听写：曹天海 宋媛媛
翻译：张勇 付娟
校对：曹天海 宋媛媛
时间轴：宋媛媛
后期和压制：曹天海
Introduction to GMP GMP介绍
Part 1 Introduction Why GMP 第一部分为什么要制定GMP规范
How would you feel if one of those new stories 如果以下突发事故发生在你的家人或朋友身上
was about a member of your family or a friend? 你会是什么感受呢
Could you accept that a crucial medical device 你可以接受一个关键医疗设备
just didn't work properly? 突然不能正常运转吗？
That wrongly labeled anesthetics we used? 我们使用的麻醉剂被打上错误的标签？
That vital medication we delivered out of date? 我们交付的重要药品已经过期？
Or a vital gas was contaminated? 或者一个重要的气体被污染了？
Ask yourself,would I work for any company 问问自己，是否在为一家公司工作，
that knowingly setup to produce 而这家公司明知生产的是
any substandard health products like these? 不合格健康产品或类似的东西？
No,of course not. 不，当然不。
No one in a right mind would. 正常人不会这样做。
And all of us are consumers, 我们所有人都是消费者，
especially when we are sick consumers, 特别当我们作为患病的消费者
Have every right to expect such items 我们有权利要求该类产品
should be completely and utterly suitable for their job. 必须完全、真实、准确地符合预定用途
In reality and quite rightly could be very upset 但人们往往感到很不安，
if they were even accidently damaged or 担心产品意外损坏
contaminated during manufacture. 或在制造过程中受到污染。
These are products that have to be 对于这些产品
taken almost entirely un-trust 我们几乎不能完全信任
because generally their quality 因为一般来说它们的质量
can't be judged before use. 不能在使用前被判断。
There's just no room for chance 没有持续的努力
in this sustained effort to achieve 我们无法确保达到
that level of confidence in the quality of every single item, 每个产品始终保持质量水平
week after week,month after month,year in,year out. 日复一日 年复一年 始终如一
What are we actually talking about? 我们到底要说什么呢？
Well,virtually any product produced 几乎任何设计和生产出来用于治疗
or designed to cure or modify our health 或改善我们的健康状况的产品，
that we apply,take orally,or inject 不管是口服、注射
not forgetting the syringe itself, 包括注射器本身
the list is very long: 这些东西的清单很长：比如
Needless say,eye drops,contact lens solution, 眼药水、隐形眼镜护理液
and lenses of course, 当然还包括隐形眼镜本身
inhalers and their contents,cough medicines and powders, 吸入器及其内容物、咳嗽药
skin treatments,orthopedic implant,anesthetics, 皮肤治疗品、整形外科植入物、麻醉药、
medical gases,sterile infusions,vaccines, 医用气体、无菌注射剂、疫苗
cough drops,and increasingly cosmetics 咳嗽滴剂和越来越多的化妆品
yes,even cosmetics. 是的，甚至连化妆品也是的。
Sadly,a handful of products do reach the market 不幸的是仍有少部分
in unsatisfactory condition. 不合格产品进入市场。
And during this program, 在今天的课程中
you'll learn how to achieve the right quality 你将学习如何获得好的质量，
and your responsibilities in personal contribution to that quality. 以及你对质量贡献的个人责任。
Part 2 GMP& Regulatory Agencies 第二部分 GMP及其监管机构
Only a very few generations ago, 在几辈人之前，
possibly not long before your grandparents were born, 也许不比你祖父母辈出生的时间早多长时间。
Someone who is injured in an accident,had an operation, 一些在事故中受伤的人
or been wounded in battle, 做过手术的人
was just likely to die from infection, 或者在战斗中受伤的人
also from the trauma or the wound itself. 可能是死于创伤或者伤口造成的感染。
Even recently,life-saving healthcare products 即使在近代，挽救生命的医疗保健产品
were often made incorrectly or contaminated, 往往被错误的制造或被污染，
causing fever and deterioration of the patient's condition 引起病人发烧和病情恶化，
and could lead subsequently to death. 并可能导致随后死亡。
One of the culprits was the manufacturing process, 其中一个“元凶”在于生产过程
But why? 但是为什么呢？
To control the quality of healthcare product, 为了控制医疗保健产品的质量，
governments created regulatory authorities, 政府设立了监管部门，
such as the FDA, 例如FDA
the United States Food and Drug Administration, 美国食品药品监督管理局
and in United Kingdom there is MHRA, 英国有MHRA
Medicines and Health-care product Regulatory Agency. 英国药品和健康产品管理局。
And similar bodies in countries 在其他生产医疗健康产品的国家
where healthcare products are manufactured. 也都有类似的机构。
Universally,this is achieved by the application of a quality system 普遍来说，此目标是通过应用质量体系
setting out principles or rules for 并设立“药品生产质量管理规范”
Good Manufacturing Practice,or GMP, 也就是GMP来实现的
sometimes called current Good Manufacturing Practice, 有时GMP也依据法规称为cGMP
or cGMP,or that by the enforce of law. “动态药品生产质量管理规范”
GMP applies the entire manufacturing process, GMP适用于整个生产过程，
and starts with incoming raw materials and components, 从原料和辅料
the warehousing and handling, 仓储和处理
the physical production of the product, 产品的生产
packaging and distribution. 到包装到销售过程。
Laboratory itself also is subject to disciplines of GMP. 实验室也应遵循GMP要求。
Most important,and the heart of the GMP GMP最重要的核心
is Quality Management& Systems. 是质量管理体系
Whether for medicines or medical devices, 无论是药品还是医疗设备，
the global GMP definition of product quality is that 全球GMP对产品质量的定义是，
it must reach the customer that is the patient, 用于患者即消费者的产品
in a state,fit for its intended purpose. 必须符合其预定用途。
“Fitness for a purpose” means being the right product, “符合预定用途”意味着：正确的产品
properly right strength,properly made, 正确的规格、正确的生产、
sealed in the right container, 正确的容器密封、
properly labeled,uncontaminated, 正确的标识、没有被污染、
and in its anticipated effective lifetime. 并且在有效期内。
In fact,the product precisely to specification, 事实上，产品要符合规范
this isn't the target for the price to each pack, 并不是具体针对
to each tablet,capsule,component, 某种特定的包装形式。
each gasule and each tube,each dressing,syringe, 比如片、胶囊、注射剂等，
each ampoule,and each whatever the final form. 无论它采用什么包装形式，都要符合要求。
The virtual,universal availability of the effective and safe healthcare products 要生产出有效安全可靠的医疗产品，
can be achieved by merging a few but comprehensive core GMP principles. 需遵循不多的但关键的GMP要求。
Naturally you will know,starting with the rule that 自然而然，你会知道，规则一开始就要求，
every action will be undertaken 每一个动作行动
only by following written instructions. 只能按照书面指令进行。
Good quality must be proven or validated and control that 每一个阶段的质量都需得到验证和控制
every stage of these storage,handling,manufacturing and packaging cycle. 包括存储，处理，制造和包装周期中。
That raw materials and components must be stored and handled correctly. 原辅料必须正确地存放和处理
That the exactly right materials must be used at all times. 任何时候都必须使用正确的合格的物料
That equipment and the environment,which is installed, 已安装的设备和环境
are appropriate for the purpose,and always properly cleaned and treated. 要满足要求，并始终正确清洗和处理。
The products will only contain ingredients and be produced as specified. 产品只能含有规定的成分并按照规定的方法生产。
That everything is correctly identified and labeled 在生产和分配的每一个阶段
at every stage of production and distribution. 都正确地识别和标记。
For everyone,production and support staff must dress and behave as required, 每个生产和支持员工必须按照规定要求着装和操作，
be properly supervised,and above all,be trained correctly. 要有必要的监督，最重要的是，要经过正确的培训。
That all work must be undertaken precisely and accurately. 所有的工作都必须精确、准确地进行。
That contamination of materials must be prevented at all times. 在任何时候都必须防止物料受到污染。
And that accurate records are kept at every stage. 而且每一个阶段都要准确的记录下来
Make no mistake,the consequence of products 不要出错，否则
as it to patient's health is awful. 会对产品本身甚至患者健康造成严重的影响。
Regulatory agencies are tasked to prevent that from happening. 监管机构的任务是防止这种（差错）情况发生
If necessary,by levying very substantial fines 如果有必要，可以进行巨额的罚款
or by stopping your production. 或责令你停止生产。
Part 3 Quality Assurance & Quality Control 第3部分质量保证和质量控制
Not that long ago,when your grandparents were still young, 不久前，当你的祖父母还年轻的时候，
quality was assessed and controlled by product testing. 产品质量的评估和控制是通过产品检测进行的。
It was assumed that by taking samples from 有人认为，通过对
a batch of finished product and then testing them, 一个批次的成品进行取样，
it would be possible to guarantee the quality of the whole batch. 然后对样品进行检测，这样的结果可以保证并代表整个批次的质量。
But think about it,in fact, 但想想看，事实上
it guarantees only the quality of each sample, 这只保证每个样本的质量，
and that never gets to the patient. 而且这些样品永远无法用到患者身上。
Virtually every domestic core industrial product we buy 事实上几乎每一个我们购买的工业产品，
can be examined or rejected or replaced 都可以被检测、拒收或更换
if found to be faulty or damaged. 如果发现它们有故障或损坏
But to test most of the items we are concerned with, 但（对于药品来说）很多我们所关注的项目要进行测试，
you must destroy them. 你就必须破坏它们。
Over the years,it became apparently better way 多年来，这显然是一种更好的方法
to ensure continuing quality standards 为了确保持续的质量标准，
is to make certain that mistakes don't happen. 不发生错误，它显然是较好的方式。
To achieve that,it was recognized that the control of quality 要实现这一目的，大家一致认为要管控好产品质量
requires two separate but interrelated functions, 需要两个既独立又相互关联的功能，
called Quality Assurance and Quality Control. 称为质量保证和质量控制。
Quality Assurance is pro-active and entails 质量保证要求我们积极主动地
the systematic analysis of each process or the pre-plan 先对每一个过程或计划进行的系统分析，
and then document or every activity will be undertaken 然后通过文件对每一个活动进行明确，
so ensure that when carried out precisely, 以确保过程能够精确执行
the outcome will be as expected. 并得到预期的结果。
This concept that quality must be built-in 质量的概念必须是
to the product from the beginning, 从一开始就植入产品中
demands that everyone and everything that may have 要求每个人和一切
even a slightest influence on the product, 可能对产品有丝毫影响的事物，
would be pre-examined and pre-determined. 都应该得到预先的检查和确认。
Consider the implication to those two words: 考虑这两个词的含义：
“everything” and “everyone”. “每件事”和“每个人”。
Because it demonstrates the formidable challenge 因为它显示了质量保证
represented by assuring quality. 所代表的艰巨的挑战。
In addition,as the people side where personnel hygiene, 此外，人员卫生方面
gowning considerations and training each had to be planned. 和更衣程序的培训应事先计划。
And of course the documented methods for handling corrective actions, 当然，应当记录各阶段整改措施的方法，
as they arise and every stage of the process, 因为它们来自于每个工艺阶段
including product recalls and product returns by customers. 包括产品召回和客户退货。
So Quality Assurance creates 所以质量保证负责创建
and documents the instructions for what will be done. 并记录将执行的操作。
Quality Control provides the physical verification 而质量控制负责已经完成
that it has been or is being done. 和正在进行的实物验证。
This includes actual sampling of incoming raw materials 包括来料时的原辅料取样
and components as well as during manufacture. 以及生产中的取样。
Quality Control sample water quality and the environment as specified. 质量控制应根据规定对水质和环境取样。
And where the environmental and process equipment cleaning 并对环境和工艺设备
has been done correctly. 正确清洗程序做了规定。
Dependent on the products being manufactured, 根据生产的产品，
Quality Control involves 质量控制部门涉及到
chemistry,biology and microbiological laboratories. 化学，生物学和微生物实验室。
To summarize,the quality department must ensure that 总体来说，质量部门必须确保
the finished product is fit for its purpose, 最终产品符合其用途。
and that each individual dose or component 并且每个最小个体的剂量和成分
is made to the correct formulation, 都是按照正确的配方制造的，
and is free from contamination. 并且不受污染。
That it will reach the patient in the correct container 给病人使用的产品要采用正确的容器或
and package to prevent damage and contamination, 包装形式以防止损坏和污染，
and will not deteriorate during distribution. 并且确保在分发使用过程中也不会变质。
Remember,before use it's virtually impossible to detect 请记住，在药品使用前几乎是不可能
whether the medicine has been made correctly. 检查其是否按照正确地方法生产
So we must be confident,absolutely assured that 因此，我们必须有确信能绝对保证
the product which has been made as specified. 产品是按规定的方法生产出来的。
Part 4 Validation 第4部分验证
“Validation” is the word that's abundant about a lot “验证”这个词被我们提及很多
often not a very fondly. 但往往没有一个明确的内容，
But it's a fundamental aspect to regulatory compliance. 但它是法规要求的一个重要内容。
And to understand GMP,you must know 要了解GMP，你必须知道
what it is and its implications. 它是什么和它的意义。
And to validate something,ask simply 要确定什么程序是否有效，只要简单问一句
“Do we prove and document that it works consistently as specified?” “我们证明并记录了该工艺持续有效吗？”
Validation is another of those simple ideas that 验证是另一个典型的例子
can become horribly complicated when actually put into practice. 一个简单的想法付诸实践的时候变得非常复杂的例子。
It's a natural extension of the principles of quality assurance, 它是质量保证原则的自然延伸，
but validations are set in addition to pre-planning. 但验证被设置在了前期规划中。
We actually prove and document that it will work 事实上我们要证明并记录某件事物
as nearly as humanly possible 100% effectively,100% of the time. 尽可能在任何时候100%有效。
Validated project makes good sense 经过验证的项目是有说服力的，
because reliable and repeatable production. 因为它的（结果是）可靠的，在生产中是可以重现的。
The outcome of good validation is cost-effective 开展良好的验证有利于节约成本，
through the reduction of equipment design failures, 通过减少设备设计失误、
production faults,rejects and reworking, 减少生产故障、废品和返工，
while achieving its goal,doing comes to quality standards. 而实现其目标，达到质量标准。
Part 5 Documentation & Change Control 第五部分文件和变更控制
Crucial principle of GMP that GMP的一个重要原则就是
nothing may be left to chance is covered by 不能留下覆盖（篡改）的机会
the fundamental rule that everything will be completely documented. 按基本规则，一切（过程）都将完全的记录下来。
When 100% accuracy and consistency of the only acceptable result, 当要求做到100%的准确和符合要求时，
it's just not realistic to rely on memorizing the word of instructions, 只依靠熟练的记忆是不可靠（不现实）的。
It's a fact of life, 这是生活中的一个事实
that regardless of our individual qualifications and good intentions, 无论我们个人的素质和意识有多好，
the only guarantee that we work to this level of consistency 能确保我们操作水平一致的唯一保证就是
is always to follow detailed,clear and written instructions. 始终按照细致、清晰、写下来的操作指南（文件）来操作。
Documentation plays a crucial role, 文件在至关重要的作用
with its twin functions to provide instructions 它主要由两方面功能
of what must happen and subsequently records， 一方面它对必须要发生的事情进行了规范，
of what did happen. 另一方面在事情发生后及时进行记录。
Instruction documents are subdivided into three categories. 指令文件会被分为3类。
Starting with specifications that specify the standards 第一类是各种质量标准，它们规定了
or measurable performance of materials to be used. 所用物料的标准或测量范围。
For example,per specification for incoming raw or primary materials 例如每一种原辅料的质量标准、
and for packaging materials 以及针对包装材料的质量标准
such as containers,labels,and product information leaflets. 例如（容器）、标签及产品说明书的标准。
Second group of instruction documents is manufacturing and packaging instructions. 第二类指令文件是生产和包装指令
And here the documents are specific to the particular product to be made, 这里的文件是针对特定的产品的。
and more detail which materials are to be used, 以及更多的细节，例如要使用什么材料
the quantities of materials needed, 所需的材料的数量，
which items of machine wheel equipment would be required, 其中的机器车轮，需要什么设备。
Only procedures and quality checks to be followed 只有规程和质量检查要遵循
are either to manufacture or to package of the product. 其制造或包装的产品（的要求）。
In batch manufacturing and batch packaging instructions, 在批生产和批包装指令中
this is used for every batch being made. 此要求适用于每批生产或包装的产品
No matter how many times this has been done before, 无论以前做过多少次，
it's essential that the new documents be referred to each time. 每一次都要用新的文件这点很重要
In fact,to ensure that this is done, 事实上，如果要确保做到这点，
each document has to be signed 那么每一个文件都要求
in the appropriate place by each person involved. 每个参与生产的人必须在适当的地方签名。
Documents in the third group are often to describe 第三类文件我们通常称为
the standard operating procedures,usually shorten to SOPs. “标准操作程序”，缩写是SOP
The detailed activities that are not specific to any one product. 这不是针对那一个特定产品的详细活动描述
They range from the methods used in warehouse operations 它们的范围包括仓库对物料操作的方法
from where the receipt and handling of raw materials,packaging items and products, 从原材料、包材、成品的接收和处理
to procedures to be followed when dispensing materials: 到物料的分发程序。
How to clean manufacturing or packaging areas,equipment 如何清洁生产或包装区，设备
What sort of clothing and other items such as eye protection 需要什么样的衣服和其他物品，如眼睛保护和手套，
and gloves are needed and how to use them 以及如何使用它们
How to operate with water system 如何操作水系统
How to clean,setup and operate each machine 如何清洁、安装和操作每台机器
Even how move materials from one place to another 甚至规定了如何将物料从一个地方移动到另一个地方
And the environmental testing. 还有环境检测
Again,note that laboratories are included 还要注意，实验室也包括在内，
so that all procedures are undertaken consistently. 要确保所有的程序（要求）都是一致的。
As are how to handle a problem arising from a state 如果发生需要立即处理的问题，
which should be made either immediately 我们应该如何处理
or in complaints being received. 或者收到投诉的时候我们应该怎么做呢？
There should be a standard operating procedure for every eventuality. 每一种可能的情况都应该有一个对应的标准操作程序。
Final group of documents is records. 最后一组文件是记录
These obviously record what's been done. 这些记录要清楚的记录下我们做了什么。
The important thing about these documents is that 关于这些文件重要的事情是，
they must record clearly and precisely, 记录必须清楚，准确，完整，
complete with the time and date when it was done, 要有完整的完成时间和日期，
at the time when it's done,not later than a day or tomorrow. 记录要即时完成不能提前或延后。
That every instruction was carried out, 每一个指令都被执行
incorrect entries must be shown as such. 错误的条目要按照以上方法标识出来。
We all make mistakes, 我们都会犯错误，
but there should be no attempt to obliterate it. 但不应该尝试删除它
Wrong entries must be corrected dated and signed 错误的条目必须修正，注明日期并签名。
Entries should be countersigned 所有记录应该由
by the supervisor or an appropriate colleague 主管或同事会签
to verify that the action has effectively been done. 以证明修改行为是有效的。。
It's not a lack of trust in you as an individual, 这样做不是说我们对你缺乏信任，而是遵循GMP原则，
but follows GMP principle that nothing can be left to chance. 不能留下任何篡改的机会。
Records are kept for very good reasons,not the least being, 我们有很好的理由要求保存记录但不是最重要的理由，
but for any problem about particular matter or batch should arise in future, 当将来某个时候某些特殊的批次或产品出现问题的时候
The records can be referred to,and corrective action taken 记录可以用来参考并采取正确的措施，
so that the mistake doesn't happen again. 避免这样的错误再次发生
No prizes for guessing that change control 毫无疑问，变更控制的作用就是
is all about controlling the inevitable changes that take place. 控制所有不可避免的变更。
GMP requires that every action is controlled by documented instructions. GMP要求每一个行为都要受到指令的控制。
So,to comply,changes to those instructions 所以，要遵守程序，涉及文件（指令）的变更必须要有记录
must be documented,issued,only obsolete documents replaced. 按规定分发，旧版的（文件或指令）要替换。
And of course,the physical aspect to the change 当然，对变化的物理方面
must also be implemented and documented. 也必须实施和记录。
And remember,only the current document is valid. 请记住，只有当前版本的文件是有效的。
So must always replace any previous version. 所以必须替换任何以前的版本。
GMP-compliant change control has a significant impact on many people. GMP变更控制对很多人都有重大影响。
Part 6 The Environment,Equipment& Maintenance 第6部分环境、设备及维修
Whether the manufacturing center is called a factory,plant or facility, 无论制造业中心是被称为制造厂、工厂还是设施，
good manufacturing practice is about making things GMP中规定良好的生产操作
using only the appropriate equipment. 必须使用合适的设备。
To be GMP-compliant,the product must be that phrase again 要符合GMP，我们就要再次强调
“fit for the intended purpose”. 产品必须“符合预期用途”
The important point is the production environment 重要的一点是生产环境
must do nothing to impair the product. 必须不会危害产品
The nature of healthcare product means that 医疗产品的特性决定了符合其用途
buildings are often designed for the purpose 用于生产该产品的建筑设计应符合其用途
or require extensive reworking to install appropriate surface finishes. 或者经过大量改造以安装适宜的表面材料。
Air handling,conditioning and filtration must permit 空调过滤系统必须能够
control of temperatures and humidity appropriate for the product, 调节温湿度以满足产品要求
while allowing people do work in comfort. 同时工作中人要感到舒适。
In order to reduce the chance of contamination, 为了减少被污染的几率，
sterile products are produced under clean condition, 无菌产品必须在清洁条件下生产
the name given to special usually called 我们给这个区域一个特别的名字
"clean room" environments “洁净区”环境
fed by high efficiency air filters, 通过高效空气过滤器进行过滤，
and built using special non-shedding surface finishes. 并使用非脱落表面涂料。
People wear all-enveloping clean room clothing and 进入洁净区的人员应穿戴能包裹全身的洁净区衣服
and must follow specific behavior characteristics 必须遵循规定的行为要求
or to limit particle sizes 或者限制直径尺寸
to below 100-200 of diameter of human hair. 小于头发直径100-200分之一的颗粒。
Normally apply to the entire clean room production suite, 通常适用于整个洁净室生产要求，
clean conditions are also used in all leakalized formats 清洁条件也通过各种形式而被使用
including open-fronted clean benches and cabinets,and isolate switch. 包括敞开的超净工作台、柜、隔离开关等部件。
As their name suggests,create clean working conditions 顾名思义，创造一个完全
completely isolated from the ambient environment. 一般环境隔离的清洁工作环境。
The crucial responsibility of quality control staff 质量控制部门人员的
is environmental monitoring, 关键责任是环境监测，
to ensure that specified criteria are maintained, 以确保指定的标准能得到保证，
and must not itself contribute to contamination 并且其自身不能产生污染
Precision and accuracy are the key words best describe GMP manufacturing. “精密”、“准确”两个词能最好地描述GMP
But these lines imply "everything is measured to find tolerances" 但这些都意味着“一切都要被测量，才能找到偏差”。
And to ensure that all gauges,dosing heads,weighing machines 确保所有压力表、定量头、称量工具
and the dozens of other similar instruments are accurate 和其他多种类似的仪器的准确性，
they must be calibrated and documented, 这些仪器必须进行校准，并记录
that regular indelible to make specific standards. 定期做出具体标准。
There's a dastardly rumor, 有一种荒唐的言论
the good manufacturing practice doesn't apply to 认为GMP不适用于
maintenance engineers and technicians because they are different. 维修工程师和技术人员，因为它们是不同的。
Obviously a myth,because it does apply to them. 很显然这是一个谬论，因为GMP同样适用于他们
Remember the phrase we use right the beginning? 还记得我们一开始说的那句话吗？
“Everyone and everything that may have a slightest influence on the product” 每个人和一切可能对产品有丝毫影响的东西，
Just reflect on the word “influence”. 只要仔细想想“影响”这个词
Perhaps starting with opportunities to cause contamination 也许从污染源开始
or very existing settings, 或者现有设置设备
both of which can happen with,well, 无论发生哪种情况
everything from water systems to raw material handling, 从水系统开始，到原辅料处理
finished goods storage,pipelines,surface finishes,soil tools, 成品的储存、管道、表面涂料、维修工具
incorrect dress for the environment, 不符合环境要求的衣服
and perhaps perish to thought non-compliance with SOPs 都会被认为不符合SOP
and we won't go on because it's far more important to address that 如果是这样那我们不会继续下去
everyone who works in a GMP-compliant plant is part of the team, 因为必须调调每个在GMP合规工厂的员工都是团队的一部分
that team can only be as good as the contribution of the weakest member. 这个团队中最薄弱的环节决定了团队工作质量的好坏。
Plant engineers are only too aware that 工厂的工程师们要意识到，
they have families,have car accidents 他们也有家庭，也可能遭遇车祸，
and surfer from conditions that need medications and surgery, 也肯能遭受疾病并需要药物和手术，
the opening headlines said it all. 开篇的标题已经说的很明白了。
Part 7 Contamination & Cleaning 第7部分污染与清洁
Right now you will appreciate that 现在你会感激
GMP-compliant product must contain only 符合GMP的产品只能含有被按配方生产的、
the materials of which it was formulated,specified and licensed. 经过检验的、得到许可的物料。
Anything else in a pack,bottle, ampoule,vial,jar,syringe is contaminant. 其他任何东西出现在包装物，西林瓶，安瓿，小瓶，瓶和注射器就是污染。
There are three forms of contaminants: 有三种形式的污染物
inert solids,viable organisms and chemicals. 惰性固体，活的生物和化学物质。
The inert solids concerned as are very small dust particles 惰性固体是指非常小的灰尘颗粒
in flakes which we shed in vast quantities every day. 在例如我们人体每天大量脱落的薄片。
Fiber smart clothing,pink flakes,and other bits of building materials, 衣服纤维、粉红片，从建筑材料脱落的碎屑
metal filings from machines and combers,its rubbers from closures, 机械脱落的金属碎屑及密封件掉落的橡胶
glass and plastics from containers,and fibers from papers and cottons. 玻璃、塑料以及纸张和棉布上的纤维。
It's almost endless these little things that float in the atmosphere 这些微小的东西几乎（多得）不可计数的，它们漂浮在大气中
then set along on surfaces or suspended liquids. 降落在物体表面或者悬浮在液体中。
When we are healthy and our bodies are battle ground 当我们健康的时候我们的身体就是战场，
because in the hidden and damp parts of earth 在泥土上上潮湿和隐蔽的地方，
that we sit and don't think about,germ warfare is rambled. 我们甚至没有意识到，细菌战正在蔓延。
On our side,other good guys, 在我们身边（好的方面来说）
the organisms inners almost that keep our bodies fitting well. 另一些有益的生物在维持我们身体的健康。
against them,other bad guys who 其他试图入侵人体的有害物质试图
attempt to invade us beat the good guys and poison our bodies. 打败有益物质，并毒害我们的身体。
Reality is that our normal bodily functions depend on 实际上，我们身体的功能是否正常取决于
the actions of countless millions of benign bacteria and other microorganisms, 数以百万计的良性细菌和其他微生物
that can be overwhelmed by malicious group 而其他微生物的过量活动
that causes biopsy,stomach or urine infections. 则可能会引起肠胃失调或者尿路感染。
Open wounds from injury or surgery are at risk from infection 手术或意外造成的开放伤口
by the malevolent organisms or by pyrogens of which more shorten. 会带来恶性生物或热源感染的风险。
The fact is when we are ill,our natural resistance in the immunity 事实上当我们生病的时候，我们免疫系统中的自然抵抗力
is severely reduced compared to our tolerance when we're healthy. 比我们健康时要弱得多。
Designed and controlled contamination of any sort, 对于符合GMP要求的工厂，
GMP places particularly emphasis on viable organisms to find us 要设计和控制任何类型的污染特别关注有繁殖能力的微生物，
living things can reproduce such as bacteria,fungi and viruses 例如细菌、真菌和病毒等
that describes microorganisms, 需要用显微镜才能观察到的
which are extremely small,so small that a million will fit on a pin head. 它们个体很小，有的小到一个针头上就有百万个。
Single bacterium has only a single cell harbor in the right conditions 一个细菌个体在适宜的条件下，
that subdivides self roughly every 20 minutes 大约每20分钟就会分裂一次。
They also have the ability to multiply very rapidly indeed. 它们具有非常快速的繁殖能力
So,after very few hours,with each new cell subdividing itself 所以，几个小时后每个新细菌细胞本身
will elaborate literally millions about the bacteria. 会分裂成数以百万计的细菌。
Think how quickly your stomach responds to infected food, 想想你的胃是多么迅速地对受感染的食物作出反应，
And how quickly that tickly feeling in your throat 想想那种喉咙发痒的感觉，
develops into a fully-fledged cold or flu. 如何迅速地发展成了一个不折不扣的感冒或流感
Or the speed with which that cut accepted and 或者没有经过清洁和消毒的
not cleaned and disinfected or its food. 伤口的感染的速度
Now to pyrogens which are anything 热源指的是任何
causes a rise in temperature in a living body. 能使活体温度上升的物质
In healthcare terms that means fever inducing. 在医疗术语，意味着诱导发烧。
The outer layer of bacteria may contain highly dangerous toxic substances 细菌的外壁含有高度危险的有毒物质
including molecules called "Endotoxins" that are in fact pyrogens. 称为“内毒素”实际上就是热原分子
So all the pyrogens are not themselves viable organisms, 所有的热原本身不是活性的生物体，
they tend to be present in those 它往往是存在于那些
And unfortunately,they remain as high risk particles 不幸的是，它们仍然是高风险的颗粒
even though the living cells may have been killed, 即使活细胞可能已经被杀死
Any chemical that's not part of product specification 不属于产品质量标准的
is obviously a contaminant. 任何一种化学物质就是污染物
But how they get into the product in the first place 但它们一开始如何进入到产品中的方式
isn't always so obvious. 去总是不明显
Generally it's through cross-contamination, 一般是通过交叉污染，
in which substances carry from one to process to another. 物质从一种工艺转移到另一种工艺。
It happens when the equipment isn't properly cleaned, 当设备没经过有适当的清洁
and materials through process A are carried through to contaminate process B. 物质通过工艺A转移到工艺B，从而造成污染。
Cross-contamination also occurs when the 交叉污染总是发生在
chemicals used in cleaning process are thoroughly in staff, 在清洁过程中使用的化学物质没有彻底清楚干净，
and contaminate the next product. 并污染下一个产品
Because when you touch one surface, 因为当你接触一个东西表面，
then another you transfer the contaminants, 接着再接触另一个东西的表面，你就转移了污染物，
and our guilty of cross-contamination. 人为造成了交叉污染。
The chemical detergents also disinfectant 我们在清洁过程中使用的化学清洁剂和消毒剂
we use when cleaning are effective 对于去除污迹是很有效的
because they flap the dirty areas and 因为它们能擦除污渍
counteractively surface tension and static charges, 并改变污迹的表面张力和静电荷，
and hold them and release the particles, 能与污迹结合释放出颗粒
send them to suspended solution, 将它们送到悬浮液体中
certainly mop or wipe and remove them bodily. 再拖布或抹布将其擦去
And the chemicals and disinfectants,for example,kill microorganisms. 对于化学品和消毒剂，它们能杀死微生物。
We have to take active steps to reduce their number 我们必须采取积极的措施，以减少它们数量，
to minimize the risks that will end up in the product. 尽量减少最终产品中的风险。
When this is done, 什时候这样做，
depends on the nature of product and stage of production. 取决于产品的性质和生产阶段
And many different types of disinfectants, 许多不同类型的消毒剂
each of which act in different ways and 每一个都有不同的作用方式，
more or less effective against different types of microorganisms. 对抗生物的作用影响也有大有小
Some are relatively gentle in the action, 有些消毒剂的效果较为柔和
for example,the 70% alcohol often uses and handles 例如，70%酒精经常使用，
but it won't kill spores, 但它不会杀死孢子，
of which much more aggressive disinfectants are needed. 我们还需要更强效的消毒剂。
Before using the disinfectants,it's important to check that 在使用消毒剂之前，有一点非常重要，
you are using the right one at right time 确认你在正确时间使用正确的消毒剂
and very important to follow the instructions precisely. 还有很重要的一点是严格遵守使用规程
Of course SOPs specify what,when and how everything 当然，SOP已经明确说明了在工厂里哪些东西，
in the plant must be cleaned and disinfected. 应该在什么时候，用什么方法进行清洗和消毒。
Part 8 Storage and Distribution 第8部分储运
The efforts of even a best run GMP production would be 即使GMP生产做的再好
pointless if incoming materials and supplies 发生以下情况也是毫无意义的
or either not specification will become contaminated 如果原材料的储藏和转运过程不规范，
while stored and moved internally. 就会成被污染。
So GMP also applies to logistics, 所以GMP也适用于物流，
see inclusive name for warehousing,materials handling and distribution. 包括“仓储”、“物料搬运”和“配送”
In fact that vendors who deliver correctly 实际上我们并不能保证供应商
in the past is no guarantee that they will do so in the future. 会一如既往地按正确方式返货
Raw materials and packaging delivered from the supplier 供应商交付的原材料和包装材料
cannot be assumed to be satisfactory 不可默认为符合要求的，
and they must always be placed in quarantine 物料必须始终放入待检区
to await quality control sampling. 等待QC部分进行抽样检验。
For labeling procedures in stores are crucial, 对存放的物料进行标识是至关重要的
as materials that pass their shelf life or wrongly identified 特别是对于超过有效期的、错误标识的、
or are contaminated and haven't been in quarantine for inspection 被污染的、未放入待检区的
or almost certainly be materials 已放入待检区还未检验的物料
must be stored in a completely secure and non-damaging way. 必须采用保证不会被破坏的、安全的方法存放。
And it's essential that items being moved are not only the right ones 重要的是，不仅要保证搬运的是正确的货物
but that carriage taken with their physical movement 还要以正确的方式进行搬运。
The care of bulk containers,their condition 要关注他们的容器包装方式和状态
cleaning and sanitization are clearly essential facts in material handling. 物料处理过程中应特别注意散装容器及其状态、清洁和消毒。
As it's the general standard of the house-keeping, 因为这是房间保持清洁的通用标准，
in areas which are often more difficult to maintain another' s. 特别对于更难以维护清洁的区域来说。
The handling and storage of finished products 成品的搬运和储存在仓库运作
is an equally important aspect to warehouse operations 也同样重要。
Each product leaving the plant will be influent 对每个出厂产品的关注必须
throughout its manufacture by the care and attention, 贯穿整个生产周期，
given when it began processing and storage, 从加工到贮存
how it would be treated during its final journey to the patient 以及如何运输到达最终患者手中的过程。
Part 9 Packaging & Labeling 第9部分包装和标签
It's so important we will repeat it, 这一点很重要，我们要再次强调：
the correct label must always be on every container. 每一个药品包装都必须有正确的标识。
GMP requires that a patient would be prescribed with the exactly the prescribed medicine. GMP要求：开给患者的药必须是符合其病症的药物
And to do this, 要做到这一点，
each product must be clearly labeled 每一件产品都必须明确标识，
so that its content can be easily read with information on 以便它可以很容易地读取有关信息
strength,quantity,batch number,method of use,and expiration date. 包括规格，数量，批号，使用方法，以及有效期等
These are called product labels. 这些被称为产品标签
Labels are also used throughout manufacture, 标签也被用于整个制造过程中，
as a formal progress in status documentation. 作为一个过程的正式文件
They are divided into two categories, 它们分为两类，
the first called "Identity Labels" 第一类称为“识别标签”
show what things are,for example, 此类标签显示的是什么东西
the content of containers and equipment 例如，具体指什么容器和设备
And supplies must be identically labeled at every stage of activity 在每一个阶段的活动中，物料必须进行标记
to indicate the material or product they contain. 以说明他们是什么物料或产品。
These must show the batch number,the material code number,and the date. 这些标签必须显示批号、物料代码和日期
The second category called "Status Labels" 第二类被称为“状态标签”
show exactly what is happening 它们显示的是任何时候
to every container or a piece of equipment at all times. 每一个容器或设备正所处的状态
Where appropriate,it must also show 在某些情况下，它还必须显示
the batch number,the material code number and the date. 批号、物料代码和日期。
As both status and identity labels must be placed on every item, 鉴于每个物品必须同时贴有识别标签和状态标签
they can often form clear mark sections of the same label. 所以它们通常可以合并为一个标签，只要有清晰的标记区分就可以
Labels are so important that there are rules for their use. 标签很重要，有它们的使用规则
For example,the control of their storage,handling. 例如，对它们的储存，使用的管控。
Writing on the labels must be clear and legible 写在标签上的内容必须清楚和清晰，
so they can be read easily. 方便阅读。
Old labels must always be removed 旧标签必须被去除
so there can be no confusion on which one is valid. 避免造成哪个标签才有效的困惑。
Any label that doesn't adhere properly 任何更换粘贴不牢固的
and may come off by accident must be replaced. 或着可能意外脱落的标签必须更换
Label must always be positioned on the body of a container 标签必须贴在容器
or a piece of equipment, 或设备的主体上
never on a lid,as this could be removed or put on something else 不能贴在盖子上因为这样可能会别移除或放到其他地方
where the contents or the status may be taken indifferently. 导致被防止的物品被错误使用。
Part 10 GMP,People& Training 第10部分人员与培训
People on training is the last section of this program, 人员培训是这个课程的最后一部分
not because the last thing matter,but the most important. 不是因为培训是最后要做的一件事，而是因为培训是最重要的事
It is said so that 有句话是这么说的：
good manufacturing practice depends totally 是否有良好的GMP完全取决于
on peopledoing the right thing in the right way 人们从是否一开始就总是在正确的时间用
at the right time,first time,every time. 正确的方法做正确的事。
That applies to every person from top management 它适用于每个高层管理人员
all the way up to those doing their work. 贯穿到具体操作的人员。
The purpose of training is to ensure that 培训的目的就是确保
each person knows and understands their part in the process, 每个人都知道并理解他们处于整个流程中的位置
and the part undertaken each and specific task. 以及他们所承担的任务。
It's worth repeating that 需要再次强调的是，
healthcare products must be made with complete adherent to specifications 医疗保健产品的生产制造必须符合质量标准、
to manufacturing,packaging instructions 生产和包装指令
and standard operating procedures. 以及标准操作规程的要求。
Mistakes occur as a result in inadequate training 差错是由于培训不到位
and not following instructions. 以及不遵循指令而导致的
Anything else is carelessness. 其他错误是粗心。
By their nature, 由于产品的特性
our products require that special attention must be paid 我们必须特别注意
to what people wear both to protect themselves and the product. 生产时要同时保护自己和产品。
Remember our first priority for controlling contamination 记住我们控制污染的首要任务
is to prevent it getting in. 是防止污染进入
Critical to this,is the way we must 这一点的关键，就是我们必须
wear the right apparel properly at all times and behave sensibly. 始终以正确的方式穿着合适的服装并且有良好操作行为。
Even the way we move when working in special environment, 甚至包括我们在特殊环境下工作时移动的方式，
for example clean rooms can be critical. 例如，洁净房间是关键。
High standards of personal hygiene must be maintained at all times, 在任何时间都要保持高标准的个人卫生
of hair,body and personal clothing. 包括头发、身体和个人服装。
It's in the nature of things 很自然地，
that microorganisms have wonderful time in restrooms, 微生物大都喜欢洗手间的环境，
which is why hands must always be washed properly 这就是为什么我们每次去过洗手间后
after visiting the toilet. 都要正确的洗手。
Protective gloves must always be worn when specified; 有规定时，必须始终戴上防护手套，
certainly no product or chemical 在整个过程中任何产品或化学产品
should be touched or handled throughout them. 都不应该穿过手套被触摸。
Anyone who has a cold or a flu or other infection 任何人患有感冒、流感或其他感染、
or has a cut or grease must report this to the supervisor, 有伤口或油脂的情况必须向主管报告，
and maybe given work areas less sensitive to such illness. 尽可能安排一些其他对疾病或伤口不太敏感的区域的工作。
There are also strict rules in warehouse,production areas and laboratories 仓库、生产区和实验室也有严格的规定
prohibiting eating,drinking,chewing and smoking. 禁止饮食、咀嚼（口香糖）和吸烟
If you are on any medication, 如果你正在服用药物
they must never be taken to the plant, 它们决不能被带进厂区
and it applies particularly to antibiotics 特别是是抗生素
in case of accidental cross-contamination of products in manufacture. 这可能在产品生产过程中造成意外的交叉污染。
Which rarely brings back where we started 这就让我们又从零开始
except that you now know 除了你已经了解到
GMP works to prevent all those unpleasing incidents from happening. GMP是如何防止那些不愉快的事件发生的。
Review #1 回顾点1
Today healthcare products have found 当今的医疗产品已经具备了
fantastic records for product quality or testimony 保证产品质量的
to good manufacturing practice GMP优秀记录和证据
Few jobs have greater personal responsibilities than yours 对于从事制造药品和医疗器械生产的人来说
making medicines and medical devices. 很少有工作需要承担比这更大的责任。
Let’s review the “Why” “What” “How” “GMP” 让我们回顾一下“为什么”、“是什么”、“怎么做”“GMP”。
Review #2 回顾点2
Regulatory agencies license and control the manufacturing,sale of 监管机构通过GMP许可和监管
healthcare products ensuring systematic formality through GMP. 医疗保健产品的制造和销售过程
The global GMP definition of product quality is that 全球GMP对产品质量的定义是
it must reach the customer,fit for its intended purpose. 用于患者的产品必须符合其预定用途。
This is not a target. It's a minimum acceptable standard. 这不是一个目标。这是一个最低限度的可接受的标准。
The core principles of GMP are based on the rule that GMP的核心原则的依据是
every action will be undertaken only by following written instructions. 每个操作只按照书面规程来进行
The raw materials and components must be stored and handled correctly. 原辅料必须正确存储和处理
The equipment and a certain environment are appropriate, 生产设备和生产环境要适宜，
properly cleaned and treated. 要有适当的清洁和处理。
The products will contain only the specified ingredients. 产品里只能含有规定的成分。
Everything must be identified and labeled 在生产和销售的每一个阶段
at each stage of production and distribution. 都必须有标识和标记。
Review #3 回顾点3
The most effective way of ensuring the quality of product 保证产品质量最有效的方法
is to make certain that mistakes don't happen. 是确保不会发生错误
This is achieved by having two separate but inter-related functions: 通过两个独立但相互关联的功能保证产品合格
Quality Assurance and Quality Control. 质量保证和质量控制。
Quality Assurance entails that systematic analysis of each process 质量保证设涉及到对每一个过程进行系统分析，
in order to pre-plan and document how every activity will be undertaken. 以便预先计划和用文件规定如何进行每一项活动。
This ensures the outcome will be as expected. 这样才能保证结果与预期的一致。
Quality Control provides the physical verifications 质量控制要求进行物理验证，
that it has been or is being done. 包括已经完成或正在进行的。
Quality Control samples raw materials,products in manufacture, 质量控制对原辅料，生产中的产品，
the utility service such as water supplies,the environment, 公用系统例如水系统和环境进行取样，
and that cleaning has been done correctly. 以及确保执行了正确的清洁工作。
The quality department,Quality Assurance and Quality Control, 质量部门，质量保证部门和质量控制部门，
must ensure that the product must fit for its intended purpose. 必须确保产品必须符合其预期的目的。
Review #4 回顾点4
To validate something means to prove and document that 验证某事意味着证明和（记录）文件，
it works consistently as specified. 能够证实它的实际状况与设计是一致的。
Each product is subject to the validation master plan and 每一个产品都要包括在验证主计划中
must remain validated for its complete life cycle. 且计划要必须包括其全部的生命周期。
A properly validated project is cost-effective 一个正确的验证项目是能产生效益的，
because it promotes reliable and repeatable production. 因为它保证了生产的可靠性和可重复性。
Review Part 5 Documentation & Change Control 回顾点5 文件和变更控制
Documentation provides instructions of what must happen 文件写明了必须要做的事情
and records of what did happen. 以及做过的事的记录。
Instruction documents include specifications, 指令文件包括质量标准
manufacturing,packaging and other instructions, 生产和包装等指令
and SOP for activities that are not product-specific. 以及一些非特定产品的标准操作程序（SOP）
Records log what has been done clearly and precisely 写记录要做到了清楚，准确
and complete with time and date 并记录完整的时间和日期
when it was done,at the time it was done. 当工作完成的时候，记录也要同步完成。
Incorrect entries must be corrected,dated,and signed, 记录中不正确的内容必须纠正，注明日期，并签名
not obliterated. 但不得删除
And it should be countersigned by the supervisor 修改的记录应该由主管
or an appropriate colleague. 或相应的同事会签
Records are kept so that if 记录应当被保存
there is a problem with a particular batch arises in the future, 以便在将来有个别批次出现的问题时，
corrective action can be taken. 可以追溯采取纠正措施
All changes must be documented,re-issued, 所有变更必须记录在案，文件需要重新分发，
and the obsolete documents replaced. 并撤销被替换文件。
And the physical aspects to the change 变更的所有物理方面内容
must also be implemented and documented. 必须实施和记录。
Review Part 6 The Environment,Equipment& Maintenance 回顾点6环境、设备及维修
Sterile products are produced under clean conditions through 无菌产品是在清洁的条件下生产的
requirement for that all of the products is the facility 要求所有产品的生产设施
must do nothing to impair product quality. 必须不损害产品质量
GMP-compliant equipment should be stored with good access, GMP标准的设备应方便存放，
be easy to clean,to set up and to maintain. 易于安装、维护和清洗。
Maintenance and engineering is as a subject to GMP as to production. 维修工作也是GMP生产操作的一部分。
The opportunity to cause the contamination 维修各方面都会
arises during every aspect to maintenance 有造成污染的风险
which is often un-supervised during shutdown periods. 特备是在停工期间不是监控的情况下。
Review #7 回顾点7
Anything other than these specified ingredients is a contaminant. 除了规定应该含有的成分以外的任何东西都是一种污染物
There are three forms of contaminant starting with inert solids, 有三种形式的污染物，先说惰性固体
such as dust particles. 如灰尘颗粒
And viable organisms including bacteria,fungi and viruses. 和有活性的有机体，包括细菌，真菌和病毒。
Pyrogens are not living organisms, 热原不是活的有机体
but anything that causes arise in temperature and fever in a living body. 但是热原可以造成活体（人体）体温的升高。
Chemicals that are not a part of product specification are contaminants. 不在产品规定内的化学物质就是污染物。
Either by cross-contamination that through inadequate cleaning 交叉污染是由于清洗不干净
carries the substances from one process to another 将物质从一个工序带到另一个工序
or the cleaning chemicals themselves cause contamination. 或者因为清洁化学品本身造成污染
People who touch one surface and transfer cross-contaminant to another. 通过接触一个表面后再接触另一个表面，人也会引起交叉污染。
The most effective defense against contamination is prevention. 防止污染最有效的防御措施是预防
The second is to remove it. 第二才是清除
If it can't be removed,neutralize it. 如果污染不能被清除，那就尽量降低（污染的影响）。
Review #8 回顾点8
GMP applies equally to logistics. GMP的规定同样适用于物流。
The name from materials handling and distribution. 物流是指材料处理和分配的过程。
Raw materials can’t be assumed to be satisfactory. 原材料不可能永远都是是令人满意的（合格的）。
They must always be placed in quarantine for quality control sampling. 他们必须被在取样室进行抽样，进行质量检验。
Materials must be stored in a completely secure and non-damaging way. 物料必须用安全的、不会被破坏的方法进行存储。
Review #9 回顾点9
The correct label must always be on every container. 在每一个容器上必须始终有正确的标签
Identity labels show what things are, 识别标签显示的是什么东西
and status labels show exactly what is happening at all times. 状态标签显示每一时刻正在发生什么。
Old labels must always be removed. 旧的标签要去除
Labels that don't adhere completely must be replaced. 没有贴牢的标签必须要更换。
Labels must be positioned on the body of a container or equipment, 标签必须安置在容器或设备的主体上，
never on the lid as this could be removed. 不能安置在盖子上，因为这样有可能被移除
Review #10 回顾点10
The success of GMP depends totally on people GMP的成功完全取决于人们始终
doing the right thing,in the right way,at right time,all the time. 在正确的时间，以正确的方式，做正确的事。
Training ensures that each person knows and understands their part in the process, 培训确保每个人都知道并理解他们在这个过程中的作用，
and how to undertake each specific task. 以及如何承担每一项具体的任务。
High standards of personal hygiene must be maintained 在任何时间都要保持高标准的
at all times of hair,body and personal clothing. 个人卫生，包括头发、身体和个人服装。
Protective gloves must be always worn when specified. 必须始终佩戴指定的防护手套。
Anyone who's ill or wounded must report the fact to the supervisor. 任何生病或受伤的人都必须向主管报告实情。
Eating in warehouse and production areas is prohibited, 在仓库和生产区域的禁止饮食、饮酒，
so is drinking,chewing and smoking. 咀嚼（口香糖）和吸烟。
For medication, 对于个人使用药物
it must be left securely outside the warehouse or production areas. 不得带进仓库或生产区域
One final point,the benefits of GMP work only if everyone, 最后一点，GMP能带来的好的效果只有在每一个人
and that means you,understand it,respect it 也就是你们理解了它，尊重它
and apply the principles for 并且运用它
every minute,of every hour,of every day,of every week,of every month, 每分每时每天每周每月
in fact,all the time. 事实上，所有时候