FDA 483表：印度Suven Life Sciences Limited

一沙一叶

Julia翻译

受检公司：Suven Life Sciences Limited

受检地址：Plot Nos. 262-271 IDA, PashamylaramSangarddy District, Telangana, India 502307

受检身份：中间体、API和制剂生产商

FEI号：1000623515

检查员：June P. Page

检查日期：2018-02-05 至2018-02-15

签发日期：2018-02-15

发布日期：2018-04-24

OBSERVATION 1 缺陷 1

Appropriate controls are not exercised over computer or related systems to assure that change in master production and control records or other records are instituted only by authorized personnel.

对计算机或相关系统未执行适当控制以确保主生产和检验记录或其它记录的变更只由经授权的人员操作。

Specifically, 具体来说

A.      Your firm has a total of (b)(4) HPLCs and (b)(4) UPLCs used to analyze raw material,finished product, and related substances for products marketed and distributed to the US. The HPLCs and UPLCs use either Empower 3 or EZ CHROM ELITE, while have audit trail capabilities. However, your firm could not provide documentation these audit trails have been electronically reviewed by quality personnel.

你公司共有XX台HPLC和XX台UPLC用于分析原料、成品和已在美国销售上市产品的有关物质。HPLC和UPLC要么使用了EMPOWER3，要么用了EZCHROM ELITE系统，具有审计追踪功能。但是，你们公司并未提交文件证明此审计追踪由质量人员进行了电子审核。

B.      Your firm’s Manager of Quality Assurance and Deputy Manager of QC verified your firm did not conduct electronic data review for any analysis performed in the QC Formulations Laboratory prior to August 2017.

你公司的QA经理和QC副经理证明你们公司在2017年8月前并未对任何QC制剂化验室所做的分析进行电子数据审核。

OBSERVATION 2 缺陷 2

Equipment and utensils are not cleaned and maintained to prevent contamination that would alter the safety, identity,strength, quality or purity of the Intermediates and APIs manufactured.

设备和工器具未清洁并保存以防止对所生产的中间体和API形成可能改变安全性、鉴别、剂量、质量或纯度的污染。

Specifically, on 05 February 2018 and 08 February 2018, during the inspection of your (b)(4) which are used in the manufacturing process for varied APIs in Production Block-(b)(4) Area. Your firm failed to adequately clean and visually inspect the following (b)(4).

具体来说，2018年2月5日和2018年2月8日，在对生产车间XX区域你们用于不同API生产工艺的XX检查期间，你们公司未能充分清洁和目视检查XX：

A.      (b)(4)-3109 is used in the production of (b)(4) API/Intermediate; I observed what appears to be discoloration resembling (b)(4) inside the (b)(4)-3109 in areasthat come into direct contact with drug product. The status of this non-dedicated (b)(4) was identified as cleaned.

(b)(4)-3109用于XX原料药/中间体的生产：我发现在XX-3109内直接接触药品的区域有类似变色的地方。该非专用XX的状态标识为已清洁。

B.      (b)(4)-3139:I observed the gasket used to protect the (b)(4) and the (b)(4) of (b)(4)-3139 was wrapped in Teflon tape and starting to unravel. I observed what appeared tobe missing pieces of the Teflon tape at the bottom of the (b)(4). In addition, Iobserved what appeared to be a white, powdery residue along the inside of the(b)(4). The status of this equipment was identified as cleaned and a visual inspection was documented in the Equipment Use Logbook.

(b)(4)-3139：我发现用于保护XX-3139的XX和XX的垫圈用聚四氟乙烯带包裹，已经开始散开。我发现在XX底部有聚四氟乙烯带掉落的碎片。另外，我发现在XX内部有白色粉状残留。该设备的状态被标为已清洁，设备使用日志上有记录目视检查。

C.      (b)(4)-3137: I observed what appears to be (b)(4) residue and black residue alongside the sides of this (b)(4). In addition, I observed the (b)(4) bolts located on the bottom of the (b)(4) that comes in direct contact with drug products to have a (b)(4) discoloration. I observed a hole at the bottom of the (b)(4) indicatingthis (b)(4) is damaged. The Equipment Use Logbook documents the equipment qualification were completed on 29 December 2017 and the status of this non-dedicated equipment was identified as cleaned.

(b)(4)-3137：我发现在此XX的边沿有XX残留和黑色残留。另外，我发现位于XX底部的XX螺栓与药品有直接接触，已有XX变色。我发现在XX底部有一个孔洞，显示XX已受损。该设备使用日志记录了该设备确认是在2017年12月29日完成的，此非专用设备的状态标识为已清洁。

OBSERVATION 3 缺陷 3

Manufacturing Batch Records are deficient.

生产批记录有缺陷。

Specifically, 具体来说

A.      On 13 February 2018, your firm failed to document in-process checks during the manufacturing of the durg product, (b)(4) Tablets, Batch #(b)(4) on Form,F/CQO-F/320, as outlined in Step (b)(4) of the Batch Manufacturing Record. However,this step was verified by your firm’s Quality Assurance.

2018年2月13日，你公司未按批生产记录第XX中所列的在表格F/CQO-F/320上记录XX片剂批号XX药品生产的中控检查。但是，该步骤经过了你公司QA的核查。

B.      Recorded weights are not verified by a second verifier.

所记录的重量并未由第二人核查。

OBSERVATION 4 缺陷 4

Procedures for sampling of raw materials were not followed.

未遵守原料取样程序。

Specifically, on 05 February 2018, Iobserved the raw material, (b)(4) (Batch #(b)(4) did not contain the appropriate number of sampled containers as written in your firm’s written procedures forraw material sampling (SOP/CQO/3024).

具体来说，2018年2月05日，我发现XX原料XX批号未按你公司书面程序“原料取样SOP/CQO/3024”从适当数量容器中取样。

OBSERVATION 5 缺陷 5

Label access is not controlled.

标签未受控。

***THIS IS A REPEAT OBSERVATION***此为重复缺陷

Specifically, the label storage room that contains printed packaging materials for (b)(4) Capsules and (b)(4) Tables was observed to be unlocked by your firm’s Corporate Quality Manager during a walkthrough of production on 12 February 2018.

具体来说，标签存贮间有XX胶囊和XX片剂的打印包材，2018年2月12日在生产部检查时发现你们公司质量经理没有锁门。

OBSERVATION 6 缺陷 6

Employees engaged in the manufacture,processing, packing, and holding of a drug product lack the training required to perform their assigned functions.

生产、加工、包装和保存药品的员工缺乏执行其指定职责所需的培训。

***THIS IS A REPEAT OBSERVATION***此为重复缺陷

Specifically, your firm failed to conductcGMP training for (b)(4) of (b)(4) selected employees performing Quality related functions, such as, production, quality control, and quality assurancein 2016.

具体来说，你公司在2016年未向XX所选履行质量相关职责的员工如生产、QC和QA执行CGMP培训。

OBSERVATION 7 缺陷 7

Your firm’s Production Quality Reviews (PQRs) are deficient.

你公司的生产质量回顾（PQR）有缺陷。

Specifically, 具体来说

A.      2017PQR for (b)(4) Capsules (review period January 2017-December 2017):

2017年XX胶囊的PQR（回顾期间2017年1月至2017年12月）

1.      Does not address corrective and preventative actions implemented for out of specification (OOS16-005) for (b)(4) content for (b)(4) Capsules (b)(4) mg, Batch #(b)(4) .

并未说明XX胶囊XX批号XX含量OOS（OOS16-005）所执行的纠正与预防措施

2.      Is missing change control (EN/CCP/17/5036) for the installation of new equipmentin the packing line (b)(4)  inserting Machine, (b)(4)  Machine, (b)(4) Labeling Machine, (b)(4) Overprinting, Leaflet in Outserter Machine, and Torque (Machines), which were qualified and installed in 2017.

缺失了在包装线XX安装新放置说明书的新设备，XX机XX贴标机XX打印机和扭力机变更控制（EN/CCP/17/5036），这些设备于2017年安装并确认。

3.      In addition, your firm’s written procedure for product Quality Review (SOP/CQO/3021), defines the product review period as a calendar year from January to December. However, the 2017 PQR for (b)(4) covers a review period of January 2016-December 2017. A Deviation was not provided.

此外，你公司书面产品质量审评程序（OP/CQO/3021）定义了产品回顾时间段为从1月至12月的自然年。但是，XX产品的2017年PQR覆盖了自2016年1月-2017年12月的时间段。未能提供偏差。

B.      Your firm’s PQR for (b)(4) Tablets does not address corrective and preventative actions implemented for an out of specification (OOS) for the following:

你公司的XX片剂PQR并未说明为以下OOS所实施的纠正和预防措施

1.      OOS 17-002: Unknown impurity peaks were found in (b)(4) Tablets, Batch (b)(4),dated 7 March 2017.

OOS17-002： 2017-3-7在XX片剂批号XX检测中发现未知杂质峰

2.      OOS 17-003: Sub-potent assay results for (b)(4) tablets, Batch #(b)(4) and Batch #(b)(4) dated 17 March 2017.

OOS17-003： 2017-3-17 XX片剂XX批次和XX批次含量结果不合格，

C.      Your firm’s APQR for (b)(4) Capsules does not address corrective and preventative actions implemented for an out of specification (OOS) for the following:

你公司的XX胶囊APQR并未说明为以下OOS实施的纠正和预防措施

1.      OOS 17-002: Unknown impurity peaks were found in (b)(4) Capsules, Batch #(b)(4) dated 7 March 2017.

OOS17-002：2017-03-07在XX胶囊XX批号中发现未知杂质峰

北重楼

谢谢分享！

预知子

谢谢分享

成慧潫

6666
谢谢分享

xqliu

学习一下啦，谢谢提供分享。

syhorchid

谢谢分享

adou

2018年2月12日在生产部检查时发现你们公司质量经理没有锁门。
这种缺陷确认第一次听说

一沙一叶

adou 发表于 2018-6-11 10:54
2018年2月12日在生产部检查时发现你们公司质量经理没有锁门。
这种缺陷确认第一次听说

质量经理还要管着标签仓库的钥匙