FDA警告信：韩国It’S Hanbul Co., Ltd.; dba Hanbul Cosmetics 20180329

Warning Letter   320-18-42

March 29, 2018

Mr. Cheol Hee Jeong, Center Manager

62, Daeseong-ro 547 Beon-gil, Samseong-myeon,Eumseong-gun

Chungcheongbuk-do 27651 Republic of Korea

Dear Mr. Jeong:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, It’S Hanbul Co., Ltd.; dba Hanbul CosmeticsCo., Ltd., 62, Daeseong-ro 547 Beon-gil, Samseong-myeon, Eumseong-gun,Chungcheongbuk-do, from November 27 to December 1, 2017.

  美国 FDA 于 2017 年 11 月 27 日至 12 月 1 日检查了你们位于韩国忠清北道的 It’SHanbul Co., Ltd.; dba Hanbul Cosmetics Co., Ltd. 生产场所。

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.

本警告信总结了制剂生产严重违反 CGMP 的行为。参见 21CFR 第 210 和 211 部分。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products 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).

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

We reviewed your December 20, 2017, response in detail.

我们详细审核了你们 2017 年 12 月 20 日发来的回复。

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

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：

1.    Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR211.194(a)).   你公司未能确保化验室记录中包括有所有测试中生成的完整数据，用以确保其符合既定规格和标准 (21 CFR 211.194(a)) 。

Your firm could not provide raw data to verify that you performed microbiological finished product testing for your over-the-counter (OTC) drug products.

你公司未能提供原始数据证明你们对你们的 OTC 药品所执行的成品微生物测试。

2.    Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR211.166(a)).   你公司未遵守设计以评估药品稳定性特性，并使用此稳定性检测结果来确定恰当的存贮条件和有效期的足够的书面检测程序 (21 CFR 211.166(a)) 。

Your stability studies are inadequate to ensure theOTC drug products you manufacture remain within specification throughout their labeled expiry period. For example, your firm has only conducted six-week accelerated stability studies to support your labeled expiry periods (e.g.,   (b)(4)  or more months). You have not conducted long term stability studies.

你们的稳定性研究不足以确保你们生产的 OTC 药品在其标示的有效期内保持在其质量标准范围内。例如，你公司只是做了 6 周加速稳定性研究来支持你们标示的有效期（例如 XX 或更多个月）。你们没有进行长期稳定性研究。

Your stability testing program is also inadequate because it does not include an assay determination of the active ingredient(s) in your OTC drug products. Furthermore, it does not include any testing methodology, testing frequency, or information regarding container/closuresystems used.

你们的稳定性测试计划也不充分，因为其中未包括有你们 OTC 药品中活性成分的含量检测。另外，其中未包括任何检验方法、检验频次或所用容器 / 密闭系统的信息。

3.    Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188). 你公司未制订批生产和检验记录，在其中记录所生的每批药品完整的生产和检验信息 (21 CFR 211.188) 。

Your batch records do not include significant production details, including but not limited to weights and measurements of raw materials used in the manufacturing process, start and stop times of   (b)(4)  processes, signatures verifying each significant step in the manufacturing process, and copies of finished product labeling.

你们的批记录未包括重要的生产细节，包括但不仅限于生产工艺所用原料的重量和测量、 XX 工艺的开始和结束时间、确认每个生产工艺重要步骤的签名以及成品标签的副本。

4.    Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR211.63).   你公司在药品生产、加工、包装或存贮中未使用经适当设计、具有足够尺寸和稳定安装便于操作达成既定目的并易于清洁和维护的设备 (21 CFR 211.63) 。

Your firm has not qualified equipment used in the production, packaging, and release testing of your OTC drug products to demonstrate that the equipment is of appropriate design to facilitate operations for its intended use.

你公司未对你们的 OTC 药品生产、包装和放行测试所用的设备进行确认以证明这些设备具有适当的设计便于其既定用途的操作。

Inadequate Response   回复不充分

Your response is inadequate because it did not provide sufficient evidence of corrective actions to bring your operations into compliance with CGMP. Your response did not include any interim measures to be taken until you complete all proposed corrective actions. Furthermore, your response did not address the effect these violations may have had on OTC drug products within expiry and currently on the U.S. market.

你们的回复是不充分的，因为回复中未提供足够的证据证明纠正措施可使得你们的运作带回 CGMP 合规轨道。你们的回复中未包括在完成所有拟定的纠正措施之前要采取的任何临时措施。另外，你们的回复并未解决这些违规可能会对美国市场上仍在有效期内的 OTC 药品产生的影响。

CGMP Consultant Recommended   CGMP 顾问建议

Based upon the nature of the violations identified atyour firm, we strongly recommend engaging a consultant, qualified as set for thin 21 CFR 211.34, to assist your firm in meeting CGMP requirements. The third-party should comprehensively audit your entire operation for CGMP compliance. Your corrective and preventive actions should be evaluated by the third party to help ensure systemic remediation before you pursue resolution of your firm’s compliance status.

依据我们在你们公司发现的违规情 况，我们强烈建议你们使用一位符合 21CFR211.34 要求的顾问来协助你们公司符合 CGMP 要求。你们的纠正和预防措施应在寻求合规状态解决方案前由第三方评估以帮助确保系统性补救。

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.

你们使用顾问并不解除你们公司符合 CGMP 的义务。你们公司的高级管理层仍负有义务全面解决所有缺陷，确保持续 CGMP 符合性。

Conclusion   结论

Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.

此函中所引用的违规并不是全部。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 March 8,2018.

FDA 已于 2018 年 3 月 8 日将你公司列于进口禁令 66-40 项下。

Until you correct all violations 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.

在贵公司未能完成所有偏差纠正并且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。