FDA 483表：西班牙Grade Biopharma S.L. 20181204

翻江鼠

受检公司：Grade Biopharma S.L.

受检地址：Parque Technologico de Leon, C/Nicostrato Vela S/N, Leon 24009, Spain

受检身份：合同无菌注射药品生产商

FEI号：3011566408

检查员：Kham Phommachanh/Consumer Safety Officer, Aditi S. Thakur/Chemist Reviewer

检查日期：2018-10-08,15 &16

签发日期：2018-10-16

发布日期：2018-12-04

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。

Preapproval Inspection (PAI) 批准前现场检查（PAI）

（原文件在此列出了检查品种，均已被遮盖）

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: 检查你公司期间我们发现

OBSERVATION 1 缺陷1

The information stated in the submitted drug application is not exactly as is on site. Specifically, drug application (b)(4) states that the firm is ready for inspection and identified as having functions, responsibilities, and operations including primary packaging and vial labeling. On site observation revealed no labeling equipment and currently site has no capability to perform labeling operations for vial. 在所提交的药品申报资料中的信息与现场情况有差异。具体来说，药品申报资料XX中声称公司已准备好接受现场检查，并说已具备相关功能、职责和操作条件包括内包和西林瓶贴标，但在现场发现并没有贴标设备，目前工厂并没有能力对西林瓶进行贴标操作。

OBSERVATION 2 缺陷 2

Labeling equipment is no qualified in preparation for commercialization of drug product. Specifically, one of the responsible functions described in the drug application (b)(4) is labeling and labeling machine is in placed to perform labeling operation for (b)(4) but is not currently qualified.贴标设备还未针对商业化药品生产进行确认。具体来说，药品申报资料XX中说该工厂负责的操作之一是贴标，XX贴标设备放在现场，但还未进行确认。

OBSERVATION 3 缺陷 3

There are no established written procedures for handling labeling and packing operations. For examples, 未制订书面的贴标处理和包装操作程序，例如：

A.    Procedures describing in sufficient detail the controls employed for the issuance of labeling are not written. 没有书面程序详细描述标签发控制

B.    Written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, examination and testing of labeling and packaging materials. 没有书面程序详细描述标签和包材接收、鉴别、存贮、取样、检查和测试

C.    Procedures designed to assure that correct labels, labeling and packaging materials are used for drug products are not written. 没有书面程序用以确保使用正确的标签和包材

OBSERVATION 4  缺陷 4

The certificate of Analysis from the drug application does not match the raw data from the analytical test records and specification sheet. Specifically, drug application (b)(4) the related substance impurities results provided in the CAO approved on 10/21/2016 for the batches (b)(4) submitted to the agency does not match the reported results on raw data on the specification sheet for all the corresponding batches.

药品申报资料中的COA与检验记录和质量标准中的原始数据不一致。具体来说，药品申报资料XX中，提交给FDA的XX批XX于20161021批准的COA中有关物质杂质结果与所有对应批次的原始数据中报告结果并不一致：

a)     For batch (b)(4) the related substance HPLC (%w/w) COA submitted in the application did not match the Analytical Development Specification申报资料中提交的XX批次有关物质HPLC（%W/W）COA与分析开发标准不一致

b)    For batch (b)(4) the related substance HPLC (%w/w) COA submitted in the application did not match the Analytical Development Specification申报资料中提交的XX批次有关物质HPLC（%W/W）COA与分析开发标准不一致

c)     For batch (b)(4) the related substance HPLC (%w/w) COA submitted in the application did not match the Analytical Development Specification申报资料中提交的XX批次有关物质HPLC（%W/W）COA与分析开发标准不一致

OBSERVATION 5  缺陷 5

Original records of analysis submitted in the drug application was not available. Specifically, the original COA record for (b)(4) for batches (B)(4) were not available. Specifically,

在药品申报资料中提交的分析数据没有原始记录。具体来说，没有XX批次XX的原始COA记录。具体如下：

a)     The original copy of the COA record approved on10/21/2016 submitted in the application for the batches (b)(4) was not available. 在申报资料中提交的XX批次于20161021批准的COA没有原始件

b)    The original copy of the COA record approved on10/21/2016 submitted in the application for the batches (b)(4) was not available. 在申报资料中提交的XX批次于20161021批准的COA没有原始件

c)     The original copy of the COA record approved on10/21/2016 submitted in the application for the batches (b)(4) was not available. 在申报资料中提交的XX批次于20161021批准的COA没有原始件

OBSERVATION 6 缺陷 6

There is no established written procedure in the event of change in the version of the Certificate of Analysis. 没有制订书面程序规定COA版本修订的处理方式。

Specifically, controls and procedures to track change history for the certificates of analysis (CoA), which document whether a drug meets specifications, to prevent unauthorized changes to a CoA after quality unit approval is deficient. For example,具体来说，为防止在质量部门批准之后对COA进行未授权修改而制订的追踪COA修改历史记录一个药品是否符合质量标准的程序有缺陷，例如

A.   (b)(4) Batch (b)(4) three version of COA approved on 10/21/2016, 03/31/2017, 10/15/2018 were found without providing any unique identification number on the documents. XX批次有3个版本的COA，批准日期分别为20161021、20170331和20181015，在文件上没有任何唯一编号

B.   (b)(4) Batch (b)(4) three version of COA approved on 10/21/2016, 03/31/2017, 10/15/2018 were found without providing any unique identification number on the documents. XX批次有3个版本的COA，批准日期分别为20161021、20170331和20181015，在文件上没有任何唯一编号

C.   (b)(4) Batch (b)(4) three version of COA approved on 10/21/2016, 03/31/2017, 10/15/2018 were found without providing any unique identification number on the documents. XX批次有3个版本的COA，批准日期分别为20161021、20170331和20181015，在文件上没有任何唯一编号

本文摘自 Julia法规翻译

syhorchid

了解一下

adou

这样也能搞FDA···

gongchi

这个就是典型的有些公司的情况，整体工作还没有完善或准备好，想着后面慢慢做，就急忙报了DMF资料，殊不知FDA给了受理号后就随时可能来检查，可是来了缺没有落实完，就等于前面的工作都白做了。

kc1711422001

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