FDA警告信：瑞士日内瓦Laboratoire Sintyl S.A.（节译）

Warning Letter 320-16-37

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Return Receipt Requested

September 29, 2016

Mr. Rémy Pfenniger  

CEO/Owner

Laboratoire Sintyl S.A.

Route Des Jeunes 23

Carouge Ge, Geneva, 1227

Switzerland

Dear Mr. Rémy Pfenniger:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Laboratoire Sintyl S.A. at Route Des Jeunes 23, Carouge Ge, Geneva, from June 20 to 23, 2016.

FDA于2016年6月20-23日检查了你们位于瑞士日内瓦的工厂。

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

本警告信总结了你们制剂生产中严重违背CGMP的情况。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 product is 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).

由于你们生产、加工、包装和存贮药品的方法、场所或控制不符合CGMP，你们的药品根据FDCA，21 U.S.C. 351(a)(2)(B)第501(a)(2)B)的规定被认定为掺假药品。

We reviewed your July 5, 2016, response in detail. In that response, you stated that you produced (b)(4) over-the-counter drug and have ceased its manufacture. You did not commit to (b)(4) and to keeping FDA informed of the (b)(4) progress. You have yet to provide FDA with any evidence to document that a (b)(4) has occurred.

我们详细审核了你们于2016年7月5日发来的回复。在回复中你们说你们生产的某OTC药品已停止生产。你们没有承诺会持续知会FDA某进展情况。你们还没有向FDA提供任何书面证据来证明某事已发生。

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

在我们检查期间，我们的调查人员发现的具体违规情况包括但不仅限于以下：

1.    You failed to establish written responsibilities and procedures applicable to the quality control unit, including the review of out-of-specification results and customer complaints. (21 CFR 211.22(d)). During the inspection, you indicated that you have no independent quality unit.

贵公司未能为质量控制部门建立书面的职责和程序，包括对OOS结果和客户投诉的审核(21 CFR 211.22(d))。在检查期间，你们说你们没有独立的质量部门。

2.    You failed to test finished batches of your drug products for the identity and strength of active ingredients. (21 CFR 211.165(a))

贵公司没有检测你们药品成品批次的活性成分的鉴别和剂量。(21 CFR 211.165(a))

3.    You failed to ensure the identity of components sourced from various suppliers, including your (b)(4) active ingredients. (21 CFR 211.84(d)(1) and (2))

贵公司未能确保来自不同供应商的成分的鉴别，包括你们的XX活性成分。(21 CFR 211.84(d)(1) and (2))

4.    You failed to clean and maintain your (b)(4) at appropriate intervals to prevent malfunctions or contamination of your drug products. (21 CFR 211.67(d)). During the inspection, we observed reddish brown discoloration consistent with rust on your (b)(4).

贵公司没有按照适当的周期清洁和维护你们的某设备防止其发生故障或对你们的药品形成污染。(21 CFR 211.67(d))。在检查期间，我们在你们某设备上发现连续的棕红色锈。

5.    You failed to establish written procedures for production and process controls, including validation protocols and reports, designed to assure that your drug products have the identity, strength, quality, and purity they purport or are represented to possess. (21 CFR 211.100(a)). During the inspection, you acknowledged that your firm has no procedures for process validation.

贵公司没有为生产和工艺控制建立书面程序，包括验证方案和报告，用以确保你们的药品具备其所既定的鉴别、剂量、质量和纯度。(21 CFR 211.100(a))。在检查期间，你们说你们公司没有工艺验证程序。

6.    You have no data to demonstrate that the chemical and physical properties of your products remain acceptable throughout their shelf lives. (21 CFR 211.166(a))

你们没有数据证明你们产品的理化特性在其货架期间是能保持可以接受。(21 CFR 211.166(a))

You distributed at least (b)(4) batches of (b)(4) Emulsion (b)(4) to the United States, despite the above violations, as well as others cited on the June 23, 2016 Form FDA-483.

在有上述违规情况，以及6月23日签发的483表中所述违规情况的前提下，你们将至少XX批次的YY产品销售至美国。

CGMP consultant recommended

If your firm resumes manufacturing drugs for the United States market, we strongly recommend engaging a consultant, qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. 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.

Conclusion

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.

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.

Failure to correct these violations may also result in FDA refusing admission of articles manufactured at Route Des Jeunes 23, Carouge Ge, Geneva, 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).

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 violations 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.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:

Philip Kreiter, Public Health Analyst

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 1000488360.

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research