From Raw Material to Final Release
1. Workflow Overview
Raw Material Receipt → Incoming Inspection → [Production Hold Point]
→ In-Process QC (Synthesis) → [Hold Point]
→ In-Process QC (Purification) → [Hold Point]
→ Final QC Release Testing → [Hold Point]
→ Certificate of Analysis → Batch Release
→ Stability Monitoring (selected batches)
2. Incoming Inspection
| Material |
Test |
Acceptance |
| Fmoc-amino acids |
HPLC purity ≥98%, identity by MS |
Certificate of Analysis verified |
| Resins |
Loading (mmol/g), swelling test |
±10% of supplier specification |
| Solvents |
GC purity, water content (KF) |
≥99.5%, ≤0.1% H₂O |
| Reagents |
Visual, lot number traceability |
Within expiry |
3. In-Process Controls
| Stage |
Test |
Frequency |
| SPPS |
Kaiser test |
After each coupling |
| Cleavage |
Crude yield, HPLC purity |
Each batch |
| Purification |
Fraction purity (analytical HPLC) |
Each fraction pool |
| Lyophilization |
Residual moisture |
Each batch |
4. Final Release Testing
| Test |
Method |
Acceptance |
| Purity |
HPLC (220 nm, 280 nm) |
≥95% / ≥98% / ≥99% |
| Identity |
ESI-MS |
±0.5 Da |
| Water Content |
Karl Fischer |
≤1.0% |
| Residual Solvents |
GC-FID headspace |
Per ICH Q3C |
| Endotoxin |
LAL |
<0.05 EU/mg |
| Peptide Content |
UV or AAA |
Report |
| Appearance |
Visual |
White to off-white powder |
5. Stability Monitoring
| Condition |
Frequency |
| −20 °C (long-term) |
0, 3, 6, 12, 24 months |
| 4 °C (refrigerated) |
0, 3, 6, 12 months |
| 25 °C / 60% RH |
0, 1, 3, 6 months |