翻译完稿 GUIDE TO INSPECTIONS OF PHARMACEUTICAL QUALITY CONTROL LAB

Pharmaceutical Quality Control Labs (7/93)

药品质量控制实验室（7/93）

GUIDE TO INSPECTIONS OF PHARMACEUTICAL QUALITY

CONTROL LABORATORIES

药品质量控制实验室检查指南

Note: This document is reference material for investigators and other

FDA personnel. The document does not bind FDA, and does no confer

any rights, privileges, benefits, or immunities for or on any person(s).

注：本文件是FDA调查员和其他人员的参考材料。该文件并没绑定FDA，也没授予任何人任何权利、特权或豁免权。

1. INTRODUCTION

1、简介

The pharmaceutical quality control laboratory serves one of the most

important functions in pharmaceutical production and control.

药品质量控制实验室在药品生产与控制的过程当中，扮演着极其重要的角。

A significant portion of the CGMP regulations (21 CFR 211) pertain to the

quality control laboratory and product testing.

CGMP当中，有相当一部分规则是关于质量控制实验室及产品检测的。

Similar concepts apply to bulk drugs.

同样的概念也适用于原辅料。

This inspection guide supplements other inspectional information contained

in other agency inspectional guidance documents.

该检查指南补充其他机构信息库中的指导文件。

For example, Compliance Program 7346.832 requiring pre-approval

NDA/ANDA inspections contains general instructions to conduct product

specific NDA/ANDA inspection audits to measure compliance with the

applications and CGMP requirements.

例如，合则计划7346.832需要预先核准NDA/ANDA检查所包含的一般性指令，并以此来指导、衡量产品的具体NDA/ANDA检查程序是否符合CGMP的要求。

This includes pharmaceutical laboratories used for in-process and finished

product testing.

这包括用于生产的制药实验室与终产品的测试。

2. OBJECTIVE

2、目的

The specific objective will be spelled out prior to the inspection.

在检查之前，具体的目标就应该阐述清楚。

The laboratory inspection may be limited to specific issues, or the

inspection may encompass a comprehensive evaluation of the laboratory's

compliance with CGMP's.

实验室检查可以仅限于具体问题或者围绕CGMP中实验室应符合的综合评价展开。

As a minimum, each pharmaceutical quality control laboratory should

receive a comprehensive GMP evaluation each two years as part of the

statutory inspection obligation.

作为最低要求，每个药品质量控制实验室都应执行自己的法定检验义务，即每两年都应该接受一次全面的GMP评估。

In general these inspections may include

-- the specific methodology which will be used to test a new product

-- a complete assessment of laboratory's conformance with GMP's

-- a specific aspect of laboratory operations

通常这个检查应该包括以下几点：

--用于测试一个新产品的特定方法

--实验室是否符合GMP的全面评估

--一种特定的实验室操作

--------------------------------------------------------陈淑贤

3. INSPECTION PREPARATION

FDA Inspection Guides are based on the team inspection approach and our

inspection of a laboratory is consistent with this concept. As part of our

effort to achieve uniformity and consistency in laboratory inspections, we

expect that complex, highly technical and specialized testing equipment,

procedures and data manipulations, as well as scientific laboratory

operations will be evaluated by an experienced laboratory analyst with

specialized knowledge in such matters.

District management makes the final decision regarding the assignment of

personnel to inspections. Nevertheless, we expect investigators, analysts

and others to work as teams and to advise management when additional

expertise is required to complete a meaningful inspection.

检查人员的委派由地区主管部门确定，然而我们希望，调查人员、分析人员和其他人员能组成—个检查组，并在需要时为了完成—项有意义的检查，可建议主管部门增加有关方面的专家。

Team members participating in a pre-approval inspection must read and be

familiar with Compliance Program 7346.832, Pre-Approval

Inspections/Investigations. Relevant sections of the NDA or ANDA should

be reviewed prior to the inspection; but if the application is not available

from any other source, this review will have to be conducted using the

company's copy of the application.

参加新药审批前检查的小组成员必须阅读并熟悉7346·832号文件即审批前检查或调查文件的内容。检查前应当审查新药申请或简略的新药申请的有关部分，如果该申请书不能从别的来源得到，可对由公司提供的副本进行审查。

Team members should meet, if possible, prior to the inspection to discuss

the approach to the inspection, to define the roles of the team members, and

to establish goals for completion of the assignment. Responsibilities for

development of all reports should also be established prior to the inspection.

This includes the preparation of the FDA 483.

如果可能的话，小组成员在检查之前就应当集中，以讨论检查方法，明确每位组员的角，并确定目标以完成委派的任务。检查前还要确定负责起草各报告，包括准备FDA483文件的责任。

The Center for Drug Evaluation and Research (CDER) may have issued

deficiency letters listing problems that the sponsor must correct prior to the

approval of NDA/ANDA's and supplements. The inspection team is

expected to review such letters on file at the district office, and they are

expected to ask the plant for access to such letters. The team should

evaluate the replies to these letters to assure that the data are accurate and

authentic. Complete the inspection even though there has been no response

to these letters or when the response is judged inadequate.

药品评价和研究中心(CDER)可能已经发出有关缺陷信件，列举出存在的各种问题。要求受检企业必须在新药申请或简略的新药申请和补充文件被批准前予以改正。希望检查组审查这些已经在FDA地区办公室归档的信件，并向药厂要求了解这些信件的内容。检查组还要评价药厂对这些信件的答复，以确保数据的准确和真实。即使药厂没有对这些信件作出答复，或者认为药厂的答复不充分，也应当完成这项检查工作。

4. INSPECTION APPROACH

检查方法

A. General

总则

In addition to the general approach utilized in a drug CGMP inspection, the

inspection of a laboratory requires the use of observations of the laboratory

in operation and of the raw laboratory data to evaluate compliance with

CGMP's and to specifically carry out the commitments in an application or

DMF. When conducting a comprehensive inspection of a laboratory, all

aspects of the laboratory operations will be evaluated.

除了采用对药品进行现行药品生产质量管理规范的—般检查方法之外，对实验室的检查还要采用察实验操作和检查原始数据的方法，以评价其符合现行药品生产质量管理规范的情况，以及实现申请书中或者药品工艺档案中约定的义务。对实验室进行综合检查时，应评价实验室操作的

各个方面。

Laboratory records and logs represent a vital source of information that

allows a complete overview of the technical ability of the staff and of

overall quality control procedures. SOPs should be complete and adequate

and the operations of the laboratories should conform to the written

procedures. Specifications and analytical procedures should be suitable and,

as applicable, in conformance with application commitments and

compendial requirements.

实验室记录和实验记录本是不可缺少的资料来源，从这些资料中可以全面了解从业人员的技术能力和全部质量控制程序。标准操作程序应当是全面而恰当的，实验室的操作应当与书面的规程相—致。规格标准和分析程序应当合适，而且也符合申请中记载的内容及法定方法的要求。

Evaluate raw laboratory data, laboratory procedures and methods,

laboratory equipment,including maintenance and calibration, and methods

validation data to determine the overall quality of the laboratory operation

and the ability to comply with CGMP regulations.

要评价原始实验数据、实验程序和方法、实验室设备，包括设备的维护和校正，以及实验方法的验证数据，以确定实验室操作的总体质量和符合现行药品生产质量管理规范的能力。

---------------------------------------------------------------------谢艳红

Evaluate raw laboratory data, laboratory procedures and methods,

laboratory equipment,including maintenance and calibration, and methods

validation data to determine the overall quality of the laboratory operation

and the ability to comply with CGMP regulations.

评估的原始实验室数据，实验程序和方法，实验室设备，包括维护和校准以及分析方法验证数据，来确定实验室操作的能力综合质量是否有能力适合CGMP法规。

Examine chromatograms and spectra for evidence of impurities, poor

technique, or lack of instrument calibration.

检查谱和光谱杂质的证据，技术差，或缺乏仪器的校准。

Most manufacturers use systems that provide for the investigation of

laboratory test failures. These are generally recorded in some type of log.

Ask to see results of analyses for lots of product that have failed to meet

specifications and review the analysis of lots that have been retested,

rejected, or reworked. Evaluate the decision to release lots of product when

the laboratory results indicate that the lot failed to meet specifications and

determine who released them.

大多数厂家使用系统为实验室测试失败调查提供调查。要求查看不符合规定批产品的已经复验的分析结果，审查分析已重新测试，拒绝，或返工。当实验室检查结果不符合规定时评价是否放行产品以及决定由谁放行。

B. Pre-Approval预审批

Documents relating to the formulation of the product, synthesis of the bulk

drug substance, product specifications, analysis of the product, and others

are examined during the review process in headquarters. However, these

reviews and evaluations depend on accurate and authentic data that truly

represents the product.

有关产品配方的文件，合成原料药，产品规格，产品分析，和其他人审查，以及其他的相关文件进行检查。然而，这些审查和评价取决于真正能代表产品准确和可靠数据。

Pre-approval inspections are designed to determine if the data submitted in

an application are authentic and accurate and if the procedures listed in the

application were actually used to produce the data contained in the

application. Additionally, they are designed to confirm that plants

(including the quality control laboratory) are in compliance with CGMP

regulations.

批准前检查的目的是确定提交申请的数据是否是真实、准确的，以及在申请中列出来的规程是否实际用于生产应用程序中包含的数据。此外，他们的目的是确认工厂（包括质量控制实验室）是在遵守CGMP要求。

The analytical sections of drug applications usually contain only test results

and the methods used to obtain them. Sponsors are not required to file all

the test data because such action would require voluminous submissions

and would often result in filing redundant information. Sponsors may

deliberately or unintentionally select and report data showing that a drug is

safe and effective and deserves to be approved. The inspection team must

decide if there is valid and scientific justification for the failure to report

data which demonstrates the product failed to meet its predetermined

specifications.

药物的应用分析部分通常只包含测试结果和获得他们所采用的方法。发起人不需要提交所有的测试数据，因为这些行动将需要提交大量文件，往往会导致提交冗余信息。发起人可以有意识的选择报告数据来证明药物是安全有效的，值得被批准。检查组必须决定如果有有效和科学的理由报告的数据表明了产品未能达到其预定的规格。

Coordination between headquarters and the field is essential for a complete

review of the application and the plant. Experienced investigators and

analysts may contact the review chemist (with appropriate supervisory

concurrence) when questions concerning specifications and standards arise.

总部和地区之间的协调是必不可少的一个完整的审查申请和工厂审查。当遇见规范和标准相关的问题时，经验丰富的调查员和分析员可联系的审查化学家适当的监管同意。

Inspections should compare the results of analyses submitted with results of

analysis of other batches that may have been produced. Evaluate the

methods and note any exceptions to the procedures or equipment actually

used from those listed in the application and confirm that it is the same

method listed in the application. The analyst is expected to evaluate raw

laboratory data for tests performed on the test batches (biobatches and

clinical batches) and to compare this raw data to the data filed in the

application.

检查应比较递交材料的结果和分析以及其他可能已经生产的批次的结果和分析。评估所有列在申请上的方法和注意的例外的程序和设备的实际使用，并确认在申请中列出的是同样的方法。分析员预计评价测试的测试批次（生化批次和临床批次）的实验室原始数据和比较原始数据和申请中的数据文件。

5. FAILURE (OUT-OF-SPECIFICATION) LABORATORY RESULTS

失败（超标）化验结果

Evaluate the company's system to investigate laboratory test failures. These

investigations represent a key issue in deciding whether a product may be

released or rejected and form the basis for retesting, and resampling.

评估该公司的OOS调查系统。这些调查代表一个关键在决定产品是否能被放行或拒绝以及作为重新检测，重新取样的基础。

In a recent court decision the judge used the term "out-of-specification"

(OOS) laboratory result rather than the term "product failure" which is more

common to FDA investigators and analysts. He ruled that an OOS result

identified as a laboratory error by a failure investigation or an outlier test.

The court provided explicit limitations on the use of outlier tests and these

are discussed in a later segment of this document., or overcome by retesting.

The court ruled on the use of retesting which is covered in a later segment

of this document. is not a product failure. OOS results fall into three

categories:

在最近的一个法院判决的法官使用术语实验室的结果“超标”（OOS）而不是“产品失败”，这是FDA调查员和分析员更为常用的。他裁定这是一个OOS结果认定为实验室误差通过一个失败的调查或异常值检验。法院提供明确的限制使用异常点检验，这些都是在后面的部分文件。讨论，或克服的复验。法院裁定这将在本文档后面的部分重新测试使用。

不是一个失败的产品。OOS结果分为三类：

-- laboratory error实验室错误

-- non-process related or operator error

非相关的过程或操作错误

-- process related or manufacturing process error

工艺或制造过程错误

------------------------------------------------------------------------------尤长友

A. LABORATORY ERRORS

实验室误差

Laboratory errors occur when analysts make mistakes in following the

method of analysis, use incorrect standards, and/or simply miscalculate the

data.

实验室误差产生于下列情况：化验员未能正确地按分析方法操作；使用不正确的标准和(或)简单地算错了数据。

Laboratory errors must be determined through a failure investigation to

identify the cause of the OOS.

实验室误差必须通过一项失败的调查来确定，以便鉴定出造成不符合规格标准的原因。

Once the nature of the OOS result has been identified it can be classified

into one of the three categories above.

—旦不符合规格标准结果的性质被确定了，就可以把它归入上述三类中的一类。

The inquiry may vary with the object under investigation.

查询可能会随着调查的目的的不同而变化。

B. LABORATORY INVESTIGATIONS

实验室调查

The exact cause of analyst error or mistake can be difficult to determine

specifically and it is unrealistic to expect that analyst error will always be

determined and documented.

要确定化验员误差或差错的确切原因是困难的，同时希望化验员误差总能确定和记录下来是不现实的。

Nevertheless, a laboratory investigation consists of more than a retest.

然而，一项实验室调查并不仅限于进行复试。

The inability to identify an error's cause with confidence affects retesting

procedures, not the investigation inquiry required for the initial OOS result.

无法有把握地鉴别误差原因会影响复检的程序，而不影响对最初的不符合规格标准结果所要求的调查询问。

The firm's analyst should follow a written procedure, checking off each step

as it is completed during the analytical procedure.

药厂化验员应当遵循书面的调查程序，如同完成分析过程—样，核对每一操作步骤。

We expect laboratory test data to be recorded directly in notebooks; use of

scrap paper and loose paper must be avoided. These common sense

measures enhance the accuracy and integrity of data.

我们希望实验室检验数据能直接记在记录本上，避免使用纸片或活页纸。这些常识性方法可以增强数据的准确性和完整性。

Review and evaluate the laboratory SOP for product failure investigations.

Specific procedures must be followed when single and multiple OOS

results are investigated.

审查和评价实验室用于进行产品不合格调查的标准操作程序，对单一和多个不符合规格标准结果的调查应遵循不同的程序。

For the single OOS result the investigation should include the following

steps and these inquiries must be conducted before there is a retest of the

sample:

对单一不符合规格标准结果，调查应包括下列步骤，并且这些调查应当在该样品被复检之前进行：

the analyst conducting the test should report the OOS result to the

supervisor.

进行检验的化验员应向主管人报告不符合规格标准结果；

the analyst and the supervisor should conduct an informal laboratory .

化验员和主管人应进行一次非正式的实验室调查。

investigation which addresses the following areas:

调查范围如下：

1. discuss the testing procedure

1.讨论检验程序；

2. discuss the calculation

2.讨论计算过程；

3. examine the instruments

3.检查仪器；

4. review the notebooks containing the OOS result.

4.审查包含不符合规格标准结果的记录本。

An alternative means to invalidate an initial OOS result, provided the

failure investigation proves inconclusive, is the "outlier" test.

如果对不合格结果的调查不能查明原因，—种可以使最初的不符合规格标准结果归于无效的变通方法是做异常值检验。

However, specific restrictions must be placed on the use of this test.

但是使用这种检验应有特别的限制：

1. Firms cannot frequently reject results on this basis.

1.公司不能经常以此为基础否定化验结果；

2. The USP standards govern its use in specific cases only.

2.美国药典标准规定异常值检验只用于特定的情况；

3. The test cannot be used for chemical testing results.

3.该检验不适用于化学分析结果；

An initial content uniformity test was OOS followed by a passing retest.

一个初始含量均匀度测试要通过一个不符合规格标准重复测试。

The initial OOS result was claimed the result of analyst error based on a

statistical evaluation of the data.

最初的不符合规格标准结果根据数据的统计评估来表明分析员的误差。

The court ruled that the use of an outlier test is inappropriate in this case..

在法则中有规定在这种情况下使用异常值检验法是不合适的...

4. It is never appropriate to utilize outlier tests for a statistically based test,

i.e., content uniformity and dissolution.

4.以统计为基础的检验(如含量均匀度和溶出度检验)不能用异常值检验。

Determine if the firm uses an outlier test and evaluate the SOP.

确定药厂是否使用异常值检验并评价其不符合规格标准。

Determine that a full scale inquiry has been made for multiple OOS results.

确定对多个不符合规格标准结果是否做了全面的查询。

This inquiry involves quality control and quality assurance personnel in

addition to laboratory workers to identify exact process or non process

related errors.

这种查询不仅与实验室工作人员有关，也涉及到质量控制和质量保证人员，以便确定误差是否与生产工艺有关。

When the laboratory investigation is inconclusive (reason for the error is

not identified) the firm:

当实验室调查不能得出结论(误差原因不明)时，该药厂：

1. Cannot conduct 2 retests and base release on average of three tests

1.不得进行两次复检和根据三次化验的平均值对产品进行放行；

2. Cannot use outlier test in chemical tests

2.不能用异常值检验做化学检验；

3. Cannot use a re-sample to assume a sampling or preparation error

3.不能用重复取样的办法假定取样或制备过程误差；

4. Can conduct a retest of different tablets from the same sample when a

retest is considered appropriate (see criteria elsewhere)

4.当确认可以复检时(见另外的标准)，可以取同一样品中的不同药片做复检。

-------------------------------------------------------------------------------王先鸣

C. FORMAL INVESTIGATIONS

正式的调查

Formal investigations extending beyond the laboratory must follow an

outline with particular attention to corrective action.

实验室之外的正式调查必须遵循特别注意纠正行动的原则。

The company must:

公司必须：

1. State the reason for the investigation说明调查的原因

2. Provide summation of the process sequences that may have caused the

problem

提供可能导致该问题的工序数据的总和

3. Outline corrective actions necessary to save the batch and prevent

similar recurrence

概述保留该批生产量和防止同类事件再次发生所必须的纠正措施

List other batches and products possibly affected, the results of

investigation of these batches and products, and any corrective action.

列出可能受影响的其他批处理和产品，这些批处理和产品以及任何纠正行动的调查结果。

Specifically:examine other batches of product made by the errant

employee or machine

特别是：检查由于员工或机器的错误引起的其他批次的产品

examine other products produced by the errant process or operation

检查由于错误的工序或操作引起的其他批次产品

4. Preserve the comments and signatures of all production and quality

control personnel who conducted the investigation and approved any

reprocessed material after additional testing

5. 质量控制人员负责引导调查和批准额外测试后原辅料在加工的批准。所有的产品和质量控制人员的意见和签名都要保留。

------------------------------------------------------------------------------------王敏

Analyst's mistakes, such as undetected calculation errors, should be

specified with particularity and supported by evidence.

分析人员的错误，如未被发现计算错误，应指定的特殊性和证据支持。

Investigations along with conclusions reached must be preserved with

written documentation that enumerates each step of the investigation.

调查并得出结论必须保留与列举调查的每个步骤的书面文件。

The evaluation, conclusion and corrective action, if any, should be

preserved in an investigation or failure report and placed into a central file.

评价、 结论和采取纠正行动，如果有的话，应保存在调查或故障报告，并放置到一个档案文件。

E. INVESTIGATION TIME FRAMES

E.调查的时间框架

All failure investigations should be performed within 20 business days of

the problem's occurrence and recorded and written into a failure or

investigation report.

20个工作日内，对问题的发生，所有故障应进行调查和记录，并写入故障或调查报告。

6.

PRODUCT FAILURES

产品的故障

An OOS laboratory result can be overcome (invalidated) when laboratory

error has been documented.

一个OOS实验室的结果是可以克服的（无效），实验室错误已被记录。

However, non-process and process related errors resulting from operators

making mistakes, equipment (other than laboratory equipment)

malfunctions, or a manufacturing process that is fundamentally deficient,

such as an improper mixing time, represent product failures.

然而，非过程和过程相关的错误造成的失误，设备（以外的实验室设备）发生故障，或制造的过程，是从根本上的缺陷，如不正确的混合时间的运营商，代表产品故障。

Examine the results of investigations using the guidance in section 5 above

and evaluate the decision to release, retest, or rework products.

检查使用指导在上文第5节的调查和评估结果决定释放，复试，或返工的产品。

ING

复验

Evaluate the company's retesting SOP for compliance with scientifically

sound and appropriate procedures.

评估公司复验的标准操作规程（SOP）是否科学合理。

A very important ruling in one recent court decision sets forth a procedure

to govern the retesting program.

在最近的一次非常重要法庭的裁决提出一个决定来指导复验程序。

This district court ruling provides an excellent guide to use in evaluating

some aspects of a pharmaceutical laboratory, but should not be considered

as law, regulation or binding legal precedent.

这个判决为药物实验室的某些方面的评估提供了一个很好的指南，但不应被视为法律，法规或具有法律约束力的判例。

The court ruled that a firm should have a predetermined testing procedure

and it should consider a point at which testing ends and the product is

evaluated.

法院裁定,一个公司应该有一个预先确定的测试程序,它应该考虑一个测试结束点和产品评估。

If results are not satisfactory, the product is rejected.

如果结果不理想，该产品将被拒收（销毁）。

Additionally, the company should consider all retest results in the context

of the overall record of the product.

此外，公司应该考虑该产品的总记录包含所有的复验结果。

This includes the history of the product.

这包括该产品的历史。

The court ordered a recall of one batch of product on the basis of an initial

content uniformity failure and no basis to invalidate the test result and on a

history of content uniformity problems with the product., type of test

performed, and in-process test results.

法庭下令召回一批产品是由于：初始含量均匀度不合格和没有根据的，无效的测试结果的基础上，在历史的含量均匀度问题的产品，执行的测试类型，测试过程中的测试结果。

Failing assay results cannot be disregarded simply on the basis of

acceptable content uniformity results.

失败的试验结果不能简单地被忽略的基础上，可接受的含量均匀度的结果。

The number of retests performed before a firm concludes that an

unexplained OOS result is invalid or that a product is unacceptable is a

matter of scientific judgment.

之前，公司进行的复验结论是一种原因不明的OOS结果是无效的，或产品是不能接受的是科学判断的问题。

The goal of retesting is to isolate OOS results but retesting cannot continue

ad infinitum.

复验的目的是隔离OOS的结果，但不能继续再测试循环往复。

In the case of nonprocess and process-related errors, retesting is suspect.

在非过程和过程相关的错误的情况下，重新测试的嫌疑。

Because the initial tests are genuine, in these circumstances, additional

testing alone cannot contribute to product quality.

因为最初的试验是真实的，在这种情况下，额外的单独测试可以有助于产品质量。

The court acknowledged that some retesting may precede a finding of

nonprocess or process-based errors.

法院承认，一些重新测试之前发现的非过程或过程为基础的错误。

Once this determination is made, however, additional retesting for purposes

of testing a product into compliance is not acceptable.

一旦作出该判定，但是，为了遵守测试产品的目的的额外复检是不能接受的。

For example, in the case of content uniformity testing designed to detect

variability in the blend or tablets, failing and non-failing results are not

inherently inconsistent and passing results on limited retesting do not rule

out the possibility that the batch is not uniform.

例如，在含量均匀度测试旨在检测变异的混合物或片，失败和失败的结果是不是本身就是矛盾的，通过在有限的复验结果的情况下，不排除可能的批次是不统一的。

As part of the investigation firms should consider the record of previous batches, since similar or

related failures on different batches would be a cause of concern.

作为调查公司的一部分，应考虑前面的批次，不同批次的自相似或相关的故障记录，将是一个值得关注的问题。

Retesting following an OOS result is ruled appropriate only after the failure

investigation is underway and the failure investigation determines in part

whether retesting is appropriate.

重新测试后的OOS结果被排除适当失败后的调查正在进行中，部分故障的排查确定是否是合适的复验。

It is appropriate when analyst error is documented or the review of analyst's

work is "inconclusive" , but it is not appropriate for known and undisputed

non-process or process related errors.

这是适当的时候分析师记录错误或审查分析师的工作是“不确定”，但它并不适合已知的和无可争议的进程或进程相关的错误。

The court ruled that retesting:

法院裁定，重新测试：

must be done on the same, not a different sample

必须是相同的，而不是一个不同的样本上进行

may be done on a second aliquot from the same portion of the sample that

was the source of the first aliquot

可以做的第二等分试样从样品的相同部分的第一等分试样的来源

may be done on a portion of the same larger sample previously collected for

laboratory purposes

可以完成相同的较大的样本以前收集的一部分上，用于实验室用途

-------------------------------------------------------------- 李杰

8. RESAMPLING

（再取样）

Firms cannot rely on resampling. The court ordered the recall of one batch

of product after having concluded that a successful resample result alone

cannot invalidate an initial OOS result. to release a product that has failed

testing and retesting unless the failure investigation discloses evidence that

the original sample is not representative or was improperly prepared.

药厂不得依赖再取样。法院下令召回一批产品后，得出的结论是一个成功的重采样的结果，不能单独判断最初的检验结果偏差结果是无效。为此来发放经检验和复检均不合格的产品，除非对不合格结果的调查查出证据表明原样品不具有代表性或准备不当。

Evaluate each resampling activity for compliance with this guidance.

评价每次再取样活动是否遵照厂本指南。

9. AVERAGING RESULTS OF ANALYSIS

平均分析结果

Averaging can be a rational and valid approach when the object under

consideration is total product assay, but as a general rule this practice

should be avoided. The court ruled that the firm must recall a batch that was

released for content uniformity on the basis of averaged test results. because

averages hide the variability among individual test results. This

phenomenon is particularly troubling if testing generates both OOS and

passing individual results which when averaged are within specification.

Here, relying on the average figure without examining and explaining the

individual OOS results is highly misleading and unacceptable.

当考察的对象是全批产品的含量测定时，平均法不失为一种合理的、有效的方法。但作为—般性原则，应避免使用平均法，因为平均数掩盖厂每个测试结果的差异性。当检验既得出不符合规格标准结果，也有单个合格的结果，而平均结果又合乎规格标准时，这种现象特别麻烦，这里，不对单个不符合规格标准结果进行审查和解释就信任平均数，极易造成误导，而且是不能接受的。

Content uniformity and dissolution results never should be averaged to

obtain a passing value.

含量均匀度和溶出度结果不允许采用平均法以获得通过。

In the case of microbiological turbidimetric and plate assays an average is

preferred by the USP. In this case, it is good practice to include OOS results

in the average unless an outlier test (microbiological assays) suggests the

OOS is an anomaly.

至于含量测定的微生物浊度分析法和培养皿分析法，美国药典优先采用平均值，在这种情况下，将不符合规格标准结果包括在平均数内较好，除非分别测定(微生物法含量测定)表明不符合规格标准结果异常。

10. BLEND SAMPLING AND TESTING

混料的取样和检验

The laboratory serves a vital function in blend testing which is necessary to

increase the likelihood of detecting inferior batches. Blend uniformity

testing cannot be waived in favor of total reliance on finished product

testing because finished product testing is limited.

实验室极其重要的一项功能就是检验混料，在提高发现劣等产品批次的可能性方面，混料检验必不可少。不能因偏好于依赖对成品的检验而放弃对混料均匀度的检验，因为成品检验有其局限性。

One court has ruled that sample size influences ultimate blend test results

and that the sample size should resemble the dosage size. Any other

practice would blur differences in portions of the blend and defeat the

object of the test. If a sample larger than the unit must be taken initially,

aliquots which resemble the dosage size should be carefully removed for

the test, retests, and reserve samples. Obviously, the initial larger sample

should not be subjected to any additional mixing or manipulation prior to

removing test aliquots as this may obscure non-homogeneity.

某法律规定，因取样量影响最终混料检验的结果，取样量应与制剂取样量相当。其他任何做法只会混淆混料各部分之间的区别，从而无法达到检验目的。如果样品的首次取样量必须大于使用的单位量，则应仔细取出与制剂取样量相当的等份用于检验、复检及留样。显然，最初的大用量样品在等份被取出前不易另行搅拌或处理，否则会掩盖样品的非均匀性。

Multiple individual blend uniformity samples taken from different areas

cannot be composited. However when variation testing is not the object of

assay testing, compositing is permitted.

用作混料均匀度测试的数个样品，如果采自不同区域，则相互之间不得混合，除非在以含量测定为目的而不是为了考察其差异性的情况下，才允许混合。

If firms sample product from sites other than the blender, they must

demonstrate through validation that their sampling technique is

representative of all portions and concentrations of the blend. This means

that the samples must be representative of those sites that might be

problems; e.g. weak or hot spots in the blend.

如果药厂的样品不是取自混合器，则应通过验证证明其取样技术能反映混料各个部分和总体的特征。也就是说，这些样品必须能够代表生产中可能发生问题的位点，如混料中的薄弱点或过热点。

11. MICROBIOLOGICAL

微生物方面

The review of microbiological data on applicable dosage forms is best

performed by the microbiologist (analyst). Data that should be reviewed

include preservative effectiveness testing, bioburden data, and product

specific microbiological testing and methods.

对制剂产品微生物学数据的审查最好由微生物学家(化验员)完成。应审查的数据包括防腐剂的有效性测试、生物负荷数据以及特定产品的微生物检验及其方法。

Review bioburden (before filtration and/or sterilization) from both an

endotoxin and sterility perspective. For drug substance labs evaluate

methods validation and raw data for sterility, endotoxin testing,

environmental monitoring, and filter and filtration validation. Also, evaluate

the methods used to test and establish bioburdens.

从细菌内毒素与无菌性两方面审查过滤前和(或)灭菌前产品的生物负荷状况。对于原料药检验实验室，要评价其方法验证以及无菌性和细菌内毒素检验、环境监测、滤器及过滤方法验证的原始数据。此外，还要评价实验室检验及确定生物负荷量所采用的方法。

Refer to the Microbiological Inspection Guide for additional information

concerning the inspection of microbiological laboratories.

参考《微生物学检验指南》，以便获取更多关于检查微生物实验室的资料。

12. SAMPLING

取样

Samples will be collected on pre-approval inspections. Follow the sampling

guidelines in CP 7346.832, Part III, pages 5 and 6.

在药品审批前检查时采集样品。依照CP7346．832第三部分，第五、六页上关于取样的指导进行取样。

13. LABORATORY RECORDS AND DOCUMENTATION

实验室记录和文件

Review personal analytical notebooks kept by the analysts in the laboratory

and compare them with the worksheets and general lab notebooks and

records. Be prepared to examine all records and worksheets for accuracy

and authenticity and to verify that raw data are retained to support the

conclusions found in laboratory results.

审查化验员保存的实验室个人分析记录，并将其与工作单及总实验室记录比较。为厂准确与可靠起见，准备检查所有记录与工作单，核实确已保留下来的原始数据，以便保证从实验室结果中得出的结论。

Review laboratory logs for the sequence of analysis versus the sequence of

manufacturing dates. Test dates should correspond to the dates when the

sample should have been in the laboratory. If there is a computer data base,

determine the protocols for making changes to the data. There should be an

audit trail for changes to data.

参照生产日期的顺序审查实验室记录的分析顺序。检验的日期应与样品确实存在于实验室的日期相符合。如果使用电脑数据库，应确定改变数据的方案，对数据变更应建立跟踪审计程序。

We expect raw laboratory data to be maintained in bound, (not loose or

scrap sheets of paper), books or on analytical sheets for which there is

accountability, such as prenumbered sheets. For most of those

manufacturers which had duplicate sets of records or "raw data",

non-numbered loose sheets of paper were employed. Some companies use

discs or tapes as raw data and for the storage of data. Such systems have

also been accepted provided they have been defined (with raw data

identified) and validated.

我们希望原始实验数据能成册保存(避免散乱或用零碎纸张记录)，或以书本、或以事先编号可以计数的化验单的形式保存。大多数生产企业复印的多套记录或“原始数据”中，不乏未标明页码的散纸片。一些公司使用磁盘或磁带记录并储存原始数据，只要表述明确(原始数据予以标明)，且经过验证，这样的系统是可以接受的。

-----------赖楷贤

Carefully examine and evaluate laboratory logs, worksheets and other

records containing the raw data such as weighings, dilutions, the condition

of instruments, and calculations.

仔细检查和评估实验室日志、工作记录以及其他一些包含原始数据的记录，如称重、稀释、仪器状态、计算等。 Note whether raw data are missing,

if records have been rewritten, or if correction fluid has been used to

conceal errors.

注意原始数据是否有缺失，记录是否被重写，或用涂改液来掩盖错误。Results should not be changed without explanation.

没有解释说明不能更改结果。

Cross reference the data that has been corrected to authenticate it.

交叉参考数据已经被纠正并经过验证。

Products cannot be "tested into compliance" by arbitrarily labeling

out-of-specification lab results as "laboratory errors" without an

investigation resulting in scientifically valid criteria.

产品检测实验室结果超标在没有科学有效的标准指导调查下不能任意被称为实验室错误。

Test results should not have been transcribed without retention of the

original records, nor should test results be recorded selectively.

测试结果在原始数据没有保留时不能被抄写，也不能有选择的记录检测结果。

For example, investigations have uncovered the use of loose sheets of paper

with subsequent selective transcriptions of good data to analyst worksheets

and/or workbooks. Absorbance values and calculations have even been

found on desk calendars.

例如，检查发现使用松散的纸张选择性记录检验员的工作表或/和工作记录中的良好的数据。吸收值和计算被发现用办公桌上台历记录。

Cut charts with injections missing, deletion of files in direct data entry

systems, indirect data entry without verification, and changes to

computerized programs to override program features should be carefully

examined.

丢失的注射图表，直接数据输入系统、间接数据输入没经过确认删除档案，以及无视程序特征更改电脑程序，都应该仔细检查。

These practices raise questions about the overall quality of data.

这些做法可以提高整体的数据质量。

The firm should have a written explanation when injections, particularly

from a series are missing from the official work-sheets or from files and are

included among the raw data.

该公司应该有书面的说明当官方的工作表或文件丢失以及其中原始数据丢失，该公司应该有书面的说明。

Multiple injections recorded should be in consecutive files with consecutive

injection times recorded.

多次注射记录应该是连续的文件，记录连续注射时间。

Expect to see written justification for the deletion of all files.

期望看到所有文件的删除的书面理由。

Determine the adequacy of the firm's procedures to ensure that all valid

laboratory data are considered by the firm in their determination of

acceptability of components, in-process, finished product, and retained

stability samples.

确定有足够的公司程序以确保所有有效的实验室数据被认为是由该公司在其确定可接受性成分、中间品、成品和保留稳定性的样品。Laboratory logs and documents when cross referenced may show that data

has been discarded by company officials who decided to release the product

without a satisfactory explanation of the results showing the product fails to

meet the specifications.

实验室记录和文件交叉引用时可能导致数据被公司人员丢失。这些人员决定放行没有令人满意的结果显示产未能符合规定的产品。

Evaluate the justification for disregarding test results that show the product

failed to meet specifications.

评估无视显示该产品不符合规定的测试结果的理由。

----------------------------------------------------------王敏

14. LABORATORY STANDARD SOLUTIONS

14.实验室的标准溶液

Ascertain that suitable standards are being used (i.e. in-date, stored

properly). 确定正在使用的标准品是合适的（也就是在有效期内，储存合适的）

Check for the reuse of stock solutions without assuring their stability.

检查是否未确定其稳定性就重复使用储备液。

Stock solutions are frequently stored in the laboratory refrigerator.

储备液通常是储存在实验室的冰箱当中。

Examine the laboratory refrigerators for these solutions and when found

check for appropriate identification.

检查实验室冰箱中的溶液，并核实它们的标识是否正确无误。

Review records of standard solution preparation to assure complete and

accurate documentation.

审查标准溶液的配制，以确保完整和准确的文件记录。

It is highly unlikely that a firm can "accurately and consistently weigh" to

the same microgram.

“准确无误的、始终如一的”称量到同一微克数对任一家公司来说是不切实际的。

Therefore data showing this level of standardization or pattern is suspect

and should be carefully investigated.

因此，数据显示，这个级别的标准或模式是值得怀疑的，应该仔细调查研究。

15. METHODS VALIDATION

15.方法验证

Information regarding the validation of methods should be carefully

evaluated for completeness, accuracy and reliability.

关于方法验证资料的评估应充分考虑其完整性、准确性和可靠性。

In particular, if a compendial method exists, but the firm chooses to use an

alternate method instead, they must compare the two and demonstrate that

the in-house method is equivalent or superior to the official procedure.

特别是，如果存在一个药典检验方法，但公司选择的是另一种方法，那么，他们必须比较这两者，并证明自己采用的方法等同或优于药典的方法。

For compendial methods firms must demonstrate that the method works

under the actual conditions of use.

企业必须证明检验方法的使用是在药典规定的条件下使用的。

Methods can be validated in a number of ways.

检验方法有多种验证方式。

Methods appearing in the USP are considered validated and they are

considered validated if part of an approved ANDA.

USP上的方法以及ANDA批准的方法都被认为是验证过的。

Also a company can conduct a validation study on their

suitability data alone is insufficient for and does not constitute method

validation.

此外，公司也可以对他们自己的方法进行有效性验证，但是系统适应性数据本身并不够，不能构成方法验证。

In the review of method validation data, it is expected that data for

repetitive testing be consistent and that the varying concentrations of test

solutions provide linear results.

在审查方法验证的数据时，希望复检的数据具有一致性，不同浓度的测试溶液提供了线性的结果。

Many assay and impurity tests are now HPLC, and it is expected that the

precision of these assays be equal or less than the RSD's for system

suitability testing.

现在用于测试含量和杂质的高效液相谱法，其测试的精度等于或小于系统适用性试验的RSD。

The analytical performance parameters listed in the USP XXII, <1225>,

under the heading of Validation of Compendial Methods, can be used as a

guide for determining the analytical parameters (e.g., accuracy, precision,

linearity, ruggedness, etc.) needed to validate the method.

在USP XXII, <1225>中（药典方法验证标题下）列出的分析性能参数，可作为指南，以确定验证方法所需要的分析参数（例如准确度，精密度，线性，耐用性等）。

16. EQUIPMENT

16.仪器设备

Laboratory equipment usage, maintenance, calibration logs, repair records,

and maintenance SOPs also should be examined.

检查实验室仪器设备的使用，维护保养情况，校正记录，维修记录及维护的标准操作规程。

The existence of the equipment specified in the analytical methods should

be confirmed and its condition noted.

确认是否具备在分析方法中使用的专用设备并注意其状态。

Verify that the equipment was present and in good working order at the

time the batches were analyzed.

检验每个批次产品时，应确保所涉及的已验证设备都在场并处于良好的工作状态。

Determine whether equipment is being used properly.

确定设备的使用是否正确。

In addition, verify that the equipment in any application was in good

working order when it was listed as used to produce clinical or biobatches.

此外，如果有设备用于临床生产或生化小试品研究，应确认它在任何时候的使用当中是否都处于良好状态。

One would have to suspect the data that are generated from a piece of

equipment that is known to be defective.

人们会怀疑一台有缺陷的设备所产生的数据。

Therefore, continuing to use and release product on the basis of such

equipment represents a serious violation of CGMP's.

因此，继续使用该设备并在此基础上发布产品时严重违反CGMP条例的。

-----------------------------------------------陈淑贤

17. RAW MATERIAL TESTING

原辅料检验

Some inspections include the coverage of the manufacturer of the drug

substance. The safety and efficacy of the finished dosage form is largely

dependent on the purity and quality of the bulk active drug substance.

Examine the raw data reflecting the analysis of the drug substance including

purity tests, charts, etc.

一些检查应包括药品生产企业的检测范围。成品剂型的安全性和有效性很大程度上依赖于活物的纯度和质量。检查体现分析药物的原始数据包括纯度试验，图表等。

Check the impurity profiles of the BPC used in the biobatch and clinical

production batches to determine if it is the same as that being used to

manufacture full scale production batches. Determine if the manufacturer

has a program to audit the certificate of analysis of the BPC, and, if so,

check the results of these tests. Report findings where there is substantial

difference in impurity profiles and other test results.

在生物利用度实验批和临床生产批中检查《英国药物处方书》杂质的大概情况，以确定它是否与在大规模生产时产生的杂质相同。确定如果药品生产企业有一个《英国药物处方书》分析的审核证书，如果是这样，请检查这些测试的结果。报告结果中和其他测试结果有很大差异的杂质。

--------------------------------------------------------------------吴佩迪

Some older compendial methods may not be capable of detecting impurities

as necessary to enable the control of the manufacturing process, and newer

methods have been developed to test these products.

旧药典不能检测出必要杂质使生产过程得到控制，而新方法已经投入检测这些产品。

Such methods must be validated to ensure that they are adequate for

analytical purposes in the control and validation of the BPC manufacturing

process.

这些方法必需经过验证确保适用于控制与验证BPC制造过程的分析目的。 The drug substance manufacturer must have complete knowledge of

the manufacturing process and the potential impurities that may appear in

the drug substance.

药品生产商必须具备制造过程及其潜在杂质出现的完整知识。

These impurities cannot be evaluated without a suitable method and one

that has been validated.

没有合适的方法和一个已验证的方案，这些杂质无法评估的。

Physical tests such as particle size for raw materials, adhesion tests for

patches, and extrusion tests for syringes are essential tests to assure

consistent operation of the production and control system and to assure

quality and efficacy.

物理试验如原料的粒度，斑块附着力试验，注射器推出试验都是基本的检测，确保产品和控制系统的持续操作，以保证质量和效力。

Some of these tests are filed in applications and others may be established

by the protocols used to manufacture the product.

这些试验需编入应用软件，其它的建立协议用于制造产品。

The validation of methods for such tests are as important as the test for

chemical attributes.

这些试验的方法验证对化学药品特性的检测是很重要的。

Physical properties tests often require the use of unique equipment and

protocols.

物理性能测试通常需要使用独特的设备和方案。

These tests may not be reproducible in other laboratories, therefore, on site

evaluation is essential.

这些测试在其它实验室是不能使用的，因此，现场的评估是必要的。

18. IN PROCESS CONTROLS AND SPECIFICATIONS

过程控制和性能规范

Evaluate the test results from in-process tests performed in the production

areas or laboratory for conformance with established sampling and testing

protocols, analytical methods, and specifications.

从生产车间或者实验室测试的完成来评估试验结果，达到符合已建立的取样和试验方案 ，分析方法，性能规范。

For example, evaluate the tests for weight variation, hardness, and friability.

These tests may be performed every fifteen or thirty minutes during

tableting or encapsulating procedures.

例如，从重量差异，硬度，易碎性评估试验。

All testing must comply with CGMP's.

所有试验必需遵守《动态药品生产管理规范》。

The drug application may contain some of the in-process testing plan,

including methods and specifications.

药品申请包含内部试验计划，包括方法和技术参数。

The inspection must confirm that the in-process tests were done, as

described in the plan, and ascertain that the results were within

specifications.

检查必须确认进程内试验已经完成,如前面描述的计划,确定结果是在规范。

The laboratory work for the lengthier tests should also be reviewed.

实验室工作较长的测试也应该被审查。

The methods used for in-process testing may differ from those used for

release testings.

进程内测试的方法应不同于放行试验。

Usually, whether the methods are the same or different, the specifications

may be tighter for the in-process tests.

通常，不管方法相同与否，性能规范必需符合进程内的测试。

A product with a 90.0%-110.0% assay release specification may have a

limit of 95.%-105.0% for the in-process blend.

90.0 ％〜110.0 ％含量的放行标准产品可能有一个限度的95 ％ 〜105.0％的过程中的混合。

Some of the tests done may differ from those done at release.

这些试验方法可能会不同于已经放行的方法。

For example, a firm may perform disintegration testing as an in-process

test but dissolution testing as a release test.

例如，一公司证实裂解试验是内进程试验，但是，溶解试验是释放试验。

Expect to see consistent in-process test results within batches and between

batches of the same formulation/process (including development or exhibit

batches).

期待看到一致的进程内的测试结果在批量和批次之间相同的配方/过程(包括开发或展览批次)

If this is not the case, expect to see scientific data to justify the variation.

如果不是这种情况,期望看到科学数据来证明这个变化。

19. STABILITY

稳定性

A stability-indicating method must be used to test the samples of the batch.

稳定性要求方法必须能用于批次的取样量。

If there is no stability-indicating assay additional assay procedures such as

TLC should be used to supplement the general assay method.

如果没有稳定性要求鉴定额外的分析程序如TLC应该用于常规的分析方法。

Evidence that the method is stability indicating must be presented, even for

compendial methods.

稳定性指示的方法必须出示，即使药典规定的方法。

Manufacturers may be required to accelerate or force degradation of a

product to demonstrate that the test is stability indicating.

生产厂家可能需要加快或促使降解产品以示范测试是符合稳定性要求。

In some cases the sponsor of ANDA's may be able to search the literature

and find background data for the specificity of a particular method.

某些情况下，新药的赞助商会查阅文献和查特异性方法的背景数据。

This information may also be obtained from the supplier of the drug

substance.

这些信息也可以从药品的供应商获得。

Validation would then be relatively straightforward, with the typical

parameters listed in the USP in chapter <1225> on validation of compendial

methods addressed as applicable.

验证将会相对简单,与典型的USP < 1225 >章列出的参数表中的验证方法同为适用的。

Evaluate the manufacturer's validation report for their stability testing. 通过稳定性测试评估生产商的验证报告。Again, review the raw laboratory

data and the results of testing at the various stations to determine if the data

actually reported matches the data found in on site records.

再一次,回顾原始实验数据和测试的结果，多方面分析确定实际数据是否匹配现场记录。

Evaluate the raw data used to generate the data filed documenting that the

method is stability indicating and the level of impurities.

评估原始数据用于生成数据记录文件,包括稳定性要求和杂质的水平。

------------------------------------------------------------------蓝志明

20. COMPUTERIZED LABORATORY DATA ACQUISITION

SYSTEMS

实验室计算机数据采集系统

The use of computerized laboratory data acquisition systems is not new and

is addressed in the following CGMP guidance documents:

实验室计算机数据采集系统的使用并不是新的规定,在以下的CGMP指南文件中有规定：

Compliance Policy Guide 7132a.07 Computerized Drug Processing:

Input/Output Checking.

符合政策指南7132a.07《计算机化药物加工：输入/输出检查》

Compliance Policy Guide 7132a.08 Computerized Drug Processing:

Identification of "Persons" on Batch Production and Control Records.

符合政策指南7132a.08《计算机化药物加工：批量生产和记录控制中人的作用的识别》

Compliance Policy Guide 7132a.11 Computerized Drug Processing: CGMP

Applicability to Hardware and Software

符合政策指南7132a.11《计算机化药物加工：硬件和软件的CGMP适用性》

Compliance Policy Guide 7132a.12 Computerized Drug Processing:

Vendor Responsibility

符合政策指南7132a.12《计算机化药物加工：供应商职责》

Compliance Policy Guide 7132a.15 Computerized Drug Processing: Source

Code for Process Control Application Programs

符合政策指南7132a.15《计算机化药物加工：过程控制应用程序的源代码》

Guide to Inspection of Computerized Systems in Drug Processing.

药物生产过程中计算机系统检查指南

It is important, for computerized and non computerized systems, to define

the universe of data that will be collected, the procedures to collect it, and

the means to verify its accuracy. Equally important are the procedure to

audit data and programs and the process for correcting errors. Several issues

must be addressed when evaluating computerized laboratory systems. These

include data collection, processing, data integrity, and security.

对于计算机化系统和非计算机化系统来说，规定数据的收集、过程及验证其准确性的方法，是很重要的。数据和程序审计，纠正错误的程序也是同等重要的。在评估实验室计算机系统时，应包含以下几个方面：数据的收集、处理、完整性、安全性。

Procedures should only be judged adequate when data are secure, raw data

are not accidentally lost, and data cannot be tampered with. The system

must assure that raw data are stored and actually processed.

当数据安全时仅评价程序是否充分，原始数据不可丢失，数据不可更改。系统必须确保原始数据的储存和实际处理。

The agency has provided some basic guidance on security and authenticity

issues for computerized systems:

FDA为计算机系统安全性和真实性提供了基本指南。

Provision must be made so that only authorized individuals can make data

entries.

应规定，只有授权人员才可以进行数据输入。

Data entries may not be deleted. Changes must be made in the form of

amendments.

输入数据不可以删除，应以修订的形式进行更改。

The data base must be made as tamperproof as possible.

应尽可能的防止篡改数据库。

The Standard Operating Procedures must describe the procedures for

ensuring the validity of the data.

标准操作规程应规定确保数据有效性的程序。

One basic aspect of validation of laboratory computerized data acquisition

requires a comparison of data from the specific instrument with that same

data electronically transmitted through the system and emanating on a

printer. Periodic data comparisons would be sufficient only when such

comparisons have been made over a sufficient period of time to assure that

the computerized system produces consistent and valid results.

实验室计算机数据获得的验证的一个基本方面是，要求从特定仪器获得的数据和通过系统电子传送或打印出来的数据进行对比。周期性数据对比需充分，当这种对比在足够长的时间里可以确认计算机系统产生稳定和有效的数据，

21. LABORATORY MANAGEMENT

实验室管理

Overall management of the laboratory work, its staff, and the evaluation of

the results of analysis are important elements in the evaluation of a control

laboratory.

在控制实验室评估中，实验室工作和人员的全面管理以及分析结果的评估都是很重要的因素。

Span of supervisory control, personnel qualifications, turnover of analysts,

and scope of the laboratory's responsibility are important issues to examine

when determining the quality of overall management and supervision of

work.

管理控制的范围、人员资格的确认、检验员的流动性、实验室职责的范围，在确认全面管理和监督工作质量时都是重点检查项目。

Individually or collectively, these factors are the basis for an objection only

when they are shown to result in inadequate performance of responsibilities

required by the CGMPs.

仅当结果显示未充分执行CGMPs要求的职责时，单个或全面的因素才能成为缺陷的依据。

Review laboratory logs for the sequence of analysis and the sequence of

manufacturing dates. Examine laboratory records and logs for vital

information about the technical competence of the staff and the quality

control procedures used in the laboratory.

按生产日期顺序和检验顺序进行实验室日志的审核。检查有关于人员技术技能和实验室质量控制程序重要信息实验室记录和日志。

Observe analysts performing the operations described in the application.

There is no substitute for actually seeing the work performed and noting

whether good technique is used. You should not stand over the analysts, but

watch from a distance and evaluate their actions.

在申请中描述观察到的检验员的操作。没有什么可以取代真实看到的工作过程和技术是否良好。你不应监督检验员,但可远距离的观察并评估他们的行动。

Sometimes the company's employees have insufficient training or time to

recognize situations that require further investigation and explanation.

有时，公司的人员没有受到足够的培训或没有足够时间进行更近一步的调查和解释。

Instead they accept unexplained peaks in chromatograms with no effort to

identify them.

相反, 没有努力鉴别就接受在谱图中出现的无法解释的山峰。

They may accept stability test results showing an apparent increase in the

assay of the drug with the passage of time with no apparent question about

the result.

也可能认可，稳定性试验结果显示，药品测试的明显增加 ，但随着时间的推移，对于结果没有没有明显的问题。

Also, diminishing reproducibility in HPLC chromatograms appearing

several hours after system suitability is established is accepted without

question.

同时可以毫无疑问的接受，系统适应性建立后几小时，高效液相谱谱图再现性减少。

Good manufacturing practice regulations require an active training program

and the documented evaluation of the training of analysts.

GMP需要有效的培训计划和培训结果评估的文件。

The authority to delete files and override computer systems should be

thoroughly examined. Evaluate the history of changes to programs used for

calculations. Certain changes may require management to re-examine the

data for products already released.

应彻底检查授权人删除文件和重写计算机系统。评估计算机项目修改历史。有些修改需要求管理者对已放行产品数据的再审查。

-----------------------------------------------------------------------贾路