3月14日，FDA发布的警告信中提及关于药品储存中缺乏温度和湿度控制的警告信，“尽管供应商的药物分析证书 （COA） 声明该药物对热、光和湿度敏感，但你们未能监控药物的储存条件，包括温度和湿度”。“你们还承认，药品、容器和封盖的储存条件也存在不足”。FDA在警告信汇中表示：“药品的保存必须在适当的条件下进行，以免影响其特性、含量、质量和纯度。”此外，警告信中还提及其他违法GMP的行为。
由于问题非常严重，FDA与该公司沟通该公司停产并召回所有药品。
具体如下：
On 14 March 2023, the U.S. Food and Drug Administration (FDA) has published a new Warning Letter. The document, which was already sent on 20 January 2023, is addressed to a company in Massachusetts, USA, which produces homeopathic finished drug products. It goes back to an inspection at the firm's drug manufacturing facility in July and August 2022.
2023 年 3 月 14 日，美国食品和药物管理局 （FDA） 发布了新的警告信。该警告信发给美国马萨诸塞州的一家生产顺势疗法成品药的公司。FDA于 2022 年 7 月和 8 月对该公司药品制造工厂进行检查。
Storage of Drug Products and Monitoring of Humidity
药品储存和湿度监测
One of the violations mentioned in the Warning Letter concerns the adequate storage and warehousing of drug products. It is particularly notable that the FDA criticizes not only the lack of temperature monitoring, but also monitoring of humidity. In this regard, the Warning Letter contains the following statement:
警告信中提及的违规行为之一涉及药品储存和仓储缺陷。特别值得注意的是，FDA不仅批评了缺乏温度监测，还批评了湿度监测。在这方面，警告信载有以下声明：
"You failed to have adequate storage and warehousing of drug products. For example, although a supplier’s certificate of analysis (COA) for a bulk drug stated that the drug is sensitive to heat, sunlight, and moisture, you failed to monitor storage conditions for the drug, including for temperature and humidity. You also acknowledged that there were inadequate storage conditions for drug products, and for your containers and closures. The holding of drug products must be performed under appropriate conditions so that the identity, strength, quality, and purity are not affected."
“你们没有足够的药品储存和仓储。例如，尽管供应商的药物分析证书 （COA） 声明该药物对热、光和湿度敏感，但你们未能监控药物的储存条件，包括温度和湿度。你们还承认，药品、容器和封盖的储存条件也存在不足。药品的保存必须在适当的条件下进行，以免影响其特性、含量、质量和纯度。
Further CGMP Violations
其他违反CGMP的行为
In the Warning Letter, the FDA also lists a number of other CGMP violations. This is mainly a matter of simple, basic requirements that should be in place in every GMP facility:
在警告信中，FDA还列出了其他一些CGMP违规行为。这主要是每个GMP设施都应具备的简单基本要求：
The firm failed to establish a quality unit (QU) with the responsibilities and authority to oversee the manufacture of the drug products.
未能建立一个质量部门（QU）来负责监督药品的生产。
The company did not have the necessary written procedures (e.g. for documented sampling, testing of components before production).
缺乏必要的书面程序（例如，书面的取样，生产前对组件进行测试）。
A program for qualifying suppliers was missing.
缺少供应商确认的计划。
No batch and control records documenting the manufacturing operations could be provided.
无法提供记录生产操作的批生产和控制记录。
No batch numbers have been assigned.
未分配批号。
Drug Production Ceased
停止药品生产
The problems were so serious that the company has stopped production and distribution of all drug products in the meantime. Furthermore, a voluntary nationwide recall of all drug products was issued.
问题非常严重，以至于该公司在此期间停止了所有药品的生产和分销。此外，还发布了对所有药品的全国自愿召回。
“On November 3, 2022, FDA held a teleconference with you. We recommended you remove any batches of drug product currently in distribution from the U.S. market and also consider ceasing further distribution.
2022年11月3日，FDA与贵公司举行了电话会议。我们建议你们从美国市场销除目前分销的任何批次的药品，并考虑停止进一步分销。
On November 5, 2022, you communicated your firm’s commitment to cease distribution of the drug product on the website, cease production and distribution of all drug products, and consider a voluntary recall all drug products.
2022 年 11 月 5 日，你们传达了贵公司的承诺，即停止分销药品，停止生产和分销所有药品，并考虑自愿召回所有药品。
On November 21, 2022, you issued a voluntary nationwide recall of all drug products.
2022年11月21日，你们在全国范围内自愿召回所有药品。
We acknowledge your commitment to cease production and distribution of all drug products.
我们知道你们承诺停止生产和分销所有药品。
In response to this letter, confirm whether you intend to resume manufacture of any drugs at this facility or any other facility in the future. If you plan to resume any manufacturing regulated under the FD&C Act, notify this office prior to resuming your manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34, to assist your firm in meeting drug CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit1 of your entire operation for CGMP compliance and evaluate the completion and efficacy of all corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.
回复此函，请确认否打算在未来恢复在该设施或任何其他设施生产任何药物。如果你们计划恢复受FD&C法案监管的任何制造，请在恢复制造业务之前通知本办公室。如果你们恢复CGMP活动，你们有责任解决所有缺陷和系统性缺陷，以确保你们的公司能够持续符合CGMP。此外，根据我们在贵公司发现的违规行为的性质，你们应该聘请符合 21 CFR 211.34 中规定的有资质的顾问来协助贵公司满足药物 CGMP 要求。顾问还应对你们的整个运营进行全面的六系统审计1，以确保CGMP合规性，并在你们寻求解决公司与FDA的合规性状态之前评估所有纠正措施和预防措施的完成情况和有效性。”
