representation-坚定信心
:
FDA Warning
Letters, Form 483 Observations and
Establishment Inspection Reports
–
Preview
FDA
警告文字,来自
483
观测资料和预先检查报告。
Important:
Warning letters and other FDA inspection
documentation
should be interpreted in
the context of full content. Just looking at
extracts may be misleading. And
sometimes they include good advice
from
the FDA not mentioned in the extracts.
重要性:
警告文字和其他的
FDA
p>
检查文件必须说明,
根据上下文包括全部内容。
仅是看摘录可能被误解。并且有时要包括从
FDA
那里征求
好的建议,而不是只
提到摘录。
FDA 483 Inspectional Observations, EIRs
& Warning Letters -
Preview keywords
and excerpts
Type
Content&deviations
Keywords, selected examples (not
complete).
Click on
(In this
Preview Mode the click will link you to the order
form)
Tell your
friends about this page
!
FDA
检查报告,
< br>EIRS
和警告文字
-
预览关键
词和摘录。
类型
内容和目录
关键词,选择事例(不用完整)
尽力画
出“
D
”来观察、印刷和
/
或下载所有文件的全部内容
。
(在这部分预览方式中,
CLICK
将使你形成定货表格。)
D
Keywords: Water
systems, diagrams, process validation, cleaning
483
85 items
validation, batch record review,
training, instrument calibration, reserve
samples, testing, product
specification, distribution records, analytical
method, USP standard,
failure investigation, labeling, SOPs
?
W-156
?
483
关键词:水系统,图表,过程确认,清洁确认,一批记
录:有回顾,培训,仪表校正,储
备样本,检测,制品技术
规格,分析方法,
USP
标准,故障调查,标签,
SOPS
。
Primary deviations:
missing diagrams, no installation qualification,
no operation qualification, no batch
record review, inadequate GMP
training,
inadequate equipment calibration, inadequate
storage of
reserve samples, SOPs not
approved, inadequate procedures for
sampling and testing
?
Examples:
-There was no diagram of the water
system
- Batch records not reviewed by
QC,
- Routine calibration
not performed according to a written program
- Conductivity meters not calibrated to
an NIST traceable device
- Batch
records lack a description of name of the
equipment
- No reference in analytical
method to recognized standard method.
- Current SOPs not reviewed and
approved by QCU
W
—
156
。
主要错误
:缺少图表,无安装资格,
无操作资格,无回
顾记录,
GMP
培训
不充分,设备刻度不清楚,储备事例不充分,
SOP
没被证明,
取样和检测程序不充分。
事例:
-
水系统没有图表
-
大批记录没有被质控回顾
-
常规表格没有根据书面程序执行
<
/p>
-
电导计没有根据
NIST
可追踪装置校准
-
大批记录缺少设备描述名字
-
没有根据分析方法涉及可识别的标准方法
-
当前
SOPS
没有被
QCU
回顾和验证
483
Keywords: Electronic records,
electronic signatures,
Part
11
, Equipment
calibration,
equipment qualification, certificate of analysis,
review of
D
关键词:电子记录,电子信号,设备刻度,分析证书,回顾记
录。
W-155
?
Primary
deviations:
missing Certificate of
Analysis, inadequate
equipment
calibration, failure to review production and
control records
by QA, no recalibration
after equipment move.
records
W-155
。
主要错误
:缺少分析证书,设备刻度不适当,缺少质保的产品
回顾和控制
记录。当设备移动后没有校准。
?
Examples:
- Failure to
establish laboratory controls which include the
calibration
of instruments, apparatus,
gauges and recording devices at suitable
intervals in accordance with an
established written program containing
specific directions, schedules, limits
for accuracy and precision and
remedial
action in the event the accuracy and/or precision
limits are
not met [21 CFR
211.160(b)(4)].
-
Specifically, your firm does not have a
Certificate of Analysis (COA)
for ...
- The procedure is unclear and is
inconsistent with the manufacturer's
recommendation which advises to
calibrate the
[redacted]
Oxygen
Analyzer each time
the analyzer is moved.
-
Failure to routinely calibrate, inspect, or check
automatic,
mechanical, or electronic
equipment according to a written program
designed to assure proper performance
[21 CFR 211.68(a)].
Specifically, your
firm has not performed any equipment qualification
on the
?
?
事例:
?
?
?
?
p>
-
缺少建立实验控制,包括器械刻度、规格、记录装置在适
当的距离,根据建立的书面表格:有特殊方向、时间表、限
制的精确度、
当重大事件发生时的矫正措施和
/
或精
确度,
所
有这些都要满足。
[21CF
R211
。
160
(
< br>b
)(
4
)
]
-
特殊性,你的公司没有分析证明书(
COA
)为了
…
.
-
程序不清晰和没包括制造商推荐信,氧分析器的每次移动
没有校准。
-
缺乏常规校
准、检查、或自动核对、机械核对,或根据书
面程序设计电子设备来确保正确的执行。<
/p>
[21CFR211.68
(
a
)
]
特殊性,
你的公
司还没有执行设备资格在可移动的低抽吸泵
系统中。
Keywords: Equipment
calibration, equipment qualification, certificate
of
D
Warning
Letter
analysis, review of
records
警告关键词:设备刻度,设备规格,分析证书,记录回顾
?
Primary deviations:
missing
Certificate of Analysis, inadequate
equipment calibration, failure to
review production and control records
by QA, no recalibration after equipment
move.
?
主要错误:
缺少分析证书,设备刻度
缺少,缺少质保的回顾生产记录和
控制记录,设备移动后没有校准。
W-154
?
-
Failure to establish laboratory controls which
include the calibration
of instruments,
apparatus, gauges and recording devices at
suitable
intervals in accordance with
an established written program containing
specific directions, schedules, limits
for accuracy and precision and
remedial
action in the event the accuracy and/or precision
limits are
not met [21 CFR
211.160(b)(4)].
-
Specifically, your firm does not have a
Certificate of Analysis (COA)
for ...
- The procedure is unclear and is
inconsistent with the manufacturer's
recommendation which advises to
calibrate the
[redacted]
Oxygen
Analyzer each time
the analyzer is moved.
-
Failure to routinely calibrate, inspect, or check
automatic,
mechanical, or electronic
equipment according to a written program
designed to assure proper performance
[21 CFR 211.68(a)].
Specifically, your
firm has not performed any equipment qualification
on the
?
?
?
事例:
事例:
-
缺少建立实验控制,包括器械刻度、规格、记录装置在适
当的距
离,根据建立的书面表格:有特殊方向、时间表、限
制的精确度、
当重大事件发生时的矫正措施和
/
或精确度,
所
有这些都要满足。
[21CFR211
。
160
(
b
)(
4
)
]
?
-
特殊性
,你的公司没有分析证明书(
COA
)为了
…
.
?
-
程序不清晰和没包括制造商推荐信,氧分析器的每次移动
没
有校准。
?
-
缺乏常规校准、检查、或自动核对、机械核对,或根据书
面
程序设计电子设备来确保正确的执行。
[21CFR211.68
(
a
)
]
?
特殊性,
你的公司还没有执行设备资格在可移动的低抽吸泵
系统中。
-
Keywords: capa, process
validation, change control, quality
systems
Warning
Letter
?
关键词:过程确认,变更控制,质量系统
警告信
W-153
Primary
deviations:
inadequate corrective and
preventive actions,
inadequate process
validation, inadequate change control
procedure
D
主要错误:
缺少足够的矫正和预防措
施、过程确认、变更控制程
序。
?
Examples:
-Failure to establish and maintain an
adequate corrective and
preventive
action procedure which ensures identification of
actions
needed to correct and prevent
the recurrence of nonconforming
product
and other quality problems, as required by 21 CFR
820.100(a)(3).
- Failure to
validate changes to your manufacturing process
with a
high degree of assurance to
ensure that specified requirements are
met as required by 21 CFR 820.75(c).
- Validation did not include
verification assurance that the changes did
not affect the device
-Failure to identify the acceptance
status of product throughout
manufacturing, packaging, labeling, and
servicing of the product to
ensure that
only product which has passed the required
acceptance
activities is distributed or
used.
?
?
事例:
-
缺少建立和维持足够的矫正和预防
程序,这能保证统一行
为所需纠正
和
预防非一致性的产品和其他质量问题再次发
生,正如
21
CFR 820.100(a)(3).
所需的。
-
对于你的产品生产过程缺乏有效的变更保证来保证特殊需求,正如
21
CFR
820.75(c).
所需。
-
p>
确认没有包括确认保证,这些改变是否会影响装置。
-
缺乏贯穿于生产、包装、标签、和产品服务的统一可接受的标准,来确
p>
保只有产品通过所需要的可接受的行为才被分发和应用。
?
?
?
Keywords: root cause, capa, compliant
handling, management
Warning
Letter
responsibility
警告信
关键词:根本原因,
CAPA
,抱怨处理,操作责任。
W-152
?
?
?
Primary
deviations:
no root cause analysis,
insufficient complaint
handling
D
主要错
误:
没有分析根本原因
,
不足的抱怨的
处理。
Examples:
- You are responsible for investigating
and determining the causes of
the
violations identified by the FDA. You also must
promptly initiate
permanent corrective
and preventive action of your quality system.
Failure to promptly correct these
deviations may result in regulatory
action being initiated by the FDA
without further notice. These actions
include, but are not limited to,
seizure, injunction, and/or civil
penalties. Additionally, no premarket
submissions for Class III devices
to
which QSR deficiencies are reasonably related will
be cleared until
the violations have
been corrected. Also, no requests for Certificates
to Foreign Governments will be approved
until the violations related to
the
subject devices have been corrected.
?
- You have
failed to establish complaint handling procedures
sufficient
to ensure that all
complaints are documented and processed in a
uniform and timely manner, as required
by 21 CFR 820.198(a).
- Management with
executive responsibility has failed to ensure that
an adequate and effective quality
system has been fully implemented
and
maintained at all levels, as required by 21 CFR
820.20
-
You have
also failed to establish a policy of overall
intentions and
direction of your firm
with respect to quality
?
?
事例:
-
你
有责任调查和决定这些违反
FDA
的一致性原因。对于你的质量
系统
你也必须迅速的发起持久的纠正和预防行动。缺乏迅速的纠正这些错误
可能导致调整的行为开始没有被
FDA
进一步发现。
这些行为包括,但
不限于,没收、命令,和
/
< br>或全民的处罚。
[
,
另外
, premarket
提议为
QSR
缺乏是合理地相关的类
III
设备不
会被清除直到侵害被改正了
]
同
样,没
有要求证明对外国政府批准直到侵害与附属的设备被改正了
?
?
?
-
你已缺
乏建立足够的抱怨操作程序来确保所有的抱怨是有一致和及时
操作的文件证明和处理,正
如
21 CFR
820.198(a).
所需。
-<
/p>
缺乏以行政责任处理来确保足够的和有效的质量系统,
而这个系统
需要
贯彻和保持在所有水平,正如
21 CFR
820.20
所需。
-
你也缺少建立关于公司质量的全面的意图和指导的政策。
Keywords: stability testing, failure
investigation, batch reprocessing,
Warning
Letter
missing records
警告信
关键词:稳定性实验,故障调查,批物料的回收,丢失的记录
W-151
?
?
?
Primary
deviations:
No adequate stability test
program, missing
failure investigation,
missing procedure for the reprocessing of
batches, missing records regarding
unexplained discrepancies
主
要错误:
没有足够的稳定性实验,
故障调查,
< br>批物料回收丢失的手续,
关于无法解释的差异缺失手续。
Examples:
- You have failed
to establish an adequate stability testing program
to
determine appropriate expiration
dates for all your drug products (21
CFR 211.166(a) and (b)
- You
have failed to investigate failures of a batch or
any of its
components to meet their
specifications (21 CFR 211.192).
- You do not maintain any written
records regarding unexplained
discrepancies and batch failures as
required by 21 CFR 211.192
- Batches
are routinely reprocessed when initial release
specifications
fail.
?
D
?
-
- None of the stability failures,
described above, were the subject of an
investigation as required by 21 CFR
211.192
- You have not established
written procedures for the reprocessing of
batches to ensure that they will
conform to all established
specifications (21 CFR
211.115).
?
?
?
?
?
?
?
事例:
-
对
于药物生产缺乏建立足够的稳定性实验来解释生产中的数据。(
21
CFR 211.166(a) and (b)
一批物料或其中的一部分缺乏失误调查来满足他们的特殊性。
(21
CFR
211.192).
-
p>
关于无法解释的差异和和批物料没有记录下来,正如
21 CFR
211.192
所提。
-
当开始发布的说明错误时没有例行公事的修改
-
没有稳定性的错误,就向上文所描述的,也是一种客观的调查,正如
< br>21 CFR 211.192
所提
< br>-
对于所有回收的物料没有建立书面程序来符合所有建立的说明。
(21
CFR 211.115).
Keywords: CAPA,
complaints, audits, document control, quality
system,
D
Warning
Letter
training
警告信
关键词:
CAPA
,抱怨,文件控制,质量系统,培训
W-150
?
Primary
deviations:
No or inadequate CAPA
system, inadequate
complaint handling
procedures,
no quality audits,
inadequate
organizational structure,
inadequate document control, failure to
review effectiveness of quality system
by management with executive
responsibility, insufficient personnel
with necessary education.
?
主要错误:
没有或缺乏足够的
CAPA
系统、不适当的抱怨处理系统,没
有质量审核,缺乏足够的组织结构,缺乏足够的文件控制,没有通过行
< br>政责任来回顾有效的质量系统,个人缺乏足够的必需教育。
?
Examples:
Significant deviations include, but are
not limited to, the following
- Analyzing processes, work operations,
complaints, returned product
and other
sources of quality data to identify existing and
potential
causes of nonconforming
product
- Investigating the cause of
nonconformities relating to product,
processes, and the quality system
- Identifying the actions needed to
correct and prevent recurrence of
nonconforming product and other quality
problems
- Verifying or validating the
CAPA to ensure that such action is
effective and does not adversely affect
the finished device
?
?
事例:
有意义的错误包括,但不是仅限于以下方面:
?
-
分析方
法,工作业务,抱怨,返回产品和其他来源,有通
过质量数据识别不合格的产品存在的和
潜在的错误。
?
< br>-
调查相关产品、程序、和其他质量系统不一致的原因。
?
-
检验和
确认
CAPA
来确保这样的做法是有效的而不是由于
已完成的装置产生相反的作用。
Keywords:
API, testing,
impurity testing, supplier testing, certificate of
D
Warning
Letter
analysis, solvent
recovery, labeling system
警告信
关键词:
API
,测试,混合物测试,厂商测试,证书分析,溶解性
恢复,标签系统。
?
Primary
deviations:
Insufficient testing of
individual batches, supplier
testing
not verified, no procedures for solvent recovery,
inadequate
proof of incoming labels.
?
?
?
p>
主要错误:
个别产品没有足够测试,供应商测试没有校验,没有程序
恢
溶解性,引入的标签没有足够的证据。
W-149
Examples:
- The laboratory
did not have an adequate impurity profile that
identifies organic, inorganic and
solvent impurities to monitor
unidentified and apparent impurities in
the API
- The microbiological
laboratory fails to document the lot number and
expiry date of xx
- The
reliability of the supplier's certificate of
analysis (COA) was not
established in
that a complete analysis was not performed with
the
COA at the appropriate intervals.
- Procedures for solvent
recovery have not been established to ensure
that solvents are controlled and
monitored
- Incoming labels received
from the vendor are not proofed against the
master label
?
?
事例:
-
实
验室没有杂质分布图分辨有机物,无机物,溶解混合物
来监控未经确认的和外观杂质。<
/p>
?
-
分析提供者证书的的可靠性不是建立在已完成的分析基础
上,在适当的
时间间隔是否符合
COA
。
?
-
溶解能
力的恢复程序还没有建立来确保溶剂可控制和监
控。
?
收到的引入标签没很好的控制。
Keywords:
API, testing, raw
data, failure investigations, equipment design,
D
Warning
Letter
English language,
equipment maintenance
警告信
关键词:
API
,测试,原始数据,失误调查,设备设计,英语,设备
维护
?
Primary deviations:
Insufficient testing of individual batches,
insufficient
recording of raw data,
inadequate failure investigation, inadequate
equipment design, inadequate equipment
maintenance
?
?
足,设备设计不足,设备维护不足
Examples:
- The individual
batches are not tested for residual solvents
- Laboratory records do not include all
raw data. For example, weights
determined during the preparation of
standard solutions were not
recorded
- Critical production deviations may
not have been investigated and
documented.
- Production
equipment was not designed to minimize
contamination
- Equipment was not
maintained in an adequate state of repair.
- If you whish to to continue to ship
APIs to the United states, you should
evaluate all equipment and written
procedures and your employees
adherence
to written procedures, for compliance with this
standards.
-
Failure to promptly correct these
deficiencies may result in the refusal
to permit entry of these APIs or
finished products made from these APIs
into the United States.
-
Please submit documentation, with English
translation, of these
corrections.
?
?
?
?
?
?
?
?
?
举例:
W-148
主要错误:
单独一批货物没有足够测试,原始数据记录不足,错误调查不
-
单独一批货物没有经残留溶剂检验。
-
实验记录没有包括所有所有原始数据。例如,重量设计在解
决标准准备时没有记录。
-
重要生产装置没有调查和备有证明文件。
-
设备在完好维修状态下没有很好的维护。
-
如果你希望继续装运
APIS
到美国,
为了适应许多标准,
你必
须估计所有设备和书面
手续和雇员坚持书面手续。
如果没有迅速的改正这些不足可能
会导致拒绝接受这些
APIS
或产品完成,这会使这些
APIS
进入美国。
-
请提交改正的英语文件,
-
Keywords:
audits, CAPA, risk
assessment, complaint handling, validation, test
Warning
Letter
equipment, training
警告信
关
键词:审核,
CAPA
,风险评估,抱怨处理,设备测试,培训
D
W-147
?
Primary
deviations:
no audits of records,
inadequate validation of
workstation
test equipment, inadequate compliant handling,
inadequate procedures for CAPA,
inadequate risk assessment.
?
?
p>
主要错误:
没有审核记录,没有充分确认工作站测试设备,没有完全
处
理好抱怨,对于
CAPA
没有充足的
手续,没有充分的风险评估
Examples:
- There is no indication that your firm
conducted periodic checks or
audits of
the records during this time to assure the
validity of the data.
- Failure to
establish and maintain procedures for implementing
corrective and preventive actions (CAPA
) to include requirements for
analyzing
processes, work operations, concessions, quality
audit
reports, quality records, service
records, complaints, returned product,
and other sources of quality data to
identify existing and potential
causes
of nonconforming product, or other quality
problems, as
required by 21 CFR
820.100(a)(1)
- For example, your firm
performed risk assessments for product
failures without documenting how the
severity or likelihood of
occurrence
used in the assessment was determined, in
violation of
your own procedures.
- For example, the validation of the
workstation test equipment used
as part
of the final device testing system; did not
include a process
capability challenge,
did not ensure that the test equipment used was
capable of functioning as necessary to
capture results at both the high
and
low ends of the test specifications, and did not
include challenges
with known failures
to ensure the equipment detected fault
conditions
?
?
?
事例:
-
没
有迹象表明你的公司进行定期检查或审计这些记录,
来确保数据的有
效性。
-
缺乏建立和保持程序,
这需要改正和预防措施的工具,
这包括维修的分
析程序,工作操作,让步,返修品,或其他的质量数据资源,以此来鉴
别现在和
潜在的不合格产品存在的原因,
或其他质量问题,
正如
. 21 CFR
820.100(a)(1)
-
例如,
确认工作站测试设备作为最后测试系统的一部分;
不包括性能测
试,不能保证过去的测试设备
有能力发挥作用,来获得所有高水
平和低水平测试规格的结果,不包括熟知的错误,
来确保设
备察觉错误情况。
Warnin
g
Letter
警告信
W-146
Keywords:
risk analysis, design validation,
change control, software testing,
acceptance criteria, quality control,
installation qualification, inspection, supplier
assessment
D
关键词:风险评估,设计确认,变更控制,软件测试,接受标准,
质量控
制,安装控制,检查,厂商评估
?
Primary deviations:
no
procedures for validating the device design,
no formal risk analysis for software
changes, no procedures for
finished
device acceptance, inadequate installation,
inadequate
inspection, no procedures
for supplier assessment.
?
主要错误:
没有装置设计的确认手续,对于软件变更没有正式
的风险评估,没有完成的可接受装置
的程序,没有充分的检
查,供应商没有评估手续。
?
Examples:
- Failure to establish and maintain
adequate procedures for validating
the
device design to ensure that the device conforms
to user needs
and intended uses and
include risk analysis, as required by 21 CFR
820.30(g) (FDA 483, Item 151.
?
?
事例:
-
- For example, a formal
risk analysis of the original system design and
software changes to correct software
bugs that caused incorrect
functionality or performance problems,
and to enhance the product,
has not
been documented. Although your software release
notes
briefly describe the nature of
unresolved software bugs in a particular
software version, they do not explain
the impact of these software bugs
on
user needs and intended uses. For example, in the
workflow
release notes, dated 6/24/04,
software version 17 described that
edema value used previously
was confusing.
?
例如:
一个对原始系统设计的正式的风险分析没有证明文件,<
/p>
改变软件以修补那些会引起错误功能和行为的软件漏洞的行
为也没
有文件证明,以及改变软件以增强生产的行为也没有
文件证明。虽然你的软件
- Status of design changes was
not documented to explain why certain
design changes were not implemented to
correct Software bugs
- The
discussion of the test releases of
software versions 36 through
40
- Failure to establish and maintain
procedures for finished device
acceptance to ensure that each
production run, lot, or batch of finished
devices is not released for
distribution until all the requirements are
completed as required by 21 CFR
820.80(d) [FDA 483 item 3]. For
example, your firm has not documented
the signature(s) of approval
needed to
release xxx for distribution
- Failure
to establish and maintain procedures for adequate
installation
and inspection, as
required by 21 CFR 820.170(a) and document the
installation activities and inspection
results, as required by 21 CFR
820.170(b) [FDA 483 Item 5]. For
example, your firm's device
installation procedure was in the draft
form at the time of our
inspection, and
your firm has not maintained records of
installation
activities and inspection
results of the retinal image acquisition
subsystem of the 3DT system at the
clinical sites.
- Failure to establish
and maintain procedures to ensure that all
purchased or otherwise received product
and services conform to
specified
requirements, as required by 21 CFR 820.50 [FDA
483, Items
10, 11, 12, and 13). For
example, your firm has not (a) evaluated the
suppliers for their ability to meet
your firm's requirements; (b) defined
the quality requirements that each
supplier must meet; (c) defined the
frequency of supplier evaluations; and
(d) documented supplier
evaluations.
Keywords:
part11
, electronic records,
electronic medical record (EMR)
Warning
Letter
system, computer validation, audit
trail, accurate and complete copies, invalid and
altered records
?
Primary deviations:
missing
documentation for validation and other
part 11 requirements
?
Examples:
Our review of the inspection results
also noted that you use an
electronic
medical record (EMR) system to maintain medical
and other
clinical data for your
patients, including study subjects . You told Mr.
xxx that data obtained during study
visits are entered directly into the
EMR, and no paper records are used. A
follow-up letter from you to
Mr. xxx,
dated January 31, 2005, detailed the name of the
EMR
system and the means by which study
subject information is entered
Please
note that Title 21, Code of Federal Regulations,
Part 11,
requirements that
must be met for any system that is being used to
maintain required records . In addition
to the information requested
above,
please submit the following:
-
documentation of the validation of your EMR system
to ensure
accuracy, reliability, and
the ability to detect invalid or altered records;
- documentation of the ability to
generate accurate and complete
copies
of records suitable for inspection, review, and
copying by the
agency;
-
documentation of a secure, computer-generated,
time-stamped audit
D
W-145
trail that can independently record the
date and time of operator
entries and
actions that create, modify, or delete electronic
records,
and to verify that record
changes do not obscure previously recorded
information.
Keywords:
complaints, suppliers, contractors, software
validation,
Warning
Letter
change control
D
W-144
?
Primary
deviations:
no or inadequate software
validation, no quality
requirements for
suppliers, contractors and consultants, no
supplier
audits, inadequate change
control
?
Examples:
-
Failure to perform
software validation, as required by xxx.
Specifically, the xxx controller unit,
software version xxx
was
changed
to xxx. The change in the
software allowed for adjustment in the speed
of the water pump, and inverse pulsing
from the A valve to the B valve
when
the speculum was clogged. Your firm did not have
any
documentation showing that the
current software version was
validated.
-
Failure to establish and maintain the
requirements, including quality
requirements, that must be met by
suppliers, contractors, and
consultants, as required by xxx.
Specifically, your firm did not have
any documentation showing audits of the
contract manufacturer
responsible for
manufacturing the disposable xxx which is used
with
the xxx. Your firm also did not
define the type and extent of control to
be exercised over the product,
suppliers, and contractors.
- Failure
of management with executive responsibility to
ensure that
an adequate and effective
quality system has been fully implemented
and maintained at all levels of the
organization, as required by 21 CFR
820.20(a). Specifically, management
with executive responsibility has
failed to ensure that an adequate and
effective quality system has
been
established. There was no management oversight for
employees responsible for
manufacturing, finished device release,
distribution, and for maintaining
quality system records.
483
Keywords:
System suitability testing, process validation,
part 11,
method
validation, OOS, laboratory controls, impurities,
QA procedures,
D
training, vendor qualification,
refractive index detector, electronic
records, stability testing
W-143
?
Primary
deviations:
no or inadequate failure
investigation,
inadequate process
validation, inadequate method validation,
inadequate instruction for testing,
insufficient justification for impurity
specifications, QA procedures not
followed, insufficient training on
cGMP
and operations, failure to establish controls and
procedures to
establish authenticity,
integrity and security of all electronic records,
failure to qualify suppliers, IQ/OQ or
equipment not performed or data
not
reviewed, no records for refractive index detector
qualification,
incomplete laboratory
records, inadequate stability
?
Examples:
- Drug products failing to
meet established specifications are not
rejected
- The xxx solution
used in the xxx assay test did not meet
USP
suitability test specification
during the analysis of Sample lot...
-
Control procedures are not established which
validate the
performance of those
manufacturing process that may be responsible
for causing variability in the
characteristics of in-process material and
the drug product.
- Initial OOS results for accuracy and
intermediate precision were
retested
with no laboratory investigation conducted; a
revised
analytical method was
developed, the samples retested, and only the
passing results reported.
- The analytical method report was not
signed off as approved until it
had
been used to test released batches
- Appropriate
controls are
not exercised over computers or related
systems to assure that changes in
master production and control
records
or other records are instituted only by authorized
personnel.
- The firm has failed to
establish controls and procedures to assure
authenticity, integrity and security of
all electronic records including
data
generated in the QC laboratory.
- All laboratory analysts and
supervisors have system administration
privileges in the firm's HPLC and GC
acquisition systems which allow
them
overwrite original raw data files.
- Refractive Index Detector used for
component testing , sugars, there
is no
record that the equipment has been
qualified
Keywords: SOPs, complaints,
annual product reviews, failure
Warning
Letter
investigations,
laboratory controls
D
W-142
?
Primary
deviations:
missing SOP to handle drug
quality complaints,
missing labels, not
following written procedures, inadequate
corrective
actions regarding failure
investigations, failure to follow laboratory
procedures
?
Examples:
- Your QCU also failed to
extend the investigation into other similar
lots
- Laboratory failed to
properly label sample preparations in your
laboratory refrigerator and workbench
areas
- Failure to follow written
procedures for Annual Product Reviews
-
Failure to follow established Standard Operating
Procedures
regarding the handling of
written and oral drug product quality
complaints
- Failure to
follow established laboratory control
procedures
Keywords: bioequivalence
study, contamination, procedures, policy,
Warning
Letter
failure investigation
D
W-141
?
Primary
deviations:
equivalency of analytical
method not
demonstrated,
inadequate approach to investigating
sources of
contamination, lack of
procedures and policies
?
Examples:
- You failed to demonstrate
that the analytical method used in this in
vivo bioavailability study was accurate
to measure the accurate
concentration
of loratadine and its metabolite
- Your
approach to investigating sources of contamination
in
bioequivalence studies is inadequate
and has resulted in the
submission of
invalid data to the agency. You should have
conducted
a systematic and thorough
evaluation to identify and correct the
source of contamination when it was
first observed.
- The
manner in which (company name) investigated the
contamination problem in this study
causes FDA to have concerns
with the
validity of other bioequivalence data generated by
(company
name).
Keywords:
number of people, stability testing, laboratory
records, data
Warning
Letter
integrity, equipment
maintenance
D
W-140
?
Primary
deviations:
no adequate number of
trained people,
laboratory records
missing, inadequate change of raw data, no
adequate equipment
maintenance
?
Examples:
-Written control procedures
not always followed when changes were
made to test methods and validated
system
- No positive control has been
used while conducting the USP test
since December 2002
-The
inappropriate change to test method was made
without Quality
Control unit review. as
a result, batches of product were released for
export to the US based on invalid USP
test results
- Written procedures for
investigating deviations were not followed on
at least six occasions in 2004, when
recording charts showed
malfunctions
- no adequate number of trained people
to carry out the
responsibilities of
your quality assurance department, ... only one
person conducted the dual functions of
quality control and quality
assurance.
- Maintenance performed on
the xxx in September and October 2003
was not correctly recorded
Keywords:
quality control unit, training, stability testing,
water
D
Warning
Letter
purification, batch
production and control records, batch record
review
W-139
?
Primary
deviations:
QC unit did not follow
written responsibilities,
employees not
trained on CGMP, no microbial analyses/or preserve
analysis on finished drug products,
water qualification, no batch record
review
?
Examples:
- SOPS have not been
approved by the quality control unit, and the
review of any complaints involving the
possible failure of a drug
product to
meet any of its specifications has not been
performed per
SOP.
-
According to the Executive Director of the firm,
the employees have
never received any
type of CGMP training
- Your firm
failed to conduct microbial analysis and/or
preservative
assays on finished drug
products as a criteria for release.
-
The firm does not have a sampling and test
procedures designed to
assure that the
water from the purification system conforms to
appropriate standards
-
Failure to have all drug product production and
control records
reviewed and approved
by the quality control unit to determine
compliance with all established,
approved written procedures before a
batch is released or
distributed.
Keywords: computer
validation, data integrity, acceptance levels,
D
Warning
Letter
method validation,
process validation, revalidation, OOS
关键词:
计算机检验,
数据完整,
容纳水平,
方法检验,
< br>过程检验,
再检验,无库存
W-138
?
Primary
deviations:
No acceptance and/or
rejection levels for
theoretical and
actual batch yields, no test method validation,
lab
computer software not validated, no
process revalidation, no OOS
?
主要错误:
没有理论上和实际上的批产量接受或、
及拒绝的标
准,实验室
的计算机软件无效,没有再检验过程,没有无库
存调查
?
Examples:
例如
-The process
validation for the product Syncro-Mate-B Implants
is
inadequate in that your firm’s 1994
retrospective valida
tion report
evaluated batches that were
manufactured and tested at a different
manufacturing facility. Your firm
failed to perform any new process
validation or revalidate the
manufacturing process, at your current site.
Additionally, your firm failed to
validate the testing methods used to
analyze the batches in your
retrospective validation report and the
equipment used to manufacture and test
the validation batches was
never
qualified.
?
生产
Syncro-Mate-B Implants
的再检验过程不恰当,您的公司的
1994
回顾
检验报告评估不同的生产设备生产及测试的批次。您的公司没有执
行人任何新的过程检验
或生产过程检验,在您的目前的位置上,加之,
您的公司没有检验用于分析在您的回顾检
验报告中的批次的测试方法
以及用于生产和测试批次的检验设备不够资格。
-
The firm’s computer
software programs which operate all of the lab
during the analysis of raw materials
and xxx finished product, have not
been
qualified and/or validated. The software programs
do not secure
files from accidental
alteration or losses of data. The functions that
modify and delete partial or whole data
files are available for use by all
analysts. In addition, the firm has not
established any security
investigation
procedures for the laboratory computer
systems. There are no
procedures for
backing-up data files and no levels of security
access
?
在原材料分析和某某总产品分析期间,
公司运行在所有实验
室的计算机软件程序不够资格或未被检验,
软件程序无法保
证数据以外修改和丢失后的安全性。
所有的分析家都可使用
部分
或全体数据文件的修改和删除功能。另外,公司没有任
何的实验室计算机系统的安全程序
,
没有回投数据文件的程
序以及已定的安全标准。
Warning
关键词:安全性,计算机验证,
QA
规程,设备清洗,
HVAC,
< br>无菌罐
W-109
?
?
established.
D
主要偏差:
QA
单元不符合规程,自动化设备没有进行验证,对审核
人员
没有限制,对设备的清洗与维护没有规程可循
例子
-QA
部门没有很好的遵循书面规程,应该对工作中的疏忽与审核负
责
-
没有保证自动化设备能满足制药所需的运行标准
[21 CFR
211.68].
例如:
-
过程控制所用的计算机没有进行确认
-
设备没有进行确认(
HVAC,<
/p>
无菌罐,纯化水系统)
-
没有限制一些非授权人员进入限制区
Warning
关键词:质量体系,管理,纠偏,预防
W-108
-
-
-
没有建立对质量体系的稳定性与有效性的审核负责的管理体系
没有建立与保存关于纠偏与维护措施的规程
没有建立与保存有关质量体系的规程
?
?
D
主要偏差:
没有管理规程,没有纠偏与预防措施,没有质量体系
例子
:
Warning
关键词
:
电子数据表的验证,数据积分,中间介质与电子文档的长期保存,
107<
/p>
电子文档的消除,清洗的验证,方法
验证,过程验证,
OOS
,事故
106
调查,培训
W-107
现在应采用充分的检查报告
(EIRs),
W-106
W-105
完整的过程是从
483 (W-105)
开始,遵循初检的充分检查报告(
W
-
106
),
063
警告信
(W-063)
,以及后续检查的
EIR (W107)
。
后续检查报告是对为了使其
达到
FDA
要求而进行的纠偏过程的详
细描述。
EIRs
:详细描述了怎样
检查,应该检查什么,应该问些什么问题以及公司应
该为什么负责。应该对
EIRs
进行审核,例如:由总办公室负责决定是否发
送警告信。
一般有
483
,
EIR
,以及来自此部门的警告信。通读这些信息有利
< br>于很好的准备检查。有利于公司了解检查中的提问类型以很好的回答那些问
题,这
样不仅可以避免收到
FDA
的警告信,还可以减少自己重做的概
率。
105
Warning
关键词:胃肠外给药的无菌制剂的生产操作,
part 11<
/p>
,
追踪审查,完整的纠
D
偏计划,环境验证
?
W-104
?
主要偏差:
缺少电子追踪审查,对第
11
部分没有计划,对无菌填充
p>
器没有作环境验证
例子:
-
此外,较高要求是将有关步骤记录到电子版
cGMP
记录中(应
满
足
21
CFR Part
11
的要求,电子记录,电子标志。
Part 11
的建
立应满足电子记录的要求,且电子标志应可靠,并与常用的书面标
p>
志和传统的手写标志相统一。电子记录与电子标志用于会议记录和
P
art 11
要求的
21CFR
p>
的
210
,
211
部分标志。
- .
< br>在给缺陷通知的回复中应出具公司的全面纠偏计划,包括纠偏周
期,记录到
Part 11
中
-
检查应对实验室电子控制体系中的不足进行公开,
这个体系主要是
对色谱仪的维护和追踪审核。
-
没有根据验证计划收集足够的样品来评估特定的材料
-
没有对
XXX
无菌填充器进行环境验证
-
对使用方法与容器的清洗没有详细的描述
Warning
关键词:
人员培训与资格,计算机系统,安装记录,验证
W-103
?
?
D
主要偏差:
缺乏或没有对员工关于计算机系统的培训,计算机系统
的安装记录不完整,计算机系统
的验证不完整
例子:
-
对员工关于用于原料筛选和生产过程的新的计算机系统的使用培
训不够完整
-
中心主管人员没有进行过任何培训,
尽管他保留了输入到计算机系
统中的安全性很高的数据记录
-
计算机系统的验证与安装记录不完整。系统的安装参照
11/1
7/2000
,但验证研究直至
4/1
9/2001
才会被正式批准。测试范围有
以下方面:
Warning
关键词:
API
p>
,
OOS,
文件,过程验证,方法验证,过
程参数的纠偏变更控制
D
W-102
?
?
p>
主要偏差:
OOS
没有文件记录,生产过程
没有验证,分析方法没有
作稳定性检查,对分析方法没有进行变更控制,关键的过程参数
没
有进行确认
例子
-
没有
文件记录对纠偏过程和实验结果
OOS
的调查
< br>
-
在检查过程中,我们的调查应参照纠偏过程的调查与
实验室结果
OOS
的调查。这些只能作为指导,但不能作为文件
-
方案没有对关键步骤、关键的过程
参数、在线测试和说明进行确定
483
关键词:网络,
WAN,LAN
,变更控制的验证,图表,
p>
IT
人员的培训,修
D
订控制,变更控制
?
W-101
?
主要偏差:
对网络系统的安装与升级的验证失败,对
IS
人员关于
GMP
的培训失败
例子
-
该程序没有通过修订号进行控制
-
整个软件结构设计没有维护内容的描述和关于最初设计说明的校
正
-
完整的表格和文字描述应能用
XXX
确定所有其他的网络程序的界
面
,详细说明
XXX
和其他哪些没有被维护或没有对原始设计说明
进
行校正的数据可以进行改变
- <
/p>
广域网(
WAN
)表格应附有适当的说明
文件使用
XXX
来识别网络
上的公共网
站,在任何的
XXX
验证文件中都没有对他进行描述
-
这些表格没有表明日期,没有文件控制号,没有审核与批准指示
-
公司对
9.8
版本的配置的修订控制体系没有达到一体化
-
没有文件记录信息技术(
IT
)人员接受过包括
cGMP
规程与该规
程涉及的一些书面文件的培训
Warning
关键词:设备条件
,临界试验,
CAPA
,人员培训,统计分析,
第
11
部分
D
W-100
?
?
p>
主要偏差:
没有将不一致性进行适当的追究调查,设备没有对所有<
/p>
的参数进行测试,没有临界试验,对不一致性的潜在原因没有进行
评价,对人员的培训不够充分,统计分析
例子
-
没有
记录证明操作参数(最大值,最小值,对照参数)核对无误,
没有文件证明采样与样品的
检测符合验证方案
-
公司没有分析、
确定和文件描述产品不一致性的潜在原因何其他质
量问题,如
…
要求
-
对产
品和质量的统计和非统计分析没有制定程序可以遵循
-
公司没有对足够的人员进行充分的培训以确保所有活动能按照
…
要
求进行正确的执行
Warning
关键词:网络系统,环境监测,记录维护,结构和功能设计,代码审核,绝
D
对代码,代码注释,
第
11
部分
?
W-099
?
主要偏差:
对计算机系统没有进行足够的回顾性验证,软件版本控
制不恰当,代码审核不完善,没
有结构和功能设计,环境监测不够
完善,维护记录不完善,对代码没有注释,代码包括绝
对代码和不
使用的代码
例子
-
对
计算机系统没有进行足够的回顾性验证,
这些系统涉及到质量保
证/质量控制,原材料的控制与发放,中间材料与成品,例如:
-
对程序的验证中没有包括结构和功能设计
-
每个程序只有一小部分进行了详细的审核
-
软件修订控制不完善
Warning
关键词:过程验证,
OOS
,微生物试验,
API
,方法验证,稳定性测试
,
记录维护
?
D
W-098
?
主要偏差:
对生产过程没有进行验证,没有建立和保存关于不能解
释的矛盾的调查的书面记录,没
有成功制定
API
的发放标准,没有
成
功的对操作和测试方法的稳定性进行验证,没有很好的对校正检
查和自动化设备的检查的
相关记录进行很好的维护
例子:
-
例如:对药品生产过程与药品生产相关设备没有进行验证
-
对产品的微生物测试没有文件记录可查,
< br>使其不具备回顾性,
也就
没有结果和依据可循
-
对校正检查和自动设备,
< br>机械或电子设备的检查的记录的维护失败
Warning
关键词:
API
,稳定性测试,原始数据,
HPLC
p>
,线性检测仪,管式加热器
D
的温度精度,线性积分仪
?
W-097
?
主要偏差
:稳定性测试不能追朔到在生产地点进行的批生产过程,
缺少原始数据,没有对线性检测
仪进行测试,没有对管式加热器和
检测仪所设置的温度的精度进行检测,
没有对
GC
和
GC
顶部单元进
行恰当的校正,没有第二个分析者或监督者对原始数据和从经质
量
合格的分析仪器所获的结果的验证进行精确性与完整性的检查。
例子
:
-
对
…
样品
的稳定性进行测试但不能向
DMF97
-
001
提供稳定性数
据来回顾批生产过程
-
对原料药与成品药没有区分,没能很好的遵循
cGMP
,没有符合
Act
的
要求
-
在设备检查过程中不能提供稳定批的现有记录的原始数据
-
对
HOLC
的校正不恰当,
没有对线性检测仪与积分仪、
注射器的选择、
管式加热器与检测仪进行校正
- <
/p>
如果直至
FDA
进行第二次检查时还没有
根据
cGMPs
对这些缺陷进行
相应改
进,将被扣留新药应用清单和原料药
(APIs)
制造等设施的
批准书。
如果不能迅速的解决这些问题将失去这些产品进入美国市场的机会
Warning
关键词:
API,
清洗验证,微生物规
程,
HOLC
,方法验证,稳定性试验,输
D
入警告
?
W-096
?
主要偏差:
API
的生产不符合
cGMP
的要求
,没能很好的建立微生
物规程,
HPLC
的分析方法没有进行,
对取样的时间间隔的稳定行测
试失败<
/p>
例子:
-
这封信是关于
FDA
对在
…
原料药生产设施的检查的。在我们的检
查中我们发
现你们对原料药
(API)
的生产与
c
GMP
的要求有较大的偏
离。
-
对用于原料药
< br>APIs
和中间产物生产所用的非反应容器、盛装容
器、
重结晶器、离心分离器和干燥器的清洗过程没有进行验证
Warning
关键词:无菌生产
,无菌过程,消毒设备,微生物污染,输入警告
W-095
?
?
D
主要偏差:
关键设备没有进行重新灭菌,对消毒设备表面的限制不
恰当,监测时间间隔过长
例子:
-
对无菌粉末的填充过程在一些关键问题上没有作恰当的处理
,如:
工作时间长短,关键设备长时间没有进行再次灭菌。
-
对消毒设备表面的限制不恰当使其对无菌生产的环境没有保证
-
如果你希望自己的产品能进入美国市场,
< br>你必须保证能遵循美国的
cGMPs
标准
-
将扣留无菌产品的生产商的任何新的申请
483
W-094
关键词:销售资格,实验
室条例,退回的产品,成品的储存,变更控制
?
D
?
主要偏差:
对销售资格和实验室条例
没有制定
SOP
,销售资格没有
文件记
录,没有对实验室条例进行审核,对退回的产品没有进行确
认,对文件和生产过程的
p>
SOP
没有进行变更控制
例子:
-
对销售资格和实验室条例没有制定
SOP
,也没有文件对其进
行管
理
-
对纯化水的测试没有根据实验室条例进行审核
Warning
关键词:
GCP,
< br>会议记录,研究审核
W-093
?
?
D
主要偏差:
对研究过程没有从头到尾进行审核,没有报告研究过程
中的一些变化,没有对
FDA
所没有预料到的一些问题进行报告,没
有
保存会议记录
例子:
-
没有及时向
IRB
、其他有关部门、
FDA
报告一些他们所没有预料
p>
到的对人类存在威胁或与相关规则与要求不符的问题
-
如果在会议的参会人员中有一个非科学领域的成员,
IRB
会拒绝对
所提交的研究进行审核
Warning
关键词:管理职责
,管理审核,
CAPA,
验证
W-092
?
?
D
主要偏差:
没有明确管理职责,没有管理审核程序,没有对改正与
预防措施制定程序
例子:
-
没能指出或证明指定的管理人员
(不对其他责任负责)
的明确职责
和其确保质量体系进行有效维修并报告对质量体系的管理职责
-
没能很好的建立和执行管理审核程序
-
对出现不一致性的产品的现有原因和潜在原因的原始数据的分
析的
预防和改正措施的执行的程序的建立失败。
-
对检查、测量和检测设备是否能达到特定的目的和达到所需的生产
结果的证明失败
Warning
关键词:
API
p>
,原始数据,数据的维护,培训
W-091
?
?
D
主要偏差:
APIs
没有按照
cGMP
的要求进
行生产,没有原始数据,
对数据的维护没有
SOP
文件,没有对
GMP
进行培训
例子:
-
这封信是关于
…
的设施的检查的。
在我们的检查中我们发现你们对
原料药
(API)
的生产与
cGMP
的要求有较大的偏离。
-
对人员的培训不够
,没有涉及对
cGMP
的培训
Warning
关键词:原始数据,
API
,方法验证,缺陷对其他
过程的影响,地方
SOPs
,
D
微生物污染,微生物检测
?
W-090
?
主要偏差:
没有记录原始数据,杂质标准没有进行恰当的确定,内
部标准已经有四个月没有数据对
其在此期间的稳定行进行保证,没
有很好的执行在线检测,对缺陷对其他过程的影响没有
进行评估,
方法验证不恰当,只有中文版的验证方案和最终验证报告。
< br>
例子:
-
在实验过程中没有恰当记录原始记录
-
回复中没有证明对其他实验过程中的类似缺陷进行审核,并已
经执
行新的
SOPs
-
对化验与杂质的实验室检测没有根据单独的药品主控文件
(DMF)
(
USP
指定的方法)中的相关描述进行
-
直到设施符合
c
GMP
,
公司仍会被拒绝作为
API<
/p>
的供应商,
或对
API
< br>进行进口警告或拒绝进入美国市场。
483
关键词:生物分析检测实验室,校正标准,承诺标准,分析天平,冷冻器,
D
冷藏库,吸液管,吸液管微机管理器
?
W-089
?
主要偏差:
SOP
允许删除校正标准,
标准中没有包含准确数据,
QC
部门没有达到承诺标准,承诺标准不够详细,分析证明书中的数据
不恰当,分析天平的使用超过了其量程,数据终止不恰当,色谱仪
的重现性只是在运行初期进行了检查,对冷冻器和冷藏库的温度没
有进行监测,使用已
经出现偏差的吸液管进行分析,对多探头型吸
液管微机管理器的验证没有制定
SOP.
例子:
-SOP #F-00
“分析执行承诺标准”的目的并不是允许
删除校正标准
以至于
QC
评价不能处在
可接受的限度之中。
-
公司采用的分
析参考标准不当,或在任何地方都使用此标准,尽管
它符合分析标准,但在某些特定的分
析中它可能达不到所要求的纯
度或效力
-
校验记录表明在一些场合所使用的吸液管出现了偏差。
p>
但没有方法
证明这些吸液管在用以分析的什么时候出现了偏差。
p>
Warning
关键词:
GLP
,主进度表,
QAU
W-088
?
?
D
主要偏差:
由
QAU
制定的
GLP
文件没有进行审核,主进度表的复
印件没有进行保存
例子:
-
没
有对所有非临床实验研究的主进度表的复印件进行保存
-
p>
没有确保
QAU
对
GLP
研究的组织学准备过程进行监测
Warning
关键词:
OOS
,电子数据表,时间标记,
HPLC
溶剂的再生,追踪审核,电
D
子记录,原始数据的书面记录,
第
11
部分
?
W-087
?
主要偏差:
对
HPLC
溶剂的再生没有进行测试,没有进行追踪审核,<
/p>
没有恰当的密码保护措施,删除电子记录
例子:
-
由两个不同的人进行三次再测试,第三个分析者只是获得了数据并
进行报告后,这批产品就被放行
-
不能证明
HPLC
溶剂进行再生后是否能达到报告中所提到的纯
度,
效力
-
没有对涉及数据计算的数字模板进行追踪审核
-
密码保护可通过系统旁路进行
-
数据档案在被拷贝后自动删除
p>
-
没有要求对分析和对电子数据表的时间日期标记进行确认
-
改变方法将其作为工作标准使用,
但不能证明它能等价于
USP
中的
方法,例如:
Warning
关键词:活性成分,稳定性实验,设备的清洗,记录,校正数据
W-086
?
?
D
主要偏差:
测试不完整,稳定性测试不恰当,对校正数据没有进行
记录,没有器具清洗规程
例子:
-
没能做到对每批药品进行实验室测试后的优先放行,以确定成品在
活性
成分的均一性与有效性等方面均能满足要求
[21 CFR 211.165
(a)]
。尤其,你不能
…
-
没能做到用可靠有效的方法对药品稳定性的书面测试计
划进行执行
[21 CFR 2 11.166
(a)(3)]
。特别是
…
-
对实验室器具的定期检查的所有数据的没有进行验证,
记录对
FTIR
分光镜和
HP
LC
分析仪的使用有关,这些仪器用于对产品和人用药
品的检测
-
没能做到对设备和器具进行恰当的定期清洗与维护
Warning
关键词:验证,再验证,临界实验,破坏性实验,原始数据,实验记录
W-085
?
?
D
主要偏差:
主要过程没有进行验证,验证前对每批的分配不完善,
没有对
OOS
的原因进行调查,实验记录中没有原始数据
例子:
-
实
验记录中没有包括实验测试过程中出现的所有原始数据
-
p>
药品的样品在整批中的分配不合理或不具代表性,如
…
-
没有对最大的一批或主要的复杂的生产工序进行
再验证
Warning
关键词:软件的验证,电子记录表,
CAPA,OOS,
培训,自检,设计审核
W-084
?
?
D
主要偏差:
软件的验证不恰当,对设计在执行前的变更的审核不恰
当,质量检查过程不恰当
例子:
-
没有作恰当的改正和维护措施(
CAPA<
/p>
),例如分析数据以确定产
生不均一产品和其他质量问题的现存原
因和潜在原因
-
软件的验证没有涉及
到电子记录表的数据输入设备
-
没能
对程序进行恰当维护和对环境进行控制
483
W-083
关键词:
GLP
,毒理学,生物学研究监测,研究指导,测试,研究报告
?
?
D
p>
主要偏差:
对测试项目的测试不恰当,没有完整的测试记录,研究<
/p>
报告不完整,没有及时更换研究主管
例子:
-
不
能保证研究中的测试项目和给药方式
#224
和
#323
对均一性、
有效性和稳定性进行恰当的测试
< br>-
在测试初期与周期性测试中使用不同的方法,记录不完整或对方法
不能进行验证,不能将它用于色谱分析的光谱中,以及环境和用于
校正的有关
原料的数量中
-
不能证明更换后的研
究主管对方案偏差和
QAU
关于研究的检查报
< br>告进行了评估。
Warning
关键词:自动化系统的验证,设备的检查与测
试,偶然性事件计划书,偏差
D
(OOS)
W-082
?
?
主要偏差:
对自动化系统的验证失败
例子:
对连接生产和质量体系的自动化系统的验证失败
不能对所有检查和测试设备是否适用于此目的和是否能满足产品的追踪
要求进
行证明。检查发现所采用的自动化模拟实验没有根据硬件和软件
C2000
版的改变作相应的更新
Warning
关键词;质量保证
部门,方法验证,实验室记录,分析设备的质量电子数据
D
<
/p>
表,数据审核,色谱峰值的重叠,
第
11
部分
?
W-081
?
主要偏差:
没有程序或程序不充分,有关培训的文件,工作表不完
整,缺少设计与控制,第
11
部分
例子:
-
对以上违规的补充,
调查员发现实验室所使用的生产过程的电子版
记录与原子吸收和
HPLC
的数据的保存缺少对其安全性与数
据完整
性的控制,这是因为没有对系统进行保密控制,没有系统备份预防
措施,没有对系统的性能进行最终检查。发现系统的设计与控制与
21CFR,
第
11
部分,电子记录的要求不符。<
/p>
-
不能证明对实验室人员进行药品检
测的特殊方法、
设备的使用方法
和有关
…
的
cGMP
等内容进行了培训。
p>
Warning
关键词:质量单位不合格,过程验证,再验证,软件验证,安全性验证,验
D1
and 483
证方案,验证标准,设备的
IQ
与
< br>OQ
,方法验证,操作范围没有进行评价,
清洗验证,<
/p>
HVAC
系统不合格,预防性维护,实验数据,计算机验证,资料
D2
变更
后的验证
,
变更控制,测试的审核与批准,主验证计划不恰当,
第
11
部
D3
分
W-075
D4
to
FDA
明确表示将继续执行
W-080
在出现了很多
GMP
问题后
Schering-Plough<
/p>
在
1998
年同意
FDA
的裁决并
D5
赔款
5000
万美元。
这是
对
FDA
所管制的公司的最大的一次评定。
这份裁决
涉及到
100
多条不同的
规定而且包括了非处方药的内容,
并且公司还同意了
D6
停止生产
73
种其
他产品(验证时间,
2002
年
5
p>
月
21
日)。
Sc
hering
收到
了
5
封警告信和
483
条款。
你可
以下载
5
封警告信
(
< br>D2
至
D6
)
< br>和
18
页
483
检查报告(
D1
)
.
这份
483
条款非常全面,可以作为检查清单来
准备
FDA
检
查。
Warnin
Keywords: Process
validation, revalidation, external
auditor
关键词
:
检验过程
,
再检验
p>
,
外聘审计员
g
警告信
W-074
Example:
例如
?
Primary
deviations:
quality system, no or
insufficient process validation, no
revalidation after changes
D
主要的错误
:
质量系统
,
没有检验过程和及检验
过程不完善
,
没有更改后的再检验
p>
.
Your firm failed to
demonstrate adequate documentation that justifies
the decision for
not revalidating the
...process after making these changes;
In order to facilitate FDA
in making the determination that such corrections
have
been made and thereby enabling FDA
to withdraw its advisory to other federal
agencies concerning the award of
government contracts, and to resume marketing
clearance for class III devices for
which a 5 1 O(k) premarket notification or
Premarket Approval application (PMA)
has been submitted, and Certificates to
Foreign Governments for products
manufactured at your Billerica and Burlington, MA
facilities, we are requesting that you
submit to this office on the schedule below,
certification by an outside expert
consultant that he/she has conducted an audit of
your establishment’s manufacturing and
quality assurance systems relative to the
requirement of the device Quality
System regulations (21 CFR Part 820).
?
您的公司没有提供恰当的文件来证
明做了改变却不进行此流程再检
验的理由
.
为了有利于
FDA
作出决定
,
p>
已经作了这种修订
,
以便于
FDA
可以收回给其他的联盟代理商关于政府契约奖励的咨询工作
,
,
还可以
恢复
3
级设备的市场清除
,
此决议已经提交了一个
510(K)
的预说明或预说
明批准
申请
(PMA),
以及授权给外国政府可以使用柏林敦,
Billerica
,<
/p>
摩络哥的
设施进行产品生产,
我们要求你
必须服从此机构的下述进度表,
并有
一个外部的专家顾问进行验
证,
此专家应指导过你公司符合设备质量
体系规则(
21 CFR Part 820).
的生产和质量检测体系
。
Warnin
Keywords: Validation,
Spreadsheet, Excel, MS Access, Excel,
Word
,
part11
关键词:检验,电子数据表,
Excel, MS
Access, Excel, Word
软件
g
警告信
W-073
D
摩
洛
?
Primary deviations:
no
validation of Excel, Access, Word
主要的错误;缺
哥
少对
Excel, Access,
Word
软件的检验
?
Example:
例如
Failure to
validate computer software used as part of the
quality system for its
intended use
according to an established protocol as required
by 21 CFR
820.70(i). For example:
Software such as Excel, Access, and Word used to
create and maintain data bases
(rejects, complaints, and concessions) and
electronic documents, is not validated.
In their response dated April 3, 2000,
your firm stated that by May 31st, they will
have identified what software is used
for data processing, and identified a
method or methods for validation and/or
verification of the software. This
response is not adequate since
...
?
没有检验作为质量体系的一部分的计算机软件是否满足
21
CFR
820.70(i)
的协议制定的应用要求
。
例如:用于创建和维护数据库(或
者拒绝,抱怨
和妥协)的
Excel, Access,
Word
软件以及电子文件都
没被检验。在他们
2000
年
4
月
p>
3
号做出的回复中,您的公司声称截
至到<
/p>
5
月
31
号,他
们要确定哪个软件用于数据的处理,以及确定一
种或几种软件的检验和查证方法。这种回
复是不恰当的,因为
Warnin
Keywords:
Validation, Spreadsheet, MS Access, Excel, effect
on other program
,
D
part11
g
关键词:检验,电子数据表
, MS Access
和
Excel
软件,对其他程序的影响
警告信
W-072
?
Primary
deviations:
insufficient validation of
Access, no validation of
impact on
other software
主要的问题:对
Access
软件的检验不充分,
没有检验对其他
软件的影响
Example:
例如
You failed to
investigate the failure of the ... when operating
in MS
Access. The system locks up at
random and it is unknown whether the
software which controls the .... during
off of MS Excel, could be similarly
affected.
当运行
MS A
ccess
软件时您没有调查某某的失败原因。此系
统会胡乱锁
住,以及当脱离
MS Excel
软件时,不明确控制
``````
的软
件是否也会受到类似的影响。
D
Warnin
Keywords:
Spreadsheet, validation, change control,
validation of corrective action
,
part11
g
关键词:电子数据表,检验,控制更改,修订行为的验证
警告信
W-071
?
Primary
deviations:
no validation of
spreadsheet, no validation of corrective
action, no documentation of
changes
主要错误
:
缺少对电子数据表的检
验,缺少对修订行为的检验,没有修订文件
?
Examples:
例如
-
Failure to validate computer software used as part
of the quality system for its
intended
use according to an established protocol as
required by 21 CFR
820.70(i). For
example, the data in the Excel spreadsheet
identified as a
of top non-conforming
components contains 16 record counts for part
number
8601618 DC converter failures
compared to 18 record counts for part number
860168 DC converter failures in the
dbase database. The spreadsheet is used
for management review of component
suppliers for all components.
- Failure
to verify or validate corrective and preventive
action to ensure that such
action is
effective and does not adversely affect the
finished device, as required
by 21 CFR
820.100(a)(4).
For example,
..
.
- Failure to
maintain records of changes to documents as
required by 21 CFR
820.40(b). For
example, ...
没有检验作为质量系统的一部分的
计算机软
件是否满足
21 CFR 820.70(i)
的协议制定的要求。例如:
在
Excel
p>
电子
数据表中的数据被认为是头等的不一致部分的“暗杀清单”,包
括使数据库中
16
记录的部分数字
86
01618 DC
转换失败以及使
18
记录的
860168 DC
转换失败
。
这种电子数据表被用于对所有单元提供的组分的检测
。
没有对修订行为和预防
性行为的核实和检验以保证此行为有效以及此行为
对精巧的设备无
反作用,正如
21
CFR 820.100(a)(4)
所述,例如:
没有进行对文件更改记录的维护,
正如
21
CFR 820.40(b)
中所要求的,
例如
:
Warnin
Keywords: Spreadsheet,
validation,
part11
关键词:电子数据库,检验
g
警告信
W-070
?
Primary
deviations:
no validation of
spreadsheets
D
p>
主要错误
:
缺少对电子数
< br>据库的检验
?
Example:
例如:
Your response indicated that Braun is
currently changing the complaint handling
system from tracking complaint
information on an ... spreadsheet to using an
off-the-shelf database system, ...
Tracker. As required by 21 CFR 820.70(i),
Automated Processes, this off-the-shelf
software shall be validated for its
intended use if Braun has not already
done so.
你的回复表明目前布劳恩正
在更改抱怨操作系统,从通过一个
数据库来追踪抱怨信息到使
用一种不用定制的
数据库系统
的追踪者。正如
21 CFR
820
.70(i)
所要求的自动化过程,假如布劳恩不是已经这样作了,这种
不用定制的软件应被检验是否满足对它的预定应用
。
Warnin
Keywords: Excel,
documentation, protection of electronic records,
back-up,
part11
g
关键词:
Excel
软件
,
文件,电子记录的
保护,备份
W-069
?
Primary
deviations:
no documentation of Excel
application software, no
protection of
electronic records
D
主要错误;没有关于
Excel
应用软件的文
件,没有对电子记录的保护
?
Example:
例如
There is no documentation covering
Excel application software, or any
procedures instituted covering the
protection of electronic records or an
established back-up system
<
/p>
没有文件涉及到了
Excel
应用软件,
或者没
有任何涉及到电子记录的保护程序及一个确定了的备份系统。
Warnin
Keywords: validation,
accurate and complete copies, limited access,
part11
关键词:检验,正确完善的拷贝,限制入口
g
W-068
?
Primary
deviations:
inadequate validation,
inaccurate and incomplete copies,
no
limited access to the system,
主要的错误:不恰当
的检验,不正确和
D
不完善的拷贝,没有限制系统入口
?
Examples:
例如
- review of your electronic complaint
files reveals they have not been properly
validated, there is no ability to
generate accurate and complete copies of records
in human readable and electronic form,
there is no protection of records to
enable their accurate and ready
retrieval, access to your system has not been
limited, as well as other significant
deficiencies.
- We strongly encourage
you to perform a thorough and complete evaluation
of
all your electronic records in
accordance with 21 CFR Part 11 as well as any
guidance generated by FDA to assure
conformance to our requirements. Do
not
limit your evaluation solely to the
examples cited above. Only electronic
records and electronic signatures that
meet 21 CFR Part 11 may be used to
satisfy the requirements of 21 CFR
820.198, Complaint Files.
您的
电子抱怨文件的审查表明它们没有被恰当的检验,
没有能力创建书面形
< br>式和电子表格形式的正确完善的记录拷贝,
没有确保正确迅速的索回的记录
保护,使用系统的权利未受限制,以及其他一些重大的不足。我们非常鼓励
你们进行一个对所有的电子记录的正确完善的评估,可以参考
21 CFR
中第
11
部分的要求或者任何来源于
FDA
的且与我们的要求一致的指南,不要将
你的
评估仅限于上述例子。只有符合
21 CFR
中第
11
部分要求的电子记录
和电子签名才满足
21 CFR
820.198
中对抱怨文件的要求。
Warnin
Keywords: networks,
testing,
critical test
,
part11
关键词:网路,测试,严格的测试
g
W-067
?
?
Primary deviations:
design
not suitable for intended use, insufficient
performance testing
D
The
network ... module design limitations, which can
only support up to four
chromatographic
acquisition systems, had up to five
chromatographic systems
connected.
There was no validation showing this configuration
to be acceptable
主要错误:设计不适合预定的应用,性能测试不足
?
某某网路模块设计了限制性,
p>
限制仅能达到支持四个层离法的获得系
统,
而此网路必须要达到五个层离法体系相关连。
没有检验表明这种
构造是可接受的
。
?
Examples:
例如
?
- The network ... module design
limitations, which can only support up to four
chromatographic acquisition systems,
had up to five chromatographic systems
connected. There was no validation
showing this configuration to be acceptable
- System testing was not conducted to
ensure that each system
as configured
could handle high sample rates.
- Validation of the system did not
include critical system tests such as volume,
stress, performance, boundary, and
compatibility
某某网路模块设计了限制性,
限制仅能达到支持四个层离法的获得系统,
此
< br>模块必须要达到五个层离法体系相关连。
没有检验表明此构造可以接受。
系
统测试不能确保已成型的每个系统都可以处理高样本率系统检验不包括
系
统临界测试,例如;容积,压力,性能,边界以及兼容性
representation-坚定信心
representation-坚定信心
representation-坚定信心
representation-坚定信心
representation-坚定信心
representation-坚定信心
representation-坚定信心
representation-坚定信心
-
上一篇:调音台(数字)中英文对照表
下一篇:民航英语教案三