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, athttp://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 结论
Deviations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these deviations, for determining the causes, for preventing their recurrence, and for preventing other deviations.
在此函中所引用的偏差并不是全部。你们有责任对这些偏差进行调查，确定原因，防止其再次发生，防止其它偏差的发生。
FDA placed your firm on Import Alert 66-40 on February 15, 2017.
FDA已于2017年2月15日发布了对你公司的进口禁令。
Until you correct all deviations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
在你公司完全整改所有偏差，由我们确认你们符合CGMP之前，FDA可能会搁置所有将你公司列为药品生产的新申报和增补申报的批准。
Failure to correct these deviations may also result in FDA continuing to refuse admission of articles manufactured at Sal Pharma 1-7-171/2 Bakaram, Hyderabad, Andhra Pradesh, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
未能纠正这些偏差可能还会导致FDA依据FDCA第801(a)(3)条和21 U.S.C. 381(a)(3)拒绝接受在上述地址生产的产品进入美国。
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your deviations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
在收到此函后，请在15个工作日内回复至本办公室。在回复中说明自从检查后，你们做了哪些工作来纠正你们的偏差，防止其再次发生。如果不能在15个工作日内完成纠正措施，说明延迟的原因以及完成计划。
Send your electronic reply to [email protected] or mail your reply to:
Hien K. Lieu
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Please identify your response with FEI 3003916387.
Sincerely,
/S/
Thomas J. Cosgrove
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
