3月14日，F(xiàn)DA發(fā)布的警告信中提及關(guān)于藥品儲存中缺乏溫度和濕度控制的警告信，“盡管供應(yīng)商的藥物分析證書 （COA） 聲明該藥物對熱、光和濕度敏感，但你們未能監(jiān)控藥物的儲存條件，包括溫度和濕度”。“你們還承認，藥品、容器和封蓋的儲存條件也存在不足”。FDA在警告信匯中表示：“藥品的保存必須在適當?shù)臈l件下進行，以免影響其特性、含量、質(zhì)量和純度。”此外，警告信中還提及其他違法GMP的行為。
由于問題非常嚴重，F(xiàn)DA與該公司溝通該公司停產(chǎn)并召回所有藥品。
具體如下：
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，美國食品和藥物管理局 （FDA） 發(fā)布了新的警告信。該警告信發(fā)給美國馬薩諸塞州的一家生產(chǎn)順勢療法成品藥的公司。FDA于 2022 年 7 月和 8 月對該公司藥品制造工廠進行檢查。
Storage of Drug Products and Monitoring of Humidity
藥品儲存和濕度監(jiān)測
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:
警告信中提及的違規(guī)行為之一涉及藥品儲存和倉儲缺陷。特別值得注意的是，F(xiàn)DA不僅批評了缺乏溫度監(jiān)測，還批評了濕度監(jiān)測。在這方面，警告信載有以下聲明：
"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."
“你們沒有足夠的藥品儲存和倉儲。例如，盡管供應(yīng)商的藥物分析證書 （COA） 聲明該藥物對熱、光和濕度敏感，但你們未能監(jiān)控藥物的儲存條件，包括溫度和濕度。你們還承認，藥品、容器和封蓋的儲存條件也存在不足。藥品的保存必須在適當?shù)臈l件下進行，以免影響其特性、含量、質(zhì)量和純度。
Further CGMP Violations
其他違反CGMP的行為
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，F(xiàn)DA還列出了其他一些CGMP違規(guī)行為。這主要是每個GMP設(shè)施都應(yīng)具備的簡單基本要求：
The firm failed to establish a quality unit (QU) with the responsibilities and authority to oversee the manufacture of the drug products.
未能建立一個質(zhì)量部門（QU）來負責監(jiān)督藥品的生產(chǎn)。
The company did not have the necessary written procedures (e.g. for documented sampling, testing of components before production).
缺乏必要的書面程序（例如，書面的取樣，生產(chǎn)前對組件進行測試）。
A program for qualifying suppliers was missing.
缺少供應(yīng)商確認的計劃。
No batch and control records documenting the manufacturing operations could be provided.
無法提供記錄生產(chǎn)操作的批生產(chǎn)和控制記錄。
No batch numbers have been assigned.
未分配批號。
Drug Production Ceased
停止藥品生產(chǎn)
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.
問題非常嚴重，以至于該公司在此期間停止了所有藥品的生產(chǎn)和分銷。此外，還發(fā)布了對所有藥品的全國自愿召回。
“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，F(xiàn)DA與貴公司舉行了電話會議。我們建議你們從美國市場銷除目前分銷的任何批次的藥品，并考慮停止進一步分銷。
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，你們傳達了貴公司的承諾，即停止分銷藥品，停止生產(chǎn)和分銷所有藥品，并考慮自愿召回所有藥品。
On November 21, 2022, you issued a voluntary nationwide recall of all drug products.
2022年11月21日，你們在全國范圍內(nèi)自愿召回所有藥品。
We acknowledge your commitment to cease production and distribution of all drug products.
我們知道你們承諾停止生產(chǎn)和分銷所有藥品。
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.
回復(fù)此函，請確認否打算在未來恢復(fù)在該設(shè)施或任何其他設(shè)施生產(chǎn)任何藥物。如果你們計劃恢復(fù)受FD&C法案監(jiān)管的任何制造，請在恢復(fù)制造業(yè)務(wù)之前通知本辦公室。如果你們恢復(fù)CGMP活動，你們有責任解決所有缺陷和系統(tǒng)性缺陷，以確保你們的公司能夠持續(xù)符合CGMP。此外，根據(jù)我們在貴公司發(fā)現(xiàn)的違規(guī)行為的性質(zhì)，你們應(yīng)該聘請符合 21 CFR 211.34 中規(guī)定的有資質(zhì)的顧問來協(xié)助貴公司滿足藥物 CGMP 要求。顧問還應(yīng)對你們的整個運營進行全面的六系統(tǒng)審計1，以確保CGMP合規(guī)性，并在你們尋求解決公司與FDA的合規(guī)性狀態(tài)之前評估所有糾正措施和預(yù)防措施的完成情況和有效性。”
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