FDA 483：金华Conba Bio-Pharm因共用食堂等交叉污染风险被列四项观察项

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受检机构/公司：Zhejiang, Jinhua Conba Bio-Pharm. Co. Ltd

城市：Jinhua, Zhejiang

类型：Finished Drug Product Manufacturer

FEI号：3003663281

检查员：

RAFEEQ A. HABEEB

检查日期：

07/24 - 07/28/2023

07/31 - 08/01/2023

西门的吐槽：大概是上半年，FDA也披露过一个案例，来自Gland Chemicals Private Limited 印度的一家药企，也是类似的缺陷，QA\\QC\\生产共用一个食堂。原先以为是孤例，但又披露一个（吐槽下，一个月没披露，19号20号两天披露了几十份483的FDA）类似案例。两次检查员并不重复（redica数据库里，这位检查员与查gland的三位，未有合作检查先例），且无合作关系，是否代表一批制剂检查员的观点？

OBSERVATION 1

观察项 1

Your firm failed to perform operations related to the manufacture, processing and packing of xxx in facilities separate from those used for other drug products for human use.

贵企业未在与其他人用药品生产所用设施相分离的设施中，开展xxx的生产、加工和包装操作。

You manufacture drug products and drug substances in xxx buildings/workshops spread in an area of approximately xxx square meters within the same facility. In addition to US products, domestic xxx including xxx xxx xxx API are manufactured in the following xxx workshops within your facility.

贵企业在同一厂区内约xxx平方米范围内分散的xxx栋厂房/车间中，生产药品和原料药。除美国市场产品外，国内xxx（包括xxx、xxx、xxx等原料药）均在贵企业厂区内下列xxx车间中生产。

You manufacture drug products xxx Tablets and xxx Solution for US market in FDF workshops xxx respectively.

贵企业分别在生产制剂（FDF）车间xxx中，生产供应美国市场的xxx片剂和xxx溶液。

Your study QA18005R4 "Risk Assessment of xxx Manufacturing on Environmental Impact" is inadequate as it does not identify all the potential risks of manufacturing of xxx on xxx products.

贵企业的研究文件QA18005R4《xxx生产对环境影响的风险评估》不充分，未能识别xxx生产对xxx产品可能造成的全部潜在风险。

A. RISK OF xxx CROSS CONTAMINATION

A. xxx交叉污染风险

1) Employees from all manufacturing buildings including employees working in FDF workshops No xxx can access one common cafeteria within the premise of the facility for breaks and meals. These common areas are non monitored for any of the xxx products and were not part of your risk assessment study.

1) 来自所有生产厂房（含xxx号制剂车间员工）的员工，均可进入厂区内的同一个公共食堂休息和用餐。这些公共区域未针对任何xxx产品进行监测，也未纳入贵企业的风险评估研究。

2) The exhaust air from the xxx FDF workshop No xxx is passed through a xxx micron) filter followed by a H13 (HEPA) filter before releasing directly into the outside. The air is not passed through a xxx xxx. The H13 filter is changed xxx and the integrity and function of the filter

2) 来自xxx号制剂车间的排风经xxx微米过滤器并随后经H13（HEPA）高效过滤器过滤后，直接排放至室外。该空气未经过xxx xxx。H13过滤器更换xxx，且该过滤器的完整性和功能

3) xxx from xxx used for xxx products in FDF workshop No xxx is released into the xxx of the building. The xxx is not passed through any filter or xxx and is not monitored for xxx residues.

3) 在xxx号制剂车间中，用于xxx产品的xxx被排放至厂房xxx。该xxx未经过任何过滤器或xxx，也未针对xxx残留进行监测。

4) In FDF workshop No xxx the exhaust air from API xxx production area of production line xxx and xxx gowning area, shower room, and container preparation areas of both line xxx and xxx is released after passing through a HEPA filter H13 and is not passed through a xxx xxx. The exhaust air from both these xxx is not monitored for residues at regular intervals.

4) 在xxx号制剂车间中，xxx生产线xxx原料药生产区以及xxx、xxx两条生产线的更衣区、淋浴间和容器准备区的排风，经H13（HEPA）过滤器过滤后排放，但未经过xxx xxx。上述两处xxx的排风未按规定的时间间隔进行残留监测。

B. INADEQUATE MONITORING OF xxx AREAS AND PRODUCTS

B. 对xxx区域和产品的监测不足

You do not monitor for xxx residues in xxx areas of your facility including FDF workshops xxx.

贵企业未对厂区内xxx区域（含xxx号制剂车间）进行xxx残留监测。

C. INADEQUATE MONITORING OF xxx AREAS

C. 对xxx区域的监测不足

Your monitoring of xxx FDF workshops xxx is not at regular frequency. You have monitored for xxx residues in FDF workshop xxx and xxx residues in workshop xxx and the last date of monitoring for each of these residues is as follows

贵企业对xxx号制剂车间的监测未按固定频率进行。贵企业对xxx号制剂车间的xxx残留、xxx号车间的xxx残留进行过监测，各项残留的最后监测日期如下：

1) xxx - 2021, March

2) xxx - 2021, June

3) xxx - 2020, May

1) xxx —— 2021年3月

2) xxx —— 2021年6月

3) xxx —— 2020年5月

You have not monitored for xxx and xxx residues in workshop xxx.

贵企业未对xxx车间进行xxx和xxx残留监测。

D. VALIDATION OF xxx DECONTAMINATION METHOD

D. xxx去污方法的验证

Your firm uses xxx to decontaminate exhaust air from few locations and also to decontaminate tools and parts. You have not done an effectiveness check/validation study to show that your decontamination solution used to clean the xxx residues is effective.

贵企业使用xxx对少数位置的排风进行去污处理，并用于工具和部件的去污。贵企业未开展有效性检查/验证研究，以证明用于清除xxx残留的去污溶液确实有效。

E. xxx ASSAY METHOD

E. xxx检测方法

Your method for detecting xxx residues is not sufficiently sensitive to detect low levels of contamination. The limit of detection for your method is not capable of detecting levels in parts per billion. The limit of detection (LOD) for your method was reported as follows:

贵企业检测xxx残留的方法灵敏度不足，无法检出低水平污染。该方法检出限达不到"十亿分之一"（ppb）水平。贵企业方法的检出限（LOD）报告如下：

xxx xxx ppm

Furthermore you have not established a detection limit for xxx.

此外，贵企业尚未建立xxx的检出限。

OBSERVATION 2

观察项 2

Employees engaged in the manufacture and processing of a drug product lack the training required to perform their assigned function.

从事药品生产和加工的员工，缺乏履行所分配职责所需的培训。

Specifically, the employees engaged in the 100% visual inspection of xxx sterile solution are not adequately trained to do visual inspection within the specified time. Your validation batch records for xxx solution shows that employees took xxx trial to complete visual inspection. However your training records for employees performing visual inspection shows that employees were allowed to take up to xxx to complete inspection of each vial. Furthermore you did not perform visual inspection using a white background. You did visual inspection using only a xxx background during both the training and inspection of all xxx validation batches.

具体而言，从事xxx无菌溶液100%目视检查的员工，未经过充分培训，无法在规定时间内完成目视检查。贵企业xxx溶液验证批记录显示，员工需经xxx次尝试方可完成目视检查；然而，贵企业目视检查员工的培训记录显示，允许员工完成每个西林瓶检查的时间最多为xxx。此外，贵企业未使用白色背景进行目视检查；在全部xxx验证批次的培训和检查中，贵企业仅使用xxx背景进行目视检查。

OBSERVATION 3

观察项 3

Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity.

实验室控制未包括建立科学合理且适当的检验规程，以确保组分和药品符合适当的鉴别、含量、质量和纯度标准。

Specifically, You do not perform growth promotion testing on all lots of prepared media. You prepare the following media for testing of incoming raw materials, xxx, finished product, and environmental samples.

具体而言，贵企业未对全部已配制培养基批次进行促生长试验。贵企业配制以下培养基，用于来料原料、xxx、成品和环境样品的检验：

1) xxx media - Testing of xxx

1) xxx培养基 —— xxx检验

2) xxx media - Mold and yeast testing of raw materials and finished products

2) xxx培养基 —— 原料和成品的霉菌及酵母菌检验

3) xxx media - Testing of finished products for E.Coli, and sterility testing of finished product for mold and yeast

3) xxx培养基 —— 成品大肠杆菌检验，以及成品霉菌和酵母菌的无菌检验

4) xxx media - Specific microbial testing of E.Coli in finished products (in media)

4) xxx培养基 —— 成品大肠杆菌特定微生物检验（培养基法）

5) xxx media - Specific microbial testing of E.Coli in finished products xxx plate)

5) xxx培养基 —— 成品大肠杆菌特定微生物检验（xxx平板法）

6) xxx media - Finished product testing for both aerobic and anaerobic microorganisms

6) xxx培养基 —— 成品需氧和厌氧微生物检验

OBSERVATION 4

观察项 4

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established.

未建立旨在防止标示为无菌的药品发生微生物污染的程序。

Specifically,

具体而言：

A) You do not test the integrity of the xxx before each batch during the manufacturing of the sterile product xxx solution. You test xxx integrity only xxx xxx or between two different products.

A) 在无菌产品xxx溶液的生产过程中，贵企业未在每一批次生产前检验xxx的完整性。贵企业仅在xxx xxx时或两种不同产品之间检验xxx的完整性。

B) You dilute xxx and filter it through a xxx micron filter to produce xxx for use in cleaning of your RABS and the surrounding areas. You do not record the concentration of xxx produced.

B) 贵企业将xxx稀释后经xxx微米过滤器过滤，制得用于清洁RABS（限制进入隔离系统）及其周边区域的xxx。贵企业未记录所制得xxx的浓度。