FDA Warning Letter: Using non-validated and not appropriate Test Methods from an Internet Search is not a good Idea

FDA警告信：使用互联网搜索的未经验证和不适当的分析方法不是一个好主意


The U.S. Food and Drug Administration (FDA) has issued a new Warning Letter. The document dated 28 June 2023 was published on the FDA webite on 18 July 2023.It refers to an inspection conducted in February 2023 at a drug manufacturing facility in Kansas, USA. The FDA writes that the company in questions manufactures over-the-counter (OTC) topical drug products, e.g. antibacterial hand soaps and hand sanitizers.

FDA近期发布了美国堪萨斯州的一家药品制造厂的警告信。警告信2023 年 7 月 18 日在 FDA 官网上发布。

The Warning Letter lists the following main violations:

警告信列出了以下主要违规行为：

QU oversight: The Quality Unit (QU) did not provide adequate oversight for the manufacture of the products. Documents were not appropriately reviewed and several out-of-specification (OOS) results were not investigated. In addition, an adequate ongoing stability program was missing.

QU监督：质量部门（QU）未能对产品的生产提供足够的监督。未能适当审查文件，也未能对多个OOS结果进行调查。此外，还缺少适当的持续稳定计划。

Identity testing: Adequate identity testing of each component lot used in the manufacture was not performed. In addition, the company used the suppliers’ certificate of analysis (COA) without establishing the reliability of the suppliers’ test analyses. This concerns propylene glycol and ethanol.

鉴定测试：没有对生产中使用的每个组分批次进行适当的鉴定测试。此外，该公司在没有确定供应商测试的可靠性的情况下使用了供应商COA。包括丙二醇和乙醇。

Laboratory controls: It was not ensured that the test methods were appropriate for their intended use. In this context, the following quote shows how problematic GMP compliance seems to be in the laboratory: "Your analysts provided our investigator with a non-validated test method from an internet search, which did not appear to be specific for your drug products, nor appropriate for any drug product."

实验室控制：未能确保分析方法适合其预期用途。以下缺陷引述显示了实验室中GMP合规性似乎存在严重问题：“你们的分析人员向我们的检查人员提供了来自互联网搜索的未经验证的分析方法，该方法似乎不适用于你们的药品，也不适合任何药品。

The FDA asked the company to provide, beside others, the following information:

FDA要求该公司提供以下信息：

An assessment and remediation plan to ensure the QU can effectively function.

评估和补救计划，以确保质量部门能够有效运行。

An assessment of the overall system for investigating deviations, discrepancies, complaints, OOS results, and failures.

对调查偏差、差异、投诉、OOS 结果和失败的整体系统的评估。

Several documents related to stability studies.

与稳定性研究有关的文件。

A comprehensive review of the material system.

对物料系统的全面审查。

A risk assessment for all drug products that contain propylene glycol and ethanol.

所有含有丙二醇和乙醇的药品的风险评估。

An assessment of the laboratory practices.

对实验室规范的评估。

The FDA concludes that"significant findings in this letter indicate that [the] QU is not able to fully exercise its authority and/or responsibilities" Based on the nature of the GMP violations, the FDA strongly recommends engaging a consultant.

FDA的结论是，“警告信中的重要发现表明，质量部门无法充分行使其权力和/或责任”。基于违反GMP的性质，FDA强烈建议聘请顾问。