FDA警告信：印度Sal Pharma

翻译：Julia 来自：蒲公英

Via UPS                                                                                 Warning Letter 320 - 17-35

Return Receipt Requested

April 20, 2017

Mr. Solomon Amrutharajan

Owner

Sal Pharma

1-7-171/2 Bakaram

Hyderabad, Andhra Pradesh 500020

India

Dear Mr. Amrutharajan:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Sal Pharma, at 1-7-171/2 Bakaram, Hyderabad, Andhra Pradesh, from June 27 to July 1, 2016.

美国 FDA 于 2016 年 6 月 27 日至 7 月 1 日检查了你们位于印度海得拉巴的 SAL PHARMA 生产场所。

This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).

本警告信总结了原料药生产严重违反 CGMP 的行为。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your API are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

由于你们的原料药生产、加工、包装或保存的方法、场所或控制不符合 CGMP 要求，你们的原料药根据 FDCA 的 501(a)(2)(B) 以及 21 U.S.C. 351(a)(2)(B) 被认为是掺假药品。

In addition, your itraconazole and lansoprazole API are misbranded under sections 502(a) and 502(b)(1) of the FD&C Act, 21 U.S.C. 352(a) and 352(b)(1).

此外，你们的伊曲康唑和兰索拉唑原料药根据 FDCA 第 502(a) 和 502(b)(1) 部分和 21 U.S.C. 352(a) 和 352(b)(1) 为贴牌药。

We reviewed your July 12, 2016, response in detail.

我们详细审核了你们于 2016 年 7 月 12 日发来的回复。

During our inspection, our investigator observed specific deviations including, but not limited to, the following.

在我们的检查期间，我们的调查人员发现的具体问题包括但不仅限于以下：

CGMP Deviations GMP 偏差

1.      Failure to transfer all quality or regulatory information received from the API manufacturer to your customers.

未能将从 API 生产商处收到的所有质量和法规信息转给你们的客户。

You omitted the names and addresses of the original manufacturers of your API on certificates of analysis (COA) you issued to your customers. You generated your COA by replacing the original manufacturers’ information with your letterhead.

你们在你们签发给客户的 COA 上略去了你们原料药的原始生产商的名称和地址。你们用你们公司的信头替代了原始生产商的信息制作了 COA 。

During our inspection, we found that two of your suppliers were not registered with the FDA as drug manufacturers at the time of inspection. However, you shipped API from these firms to the United States, and declared on importation documents and the COA that you provided to your customers that you were the manufacturer. Your failure to declare the original manufacturers on your importation documents and COA provided to your customers enabled the entry of unregistered firms’ products into the United States.

在我们的检查中，我们发现你们的 2 个供应商在检查进行时还没有在 FDA 注册为药品生产商。但是，你们将来自这些公司的 API 发往美国，并在你们提交给客户的进口文件和 COA 上声明你们是生产商。你们未在你们提交给你们客户的进口文书和 COA 上指明原始生产商， 这样让未经登记的公司产品进入了美国。

Customers and regulators rely on COA for information about the quality and source of drugs and their components. Omitting information from COA compromises supply-chain accountability and traceability, and may put consumers at risk.

客户和法规监管者依赖于 COA 上关于药品及其成分的质量和来源。略去 COA 上的信息会让供应链可靠性和可追溯性受损，可能会将患者置于风险之中。

2.      Failure to relabel and hold API under appropriate CGMP controls.

未能标识并将原料药置于适当的 CGMP 控制之下。

During the inspection, you stated that you (b)(4) drive your car and pick up API from various suppliers, relabel API (b)(4) with Sal Pharma’s information, and then transport API to your clearing agent. You stated that you cannot confirm whether or not your clearing agent securely stores API in a temperature-controlled environment.

在我们检查期间，你们声称你们的 XX 驾驶你们的小车，从不同的供应商处提取原料工药，使用 SAL PHARMA 的信息重新标识原料药 XXX ，然后将原料药运给你们的清关代理。你们声称你们不能确定你们的清关代理是否将原料药安全地存贮在温控环境下。

Repackaging, relabeling, and holding of API must be performed under appropriate CGMP controls to avoid loss of API identity or purity.

原料药的重新包装、重新标识和保存必须在适当的 CGMP 控制下实施以避免原料药的识别和纯度丧失。

You stated in your response that you intended to suspend exports to the United States and would address FDA’s observations prior to resuming exports to the United States. Your response is inadequate because you did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP prior to resuming distribution.

你们在回复中声称你们有意暂停出口至美国，会在恢复出口美国之前解决 FDA 发现的缺陷问题。你们的回复是不充分的，因为你们没有提供充分的纠正措施详细信息和证据，使得你们的操作在恢复销售之前回复符合 CGMP 的轨道。

In response to this letter, provide the following:

在回复此函时，请提交以下内容：

• written procedures for the transfer of quality and regulatory information to your customers, including specific details of the information you will transfer;

• 将质量和法规信息转移给你们客户，包括你们要转移的信息的具体细节的书面程序

• a plan to establish, document, and implement an effective system for managing quality, including written procedures for CGMP related activities and the personnel responsible for oversight;

• 建立、记录和实施一个有效的系统来管理质量，包括 CGMP 有关活动和人员监管职责的书面程序的计划

• corrective actions for establishing and maintaining adequate storage conditions.

• 建议和维护充分的存贮条件的纠正措施

CGMP consultant recommended 建议聘请 CGMP 顾问

Based upon the nature of the deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations and assist your firm in meeting CGMP requirements.

基于我们在你们公司所发现的偏差的情况，我们强烈建议你们聘请一位有资质评估你们的操作的顾问，协助你们公司符合 CGMP 要求。

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.

你们聘请顾问并不能免除你们公司符合 CGMP 的义务。你们公司的执行管理人员仍负有全面解决所有缺陷，确保持续符合 CGMP 的义务。

Additional API CGMP guidance 其它原料药 CGMP 指南

FDA considers the expectations outlined in ICH Q7 in determining whether API are manufactured in conformance with CGMP. See FDA’s guidance document, Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, for guidance regarding CGMP for the manufacture of API, at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073497.pdf .

FDA 在确定原料药生产是否符合 CGMP 时考虑的是 ICH 17 中列出的要求。参见 FDA 指南文件， Q7 原料药优良生产规范。

Misbranding Violations 冒牌违规

The itraconazole and lansoprazole API labels identify Sal Pharma but do not designate the firm’s role. Since these API labels bear only Sal Pharma’s name without further qualifications, the labels falsely represent that Sal Pharma is the sole drug manufacturer. (See 21 CFR 201.1(h)(2)). Therefore, the itraconazole and lansoprazole API are misbranded under section 502(a) of the FD&C Act because the labels are false and misleading.

伊曲康唑和兰索拉唑原料药标签标识为 SAL PHARMA ，但并没有写明公司的身份。由于这些原料药的标签只贴有 SAL PHARMA 的名称，而没有更多的确认，标签虚假地表现了 SAL PHARMA 是唯一的药品生产商（参见 21 CFR 201.1(h)(2) ）。因此，伊曲康唑和兰索拉唑原料药由于虚假标签和误导根据 FDCA 第 502 （ a ）部分被认为是冒牌药品。

Conclusion