荷兰Delarange Cosmetics & Healthcare BV（节译）

Warning Letter 320-16-36

Via UPS                                                                                

Return Receipt Requested

September 29, 2016

Mr. Wim Van R?, Owner and CEO

Delarange Cosmetics & Healthcare BV

Edisonweg 36, 3899 AZ

Zeewolde, The Netherlands

3890 AA

Dear Mr. Van R?:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Delarange Cosmetics & Healthcare BV at Edisonweg 36, 3899 AZ, Zeewolde, from May 30 to June 3, 2016.

FDA于2016年5月30日至6月3日检查了你们位于荷兰的工厂。

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 June 21, 2016, response in detail. Your response states that since you (b)(4) drug product for the U.S. market, “and because (b)(4), we have decided to inform our client ((b)(4)) about our decision to no longer produce (b)(4)product for the U.S. market.” You also stated that you “choose not to enter into substantive discussion about the observations described.” You did not commit to any corrective actions regarding the CGMP violations observed on the inspection.

我们详细审核了你们于2016年6月21日发来的回复。回复中说由于你们生产的药品供应美国市场，由于XX原因，现决定通知客户不再生产美国市场的药品。你们还声称你们“选择不再对所述的缺陷进行实质性的讨论”。你们没有承诺任何关于在检查期间发现的CGMP违规情况的纠正措施。

Our investigator observed specific violations, including, but not limited to, the following.

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.    Your firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. (21 CFR 211.165(a))

你们公司在药品放行前没有对每个批次制剂进行适当的化验室检查，获得符合药品最终质量标准的结果，包括每种活性成分的鉴别和剂量。(21 CFR 211.165(a))

You stated to our investigator you did not test your finished product for assay, and that you have not established final specifications release testing of your drugs.

你们对我们的调查人员说你们没有检测成品的含量，也没有为你们药品的放行检测建立最终质量标准。

2.    Your firm failed to establish a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products. (21 CFR 211.22(a))

你们公司没有建立质量控制部门，赋予其职责和权力来批准或拒收所有部件、药品容器、密闭器、中间物料、包装物料、标签和制剂。(21 CFR 211.22(a))

You stated to our investigator that your firm does not have a quality unit to review and approve the release of your drugs.

你们对我们调查人员说你们公司没有捏部门审核和批准药品放行。

3.    Your firm failed to establish and follow written procedures for cleaning and maintenance of equipment. (21 CFR 211.67(b))

你们公司没有建立和遵守书面的设备清洁和维保程序。(21 CFR 211.67(b))

You manufacture (b)(4) for the U.S. market on the same equipment that you use for manufacturing other products – including (b)(4). Your failure to adequately clean equipment between products risks contaminating your drugs with other potentially toxic chemicals.  

你们用于生产美国市场销售的XX所用的设备也用于生产其它药品，包括YY产品。你们没有在更换产品时对其进行充分的清洁，使得你们生产的药品与其它潜在毒性化学品之间有污染风险。

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.

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. Using a consultant does not relieve your firm’s obligation to comply with CGMP. Notify this office, in writing, of the specific steps that you have taken to correct violations and prevent recurrence. Provide supporting documentation. If your firm cannot complete corrective actions, state the reasons and the date by which your firm will have completed the corrections.

Until you completely correct all violations and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. Failure to correct these violations may also result in FDA refusing admission of articles manufactured at Delarange Cosmetics and Healthcare BV, Edisonweg 36, 3899 AZ, Zeewolde, 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).

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

            Carla A. Norris, 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 3009499217.

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research