Signal Management Plan — GLPI-103
| Field | Value |
|---|---|
| Document ID | SIGNAL-001 |
| Version | 1.0 |
| Status | Final (portfolio) |
| Compound | GLPI-103 (GLP-1 / Apelin [APJ] receptor dual agonist) |
| Sponsor | Virtual Biopharma Inc. |
| Standard(s) | GVP Module IX (R1) (Signal Management) · ICH E2E · CIOMS VIII |
| Confidentiality | Confidential |
[MOCK — deep-knowledge assumption]Defines the process for the detection, validation, prioritisation, assessment, and management of safety signals for GLPI-103 across development and post-authorization.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-30 | Pharmacovigilance | Initial Signal Management Plan |
1. Scope and Roles
Covers all sources of safety data (clinical trials, spontaneous reports, literature, registries, regulatory databases). The Safety Management Team (qualified PV physician + epidemiologist + biostatistician) owns the process; the EU-QPPV has oversight (GVP IX).
2. Data Sources for Signal Detection
- Clinical-trial SAE/AESI data and aggregate analyses (DSUR; CSR-301).
- Post-authorization: spontaneous reports (company safety database), regulatory databases (FAERS, EudraVigilance, KAERS), literature, and solicited programs.
3. Signal Detection Methods
- Qualitative: medical review of individual case safety reports (ICSRs), case-series review, and review of designated medical events.
- Quantitative (post-launch): disproportionality analysis (PRR, ROR, EBGM/empirical Bayes) on the spontaneous database with predefined thresholds; time-to-onset and observed-vs-expected analyses for AESIs.
- Targeted monitoring of the predefined safety concerns (RMP) and adverse events of special interest.
4. Adverse Events of Special Interest (targeted)
Gastrointestinal events; acute pancreatitis; thyroid C-cell neoplasia/MTC; hypoglycaemia (with secretagogues/insulin); cardiovascular/heart-rate effects (APJ mechanism); hepatic events (eDISH/Hy's-law monitoring); hypersensitivity/immunogenicity.
5. Signal Validation, Prioritisation, and Assessment
- Validation: determine whether the data warrant further evaluation (strength of evidence, clinical relevance, novelty).
- Prioritisation: by seriousness, severity, reversibility, and public-health impact; high-priority signals are expedited.
- Assessment: structured benefit-risk evaluation using all available data; documented with a recommendation.
6. Outcomes and Risk Minimisation
Possible outcomes: refute, keep under monitoring, or confirm. Confirmed signals trigger labeling changes, RMP updates (new identified/potential risk, additional risk-minimisation/aRMM), DHPC, and regulatory notification; tracked to closure in the signal-tracking log and reflected in the next PBRER (PSUR-001).
7. Timelines, Documentation, and Governance
Signals are logged with detection date, status, and milestones; statutory timelines (e.g., EU emerging-safety-issue notification; validated-signal assessment) are met. Decisions and CAPAs are governed per PM-005 and the issue/CAPA process (QA-003).