Stability Summary — GLPI-103
| Field | Value |
|---|---|
| Document ID | M3-STAB |
| Version | 2.0 (expanded) |
| Standard | ICH Q1A(R2) · Q1B · Q1D · Q1E · Q5C · Q3B(R2) |
| Confidentiality | Confidential |
[MOCK — deep-knowledge assumption]Stability protocols, data summary, degradation analysis, and shelf-life/retest justification for the drug substance and both drug products.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | CMC / Stability | Initial |
| 2.0 | 2026-06-30 | CMC / Stability | Expanded — full study design, datasets, degradation pathways, Q1E regression, storage statements, commitment |
1. Study Design (Q1A(R2)/Q1D)
| Condition | Drug substance (−20 °C) | IV product (2–8 °C) | Oral product (≤30 °C) |
|---|---|---|---|
| Long-term | −20 °C, ≥24 mo | 5 °C, ≥24 mo | 25 °C/60% RH, ≥24 mo |
| Intermediate | 5 °C | — | 30 °C/65% RH |
| Accelerated | 25 °C/60% RH, 6 mo | 25 °C, 6 mo | 40 °C/75% RH, 6 mo |
| Batches | 3 registration | 3 | 3 |
| Bracketing/matrixing (Q1D) applied across strengths/container sizes where justified. Stability-indicating methods: RP-HPLC (assay/related substances), SE-HPLC (aggregates), plus appearance, water (KF), pH, dissolution (oral), preservative content, sub-visible particles/sterility/endotoxin (IV). |
2. Data Summary (illustrative — long-term)
| Attribute | Drug substance (−20 °C, 0→24 mo) | IV (5 °C, 0→24 mo) | Oral (25 °C, 0→24 mo) |
|---|---|---|---|
| Assay (%) | 99.4 → 98.8 | 99.8 → 98.3 | 99.1 → 97.4 |
| Total related substances (%) | 1.0 → 1.4 | 1.4 → 2.8 | 1.8 → 3.2 |
| Aggregates (%) | 0.4 → 0.6 | 0.6 → 1.2 | n/a |
| Dissolution (oral, % at 30 min) | — | — | 94 → 90 |
| Water (%) | 6.8 → 7.2 | — | 3.0 → 4.1 |
| Sterility / endotoxin (IV) | — | conforms | — |
All attributes remained within the proposed specifications at long-term conditions through 24 months; accelerated conditions showed the expected, controlled increase in related substances/aggregates (substance/IV) and moisture-mediated change (oral), informing handling and packaging.
Out-of-trend investigation (QA-003 ISS-008): an oral-tablet batch at 40 °C/75% RH trended toward the related-substances limit by 6 months. Root cause = moisture ingress (desiccant capacity insufficient for the hygroscopic SNAC/peptide tablet). Assessment confirmed no impact on long-term (≤30 °C) shelf life; CAPA moved the primary pack to an Alu/Alu blister (with increased desiccant for the HDPE-bottle presentation) and tightened the water-content release limit — a worked example of stability issue management.
3. Degradation Pathways
Principal pathways, confirmed by forced-degradation (acid/base/oxidative/thermal/photolytic) with peak-purity: oxidation (Met/Trp), deamidation (Asn→isoAsp), aggregation/dimerisation (substance and IV), and moisture-mediated hydrolysis of the peptide/enhancer in the tablet. Each degradant is tracked by the stability-indicating method and qualified (Q3B).
4. Photostability & In-Use
Photostability (Q1B) showed the bulk substance and unprotected solution are light-sensitive; the container-closure provides adequate protection. In-use stability supports a 6-week period for the multidose IV pen at ≤30 °C after first use, and once-opened conditions for the desiccated oral bottle.
5. Shelf-Life / Retest Justification (Q1E)
Statistical evaluation (regression with poolability testing across batches; extrapolation per Q1E) supports:
- Drug substance: re-test period 24 months at −20 °C.
- IV product: shelf life 24 months at 2–8 °C (do not freeze).
- Oral product: shelf life 24 months at ≤30 °C, protected from moisture (keep desiccant). A post-approval commitment (ongoing) stability programme continues on the first commercial batches and ≥1 batch/year thereafter.