Summary of additional comments
补充意见摘要
1. OOS Investigation Process & Decision Trees (Most Frequent)
1. OOS 调查流程与决策树（提及频率最高）
Many respondents requested clearer guidance on:
许多受访者请求更清晰的指南：
When to move between Phase I, Phase Ib, Phase II, and Phase III investigations.
何时在第一阶段、第一阶段b、第二阶段和第三阶段调查之间转换。
When and how to perform hypothesis testing.
何时及如何进行假设检验。
Expectations for root cause confirmation.
根本原因确认的期望。
Handling investigations when no root cause is identified.
当未识别出根本原因时如何处理调查。
Approval requirements for hypothesis plans (Analyst, SME, QA, etc.).
假设方案的审批要求（分析员、主题专家、QA等）。
Clear decision trees and worked examples.
清晰的决策树和实际案例。
Summary of additional comments
补充意见摘要
Representative requests
代表性请求
When is hypothesis testing mandatory?
何时强制进行假设检验？
What is acceptable during Phase I hypothesis testing?
第一阶段假设检验中什么是可接受的？
How should inconclusive OOS investigations be handled?
应如何处理无结论OOS调查？
What happens when a laboratory error is suspected but not proven?
当怀疑存在实验室错误但无法证实时怎么办？
Summary of additional comments
补充意见摘要
2. Retesting, Resampling & Replicate Testing
2. 复测、重新取样与重复检验
A major topic was how additional testing should be performed and interpreted. Requests included:
一个主要话题是如何执行和解读附加检验。请求包括：
Number of replicates required.
所需重复次数。
When a second analyst should be involved.
何时应涉及第二名分析员。
Acceptance criteria for retesting.
复测的验收标准。
Treatment of fresh samples.
新样品的处理。
Clarification between:
澄清以下区别：
·• Confirmatory testing
• 确认性检验
·• Repeat testing
• 重复检验
·• Retesting
• 复测
·• Resampling
• 重新取样
·• Retain sample testing
• 留样检验
Several comments requested examples and statistical justification.
若干评论请求提供示例和统计论证。
Summary of additional comments
补充意见摘要
3. Root Cause Analysis & Human Error
3. 根本原因分析与人为差错
Respondents want more practical guidance on:
受访者希望获得更多实用指南：
Conducting effective root cause analysis.
开展有效的根本原因分析。
Determining when human error is justified.
确定何时可将人为差错作为正当理由。
Repeated human errors by different analysts.
不同分析员的重复人为差错。
Manufacturing calculation errors.
生产计算错误。
CAPA expectations after confirmed root causes.
确认根本原因后的CAPA期望。
Examples of inadequate root cause investigations.
根本原因调查不充分的案例。
Summary of additional comments
补充意见摘要
4. OOT / OOE / Trending Guidance
4. OOT / OOE / 趋势分析指南
Many comments indicated that guidance on is either missing or insufficient:
许多评论表明，以下方面的指南缺失或不足：
OOT (Out of Trend)
OOT（超趋势）
OOE (Out of Expectation)
OOE（超期望）
Trend analysis
趋势分析
Specific requests:
具体请求：
How to establish robust OOT criteria.
如何建立稳健的OOT标准。
How to perform trend analysis.
如何执行趋势分析。
OOE/OOT guidance beyond assay testing.
除含量测定检验外的OOE/OOT指南。
Contract laboratory OOT tracking
合同实验室OOT追踪
Summary of additional comments
补充意见摘要
5. Statistical Interpretation & Reportable Results
5. 统计解读与报告结果
Numerous respondents requested clarification on:
众多受访者请求澄清：
Whether OOS should be based on:
OOS应基于：
·• Single results
• 单一结果
·• Mean values
• 平均值
·• Reported results
• 报告结果
Outlier treatment.
异常值处理。
Borderline results.
边缘结果。
Statistical rationale for limiting retests.
限制复测次数的统计依据。
Handling tests where averaging may not be appropriate.
处理可能不适合取平均值的检验。
Examples included dissolution, content uniformity, particle size, and attribute testing.
示例包括溶出度、含量均匀度、粒度和属性检验。
Summary of additional comments
补充意见摘要
6. Special Testing Types (Microbiology, Biologics, Non-Chromatographic Methods)
6. 特殊检验类型（微生物学、生物制品、非色谱方法）
A strong theme was that current guidance appears focused on small-molecule analytical chemistry.
一个强烈的主题是，现行指南似乎侧重于小分子分析化学。
Requests for dedicated guidance on:
请求提供以下方面的专用指南：
Microbiological OOS/OOX investigations.
微生物OOS/OOX调查。
Biological products and biologics.
生物制品和生物制剂。
Biological test systems and microbiological data deviations (MDDs).
生物检验系统和微生物数据偏差（MDDs）。
Non-chromatographic methods:
非色谱方法：
·• Karl Fischer
• 卡尔费休法
·• Potentiometric titration
• 电位滴定法
·• Other physical tests.
• 其他物理检验。
Summary of additional comments
补充意见摘要
7. Contract Laboratory Perspective
7. 合同实验室视角
Several respondents identified themselves as contract laboratories and requested:
若干受访者自称为合同实验室，并请求：
Guidance tailored to organizations that perform testing only.
专为仅执行检验的组织量身定制的指南。
Clarification of responsibilities when manufacturing investigations are outside their control.
当生产调查超出其控制范围时的职责澄清。
Expectations for OOS/OOT tracking when only CoAs are received.
仅收到检验报告（CoA）时的OOS/OOT追踪期望。
When Phase II investigations are applicable for contract labs.
合同实验室适用的第二阶段调查。
Summary of additional comments
补充意见摘要
8. Documentation, Governance & QA Oversight
8. 文件、治理与QA监督
Frequent requests included:
频繁请求包括：
Documentation requirements for each investigation phase.
各调查阶段的文件要求。
Deviation initiation requirements.
偏差发起要求。
QA review and approval expectations.
QA审核与批准期望。
Regulatory notification timelines.
法规通知时限。
Health authority notification requirements.
监管机构通知要求。
Impact assessment requirements.
影响评估要求。
Summary of additional comments
补充意见摘要
9. Manufacturing & IPC Investigations
9. 生产与IPC调查
Comments requested additional clarity on:
评论请求对以下方面提供更多澄清：
In-process control (IPC) OOS events.
过程控制（IPC）OOS事件。
Manufacturing calculation errors.
生产计算错误。
Batch disposition when root cause remains unconfirmed.
根本原因仍未确认时的批次处置。
Relationship between manufacturing investigations and laboratory investigations.
生产调查与实验室调查之间的关系。
Summary of additional comments
补充意见摘要
10. Guidance Format Improvements
10. 指南格式改进
Respondents repeatedly asked for:
受访者反复要求：
More examples.
更多示例。
Case studies.
案例研究。
Decision trees.
决策树。
Practical scenarios.
实际场景。
