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受检机构/公司：Taenaka Kogyo Co., Ltd.
城市：Mobara, Chiba, 297-0033, Japan
类型：Active pharmaceutical ingredient manufacturer活性物质生产商
FEI号：3003282619
OBSERVATION 1
Training is not regularly conducted by
qualified individuals, does not cover the particular operations that employees
perform and GMP as it relates to the employees' functions, and is not
periodically assessed.
有资质的人员未定期进行培训，未涵盖员工执行的具体操作以及与员工职能相关的GMP，并且未定期进行评估。
西门：一般最严重的发现项，会放在越靠前，这里是先培训和资质维护、生产的压差维持&生产没有压差报警且生产期间无人监视压差、稳定性箱&培养箱温湿度报警下班后无报警通知流程，检测物料的放行不充分。
这里，也代表了一个检查员心里，优先级，尤其这是个原液厂家。对于原液，压差高于温度，对于压差的关注才是防污染的关键。温度湿度超出一点，或一段时间，其实对于产品影响不大。
Specifically,具体来说，
Your firm does not provide adequate
training and assessment of employees performing visual examination of finished
drug substances to ensure they are capable of observing the types of
contaminants such examinations are intended to detect.
贵公司未为执行成品灯检的员工提供足够的培训和评估，以确保他们能够发现此类检查旨在检测的污染物类型。
西门：这里是他们家原液的物料中，有个目检步骤，参考制剂灯检要求来要求他们了。
Your production process for xxx includes a
100% visual examination step in which the xxx material is xxx visually examined
for contaminants.
贵公司用于xxx的生产流程包括一个100%灯检步骤，在此步骤中，xxx物料被xxx目视检查是否有污染物。
Your training process for operators
performing these inspections does not include an assessment to determine
whether or not the operators are capable of observing the types of contaminants
such examinations are intended to detect.
贵公司对执行这些检查的操作员的培训流程不包括评估，以确定操作员是否能够发现此类检查旨在检测的污染物类型。
Since the beginning of 2022, your firm has
manufactured, released, and distributed xxx lots of this drug substance,
totaling approximately xxx.
自2022年初以来，贵公司已生产、放行并分发了xxx批次的原液，总计约xxx。
OBSERVATION 2
Ventilation systems, including equipment
for control of air pressure, are not adequately designed and constructed to
minimize risks of contamination.
通风系统，包括控制空气压力的设备，设计和建造不充分，未能最小化污染风险。
Specifically,具体来说，
The production suites used by your firm in
the manufacturing of drug substance lots are not adequately equipped to prevent
contamination of in-process substances from the neighboring outside
environment.
贵公司在生产原液批次时使用的生产车间装备不足，无法防止在处理物质受到邻近外部环境的污染。
a) The heating, ventilation, and air
conditioning (HVAC) system used to establish the specified differential
pressure between the production suites and the neighboring outside environment
are not sufficient to ensure this pressure differential is maintained.
用于建立生产车间与邻近外部环境之间规定的压差压力的供暖、通风和空调（HVAC）系统不足以确保维持这种压差。
On 04/09/24, I observed the gauge
displaying the pressure differential between the Plant xxx No. xxx Room and the
outside environment drop to less than xxx Pa, which is below the specified
range of xxx kPa.
在04/09/24，我观察到显示工厂xxx号xxx房间与外部环境之间压差的仪表下降到少于xxx帕斯卡，这低于规定的xxx千帕斯卡范围。
Across this differential, the No. xxx Room
is designed to contain higher air pressure than the outside environment to
prevent unfiltered air from entering the area while in-process drug substances
are exposed.
在这个压差中，xxx号房间被设计成比外部环境包含更高的空气压力，以防止未过滤的空气在原液暴露时进入该区域。
b) The monitoring devices used to ensure
the differential pressure between the production suites and the neighboring
outside environment are not equipped with alarm systems to alert personnel to
pressure excursions.
用于确保生产车间与邻近外部环境之间压差的监测设备没有配备警报系统来提醒人员注意压力偏差。
西门：都4204年了，车间压差还要用压力表……
The gauge displaying the pressure
differential between the Plant xxx No.xxx Room and the neighboring outside
environment is not visible to production operators at work inside the suite,
and no personnel are assigned to monitor the gauge while manufacturing
operations are taking place inside the suite.
显示工厂xxx号xxx房间与邻近外部环境之间压差的仪表对在车间内工作的生产线操作员是不可见的，并且在车间内进行生产操作时没有人员被指派来监控仪表。
西门：没有自动化，估计是一日两三次记录，这种没法监控的压差报警，现在是不被认可的，尤其现在annex中 报警是个很重要部分，老美也是annex1的联合作者
Lots of xxx drug substance are xxx in the
Plant No Room.
许多xxx原液在工厂xxx号房间中xxx。
OBSERVATION 3
Facilities for the storage of materials
under controlled temperature and humidity conditions are not sufficiently
monitored to ensure the material characteristics of items stored inside them
are maintained.
用于在受控温度和湿度条件下储存物料的设施没有得到充分的监控，以确保储存在其中的物品的物料特性得以保持。
Specifically,具体来说，
The controlled temperature storage chambers
used by your firm to store various materials involved in GMP drug substance
manufacturing operations are not monitored in a way that ensures temperature
excursions are addressed in a timely manner.
贵公司用于储存参与GMP原液制造操作的各种物料的控温储存室没有得到及时处理温度偏差的监控方式。
The alarm systems installed on such units
throughout your facilities are configured to send email notifications to your
Quality Control (QC) Manager, QC Test Manager, and Analytical Equipment Manager
in the event one or more of the chambers experiences a temperature excursion.
在贵公司的设施中安装在这些单元上的报警系统配置为在任一储存室经历温度偏差时向贵公司的质量管理（QC）经理、QC测试经理和分析设备经理发送电子邮件通知。
However, your firm has not established
procedures or policies to ensure any of these personnel monitor their email for
notifications outside of your office hours of 8:00 am to 5:00 pm,
Monday-Friday.
然而，贵公司没有建立程序或政策来确保这些人员在周一至周五早上8:00至下午5:00的办公时间之外监控他们的电子邮件以获取通知。
西门：这里，其实我不理解，是没法安装手机邮箱么，还是没法做接口。按照我理解一个报警至少有两种报警通知方式是必须要的（当然国内GSP强制要求了），所以定期的假阴性确认也是很有必要，对于产品贮存的报警优先级别很高
Chambers monitored per this system include
but are not limited to the following:
按照此系统监控的储存室包括但不限于以下内容：
a) Stability chambers used to store drug
substance samples held for stability studies,
用于储存稳定性研究中持有的原液样本的稳定性储存室，
b) Incubators used to promote microbial
growth of finished drug substance, water, and environmental monitoring samples.
用于促进成品原液、水和环境监测样本的微生物生长的培养箱。
OBSERVATION 4
Testing designed to ensure that API
specifications for microbiological purity and appropriate action limits for
total microbial counts and objectionable organisms are met is not conducted in
a way that ensures the validity of results.
旨在确保API规范的微生物纯度和适当的总微生物计数及有害生物行动限值得到满足的测试，并没有以确保结果有效性的方式进行。
Specifically,具体来说，
xxx of the growth media plates purchased by
your firm in their xxx form are tested to demonstrate their ability to grow
colonies of microorganisms, regardless of the number of media plate lots
received that xxx in 2023, your firm received xxx growth media plates each from
manufacturer's lots xxx however growth promotion testing was only performed on
lot xxx.
xxx形式的生长培养基板xxx被测试以展示它们生长微生物菌落的能力，无论在2023年收到的培养基板批次数量是多少，贵公司每批从制造商那里收到xxx生长培养基板，然而，仅对批次xxx进行了生长促进测试。
These plates are used to perform Total
Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) testing
for the release of xxx and xxx lots, respectively, since the beginning of 2022.
这些板被用来执行自2022年初以来分别释放的xxx和xxx批次的总需氧微生物计数（TAMC）和总酵母及霉菌计数（TYMC）测试。
