設 GxP R 項目

立 R 項目之構合 GxP 規（21 CFR Part 11、EU Annex 11）。

用時

• 受規之境（藥、生技、醫器）始 R 析項目乃用
• 為臨床試驗析設 R 乃用
• 為註冊提交立可驗之計算境乃用
• 施 21 CFR Part 11 或 EU Annex 11 之求乃用

入

• 必要：項目之範與規之框（FDA、EMA、或二）
• 必要：欲驗之 R 版與包版
• 必要：驗策（風險為基）
• 可選：既有計算系之 SOP
• 可選：質管之集求

法

第一步：立可驗之項目構

gxp-project/
├── R/                          # Analysis scripts
│   ├── 01_data_import.R
│   ├── 02_data_processing.R
│   └── 03_analysis.R
├── validation/                 # Validation documentation
│   ├── validation_plan.md      # VP: scope, strategy, roles
│   ├── risk_assessment.md      # Risk categorization
│   ├── iq/                     # Installation Qualification
│   │   ├── iq_protocol.md
│   │   └── iq_report.md
│   ├── oq/                     # Operational Qualification
│   │   ├── oq_protocol.md
│   │   └── oq_report.md
│   ├── pq/                     # Performance Qualification
│   │   ├── pq_protocol.md
│   │   └── pq_report.md
│   └── traceability_matrix.md  # Requirements to tests mapping
├── tests/                      # Automated test suite
│   ├── testthat.R
│   └── testthat/
│       ├── test-data_import.R
│       └── test-analysis.R
├── data/                       # Input data (controlled)
│   ├── raw/                    # Immutable raw data
│   └── derived/                # Processed datasets
├── output/                     # Analysis outputs
├── docs/                       # Supporting documentation
│   ├── sop_references.md       # Links to relevant SOPs
│   └── change_log.md           # Manual change documentation
├── renv.lock                   # Locked dependencies
├── DESCRIPTION                 # Project metadata
├── .Rprofile                   # Session configuration
└── CLAUDE.md                   # AI assistant instructions

得：完之目構存，含 R/、validation/（含 iq/、oq/、pq/）、tests/testthat/、data/raw/、data/derived/、output/、docs/。

敗則：目缺，以 mkdir -p 立。驗在項目根。既項目，唯立缺者，勿覆既構。

第二步：立驗之計

立 validation/validation_plan.md：

# Validation Plan

## 1. Purpose
This plan defines the validation strategy for [Project Name] using R [version].

## 2. Scope
- R version: 4.5.0
- Packages: [list with versions]
- Analysis: [description]
- Regulatory framework: 21 CFR Part 11 / EU Annex 11

## 3. Risk Assessment Approach
Using GAMP 5 risk-based categories:
- Category 3: Non-configured products (R base)
- Category 4: Configured products (R packages with default settings)
- Category 5: Custom applications (custom R scripts)

## 4. Validation Activities
| Activity | Category 3 | Category 4 | Category 5 |
|----------|-----------|-----------|-----------|
| IQ | Required | Required | Required |
| OQ | Reduced | Standard | Enhanced |
| PQ | N/A | Standard | Enhanced |

## 5. Roles and Responsibilities
- Validation Lead: [Name]
- Developer: [Name]
- QA Reviewer: [Name]
- Approver: [Name]

## 6. Acceptance Criteria
All tests must pass with documented evidence.

得：validation/validation_plan.md 完備，含範、GAMP 5 風險類、驗活動矩陣、職責、受準。計引特之 R 版與規框。

敗則：規框不明，諮組之 QA 求適 SOP。計未審而批，勿進驗活動。

第三步：以 renv 鎖依

# Initialize renv with exact versions
renv::init()

# Install specific validated versions
renv::install("[email protected]")
renv::install("[email protected]")

# Snapshot
renv::snapshot()

renv.lock 文件為受控之包目。

得：renv.lock 存附諸需包之確版號。renv::status() 報無患。每包版皆鎖（如 [email protected]），非浮。

敗則：renv::install() 於特版敗，察其於 CRAN 檔存否。歷版用 renv::install("package@version", repos = "https://packagemanager.posit.co/cran/latest")。

第四步：施版控

git init
git add .
git commit -m "Initial validated project structure"

# Use signed commits for traceability
git config user.signingkey YOUR_GPG_KEY
git config commit.gpgsign true

得：項目入 git 版控附簽提交。首提交含可驗之構與 renv.lock。

敗則：GPG 簽敗，以 gpg --list-secret-keys 驗 GPG 鑰之配。無 GPG 之境，書其偏，用無簽提交附人手審於 docs/change_log.md。

第五步：立 IQ 之協

validation/iq/iq_protocol.md：

# Installation Qualification Protocol

## Objective
Verify that R and required packages are correctly installed.

## Test Cases

### IQ-001: R Version Verification
- **Requirement**: R 4.5.0 installed
- **Procedure**: Execute `R.version.string`
- **Expected:** "R version 4.5.0 (date)"
- **Result**: [ PASS / FAIL ]

### IQ-002: Package Installation Verification
- **Requirement**: All packages in renv.lock installed
- **Procedure**: Execute `renv::status()`
- **Expected:** "No issues found"
- **Result**: [ PASS / FAIL ]

### IQ-003: Package Version Verification
- **Procedure**: Execute `installed.packages()[, c("Package", "Version")]`
- **Expected:** Versions match renv.lock exactly
- **Result**: [ PASS / FAIL ]

得：validation/iq/iq_protocol.md 含 R 版驗、包裝驗、包版驗之試例，各附明預期與過/敗欄。

敗則：IQ 模不合組之 SOP 之求，存其要欄而適其式（求、程、預期、實得、過/敗）。諮 QA 之認模。

第六步：寫自動之 OQ/PQ 試

# tests/testthat/test-analysis.R
test_that("primary analysis produces validated results", {
  # Known input -> known output (double programming validation)
  test_data <- read.csv(test_path("fixtures", "validation_dataset.csv"))

  result <- primary_analysis(test_data)

  # Compare against independently calculated expected values
  expect_equal(result$estimate, 2.345, tolerance = 1e-3)
  expect_equal(result$p_value, 0.012, tolerance = 1e-3)
  expect_equal(result$ci_lower, 1.234, tolerance = 1e-3)
})

得：自動試文件存於 tests/testthat/，覆 OQ（每函操作之驗）與 PQ（端到端驗於獨算之參值）。試用明數容差。

敗則：獨算之參值（如自 SAS）尚未得，立占位試以 skip("Awaiting independent reference values") 並書於追溯矩陣。

第七步：立追溯矩陣

# Traceability Matrix

| Req ID | Requirement | Test ID | Test Description | Status |
|--------|-------------|---------|------------------|--------|
| REQ-001 | Import CSV data correctly | OQ-001 | Verify data dimensions and types | PASS |
| REQ-002 | Calculate primary endpoint | PQ-001 | Compare against reference results | PASS |
| REQ-003 | Generate report output | PQ-002 | Verify report contains all sections | PASS |

得：validation/traceability_matrix.md 連每求至少一試例，每試例皆連於求。無孤求或孤試。

敗則：求未試，立其試例，或書風險為基之排除由。試無連求，連於既求或除之為範外。

驗

• 項目構合所書模
• renv.lock 含諸依附確版
• 驗計完而批
• IQ 協行而成
• OQ 試例覆諸配功
• PQ 試驗於獨算之果
• 追溯矩陣連求於試
• 變控程已書

陷

• install.packages() 無版鎖：常用 renv 附鎖版
• 缺審計線：每變必書。用 git 簽提交
• 過驗：用風險為基。非每 CRAN 包皆需 Category 5 之驗
• 忘系統級之認：OS 與 R 之裝亦需 IQ
• 無獨驗：PQ 宜比於獨算之果（SAS、人手算）

參

• write-validation-documentation — 詳之驗文檔之立
• implement-audit-trail — 電錄與審計線
• validate-statistical-output — 雙程與出之驗
• manage-renv-dependencies — 為驗境之依鎖