FDA警告信：杭州嘉禾有限公司

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FDA发布了关于杭州嘉禾日用品有限公司的警告信，警告信缺陷包括该公司药品生产过程中违反CGMP的重大缺陷：

1.      Your firm failed to have, 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 (21 CFR 211.165(a)).

未能在放行前对每批药品进行适当的化验室检测，确定其是否符合药品最终质量标准，包括每种活性成分的鉴别和剂量(21 CFR211.165(a))。

Your firm released your over-the-counter (OTC) drug products, (b)(4) Lotion (active ingredient: (b)(4)), (b)(4) Cream (active ingredient: (b)(4)), and (b)(4) Cream (active ingredientb)(4)), without adequate testing for the identity and strength of active ingredients. Without this testing, you cannot determine if your drug products conform to specifications.

贵公司放行了你们的OTC药品，XX液（活性成分XX）、XX膏（活性成分XX）和XX膏（活性成分XX），却并未对活性成分的鉴别和剂量进行足够的检验。没有此检验，你们无法确定你们的药品是否符合质量标准。

2.      Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR211.84(d)(1) and (2)).

未能执行至少一项检测来确认药品的每种成分的鉴别。也未能对供应商检测结果以适当时间间隔进行验证来建立供应商分析的可靠性 (21 CFR 211.84(d)(1) and (2))。

Your firm failed to test incoming raw materials, including the active ingredients (b)(4) and (b)(4), and you also lacked testing of inactive ingredients such as (b)(4), for identity, purity, strength, and other appropriate quality attributes. Instead, your firm relied on certificates of analysis (COA) from suppliers without establishing the reliability of the suppliers’ analysis through appropriate validation.

贵公司未能检查进厂物料，包括活性成分XX和XX；你们亦未对非活性成分如XX检测其鉴别、纯度、剂量和其它适当的质量属性。相反，你公司依赖于供应商的COA，而并未通过适当的验证建立供应商分析的可靠性。

3.      Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

未能彻底调查所有已放行和未放行批次或其成分与其质量标准之间的未能解释的差异或不合格情形(21 CFR 211.192)。

You initiated an investigation on January 29, 2018, after you observed that the primary packaging (tube) of a reserve sample of (b)(4),lot (b)(4), had turned from (b)(4) (at the time of release) to yellow. Your investigation determined that your supplier sent the wrong material for primary packaging. You also failed to evaluate the effects of this deviation on the drug product within the container. In addition, you failed to determine whether other distributed batches of drug products may also have been affected by incorrect packaging material.

你们于2018年1月29日在发现一个XX批号XX的留样内包（管）从XX（放行时）变更黄色之后启动了一个调查。你们的调查确定是你们的供应商发错了内包物料给你们。你们亦未评估此偏差对你们容器内产品的影响。此外，你们未检查是否有其它已销售药品批号可能亦受到错误包材的影响。

4.      Your firm failed to establish adequate 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 (21CFR 211.100(a)).

你公司未建立设计用以确保你们生产的药品具备其理应具备的鉴别、剂量、质量和纯度的生产和工艺控制书面程序(21 CFR 211.100(a))。

You have not validated the processes you use to manufacture drug products. For example, you did not conduct process performance qualification studies, and you lack an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. See FDA’s guidance document, Process Validation: General Principles and Practices, for general principles and approaches that FDA considers appropriate elements of process validation, athttps://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf.

你公司未验证用于生产你们的药品的工艺。例如你们未能执行工艺确认研究，缺乏持续计划监测工艺控制以确保生产操作稳定和药品质量一致。参见FDA官网指南。

Responsibilities as a contractor

作为合同商的职责

Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.

药品生产必须符合CGMP要求。FDA了解许多药品生产商会使用独立的合同商如生产场所、检测实验室、包装商和标签商。FDA将合同商作为是生产商的延伸。

You are responsible for the quality of drugs you produce as a contract facility, regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, andpurity. See FDA’s guidance document, Contract Manufacturing Arrangements for Drugs: Quality Agreements, at https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf.

不论你们与药品所有者是否签订有协议，你们都对你们作为合同生产场所生产的药品质量负有责任。你们应确保药品生产符合FDCA第501(a)(2)(B)部分的安全、鉴别、剂量、质量和纯度要求。参见FDA指南。

Overall Response

整体回复

In your response, you acknowledged the signifigance of the CGMP observations; however, you provided limited corrective actions and did not provide sufficient detail and evidence to support that your proposed corrective actions will bring your operations and distributed drug products into compliance with CGMP. In your response you also stated that you are “acosmetics manufacturer, [and you] . . . have no intention of making any drug products,” and that you will work with your client to update your product labels.

在你们的回复中，你们说已知晓CGMP缺陷的严重性，但是你们只提供了有限的纠正措施，且并未提交详细的内容和证据来支持你们所拟定的纠正措施可以使得你们的操作和已销售的药品符合CGMP。在你们的回复中，你们还声称你们“作为一个化妆品生产商，【并且你们】……无意生产任何药品，”你们会与你们的客户合作更新你们的产品标签。

As stated in this letter, the products you manufactured and distributed to the U.S. are considered drug products. Section 201(g)(1) of the FD&C Act defines drugs, in part, by their intended use, as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”

正如此函所声明，你们所生产和销往美国的产品被认为是药品。FDCA第201(g)(1)部分定义药品时，一部分是依据其用途的，药品是“用于诊断、治愈、治疗或防治疾病的物品”和“用于影响人体或其它动物身体结构或功能的物体（食品除外）”。

We strongly recommend engaging a consultant to assist your firm in meeting the applicable CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.

我们强烈建议你们聘请一位顾问来协助你们公司符合适用的CGMP要求。你们聘用顾问并不能解除你们公司符合CGMP的义务。你们公司的执行管理层仍负有全面解决所有缺陷和确保持续CGMP符合性的义务。

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