2018年12月19日,FDA官网发出对河北西尔欧(中国)医疗设备有限公司(美国CAO Group,Inc.中国分公司)的警告信:

缺陷翻译如下:

Warning Letter 320-19-05

Cao Medical Equipment Co., Ltd.

西尔欧(中国)医疗设备有限公司(美国CAO Group,Inc.中国分公司)

Number 19 Baihe Road, Langfang Industrial Zone

Langfang, Hebei, 065001

CHINA

河北省廊坊市廊坊经济技术开发区百合道19号

1.      Your firm failed to perform, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release, and for each batch of drug product required to be free of objectionable microorganisms, appropriate laboratory testing, as necessary (21 CFR 211.165(a) and (b)).

贵公司未能在放行前对每批药品进行适当的实验室判定, 以确定是否符合药品的最终标准, 包括每种活性成分的鉴别和含量, 以及对每批要求无致病菌的药品(21 cfr 211.165(a) 和 (b))。

You manufacture (b)(4) drugs intended for use during (b)(4) procedures and applied to (b)(4). Drugs applied to (b)(4) must be free of objectionable microorganisms. However, you failed to test your finished drug products for total aerobic microbial count and objectionable microorganisms prior to release and distribution. In addition, you also failed to test each batch of drug products for identity and strength of active ingredients prior to release and distribution. Without this testing, you do not have scientific evidence that all drug product batches you manufactured meet their established specifications prior to release.

你们生产在XX期间使用并用于XX的药品。用于XX的药品应不含致病菌。然而, 在放行和分销之前, 你们未能检验你们的成品药物产品的总好氧微生物和致病菌数量。此外, 在放行和分销之前, 你们也未能对每批药物产品的活性成分的鉴别和含量进行测试。如果没有这种测试, 你就没有科学证据表明你们生产的所有药品批次在放行前都符合其既定标准。

2.      Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

贵公司未能对每个成分进行鉴定并确认其纯度、含量和质量符合所有适当的书面标准。贵公司也未能以适当的时间间隔 (21 cfr 211.84(d)(1) 和 (2)) 验证和确定原料供应商检验报告的可靠性。

Your firm failed to test incoming active pharmaceutical ingredients and other components used to manufacture your drug products to determine their identity, purity, strength, and other appropriate quality attributes. Instead, your firm relied solely on certificates of analysis (COA) without verification of your suppliers COA, or in other instances, you used components to manufacture drugs without having received a COA.

贵公司未能对药品的生产所用原料和其他组分进行检验, 以确定其鉴别、纯度、含量和其他适当的质量属性。相反, 贵公司仅仅依赖于供应商的检验报告书(COA)但却未对供应商COA进行确认, 或者在某些情况下, 你们甚至未收到COA就将其投入生产。

Your firm also uses glycerin as an ingredient in (b)(4) drug products. Your firm failed to analyze lots of glycerin raw material from your supplier for the presence of diethylene glycol (DEG) and ethylene glycol (EG) prior to releasing it for use in drug product manufacturing. DEG contamination in glycerin has resulted in various lethal poisoning incidents in humans worldwide.

贵公司使用甘油作为 (b)(4) 药品的组分。贵公司在放行用于药品生产之前,未能对多批来自供应商的甘油原料进行检验,以确定是否含有二甘醇 (DEG) 和乙二醇 (EG)。甘油中的 DEG污染导致了全世界人类的各种致命中毒事件。

See FDA’s guidance document Testing of Glycerin for Diethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing glycerin, at https://www.fda.gov/downloads/Drugs/Guidances/ucm070347.pdf.

请参阅FDA指导文件<甘油中二甘醇含量测定>:https://www.fda.gov/downloads/Drugs/Guidances/ucm070347.pdf,可帮助你们满足CGMP要求。

3.      Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).

贵公司用于药品生产、加工、包装或贮存的设备没有适当的设计、足够的尺寸、适当的安装,以使其运转符合预定用途以及便于清洁和维护 (21 cfr)211.63)。

You failed to adequately design, qualify, and control your (b)(4) system used to manufacture drug products. You do not test your source (b)(4) or your production (b)(4) before use in manufacturing. A (b)(4) at your facility is (b)(4) and open to the outdoor environment where it is exposed to vermin, animal waste, and various contaminants.

你们未能充分设计、确认和控制用于药品生产的 (b)(4) 系统。在投入生产之前, 你们不会检验(b)(4)源 或(b)(4)生产。你们的工厂中的一个(b)(4)是 (b)(4)的,而且对室外环境开放,暴露在害虫、动物粪便和各种污染物之下。

You lack adequate installation, operational, and performance qualifications to ensure your (b)(4) system is capable of sustainably producing (b)(4) of adequate quality for its intended use in drug products. In addition, you do not protect your (b)(4) from the ingress and proliferation of objectionable microorganisms.

你们缺乏充分的安装、运行和性能确认, 无法确保你们的 (b)(4) 系统能够持续地生产出具备足够质量的(b)(4)。此外, 你们未能保护你们的 (b)(4) 免受致病微生物的进入和扩散。

4.      Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

贵公司未能建立生产和工艺控制的书面程序, 以确保所生产的药品具有其声称或应有的鉴别、含量、质量和纯度 (21 cfr 211.100(a))。 

You have not validated the processes used to manufacture your drug products, you did not define or identify critical process parameters, and you lack an ongoing program for monitoring process controls to ensure stable manufacturing operations and consistent drug quality.

你们没有验证用于生产药品的工艺, 没有定义或识别关键工艺参数, 也缺乏持续的工艺控制程序来确保稳定的生产操作和一致的药物质量。

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and elements of process validation at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf

请参阅FDA的指导文件<工艺验证: 一般原则和规范>https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf

来源:GMP办公室