Analytical Methods & Validation Summary — GLPI-103
| Field | Value |
|---|---|
| Document ID | M3-AMV |
| Version | 2.0 (expanded) |
| Standard | ICH Q2(R2) · Q6B · Q14 (analytical procedure development) |
| Confidentiality | Confidential |
[MOCK — deep-knowledge assumption]Analytical procedures and their validation supporting drug-substance and drug-product control (M3-S/M3-P), including an analytical-lifecycle (Q14) view and a worked method-transfer investigation.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | Analytical Development | Initial |
| 2.0 | 2026-06-30 | Analytical Development | Expanded — validation results, ATP/Q14, system suitability, method-transfer investigation (ISS-009) |
1. Analytical Target Profile (ATP, Q14)
Each procedure was developed against a pre-defined ATP (what the method must measure and how well) using analytical QbD; method operable design regions were established for the critical chromatographic methods, supporting robustness and post-approval flexibility.
2. Methods & Validation Results (ICH Q2(R2))
| Method | Purpose | Key validated performance [MOCK] |
|---|---|---|
| RP-HPLC — assay | content | accuracy 98–102% recovery; intermediate precision RSD ≤1.5%; linear r²>0.999 (50–150%) |
| RP-HPLC — related substances | impurities | LOQ 0.05%; specificity (peak purity in forced deg.); RSD ≤5% at QL; robust to ±2 °C, ±0.1 pH, ±2% organic |
| SE-HPLC | aggregates | LOQ 0.1%; precision RSD ≤5%; resolves dimer/HMW from monomer |
| Peptide map + LC-MS/MS | identity/structure | specificity; ≥95% sequence coverage |
| Ion chromatography | acetate/TFA counter-ion | accuracy, precision, linearity |
| Karl Fischer | water | accuracy, repeatability |
| LAL (kinetic) | endotoxin | compendial validation; non-interference |
| Dissolution (oral) | release / BA surrogate | precision, robustness; discriminating for compression force |
| Cell-based bioassay | GLP-1R / APJ potency | relative potency 80–125%; intermediate precision RSD ≤10% |
3. Stability-Indicating Capability
RP-HPLC and SE-HPLC resolve all forced-degradation products (acid/base/oxidative/thermal/photolytic) from the main peak with confirmed peak purity, qualifying them as stability-indicating (M3-STAB §3).
4. System Suitability & Method Transfer — incl. Investigation ISS-009
System-suitability criteria (resolution, tailing, repeatability, signal-to-noise) are defined for each chromatographic method. During transfer of the related-substances RP-HPLC method to the QC laboratory, an out-of-expectation variability in the resolution of a critical impurity pair was observed (QA-003 ISS-009). Root-cause investigation identified column lot-to-lot selectivity variability; the transfer was re-qualified with bracketing reference standards. CAPA: a column-qualification requirement and a tightened system-suitability resolution criterion (≥1.5) were added to the method, with a designated stationary-phase chemistry — preventing recurrence. The event is a worked example of analytical lifecycle management (Q14).