Issue & CAPA Log — GLPI-103 Program
| Field | Value |
|---|---|
| Document ID | QA-ISSUE |
| Version | 2.0 |
| Standard | ICH Q10 (CAPA) · Q9(R1) (QRM) · E6(R3) |
| Confidentiality | Confidential |
Central register of program issues and Corrective and Preventive Actions (CAPA) across CMC, nonclinical, clinical, and data-pipeline workstreams. Each entry records the issue, root-cause analysis, correction, corrective and preventive action, and verification before closure — the program's worked record of issue management.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | Quality Assurance | Initial log (resolved data-pipeline issues) |
| 2.0 | 2026-06-30 | Quality Assurance | Expanded — added CMC manufacturing/analytical/stability, nonclinical, and clinical issues with full RCA/CAPA |
A. Data-Pipeline / Analysis Issues
| ID | Severity | Description | Root cause | Corrective action | Preventive action | Status |
|---|---|---|---|---|---|---|
| ISS-001 | High | TFL Table 1 identical across arms | Broken pivot collapsed arms | Rewrote generate_table1 per-arm |
verify_pipeline "Table 1 differs by arm" |
Closed |
| ISS-002 | High | TEAE table/prop-test hardcoded vs AE data | Demonstration hardcode | Derived from ae_events.csv |
reconcile/verify safety checks | Closed |
| ISS-003 | High | ADSL strata randomly generated | build_adsl rng.choice |
Carry real STRAT from IRT record | "STRAT≈baseline" check | Closed |
| ISS-004 | Medium | SC Korean values garbled in XPORT | cp949/UTF-8 in XPORT v5 | Map to English CDISC CT | validate_cdisc CT checks |
Closed |
| ISS-005 | Low | Build crash on em-dash (cp949 console) | Non-ASCII console output | ASCII console messages | — | Closed |
| ISS-006 | Medium | 5 docs missing Change History | Template not applied | Added Change History | check_format C2 (R1) |
Closed |
| ISS-016 | Medium | SDTM DM did not carry 2 deaths present in AE/ADSL | Death flag not propagated when data enrichment added deaths | Derive DM DTHFL/DTHDTC from disposition |
DM↔AE↔ADSL death-count cross-check | Closed |
| ISS-017 | Low | config.yaml parameters inconsistent with code/data |
Config not wired to the build path | Corrected values + documented authoritative source | — | Closed |
B. CMC / Manufacturing & Analytical Issues
| ID | Severity | Description | Root-cause investigation | Corrective action | Preventive action (CAPA) | Status |
|---|---|---|---|---|---|---|
| ISS-007 | High | OOS — IV drug product: batch DP-IV-003 exceeded the sub-visible-particle / aggregate limit (SE-HPLC 2.4% vs ≤2.0%) | Temperature excursion of bulk solution during a hold step promoted interfacial aggregation; confirmed by reproduction study | Batch rejected; investigation per OOS SOP (Phase Ia/Ib) | Increased polysorbate-80 control range; added a bulk-hold temperature CPP + alarmed monitoring; re-trained operators | Closed |
| ISS-008 | High | OOT — oral tablet stability: a 40 °C/75% RH batch trended toward the related-substances limit by 6 months | Moisture ingress; desiccant capacity insufficient for the hygroscopic SNAC/peptide tablet | Extended testing + risk assessment (no marketed impact) | Packaging change to Alu/Alu blister (primary) / increased desiccant (HDPE); tightened water-content release limit | Closed |
| ISS-009 | Medium | Analytical method transfer: related-substances RP-HPLC gave variable resolution of a critical impurity pair at the QC site | Column lot-to-lot selectivity variability | Re-qualified the transfer with bracketing standards | Added column-qualification (system-suitability resolution ≥1.5) and a designated column chemistry to the method (M3-AMV) | Closed |
| ISS-010 | Medium | PPQ deviation: drug-substance PPQ batch 2 showed a transient blend/charge inhomogeneity flag at the lyophiliser load | Uneven shelf loading at scale | Batch met all CQAs (deviation assessed not impacting quality) | Revised loading pattern + IPC; added to CPV monitoring | Closed |
| ISS-011 | Medium | Impurity above ID threshold: an early DS lot showed a des-Gly deletion sequence at 0.18% | Incomplete coupling at a sterically hindered residue | Re-purified; impurity structurally characterised & qualified (Q3A) | Switched the difficult coupling to a pre-formed dipeptide fragment; added coupling-completion IPC | Closed |
C. Nonclinical Issues
| ID | Severity | Description | Investigation | Action | Status |
|---|---|---|---|---|---|
| ISS-012 | High | Carcinogenicity finding: dose-related thyroid C-cell hyperplasia/adenoma in the 2-year rat | Mechanistic follow-up (C-cell GLP-1R density, calcitonin, species comparison) established the effect as rodent-specific | Human-relevance assessment filed (M4-2.3 §4); risk carried as a labeled class contraindication (MTC/MEN-2) + RMP | Closed (managed) |
| ISS-013 | Medium | Bioanalytical interference: ADA assay drug-tolerance insufficient at high concentrations | Free-drug interference in the bridging ELISA | Added acid-dissociation pre-treatment; re-validated | Closed |
D. Clinical / Operational Issues
| ID | Severity | Description | Investigation | Action | Status |
|---|---|---|---|---|---|
| ISS-014 | Medium | Enrollment: screen-failure rate ~45% vs ~30% planned → slower randomization | Realistic source-population HbA1c/BMI distribution stricter than assumed | Activated additional sites; protocol re-training on eligibility | Closed (documented in CSR-301 §10.1; PROT deviation note) |
| ISS-015 | Low | Visit-window deviations flagged by DQE (>±7 days) | Site scheduling around holidays | Queries issued & resolved; categorised minor (no PPS impact) | Closed (QA-002; DQE query log) |
Process
Issues are logged with severity and a documented root-cause analysis (e.g., fishbone/5-Whys); a correction addresses the immediate issue and a CAPA (preferably verified by an automated check or a validated control) is implemented before closure. Quality-impacting issues are escalated to program governance per PM-005; CMC issues feed the Product Quality Review and Continued Process Verification (M3-PV).