📚 Part of the GLPI-103 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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Mock / simulation document

This is a mock / simulation document, made for a portfolio and for learning. The drug (GLPI-103), the sponsor, the people, and the data are all fictional. It is not a real regulatory submission and has no clinical, legal, or regulatory standing. What is real is the shape of the thing — the document structure, the standards it follows, and the analysis methods; the content inside is illustrative.

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About this document — a plain-language guide

What it is. The issue and CAPA (Corrective and Preventive Action) log.

Why it exists. When quality issues arise, a mature system records them, fixes the immediate problem (corrective) and prevents recurrence (preventive). The log is the evidence that quality is actively managed (ICH Q10).

How it is produced here. It is a quality record: a plan or log that shows how the program controls quality and builds the audit trail sitting behind every other document.

Format & governing standard. ICH Q10 (CAPA) · Q9(R1) (QRM) · E6(R3)

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).