翻译： JULIA 来源：Julia法规翻译
受检公司：Lupin Limited
受检地址：Unit 3, Plot No. M-1, Sez, Phase Ii, Misc Zone, Apperal Park,Dist Dhar, Pithampur, Madhya Pradesh, 454775 India
受检身份：制剂生产商
FEI号：3009107538
检查员：YasaminAmeri/Chemist/Biologist
检查日期：2018-10-08至 2018-10-18
签发日期：2018-10-18
发布日期：2018-11-05
This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations. And do not represent a final agency determination regarding your compliance if you have an objection regarding an observation, or have implemented, or plan to implement corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA to address above. If you have any questions, please contact FDA at the phone number and address above.
本文件列出了FDA代表在对你工厂检查期间所发现的问题。这些只是检查发现，并不代表FDA对你公司合规性的最终结论。如你们对某一缺陷有异议，或已实施或计划实施纠正措施来纠正某个缺陷，你们在检查期间与FDA代表讨论你们的异议与措施，或通过上述地址向FDA提交资料。如有问题，请通过上述地址电话与FDA取得联系。
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: 检查你公司期间我们发现
Drugs 药品
OBSERVATION 1 缺陷1
Control procedures are not established which monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. 未建立控制程序监控输出，未验证可能导致中间体和制剂成品特性波动的生产工艺性能。
Specifically, 具体来说，
a) Your process performance qualification (PPQ) study is deficient in that you did not include the second exhibit batch for(b)(4) mg, lot# (b)(4) which failed (b)(4). You rejected this batch and did not include it in your PPQ report.
你们的工艺性能确认（PPQ）研究有缺陷，其中未包括第二批申报批次，该批次XX不合格。你们拒收了该批，并未将其包括在你们的PPQ报告中。
During the inspection, you stated this batch was a product development batch manufactured before exhibit batches and production process is recorded in PD notebooks. WhenI asked for the production records and copies of the PD notebooks, you stated that this batch was the first exhibit batch and failed (b)(4). Review of your SAP records showed that this batch was the second exhibit batch, then you admitted that this batch was the second exhibit batch which failed (b)(4) and you rejected the batch.
在检查期间，你们声称该批次是研发批次，是在申报批之前生产的，其生产工艺记录在PD笔记本上。当我索要生产记录和PD笔记本的副本时，你们声称该批次是申报批次的第一批，XX不合格。检查你们的SAP记录则显示该批次是第二个申报批次，然后你们承认说该批确实是第二个申报批准，但因XX不合格而拒收了。
b) Additionally, after observing I out of (b)(4) failed the (B)(4) weight in exhibit batch #(b)(4) instead of investigation and (b)(4) more data, you revised the exhibit batch record and removed “(b)(4) weight measuring” requirement.
另外，你们在发现XX申报批中XX重量不合格时，你们并不是进行调查并查看更多数据，而是修改了申报批次的记录，从中删除了“XX称重”的要求。
OBSERVATION 2 缺陷 2
Written procedures for cleaning and maintenance fail to include description in sufficient detail of methods, equipment and materials used, description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance and instructions for removal or obliteration of previous batch identification, 书面清洁和维护程序未包括对所用方法、设备与物料的详细描述、对设备拆卸与装配方法的详细描述，不足以确保进行恰当的清洁与维护，以及指导清除或除去前一批次的物料。
Specifically, 具体来说
a) Cleaning validation and verification for rooms and equipment used for (b)(4) filling, and (b)(4) of (b)(4) mg are deficient. You have not performed full cleaning studies on dedicated equipment and cleaning validation on production room #(b)(4) which is a multi-use room and is used for (b)(4) of (b)(4) as well as filling of (b)(4) and other potent drug products such as (b)(4) solutions, (b)(4) drug products, etc. to ensure preventing cross contamination and carry over.
XX灌装与XX品种XXmg所用房间与设备清洁验证和定期确认有缺陷。你们对专用设备进行了全面清洁研究，对共用生产房间XX进行了清洁验证以确保能防止交叉污染和残留，该房间亦用于XX灌装和其它高活性药品如XX溶液、XX药品等的生产。
You failedto provide a proper study and execution plan for validation and verification ofthe cleaning. During the inspection you stated you conduct Type (b)(4) cleaning, which is a (b)(4) for cleaning of equipment used in production of (b)(4)mg since they are dedicated equipment. Later, you stated you perform Type (b)(4) cleaning, which is a (b)(4) on production of (b)(4) mg even though they are dedicated equipment. On Tuesday Oct. 16, 2018 (two days before inspection closing day) you provided a series of data showing swab sample results for different production equipment for (b)(4) and stated you have done a few studies and determined the hold time for cleaned equipment.
你们未能提供一份适当的清洁验证与确认研究和执行计划。在检查期间，你们声称你们执行了X类清洁，这是用于XXmg生产的设备的清洁程序，但它们是专用设备。后来，你们声称说你们执行了X类清洁，而这类清洁是XXmg生产的设备清洁程序，亦是专用设备。2018-10-16（检查结束之前2天），你们提供了一套数据显示不同生产设备的XX擦拭取样结果，声称你们已进行了一些研究，并确定了清洁后设备的保持时间。
b) Your batch record for (b)(4) of (b)(4) is missing type of cleaning and cleaning instructions on (b)(4) unit and there is no computer station inside the (b)(4) room for the operator to access and retaining SOP electronically.
你们的XX与XX批记录里并没有XX单元的清洁类型与清洁指令，在XX房间里亦没有计算机让操作人员可以获取电子SOP。
OBSERVATION 3 缺陷 3
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. 未对计算机或相关系统采取适当的控制用以确保只有经授权的人员才可修改主生产和检验记录或其它记录。
Specifically, 具体来说
a) Control over the computerized system in QC laboratory is deficient. Your QC laboratory Manager has permission to allow modification tothe sequences in HPLC and GC systems. Your QC laboratory review does not review the modification to the sequence after unlocking and change to the sequence. Your QC reviewer even stated that they do not investigate modifications to thesequences during normal review process and accepts the audit trail report as “sequence modified”.
对QC实验室的计算机化系统控制有缺陷。你们的QC实验室经理有权限对HPLC和GC系统的序列进行修改。你们的QC实验室审核并不会审核解锁之后的序列修改及变更。你们的QC审核员甚至声称他们在日常审核过程中并不会对序列修改进行调查，并且会接受“序列已修改”的审计追踪报告。
You stated that the unlocking permissions should be approved by QA and are kept in modified folder for that specific sequence. You failed to provide a copy of a modified sequence which is approved by QA. When I asked for traceability of the permissions you stated that the permission records are not traceable.
你们声称解锁权限要由QA批准，并保存在特定序列的修改后文件夹中。当我索要许可追溯时，你们未能提供修改后由QA批准的序列副本，你们声称许可记录是不能追溯的。
b) Your procedure (QCD-60, QCD61, and ITP-034) for control of computerized systems does not have instruction modification control over sequences in HPLC and GC and (b)(4) creation of folders standalone instrument such as FTIR, UV-Vis, etc., and locking of the folders at the (b)(4).
你们的计算机化系统控制程序（QCD-60、QCD61和ITP-034）中并没有修改HPLC和GC中序列的控制权修改指导，以及为单机版仪器如FTIR、紫外-可见光等创建文件夹和在XX锁定这些文件夹的指导。
OBSERVATION 4 缺陷 4
Sampling procedures are deficient regarding sampling components from the top, middle, and bottom of container 取样程序有缺陷，未规定要从容器的顶部、中间和底部取样。
Specifically, your sampling practice for removal of samples for APIs and (b)(4) is deficient in that you do notcollect samples from different locations of material containers (top, middle and bottom). You use sampling (b)(4) for collecting samples of APIs which come in different size containers (b)(4) and (b)(4) from bags packed in a (b)(4) boxes.
具体来说，你们的API和XX取样操作是有缺陷的，你们没有从物料容器的不同位置采集样品（上中下）。你们使用了XX取样用于采集API样品，这些API进厂时装在不同尺寸容器XX和X箱里包装的袋子XX中。
Device 器械
OBSERVATION 5 缺陷5
Procedures for acceptance of incoming product have not been adequately established. 进厂产品的接收程序不完善。
Specifically, your procedure for receiving and inspection of (b)(4) is deficient in that you do not perform functional test on the received device before release the device for use. This device is used for delivery of (b)(4)mg.
具体来说，你们的XX接收和检查程序是有缺陷的，你们并未对所收到的器械进行功能性测试即放行使用。该器械是用于XXmg给药的。
*DATES OF INSPECITON
2018-10-08 至2018-10-12 （周一至周五）
2018-10-15至2018-10-18（周一至周四）
