GMP缺陷分类
Health Products and Food Branch Inspectorate
健康产品与食品检查部
Guide-0023
指南-0023
Risk Classification of GMP Observations,
2003edition
GMP缺陷的风险分类
2003版
Supersedes:
June1st,2000edition
替代2000年6月1日版本
Date issued:April4th,2003
2003年4月4日颁布
Date of implementation:June1st,2003
2003年6月1日执行
Ce document est aussi disponible en fran?ais.
本文可提供法语版
翻译者：张磊上海中信国健药业有限公司
校对：张华上海市食品药品监督管理局认证审评中心
TABLE OF CONTENTS
目录
1.0PURPOSE目的 (4)
2.0BACKGROUND背景 (4)
3.0SCOPE范围 (4)
4.0DEFINITIONS定义: (5)
5.0GUIDE指南 (8)
5.1Assignment of the risk to an observation缺陷的风险评定 (8)
5.2Assignment of the inspection rating检查结果分级的评定 (8)
5.2.1Risk1observation:1类风险缺陷 (8)
5.2.2Risk2observation:2类风险缺陷 (9)
5.2.3Risk3observations:3类风险缺陷 (9)
5.3Additional guidance补充指南 (9)
Appendix1附录1 (11)
Appendix2附录2 (14)
Appendix3附录3 (25)
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations 1.0PURPOSE目的
To classify the observations noted during establishment inspections according to their risk.
对企业检查中记录的缺陷根据其风险进行分类。
To ensure uniformity among the inspectors of the Health Products and Food Branch Inspectorate(the Inspectorate)in the attribution of the rating following establishment inspections.
确保食品与健康产品检查部（检查机构）的检查员采用一致的标准，在企业检查后进行分级。
To inform the industry of the situations that the Inspectorate considers unacceptable and that will generate a Non Compliant(NC)rating following an inspection.
将检查机构不认可的情况，以及导致检查后判为不合格（NC）的情况告知制药行业。
2.0BACKGROUND背景
During an establishment inspection,deviations from the Food and Drug Regulations and the current edition of the Good Manufacturing Practices(GMP)guidelines are noted by the inspector and these deviations appear as observations in the inspection exit notice.A judgement based on these observations is then made by the inspector and an overall recommendation for the continuation or issuance of the establishment licence(rating of Compliance)or not to continue or issue the licence(rating of Non-Compliance)is given.Attribution of a NC rating may have serious consequences for a company,ranging from the implementation of important corrective measures to the temporary suspension or termination of the Establishment Licence(EL).Therefore,these situations of non-conformity have to be well defined, unambiguous and directly supported by the applicable regulations.
企业检查过程中，检查员应记录偏离《食品和药品法》和现行版GMP指南的偏差，这些偏差会作为缺陷出现在检查结束通知中。检查员根据这些缺陷作出判断，并给出综合性的推荐意见，即延续或颁发《企业许可证》（评定等级为符合C）或不延续或不颁发《企业许可证》（评定等级为不符合NC）。获得不符合（NC）的评定等级可能会给企业带来严重的后果，即可从实施重大的整改措施到暂时停业或吊销《企业许可证》（EL）。因此，所有不符合（NC）的情况必须有明确的定义，没有歧义，并有相适应的法规直接支撑。
3.0SCOPE范围
The definition of a drug in Canada covers a wide variety of products ranging from pharmaceuticals and biologics to natural health products such as homeopathics and herbal preparations.This guidance document covers all such products to which Division2of Part C of the Food and Drug Regulations applies and is based on the current edition of the GMP Guidelines.It is recognised that the evaluation of the conformity to the GMP should be commensurate with the risk involved taking into account the nature and extent of the deviation in relation with the category of products evaluated.Nonetheless,most of the
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations situations involving fraud,misrepresentation or falsification of products or data will generate a NC rating, irrespective of the category of products involved.
在加拿大，药品的定义涵盖了范围很广的各类产品，从药品、生物制品到天然的健康产品（如顺势疗法制剂和草药）。本文依照现行版GMP指南制订，适用于所有《食品药品法》C部第2类所规定的产品。人们已认识到，对是否符合GMP的审评与相关风险有关联，这些风险应综合考虑偏差的性质、严重程度以及所评估产品的类别。但不管是哪类产品，大多数涉及假药、欺诈或篡改产品或数据的情况都会导致不符合（NC）的评定结果。
The appendices attached to the present document describe the observations related to each category of risk. Please note that the list of observations in each appendix is not exhaustive and that additional observations may be added where appropriate.
本文附录述及与每一类风险相对应的缺陷。请注意，每个附录未全部列举所有的检查缺陷，可根据需要增加其它的缺陷。
The numbering system assigned to each section in the appendices is a reference to the applicable regulations in the current edition of the GMP guidelines.
附录中每一节中的数字是现行版GMP指南中所适用的法规编号。
4.0DEFINITIONS定义:
The following definitions are provided to complement those already available under the glossary of terms
in the current edition of the GMP Guidelines or other related documents referenced in the GMP Guidelines.
以下定义是对已有术语的补充，这些术语收载在现行版GMP指南或GMP指南所依据的其它相关文
件中。
Observation缺陷:
A deviation or deficiency to GMP noted by an inspector during the inspection of a drug establishment
that is confirmed in writing to the company in the exi t notice.The observations are classified as “Critical”,“Major”and“Other”and are assigned a risk classification,ranging from1for“critical”to2for “major”to3for“other”.
是指药品企业检查过程中，所有检查员记录的偏差或不足，这些偏差或不足经确认后写入
检查结束通知中。缺陷分为“严重”、“主要”和“其它”，并分别用1（对应“严
重”）、2（对应“主要”）、3（对应“其它”）表示其风险等级。
Critical observation严重缺陷:
Observation describing a situation that is likely to result in a non-compliant product or a situation that
may result in an immediate or latent health risk and any observation that involves fraud, misrepresentation or falsification of products or data.
严重缺陷包括易造成产品不合格，或可能对健康立即造成风险或造成潜在风险的缺陷，以及任
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations 何涉及假药、欺诈或篡改产品或数据的缺陷。
Appendix I lists observations that the Inspectorate considers critical which will be assigned a Risk1.
附录1列出了检查机构认为属于1类风险的严重缺陷。
Major observation主要缺陷:
Observation that may result in the production of a drug not consistently meeting its marketing authorization.
主要缺陷是指造成药品不能持续符合上市许可要求的缺陷。
Appendix2lists observations that are considered major and which will be assigned a Risk2Certain Risk2observations may be upgraded to Risk1.They are indicated with an arrow(↑).
附录2列出了检查机构认为属于2类风险的主要缺陷。有些2类风险的缺陷可上升为1类风险的缺陷，这些缺陷用箭头（↑）标明。
Other observation其它缺陷:
Observation that is neither critical nor major but is a departure from the GMP.
其它缺陷是指既非严重又非主要、但偏离GMP要求的缺陷。
“Other”observations are not listed as such(Observations that are neither critical nor major are considered as“other”and will be assigned a Risk3).Appendix3lists Risk3observations that may be upgraded to Risk2.
“其它”类别的缺陷（所有既非严重又非主要的缺陷，都被认为是属于3类风险“其它”缺陷）未列举。附录3列举的3类风险的缺陷，可以上升为2类风险的缺陷。
Critical product极高风险产品:
A critical product is one for which anyof the following criteria may apply:
适用以下任何一条标准的产品属极高风险产品：
§ narrow therapeutic window治疗范围窄
§ high toxicity高毒性
§ sterile product无菌产品
§ biological drug生物制品
§complex manufacturing process:
生产工艺复杂：
Process for which slight deviations in the control of parameters could result in a non-uniform
product or a product not meeting its specifications.As example,powder mixing or granulation for low dosage solid forms,long acting/delayed action products,sterile products.
是指参数控制的微小偏差即可造成产品不均一或不符合质量标准的工艺，如：小剂量固
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations 体制剂中的粉末状物料混合与制粒、长效或缓释产品、无菌产品。
Note注意:
OTC low dosage vitamins and minerals preparations and Category4products(as listed in Interpretation 2.3under section C.02.028)should not be considered as critical products even when the manufacturing processes involved are complex.
尽管生产工艺复杂，但非处方（OTC）低剂量维生素和矿物元素类制剂以及4类产品（参见C.02.028节下2.3的解释）不认为是极高风险产品。
High risk product高风险产品:
Any product that may trigger a health risk even at low levels,following cross-contamination.Those include but are not limited to penicillins,certain cytotoxic and biological products.
是指即使小剂量、有交叉污染也能引发健康风险的产品，这类产品包括但不仅限于青霉素类、某些有细胞毒性的产品和生物制品。
Low Risk product低风险产品:
Products such as Category4product(as listed in Interpretation2.3under section C.02.028),natural health products including vitamins and minerals preparations that are not a schedule drug or a sterile drug,and certain topical non prescription veterinary formulations registered as“old drugs”.
是指4类产品（参见C.02.028节下2.3的解释）、天然健康产品（包括维生素和矿物元素类制剂），它们未列在目录中或者不是无菌产品，以及某些注册为“老药”的非处方兽用级局部
用药。
Acronyms缩写:
C:Compliant符合
CIP:Clean-In-Place在线清洁
COA:Certificate of Analysis检验报告
EL:Establishment Licence企业许可证
GMP:Good Manufacturing Practices药品生产质量管理规范
HVAC:Heat,Ventilation,Air Conditioning空调净化系统
IRS:Inspection Reporting System检查报告系统
MRA:Mutual Recognition Agreement互认协议
NC:Non-compliant不符合
OTC:Over-The-Counter非处方药
PM:Packaging Material包装材料
PW:Purified Water纯化水
QC:Quality Control质量控制部门
RM:Raw Material原辅料
WFI:Water For Injection注射用水
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations 5.0GUIDE指南正文
5.1Assignment of the risk to an observation缺陷的风险评定
Whereas it is recognized that it is impossible to encompass every situation that may generate a risk,the following principles should be considered:
尽管认识到不可能列举出每一种会导致风险的情况，但应考虑以下准则：
-The risk assigned will be in relation to the nature of the deviation as well as the number of occurrences.
所评定的风险与偏差的性质与出现次数有关。
-Generally,when only low risk products are involved,a risk1will not be assigned to observations described in Appendix1,except for extreme situations such as fraud or
widespread cross-contamination,infestation or unsanitary conditions.
一般而言，当涉及的产品为低风险产品时，附录1中所述的缺陷不会被评定为1类风
险，除非发现极端情况，如：假药或大范围的交叉污染、虫害成群出没或不卫生的情
形。
-Where a risk2observationis re-evaluated as a risk1(risk2observation with an arrow),this situation is immediately brought to the attention of the company’s officials,proper explanation
will be provided to the establishment and this explanation should be captured in the“Inspector’s Comments”field of the“Inspection Summary”in the IRS.
当属2类风险的缺陷重新评估为1类风险（标有箭头的属2类风险的缺陷）时，这种情况应立即引起企业负责人的注意，应向企业进行适当解释，解释的内容应记录在IRS“检查报告总结”的“检查员意见”栏中。
5.2Assignment of the inspection rating检查结果分级的评定
The overall inspection rating assigned is based on the risk involved taking into account the nature and extent of the deviations with the category of products evaluated.
所有检查结果是根据相关风险评定的，这些风险综合考虑了偏差的性质、严重程度以及所评估产品的类别。
5.2.1Risk1observation:1类风险缺陷
Generally,a NC rating is assigned when a Risk1observation is noted during an inspection.
一般而言，当检查中记录有1类风险的缺陷，即评定为不符合（NC）。
Such situation is immediately brought to the attention of the company’s officials.The Inspectorate management is to be notified in a timely manner.
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations 这类情况应立即引起企业负责人的注意，并应及时向检查机构的管理层报告。
Where in the opinion of the inspector the resulting products present a significant health hazard, appropriate enforcement actions may be initiated.
如果检查员认为产品会导致重大健康危害，可以启动适当的强制措施。
5.2.2Risk2observation:2类风险缺陷
Generally,a C rating is assigned when Risk2observations are noted during an inspection.However,a NC rating may be assigned in the following situations:
一般而言，当检查中记录有2类风险的缺陷，即评定为符合（C），但在下列情形下，评定为不符合（NC）：
§When numerous Risk2observations are noted during an inspection indicating that the company does not control its processes and operations sufficiently.
当检查中记录的大量2类风险的缺陷，显示出企业未对工艺和操作进行足够的控制。
§Repetition of many Risk2observations noted during previous inspections indicating that the company did not:
许多前次检查发现的属2类风险的缺陷重复出现，显示出企业：
§implement the corrective actions submitted following the previous inspection or
没有按照前次检查后提交的计划实施整改措施，或
§did not put in place adequate preventive actions in a timely manner to avoid recurrence of such deviations.
没有及时采取足够的预防措施以防止此类偏差再次发生。
5.2.3Risk3observations:3类风险缺陷
A C rating will be assigned in all situations where only Risk3observations are noted.
如果仅记录有3类风险的缺陷，则评定为符合（C）。
5.3Additional guidance补充指南
When a NC rating is assigned,the inspector will issue a draft Inspection Exit Notice during the exit meeting.The draft inspection exit notice will be reviewed for quality assurance purposes before the final report is issued to an establishment.
当评定结果为不符合（NC）时，检查员将在末次会议上提交草拟的检查结束通知，为达到质量保证的目的，该草拟通知在最终报告发送企业前还要进行审核。
When observation(s)leading to a NC rating are made,the Inspection Exit Notice could be issued with
a C rating if,during the inspection:
当有导致评定结果为不符合（NC）的缺陷时，如果检查期间出现以下情形的，可以发出符合（C）结论的检查结束通知：
Health Products and Food Branch Inspectorate Risk Classification of GMP Observations -the establishment immediately implements all necessary actions to resolve the cause(s)of the
observation(s)leading to the NC rating and,
企业立即采取所有必要的措施以消除导致缺陷发生的原因，这些缺陷会导致不符合（NC）的结论，并且
-sufficient assurance can be provided to prevent a recurrence.
有足够的保证可防止缺陷再次发生。
In such instances,the risk assigned to the observation will remain the same.
在这种情形下，对缺陷所作的风险评定仍保持不变。
If the management of the company wishes to dispute the results of the inspection report,the“Dispute resolution and appeals”mechanism described in the GMP and EL Enforcement Policy POL-0004 should be followed.
如果企业管理层希望对检查报告结果提出争议，应遵照执行GMP与EL强制执行政策POL-0004中的“争议解决与上诉”制度。
Appendix1附录1
Risk1(Critical)Observations1类风险（严重）缺陷
Premises C.02.004厂房
-No air filtration system to eliminate airborne contaminants that are likely to be generated during fabrication or packaging.
无空气过滤系统以消除生产或包装时容易产生的空气污染。
-Generalized malfunctioning of the ventilation system(s)with evidence of widespread cross-contamination.
大范围交叉污染的证据表明通风系统普遍存在故障。
-Inadequate segregation of manufacturing or testing areas from other manufacturing areas for high risk products.
生产区或检验区未与其它用于高风险产品的生产区有效分隔。
Equipment C.02.005设备
-Equipment used for complex manufacturing operations of critical products not qualified and with evidence of malfunctioning.
极高风险产品的复杂生产操作用设备未经确认符合要求，且有证据表明存在故障。Personnel C.02.006人员
-Individual in charge of Quality Control(QC)or production for a fabricator of critical/high risk products does not hold a university degree in a science related to the work being conducted and does not have sufficient practical experience in their responsibility area.
极高风险、高风险产品生产企业的质量控制（QC）或生产负责人无与其从事工作相关领域的大学学历，且对其负责的工作缺乏足够的实践经验。
Sanitation C.02.007 C.02.008卫生
-Evidence of widespread accumulation of residues/extraneous matter indicative of inadequate cleaning.
有证据表明存在到处有残留物积聚／有清洁不充分导致的异物。
-Evidence of gross infestation.
有大量虫害的证据。
Raw Material Testing C.02.009 C.02.010原辅料检验
-Evidence of falsification or misrepresentation of analytical results.
有证据表明伪造或篡改分析结果。
-No evidence of testing(COA)available from the supplier/synthetizer and no testing done by the Canadian fabricator.
无证据表明供应商／生产商已做检验（出具检验报告），且加拿大境内的生产企业也未做检验。
Manufacturing Control C.02.011 C.02.012生产控制
-No written Master Formula.
无书面的生产处方。
-Master Formula or manufacturing batch document showing gross deviations or significant calculation errors.
生产处方或生产批记录显示有明显的偏差或重大的计算错误。
-Evidence of falsification or misrepresentation of manufacturing and packaging orders.
有证据表明伪造或篡改生产和包装指令。
Quality Control Department C.02.013 C.02.014 C.02.015质控部门
-No person in charge of QC available on premises in Canada.
加拿大境内的工厂中无质量控制（QC）负责人。
-QC department not a distinct and independent unit,lacking real decisional power,with evidence that QC decisions are often overruled by production department or management.
质量控制部门不是明确的独立机构，缺乏真正的决定权，有证据表明质量控制部门的决定常被生产部门或管理层否决。
Finished Products Testing C.02.018 C.02.019成品检验
-Finished product not tested for compliance with applicable specifications by the importer/ distributor before release for sale and no evidence is available that the products have been tested by the fabricator.
批准放行销售前，进口商／分销商未按照所适用的质量标准对成品进行检验，且无证据显示生产企业已完成检验。
-Evidence of falsification or misrepresentation of testing results/forgery of COA.
有证据表明伪造或篡改检验结果／伪造检验报告（COA）。
Records C.02.020to C.02.024记录
-Evidence of falsification or misrepresentation of records.
有证据表明伪造或篡改记录。
Stability C.02.027 C.02.028稳定性
-No data available to establish the shelf-life of products.
无确定产品效期的数据。
-Evidence of falsification or misrepresentation of stability data/forgery of COA.
有证据表明伪造或篡改稳定性考察数据／伪造检验报告（COA）。
Sterile Products C.02.029无菌产品
-Critical sterilization cycles based on Probability of Survival not validated.
采用残存概率法的关键灭菌程序未经验证。
-Water for Injection(WFI)systems not validated with evidence of problems such as microbial /endotoxin counts not within specifications.
注射用水（WFI）系统未经验证，有证据表明存在微生物／内毒素超标的情况。
-No media fills performed to demonstrate the validity of aseptic filling operations.
未做培养基灌装验证以证明无菌灌装操作的有效性。
-No environmental controls/No monitoring for viable microorganisms during filling for aseptically filled products.
无菌灌装产品在灌装期间无环境控制／未监控微生物。
-Aseptic filling operations maintained following unsatisfactory results obtained for media fills.
培养基灌装验证失败后仍继续进行无菌灌装生产。
-Batches failing initial sterility test released for sale on the basis of a second test without proper investigation.
未对首次无菌检查不合格进行彻底调查，就根据复试结果批准放行产品。
Appendix2附录2
Risk2(Major)Observations2类风险（主要）缺陷
Premises C.02.004厂房
-Malfunctioning of the ventilation system that could result in possible localized or occasional cross-contamination.
有可能导致局部或偶发交叉污染的通风系统故障。
-Maintenance/periodic verification such as air filter replacement,monitoring of pressure differentials not performed.(↑)
未对如空气过滤器的更换、压差监控进行维护/定期确认。（↑）
-Accessory supplies(steam,air,nitrogen,dust collection,etc...)not qualified.
辅助系统（蒸汽、空气、氮气、捕尘等）未经确认符合要求。
-Heat Ventilation Air Conditioning(HVAC)and purified water(PW)system not qualified.
空调净化系统和纯化水（PW）未经确认符合要求。
-Temperature and humidity not controlled or monitored when necessary(e.g.storage not in accordance with labelling requirements).
未根据需要控制或监测温湿度（如未按标示的要求贮存）。
-Damages(holes,cracks or peeling paint)to walls/ceilings immediately adjacent or above manufacturing areas or equipment where the product is exposed.
与生产区或产品暴露的设备直接相邻或位于其上方的墙面／天棚有损坏（破洞、裂缝或油漆剥落）。
-Un-cleanable surfaces created by pipes,fixtures or ducts directly above products or manufacturing equipment.
因管道或固定设备造成有无法清洁的表面，或有灰尘直接位于产品或生产设备
的上方。
-Surfaces finish(floors,walls and ceilings)that do not permit effective cleaning.
表面外层涂料（地面、墙面和天棚）无法进行有效清洁。
-Unsealed porous finish in manufacturing areas with evidence of contamination(mildew,mould, powder from previous productions,etc..)(↑)
有证据表明生产区域内未密封的孔洞表面存在污染（长霉、霉斑、来自以往生产的粉尘等）。（↑）
-Insufficient manufacturing space that could lead to mix-ups.(↑)
生产区域空间太小，可能导致混淆。（↑）
-Physical and electronic quarantine accessible to unauthorized personnel/Physical quarantine area not well marked and/or not respected when used.(↑)
未经授权的人员可进入物理和电子分隔的待验区域／物理分隔的待验区域无良好标志，且／或未按规程使用。（↑）
-No separate area/Insufficient precautions to prevent contamination or cross-contamination during RM sampling.
原辅料取样无独立区域／没有足够的预防措施以防止原辅料取样中的污染或交叉污染。Equipment C.02.005设备
-Equipment does not operate within its specifications.(↑)
设备未在规定的标准范围内运行。（↑）
-Equipment used for complex manufacturing operations not qualified.(↑)
用于复杂生产工艺的设备未经确认符合要求。（↑）
-Clean in Place(CIP)equipment not validated.
在线清洁（CIP）设备未经验证。
-Tanks for manufacturing of liquids and ointments not equipped with sanitary clamps.
液体制剂或油膏剂的生产罐未安装卡箍式卫生接头。
-Stored equipment not protected from contamination.(↑)
未对存放的设备采取防止污染的措施。（↑）
-Inappropriate equipment for production:surfaces porous and non-cleanable/material to shed particles.(↑)
设备不适用于生产：表面多孔且无法清洁／材质有颗粒物脱落。（↑）
-Evidence of contamination of products by foreign materials such as grease,oil,rust and particles from the equipment.(↑)
有证据表明产品已被设备上的异物（如润滑油、机油、铁锈和颗粒）污染。（↑）
-No covers for tanks,hoppers or similar manufacturing equipment.
大罐、料斗或类似的生产设备没有盖子。
-No/inadequate precautions taken when equipment such as oven or autoclave contains more than one product(possibility of cross-contamination or mix-ups).(↑)
设备（如烘箱或灭菌柜）存放有多个产品时（有可能交叉污染或混淆），没有采取措施或措施不当。（↑）
-Equipment location does not prevent cross-contamination or possible mix-ups for operations performed in common area.(↑)
在共用区域内，设备安装的位置不能防止操作中的交叉污染或可能的混淆。（↑）
-PW system not maintained or operated to provide water of adequate quality.(↑)未维护或运行纯化水（PW）系统以提供质量合格的生产用水。（↑）
-Leaking gaskets.
垫圈不密封。
-No calibration program for automatic,mechanical,electronic or measuring equipment/no records maintained.
无自动化设备、机械设备、电子设备或测量设备的校验计划／未保存校验记录。
-No equipment usage logs.
无设备使用记录。
Personnel C.02.006人员
-Individual in charge of QC or Production for a fabricator,packager/labeller or tester does not hold
a university degree in a science related to the work being conducted or does not have sufficient
practical experience in their responsibility area.
负责生产、包装／贴签的生产部门负责人或负责检验的质量控制部门负责人无与其从事工作相关领域的大学学历，或对其所负责的工作缺少足够的实践经验。
-Individual in charg e of QC for a distributor,importer or wholesaler is not qualified by academic training and experience.
分销商、进口商或批发商的质量控制部门负责人不符合大专培训与工作经验的资质要求。
-Delegation of responsibilities for QC or Production to insufficiently qualified persons.
委托无足够资质的的人员履行质量控制（QC）部门或生产部门的职责。
-Insufficient personnel for QC or Production operations resulting in a high probability of error.
质量控制与生产部门人员不足，导致差错率高。
-Insufficient training for personnel involved in production and QC resulting in related GMP deviations.
生产与质量控制（QC）的有关人员培训不足，导致发生相关的GMP偏差。
Sanitation C.02.007 C.02.00↑清洁
-Sanitation program not in writing but premises in acceptable state of cleanliness.
厂房虽然洁净，但缺少书面的卫生清洁规程。
-No Standard Operating Procedure(SOP)for microbial/environmental monitoring,no action limits for areas where susceptible non-sterile products are manufactured.
无微生物／环境监控的标准操作规程（SOP），易受污染的非无菌产品生产区未设纠偏限度。
-Cleaning procedure for production equipment not validated(including analytical methods).
生产设备的清洁方法（包括分析方法）未经验证。
-Cleaning procedure for production equipment not validated when non-dedicated equipment is used for high risk products(↑).
非专用设备用于高风险产品生产时，生产设备的清洁方法未经验证。（↑）
-Incomplete health requirements.
健康要求内容不完整。
Raw Material Testing C.02.009 C.02.010原辅料检验
-Reduce testing program in place without adequate certification of the vendors/suppliers.
未对销售商／供应商进行足够的审计即实施减少检验计划。
-Water used in the formulation is not of acceptable quality.
生产用水的质量不符合要求。
-No identity test performed by the manufacturer after receipt on it’s premises/Testing for identity not done on each container for APIs or after manipulation or repackaging by third party.
企业接收物料后未在工厂内做鉴别试验／未对每个容器中的原料药，或经第三方处理或再包装后的原料药做鉴别试验。
-COA showing incomplete testing.
检验报告显示检验项目不全。
-Incomplete specifications.
质量标准内容不完整。
-Specifications not approved by QC.
质量标准未经质量控制部门（QC）批准。
-Test methods not validated.
检验方法未经验证。
-Use of API after the retest date without proper retesting.
超过复验期的原料药未经适当复验即使用。
-Use of inactive RM after the expiration date without proper retesting.
超过有效期的辅料未经适当复验即使用。
-Multiple lots comprising one reception not considered as separate for sampling,testing and release.
一次接收的物料由多个批次构成，未考虑分开取样、检验与批准放行。
-No SOP for conditions of transportation and storage.
运输和贮存条件无SOP规定。
-Certification of brokers or wholesalers allowed without proper documentation.
对中间商或批发商的审计无文件记录。
Manufacturing Controls C.02.011 C.02.012生产控制
-Master Formulae prepared/verified by unqualified personnel.
生产处方由无资质人员编写／核对。
-Complex production processes not validated.(↑)
复杂的生产工艺未经验证。（↑）
-Incomplete validation studies/reports for complex manufacturing process(lack of evaluation/ approval).
复杂生产工艺的验证研究／报告内容不完整（缺少评估/批准）。
-Changeover procedures for manufacturing of medicinal/non-medicinal products are not validated or not available.
无药品／非药品生产的品种更换规程，或该规程未经验证。
-Unapproved / undocumented major changes compared to Master Production Documents. (↑ )生产工艺规程上的主要变更未经批准／无书面记录。（↑）
-Deviations from instructions during production not documented and not approved by QC.
生产中的偏差无书面记录，且未经质量控制部门（QC）批准。
-Discrepancies in yield or reconciliation following production not investigated.
未对生产收率或物料平衡的偏差进行调查。
-Line clearance between production of different products not covered by SOP and not documented.
SOP未包括生产不同产品之间的清场，且无书面记录。
-No regular checks for measuring devices/no records.
未定期检查测量器具／无检查记录。
-Lack of proper identification of in-process materials and production rooms resulting in a high probability of mix-ups.
生产操作间和中间物料缺少适当的标识，易造成混淆。
-Inadequate labelling/storage of rejected materials and products that could generate mix-ups.
不合格的物料和产品标识／贮存不当，可能引起混淆。
-Upon receipt,bulk and in-process drugs,RM and PM not held in quarantine until released by QC.
物料接收后，待包装产品、中间品、原辅料和包装材料未在待检区存放，直到质量控制部门（QC）批准放行为止。
-Production personnel using bulk and in-process drugs,RM and PM without prior authorization by QC.
(↑ )
未经质量控制部门（QC）的批准，生产人员即使用待包装产品、中间品、原辅料和包装材料。（↑）
-Inadequate/inaccurate labelling of bulk/in-process drugs,RM and PM.
待包装产品、中间品、原辅料和包装材料标识不当／不正确。
-RM dispensing not done by qualified persons,according to an SOP.
未按SOP由有资质的人员对原辅料进行配料。
-Master Formulae incomplete or showing inaccuracies in the processing operations.
生产处方不完整，或在生产操作过程中显示出生产处方不准确。
-Changes in batch size not prepared/verified by qualified personnel.
生产批量的变更未经有资质的人员准备／审核。
-Inaccurate/incomplete information in manufacturing/packaging batch documents.
生产／包装批文件的内容不准确／不完整。
-Although documented,combination of batches done without QC approval/not covered by SOP.
尽管有文件记录，但未经质量控制部门（QC）批准即合并批号／SOP未涵盖此内容。
-No written procedures for packaging operations.
无包装操作的书面规程。
-Non-standard occurrences during packaging not investigated by qualified personnel.
包装过程中出现的异常情况未经有资质人员的调查。
-Inadequate control of coded and non-coded printed PM(including storage,dispensing,printing, disposal).
打印批号、未打印批号的印刷包装材料（包括储存、发放、打印和销毁）控制不严。
-No or inadequate self-inspection program/Program does not address all applicable sections of GMPs/ Records incomplete or not maintained.
无自检计划缺少或自检计划不完全／自检计划未说明适用GMP所有方面的要求／自检记录内容不完整或未保存。
-Products imported from foreign sites that are not listed on the Foreign Site Annex of the Establishment Licence (↑ )
产品从海外工厂进口，但海外工厂未列入企业许可证的海外工厂附录（译者注：该附录由加拿大健康产品和食品检查部公布在网上）中。（↑）
-Recall:
药品召回：
-Absence of recall procedure combined with distribution practices that would not permit an adequate recall(distribution records unavailable or not kept).
无药品召回规程，且发货操作的方式无法实施完全召回（无发货记录或未保存记
录）。
-Improper quarantine and disposal practices that would allow recalled/rejected units to be returned for sale.
隔离和处理方式不当，会导致召回的产品、退货重新发货销售。
Quality Control Department C.02.013 C.02.014 C.02.015质量控制部门
-Inadequate facilities,personnel and testing equipment.
设施、人员和检验仪器不完备。
-No authority to enter production areas.(↑)
无权进入生产区域。（↑）
-No SOPs approved and available for sampling,inspection and testing of materials.
无物料取样、检查和检验的SOP或相关SOP未经批准。
-Products made available for sale without approval of QC department.(↑)
产品未经质量控制部门（QC）批准即可销售。（↑）
-Products released for sale by QC without proper verification of manufacturing and packaging documentation.
质量控制部门（QC）未经正确核对生产与包装的文件记录，即批准销售产品。
-Deviations and borderline conformances not properly investigated and documented,according to a SOP.
偏差和勉强符合要求的情况未按照SOP正常调查并做书面记录。
-RM/PM used in production without prior approval of QC.
原辅料与包装材料未经质量控制部门（QC）事先批准即用于生产。
-Reprocessing / Reworking done without prior approval of QC department. (↑ )
未经质量控制部门（QC）事先批准即进行再加工／返工操作。（↑）
-No system for complaint handling and returned goods.
无投诉与退货处理系统。