质量以及药品生产和质量管理
质量以及药品生产和质量的管理
质量以及药品生产和质量管理
GMP:验证
演讲者: Dr A J van Zyl
科技官员: WHO
HTP/PSM/QSM
vanzyla@
质量以及药品生产和质量管理
演讲纲要
讨论GMP与验证之间的关键关系
规范和标准
由TRS和WHO网站各自发布
正文的简介
附加文件发表TRS 937
验证
Part 1. 关于验收和验证的概述
Part 2. 空调通风和给水系统的验收
Part 3. 清洁工作的验收
Part 4. 分析方法的验收
Part 5. 计算机系统验收
Part 6. 生产设备和系统的验收
Part 7. 非无菌生产环节的验收
验证
验证是GMP的必要组成，也是QA的一部分
基本要素包括:
产品的安全，优质，高效。
质量来自生产，而非来自监测
需要对生产的关键环节进行验证
要保证产品质量稳定并达标。
1.
验证
验证相关的文件:
SOPs
规范
验证主计划模板(VMP)
验收设计和报告
验证设计和报告
1.
验证
指南范围
WHO指南关注于验证的总体概念
它只是一个概括的指南
原则对于原料药和成品药的生产和质控有意义
对于特殊产品工艺（如无菌产品的生产）的验证需要指南范畴以外更多更全面的考虑。
验证
不同种的验证，有不同的影响因素。
生产厂商应制定验证以确保
符合注册要求
产品质量，安全，和稳定
指南的综述可以引用于以下的验证:
基础设施, 设备, 工艺和系统
流程和工序
附件中提到了更多特殊的规则
半自动，全自动清洗系统和其他特殊情况应单独对待
–
验证
词汇…
参见指南中的定义
校准: 在特定条件下开展的一项工作, 测量仪器或系统获得的数据（重量，温度，pH）间的关系，以及对应的参照标准。要建立测量结果的接受限度。
3.
验证
Qualification and Validation
Qualification 和 validation 是同一个概念的主要成分
qualification 通常指仪器，设备和系统。
validation通常指工艺和流程
从这种意义上讲, （qualification is part of validation）质控是验证的一部分
4.
验证
验证的步骤
二个基础步骤:
测试中获得的资料（前瞻性和并行性验证）
对累积（历史）的数据的分析（回顾性验证）
如果可能，推荐进行前瞻性验证。
不推荐进行回顾性验证。
回顾性验证不适用于无菌产品。
验证
前瞻和并行验证可能包括
扩大的产品检测（extensive product testing）,可能会涉及到扩大样品检测（对单个结果的信任限度的测量）以及批间，批内均匀性的证明。
模拟流程试验
最坏条件的测试,以考察流程的稳固性
在日常生产流程中进行参数的监督有助于获得额外的关于流程可靠性的资料。
验证
验证的范围
验证需要足够的合适的下属机构，包括：
组织，文件，人力，经费
管理人员和质控人员的参与
人员应具备适合的能力和经验
在验证前应进行额外的准备和计划
对验证工作进行专门的计划
验证要按照文件中的方案涉及和流程进行
–
验证
进行验证的范围 (2)
应这样进行验证:
新的设施，装置，器械和系统，以及工艺和流程。
按照规律的周期进行
当生产情况发生了重大改变的时候
周期性复验证可以被取代么?
验证要与书面方案一致。
应准备验证结果的书面报告。
间隔固定时间进行验证
至少在３个连续批次（成品药） 以证明生产稳定性 （应该考虑到最坏情况）
–
验证
Scope of validation (3)
区别质控和验证
质控(对每个批次进行，目的在于连续的监督生产）
证明新的生产方式，方法的适应性。
方法，物料和设备以检验合格品的收率的一致性。
生产厂家来确定哪项验证是必要的。
要对重要的改变（设备，仪器，工艺）进行验证。
为决定验证范围要进行风险评估
–
验证
验收
在进行工序验证之前就应当完成质量检查。
需要有一个合理的系统的工序
从生产设施，设备，仪器器械的设计阶段开始
主要的设备和重要的仪器以及系统一般需要IQ,OQ,PQ．
,
验证
校准 和 鉴定
按照规则的周期进行。
拥有资质，并受过训练的负责人。
有效的校准方案和信息。
校准标准和限度，负责人，校准周期，记录，以及必要时采取的行动。
–
验证
校准 和 鉴定
标准化操作的可描述性
（国家的，地区的，国际的标准）
校准设备，器械，以及其他仪器要进行编码和鉴定
依据实践，标明校准和复校准的情况
如果一段时间没有使用了
校准和性能情况应得到证实
使用前确认符合要求
–
验证
用合适的标签指明校准状况
可记录的.
设备
日期
人员
标准
适当的范围和条件
验证
文件资料
(VMP)验证主计划模板
验证设计方案
验证报告
SOPs
其他?
验证
验证主计划模板 (VMP)
包括验证计划的关键元素
简而言之，至少包括:
验证方针
验证活动组织组成
验证的设施，系统，设备，工序的总录
文件格式（方案，报告）
计划并制定日程
参考对照已有的材料
8.
验证
验收和验证方案
记述研究应如何开展:
研究的目的
研究机构
负责人
依照SOPs要求执行
使用的设备
产品和工艺的规则和标准
验证的类别
–
验证
验收和验证执行情况的书面报告
验证方案计划至少应包含:
试验的题目和目的，参照资料的详情
使用的设备，程序，操作步骤和检测方法
对比预先设计的接受限度，对结果进行评价，分析，比较。
–
验证
计划中应指明需要进行复验证的变化:
生产初始原料的改变
工序转移到不同场所
生产环节中首层包装材料的变化
设备的改变
生产地点和辅助系统的改变
出现质量下降的迹象
在已有知识的基础上有了新的发现
辅助系统的改变
包括物理学改变，例如密度，粘性，颗粒尺寸可能影响到流程和产品的因素
可能影响流程的设备的改变
用塑料代替了玻璃
混合时间和干燥温度
额外的电子感应系统，安装新的设备，机械和仪器的重要的调校或故障
区域的重新布置，或者新的给水系统
新技术
验证
变更管理
依据SOP，任何改变都有可能影响已合格的系统和设备，已验证的工序／流程。
描述需要采取的行动，包括质量控制和验证的需求和范围。
任何更改都要提出正式申请，记录在案并得到认可，方可执行。
记录要妥善保存
–
验证
搅拌机
讨论对一个新安装的搅拌机的质量验收。
验证
质量验收的步骤
设计 验收
安装 验收
操作 验收
性能 验收
验证
质量验收的步骤
.
设计 验收
安装 验收
操作 验收
性能 验收
变更管理
验证
质量复查
决定日程
具体因素而定的周期
校准，保养和鉴定的结果
周期
变更后
部分变更管理的操作
根据风险评估制定的范围
–
验证
对于没有进行过DQ,IQ的“老”的生产厂家的已经投入使用的系统设备，怎么办呢？
验证
对于已经使用的设备系统的质量验收
能支持，证明设备系统操作运行正常以及性能情况的数据。
应当包含操作运行参数和中要变量的限度，校准，保养，预防性保养，标准化操作规程和记录。
–
验证
验证
Part 1. 验收和验证的概述
Part 2. 空调通风和给水系统的验收
Part 3. 清洁工作的验收
Part 4. 分析方法的验收
Part 5. 计算机系统验收
Part 6. 生产设备和系统的验收
Part 7. 非无菌生产环节的验收
其设计，安装和功能参数的说明
规格和要求
使用指南
操作步骤
对性能控制，监控的指南和记录。
维护指南和记录
人员培训
程序和记录
帮助交付使用验收和保养的文件
HVAC
HVAC
验证，是一项大规模的作业。
对于空调系统的验收是覆盖全局的庞大工作的一部分。
参阅完整指南在 "Validation" WHO TRS, No. 937, 2005, Annex 4
基于一定风险的空调通风系统验收
HVAC
例举考虑的方面
DQ –系统的设计和升级
（部件，需要的空气处理方式，建造材料等）
IQ –安装验收
相关部件如：导管，过滤器，控制器，监视器，传感器等。
包括有关方面的校准
HVAC
验收工作中应包括代表性参数（基于风险评估）
温度
相对湿度
输送，反回，排放气体量。
室内空气换气率
室内气压（压差）
HVAC
验收工作中应包括代表性参数（基于风险评估）
房间洁净等级
颗粒物质，微生物（有活性的，无活性的）
高效粒子空气过滤器穿透测试。
密封系统风速
报警系统
HVAC
测试管理:
生产着确定其时间间隔，操作步骤
设备类型和保养程度的影响
检测方法亦参看 ISO 14644
复验收和变更管理
– ,
HVAC
空调通风系统稳定性检测的日程
*试验操作参看ISO 14644
8. Table 3
试验操作及重点
最短间隔
目标
检测参数
颗粒计数和位置
6-12个月，据类型决定
验证清洁程度
颗粒计数检测
测量空气压差
12 个月
确保没有交叉污染
空气压差
测量输送，返回空气，计算换气率
12 个月
验证换气率
空气流量
测量空气流速
12 个月
验证单向气流，和密封状况
空气流速
HVAC
建议的检测
*Test procedure as per ISO 14644
8. Table 3
试验操作及重点
最短间隔
目标
检测参数
滤材和过滤器密封完整性
12 个月
验证过滤器完整性
过滤器漏失量
气流方向和压差
12 个月
检验无交叉污染
密封系统的泄漏
最多用15分钟
12 个月
验证自净化时间
自净化 (time)
气流方向记录在案
12 个月
验证需要的气流模式
气流形象化
定义条件
air
完工时
air
air
闲置时
运行时
HVAC
例举验收时应考虑的一些方面（OQ,PQ）
检测
对过滤器施不同的压力
紊流的
描述
单向气流
房间压差
气流速度，均匀度
气流镕基/比率
平行性
气流模式
2
2
N/A
2, 3
2, 3
任意
2
2
2
N/A
2
3
1 := 执行IQ使用
2 = 执行OQ使用
3 =执行PQ使用
HVAC
给水系统
三阶段
为时12-13个月的测验期
集中系统验收
系统能够不间断，无偏差的稳定工作
在检测操作中，应包括以下步骤：
依照方案进行化学，微生物测试
制药用水
进行系统监控
在第三阶段之后，要进行复查
基于复查的结果，制定日常监控方案
监控包括线上监控和线下样品检测
趋势数据分析
制药用水
(2)系统复查
复查应覆盖如下方面.
自上次复查以来做出的改变
系统性能
可靠性
质量趋势
失败事件
调研
超出规范的监控
安装的变化
设备更新文件
说明书
现行 SOP 清单
制药用水
药品生产和质量管理
CGMP的限定
文中有一些相同的要求. 不同之处（包括WHO关注的方面）的如下:
依照GMP，每个医药企业都应该说明用何种验收验证方法证明其产品生产中关键环节的监控。
在验证主一个医药公司的严正计划模板中应明确验收和验证的关键要素。
验收和验证应建立并提供如下记录基础设施，辅助设施，仪器设备，和DQ。
验收和验证不是一次性的操作而是自第一次完成之后的持续计划，其基础就是年检。
药品生产和质量管理
CGMP的限定
.对于继续的委托验证应该被记录在相关公司的文件中，例如质量手册，验证住计划模板
执行验证的责任应当明确
验证研究是GMP的必要组成。
要依据验证的结果来建立方法和流程
要对验证的分析检测方法，自动化系统，清洁工艺给予足够重视。
验证
总结
验证
总结
前瞻性验证
验证
总结
前瞻性验证
并行性验证
验证
总结
前瞻性验证
并行性验证
回顾性验证
验证
总结
前瞻性验证
并行性验证
回顾性验证
复验证
验证
总结
前瞻性验证
并行性验证
回顾性验证
变更管理
复验证
质量以及药品生产和质量管理
谢谢
World Health Organization
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1. Introduction
Validation is an essential part of good manufacturing practices (GMP). It is,
therefore, an element of the quality assurance programme associated with a
particular product or process. The basic principles of quality assurance have
as their goal the production of products that are fi t for their intended use.
These principles are as follows:
• Quality, safety and effi cacy must be designed and built into the product.
• Quality cannot be inspected or tested into the product.
• Each critical step of the manufacturing process must be validated. Other
steps in the process must be under control to maximize the probability
that the fi nished product consistently and predictably meets all quality
and design specifi cations.
Validation of processes and systems is fundamental to achieving these goals.
It is by design and validation that a manufacturer can establish confi dence that
the manufactured products will consistently meet their product specifi cations.
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Documentation associated with validation includes:
— standard operating procedures (SOPs)
— Specifications
— Validation master plan (VMP)
— Qualification protocols and reports
— Validation protocols and reports.
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These guidelines focus mainly on the overall concept of validation
and are intended as a basic guide for use by GMP inspectors and manufac-
turers. It is not the intention to be prescriptive in specifi c validation requirements.
This document serves as general guidance only, and the principles
may be considered useful in its application in the manufacture and control
of active pharmaceutical ingredients (APIs) and fi nished pharmaceutical
products. Validation of specifi c processes and products, for example in sterile
product manufacture, requires much more consideration and a detailed
approach that is beyond the scope of this document.
There are many factors affecting the different types of validation and
it is, therefore, not intended to defi ne and address all aspects related to one
particular type of validation here.
Manufacturers should plan validation in a manner that will ensure
regulatory compliance and ensuring that product quality, safety and consistency
are not compromised.
The general text in the main part of these guidelines may be applicable
to validation and qualification of premises, equipment, utilities and
systems, and processes and procedures. More specifi c principles of quali-
fi cation and validation are addressed in the appendices. Semi-automatic or
fully automatic clean-in-place (CIP) systems and other special cases should
be treated separately.
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There are many factors affecting the different types of validation and
it is, therefore, not intended to defi ne and address all aspects related to one
particular type of validation here.
Manufacturers should plan validation in a manner that will ensure
regulatory compliance and ensuring that product quality, safety and consistency
are not compromised.
The general text in the main part of these guidelines may be applicable
to validation and qualification of premises, equipment, utilities and
systems, and processes and procedures. More specific principles of quali
fication and validation are addressed in the appendices. Semi-automatic or
fully automatic clean-in-place (CIP) systems and other special cases should
be treated separately.
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It is important that you read the guidelines and familiarize yourself with the terms and definitions in the Glossary part. You should know what the terms mean, and also the differences between different concepts including calibration and qualification.
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4. Relationship between validation and qualification
Validation and qualification are essentially components of the same concept.
The term qualification is normally used for equipment, utilities and systems,
and validation for processes. In this sense, qualification is part of validation.
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5. Validation
Approaches to validation
There are two basic approaches to validation — one based on evidence
obtained through testing (prospective and concurrent validation), and
one based on the analysis of accumulated (historical) data (retrospective
validation). Whenever possible, prospective validation is preferred. Retrospective
validation is no longer encouraged and is, in any case, not applicable
to the manufacturing of sterile products.
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Both prospective and concurrent validation, may include:
• extensive product testing, which may involve extensive sample testing
(with the estimation of confidence limits for individual results) and the
demonstration of intra- and inter-batch homogeneity;
• simulation process trials;
• challenge/worst case tests, which determine the robustness of the process;
and
• control of process parameters being monitored during normal production
runs to obtain additional information on the reliability of the process.
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Scope of validation
There should be an appropriate and suffi cient system including organizational
structure and documentation infrastructure, suffi cient personnel
and fi nancial resources to perform validation tasks in a timely manner. Management
and persons responsible for quality assurance should be involved.
Personnel with appropriate qualifications and experience should
be responsible for performing validation. They should represent different
departments depending on the validation work to be performed.
There should be proper preparation and planning before validation is
performed. There should be a specifi c programme for validation activities.
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Validation should be performed:
— for new premises, equipment, utilities and systems, and processes and
procedures;
— at periodic intervals; and
— when major changes have been made.
(Periodic revalidation or periodic requalification may be substituted, where
appropriate, with periodic evaluation of data and information to establish
whether requalification or revalidation is required.)
Validation should be performed in accordance with written protocols.
A written report on the outcome of the validation should be produced.
Validation should be done over a period of time, . at least three
consecutive batches (full production scale) should be validated, to demonstrate
consistency. Worst case situations should be considered.
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There should be a clear distinction between in-process controls and
validation. In-process tests are performed during the manufacture of each
batch according to specifi cations and methods devised during the development
phase. Their objective is to monitor the process continuously.
When a new manufacturing formula or method is adopted, steps
should be taken to demonstrate its suitability for routine processing. The
defi ned process, using the materials and equipment specifi ed, should
be shown to result in the consistent yield of a product of the required
quality.
Manufacturers should identify what validation work is needed to
prove that critical aspects of their operations are appropriately controlled.
Signifi cant changes to the facilities or the equipment, and processes that
may affect the quality of the product should be validated. A risk assessment
approach should be used to determine the scope and extent of validation
required.
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6. qualification
qualification should be completed before process validation is performed.
The process of qualification should be a logical, systematic process
and should start from the design phase of the premises, equipment, utilities
and equipment.
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7. Calibration and verifi cation
Calibration and verifi cation of equipment, instruments and other
devices, as applicable, used in production and quality control, should be
performed at regular intervals.
Personnel who carry out calibration and preventive maintenance
should have appropriate qualifications and training.
A calibration programme should be available and should provide information
such as calibration standards and limits, responsible persons, calibration
intervals, records and actions to be taken when problems are identifi ed.
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There should be traceability to standards (. national, regional or
international standards) used in the calibration.
Calibrated equipment, instruments and other devices should be labelled,
coded or otherwise identifi ed to indicate the status of calibration and
the date on which recalibration is due.
When the equipment, instruments and other devices have not been
used for a certain period of time, their function and calibration status should
be verifi ed and shown to be satisfactory before use.
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The trainer should explain briefly which types of documents are associated or needed as part of a validation/qualification exercise. Explain that some of these will be discussed in detail in the following slides
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8. Validation master plan
The validation master plan (VMP) should refl ect the key elements of the
validation programme. It should be concise and clear and contain at least
the following:
— a validation policy
— organizational structure of validation activities
— summary of facilities, systems, equipment and processes validated and
to be validated
— documentation format (. protocol and report format)
— planning and scheduling
— change control
— references to existing documents.
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9. qualification and validation protocols
There should be qualification and validation protocols describing
the qualification and validation study to be performed.
As a minimum the protocols should include the following signifi cant
background information:
— the objectives of the study
— the site of the study
— the responsible personnel
— description of SOPs to be followed
— equipment to be used; standards and criteria for the relevant products
and processes
— the type of validation
— the processes and/or parameters
— sampling, testing and monitoring requirements
— predetermined acceptance criteria for drawing conclusions.
There should be a description of the way in which the results will be
analysed.
The protocol should be approved prior to use. Any changes to a protocol
should be approved prior to implementation of the change.
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10. Qualification and validation reports
There should be written reports on the qualification and validation
performed.
Reports should refl ect the protocols followed and include at least the
title and objective of the study; reference to the protocol; details of material,
equipment, programmes and cycles used; procedures and test methods.
The results should be evaluated, analysed and compared against the
pre-determined acceptance criteria. The results should meet the acceptance
criteria; deviations and out-of-limit results should be investigated. If these
deviations are accepted, this should be justifi ed. Where necessary further
studies should be performed.
The departments responsible for the qualification and validation
work should approve the completed report.
The conclusion of the report should state whether or not the outcome
of the qualification and/or validation was considered successful.
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The quality assurance department should approve the report after
the fi nal review. The criteria for approval should be in accordance with the
company’s quality assurance system.
Any deviations found during the validation process should be acted
upon and documented as such. Corrective actions may be required.
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Revalidation after change
Revalidation should be performed following a change that could
have an effect on the process, procedure, quality of the product and/or the
product characteristics. Revalidation should be considered as part of the
change control procedure.
The extent of revalidation will depend on the nature and signifi cance
of the change(s).
Changes should not adversely affect product quality or process
characteristics.
Changes requiring revalidation should be defi ned in the validation
plan and may include:
• changes in starting materials (including physical properties, such as density,
viscosity or particle size distribution that may affect the process or product);
• change of starting material manufacturer;
• transfer of processes to a different site (including change of facilities and
installations which infl uence the process);
• changes of primary packaging material (. substituting plastic for glass);
• changes in the manufacturing process (. mixing times or drying temperatures);
• changes in the equipment (. addition of automatic detection systems,
installation of new equipment, major revisions to machinery or apparatus
and breakdowns);
• production area and support system changes (. rearrangement of areas,
or a new water treatment method);
• appearance of negative quality trends;
• appearance of new fi ndings based on current knowledge, . new technology;
• support system changes.
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12. Change control
Changes should be controlled in accordance with a SOP as changes
may have an impact on a qualifi ed utility, system or piece of equipment, and
a validated process and/or procedure.
The procedure should describe the actions to be taken, including the
need for and extent of qualifi cation or validation to be done.
Changes should be formally requested, documented and approved
before implementation. Records should be maintained.
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The trainer should invite discussion from participants on the approach, stages, parameters to be considered in the qualification of equipment. Use examples of pieces of equipment.
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Stages of qualification
There are generally, four stages in qualification. Can you name them?
Design qualification
Installation qualification
Operational qualification
Performance qualification
Change control
We will look into more detail on these stages in the next slides.
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Stages of qualification
There are generally, four stages in qualification. Can you name them?
Design qualification
Installation qualification
Operational qualification
Performance qualification
Change control
We will look into more detail on these stages in the next slides.
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Requalification
Requalification of systems and equipment should be done in accordance with a defined schedule. The frequency of requalification may be determined on the basis of factors such as the analysis of results relating to calibration, verification and maintenance.
There should be periodic requalification.
There should be requalification after changes. The extent of requalification after the change should be justified based on a risk-assessment of the change. Requalification after change should be considered as part of the change control procedure.
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Qualification of “in-use” systems and equipment
The manufacturer should have data to support and verify the suitable operation and performance of systems and equipment.
This should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records.
On the basis of this, OQ and PQ could be done (protocol and reports prepared).
Remember – can still do requalification!
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Group session (Example)
The trainer could ask the participants to discuss the approach of qualification for a piece of equipment. Present the participants with a schematic drawing of equipment, or a manual and related documentation, and ask them to discuss key aspects in the different stages of qualification.
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Qualifi cation
Validation is a many-faceted and extensive activity and is beyond
the scope of these guidelines. Qualifi cation and validation guidelines are
included in: Expert Committee on Specifi cations for Pharmaceutical Preparations.
Fortieth report. Geneva, World Health Organization, 2005 (WHO
Technical Report Series, No. 937), Annex 4 (see also Fig. 28).
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For a pharmaceutical facility, based on a risk assessment, some of
the typical HVAC system parameters that should be qualifi ed may include:
— temperature
— relative humidity
— supply air quantities for all diffusers
— return air or exhaust air quantities
— room air change rates
— room pressures (pressure differentials)
— room airfl ow patterns
— unidirectional fl ow velocities
— containment system velocities
— HEPA fi lter penetration tests
— room particle counts
— room clean-up rates
— microbiological air and surface counts where appropriate
— operation of de-dusting
— warning/alarm systems where applicable.
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The maximum time interval between tests should be defi ned by the
manufacturer. The type of facility under test and the product level of protection
should be considered.
Note: Table 3 gives intervals for reference purposes only. The actual test periods
may be more frequent or less frequent, depending on the product and process.
Periodic requalifi cation of parameters should be done at regular
intervals, . annually.
Requalifi cation should also be done when any change, which could
affect system performance, takes place.
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This slide shows a series of tests to be carried out during qualification.
There are different tests for the turbulent and for the uni-directional air flows.
The differential pressure on filters is an indication of the clogging of the filters: with the charging of dust on the filters, the differential pressure will increase.
In order to keep the volume of air constant, the fan speed may increase, with the following consequences:
Damage to filters, and passage of unfiltered air
Particles and micro-organismes will be “pushed” through the filter units.
(Inspectors should check whether pressure differential manometers are installed on the AHUs. Without this means of monitoring the filters, the system could go out of control causing contamination problems.)
Airflow patterns are interesting to visualize (smoke tests), as zones without proper flushing can be easily identified.
It is also important to monitor air flow velocities for each HEPA filter according to a program of established intervals because significant reductions in velocity can increase the possibility of contamination, and changes in velocity can affect the laminarity of the airflow.
Airflow patterns should be tested for turbulence, as these can interfere with the flushing action of the air.
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Qualification
WPU, PW, HPW and WFI systems are all considered to be direct impact, quality critical systems that should be . The should follow the validation convention of design review or design (DQ), installation (IQ), operational (OQ) and performance (PQ).
This guidance does not the standard requirements for the conventional validation stages DQ, IQ and OQ, but concentrates on the particular PQ approach that should be used for WPU systems to demonstrate their consistent and reliable performance. A three-phase approach should be used to satisfy the objective of proving the reliability and robustness of the system in service over an extended period.
Phase 1. A test period of 2–4 weeks should be spent monitoring the system intensively. During this period the system should operate continuously without failure or performance deviation. The following should be included in the testing approach.
• Undertake chemical and microbiological testing in accordance with a plan.
• Sample the incoming feed-water daily to verify its quality.
• Sample after each step in the process daily.
• Sample at each point of use and at other sample points daily.
• Develop appropriate operating ranges.
• Develop and .nalize operating, cleaning, sanitizing and maintenance procedures.
• Demonstrate production and delivery of product water of the required quality and quantity.
• Use and the standard operating procedures (SOPs) for operation, maintenance, sanitization and troubleshooting.
• Verify provisional alert and action levels.
• Develop and test-failure procedure.
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Continuous system monitoring
After completion of phase 3 of the programme for the WPU system, a system review should be undertaken. Following this review, a routine monitoring plan should be established based on the results of phase 3.
Monitoring should include a combination of online instrument monitoring of parameters such as .ow, pressure, temperature, conductivity and total organic carbon, and sample testing for physical, chemical and microbiological attributes. samples should be taken from points of use and sample points. Samples from points of use should be taken in a similar way to that adopted when the water is being used in service.
Tests should be carried out to ensure that the selected pharmacopoeia has been , and should include, as appropriate, determination of conductivity, pH, heavy metals, nitrates, total organic carbon, total viable count, presence of pathogens and endotoxins. Monitoring data should be subject to trend analysis.
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Ask te participants about principle elements of the topic on the slide
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Ask te participants about principle elements of the topic on the slide
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Ask te participants about principle elements of the topic on the slide
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Ask te participants about principle elements of the topic on the slide
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Ask te participants about principle elements of the topic on the slide
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Ask te participants about principle elements of the topic on the slide
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