Control Strategy — GLPI-103
| Field | Value |
|---|---|
| Document ID | M3-CS |
| Version | 2.0 (expanded) |
| Standard | ICH Q8(R2) · Q9(R1) · Q10 · Q11 · Q12 |
| Confidentiality | Confidential |
[MOCK — deep-knowledge assumption]Integrated control strategy linking the CQAs (M3-QTPP) to material/process controls and release/stability specifications across the lifecycle.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | CMC | Initial control strategy |
| 2.0 | 2026-06-30 | CMC | Expanded — five control elements, CPP target ranges, IPCs, analytical and lifecycle control |
1. Control-Strategy Framework
A holistic, risk-based control strategy (ICH Q10) assures each CQA (M3-QTPP §2) through five complementary elements: (1) input-material controls, (2) process design + critical-process-parameter (CPP) control, (3) in-process controls (IPCs), (4) release & stability specifications, and (5) procedural/facility (GMP) controls. CPPs and proven acceptable ranges were established by quality risk management (ICH Q9; FMEA) and design-of-experiments characterisation.
2. Drug Substance — CPP / IPC Map
| Step | CPP / IPC (target) | CQA assured |
|---|---|---|
| SPPS coupling | coupling completion (free amine ≤0.5%); reagent equivalents; temperature | sequence fidelity → deletion impurities |
| Side-chain lipidation | orthogonal deprotection completeness; acylation completion | des-lipid impurity |
| Cleavage / deprotection | scavenger composition; time/temperature | side-chain integrity, related substances |
| Preparative RP-HPLC | gradient, load factor, pooling criterion (purity ≥95%, single max ≤1.0%) | related substances, des-lipid, aggregates |
| Salt exchange | acetate buffer, residual TFA endpoint | counter-ion, residual TFA |
| Lyophilisation | shelf temperature, vacuum, endpoint | water content, stability |
3. Drug Product — Control Map
| Product | Step | CPP / IPC (target) | CQA assured |
|---|---|---|---|
| IV | compounding | bulk pH 7.2–7.6; pre-filtration bioburden ≤10 CFU/100 mL | assay, stability, sterility assurance |
| IV | sterile filtration | filter integrity (pre/post bubble-point); redundant 0.22 µm | sterility |
| IV | aseptic fill | fill weight, environmental monitoring, media-fill validation | sterility, extractable volume |
| Oral | blending | blend uniformity (RSD ≤5%) | content uniformity |
| Oral | compression | compression force → hardness, friability, disintegration | dissolution, content uniformity |
4. Analytical Control Strategy
Release and stability specifications (M3-S §S.4; M3-P §P.5) employ stability-indicating RP-HPLC (assay/related substances), SE-HPLC (aggregates), functional bioassays (GLP-1R/APJ potency), and compendial sterility/endotoxin/particulate tests; all methods validated per ICH Q2(R2) (M3-AMV). The strategy balances end-product testing with upstream control of CQAs that cannot be fully assured at release (e.g., sterility assurance, aggregation propensity).
5. Lifecycle Management (Q10 / Q12)
Continued process verification (CPV) monitors CPPs/CQAs across commercial production; change management and the defined Established Conditions (ICH Q12) govern post-approval changes with appropriate reporting categories; an ongoing/commitment stability programme (M3-STAB) and the Product Quality Review maintain the validated state.