FDA给巴西一药厂的警告信（节译）

julia朱玉姣

原文官网http://www.fda.gov/ICECI/Enforce ... /2016/ucm518694.htm

ViaUPS                                                                                     Warning Letter 320-16-30

Return Receipt Requested

August 25, 2016

Mr. Fabio Pergher

Technical Director

Lima & Pergher Industria e Comercio S/A

Avenida Airton da Silva 740

Distrito Industrial – Uberlandia

State of Minas Gerais 38402 – 100

Brazil

Dear Mr. Pergher,

The U.S. Food and Drug Administration (FDA) inspected your drugmanufacturing facility, Lima & Pergher Industria e Comercio at RuaEngenheiro Diniz 2069, B. Martins, Uberlandia, State of Minas Gerais, fromFebruary 29 to March 3, 2016.  

  美国FDA于2016年2月29日至3月3日检查你们位于巴西的药品生产工厂。

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

  本警告信总结了制剂严重违反CGMP的问题。参见 21 CFR, parts 210 and 211。

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

鉴于你们生产、加工、包装和保存的方法、设施或控制不符合CGMP要求，你们的制剂根据FDCA501(a)(2)(B)和21 U.S.C.351(a)(2)(B)规定被判定为掺假药品。

We reviewed your firm’s March 18, 2016, response in detail and acknowledgereceipt of your subsequent correspondence.

  我们详细审核了贵公司于2016年3月18日及之后发出的回复。

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

  我们的检查人员发现的具体违规情况包括但不仅限于以下：

1.    Your firm failed to establish adequate writtenresponsibilities and procedures applicable to the quality control unit (21 CFR211.22(d)).

贵公司未能建立足够的质量控制部门书面职责和程序(21 CFR 211.22(d))。

You failed to implement written procedures for the following:

贵司未能实施以下书面程序：

• Responsibility of     the Quality Control Unit (QCU) to review and approve all drug product     production and control records.
• 质量控制部门（QCU）审核和批准所有药品生产和检验记录的职责
• Responsibility of     the QCU unit to handle, review, process, and document change controls,     out-of-specification test result investigations, and deviation investigations.
• QCU处置、审核、处理、和记录变更控制、OOS结果调查和偏差调查的职责
  

2.    Your firm failed to establish and follow appropriatewritten procedures, designed to prevent objectionable microorganisms in drugproducts not required to be sterile (21 CFR 211.113(a)).  

贵司未能建立和遵守适当的书面程序，用于防止非无菌药品中的致病菌(21 CFR 211.113(a))。

Your firm failed to perform microbiological testing on each lot offinished product.  

贵司未能对每批制剂成品实施微生物检测。

3.    Your firm approved and released for use one or morelots of components, drug product containers, or closures that did not meet theappropriate written specifications of identity, strength, quality, and purity andrelated tests under 21 CFR 211.84(d) (21 CFR 211.84(e)).

贵司批准和放行使用不符合书面质量标准中鉴别、剂量、质量和纯度及相关测试的一批或多批部件、药品容器或密闭器(21 CFR 211.84(e)).

You used (b)(4) to manufacture finished dosage form drug products. (b)(4)is the minimum acceptable quality standard for manufacture of dosage formproducts. In addition, the (b)(4) used in the production of (b)(4)must meet appropriate quality standards.

贵司使用了某原料生产制剂。所生产的药品剂型最低可接受质量标准是XX。另外，用于XX生产的YY必须符合恰当的质量标准。

4.    Your firm failed to ensure that its drug product borean expiration date that was supported by appropriate stability testing (21 CFR211.137(a)).

贵司未能确保为其药品给定有效期，由恰当的稳定性试验来支持(21 CFR 211.137(a))。

Your firm had no stability data to support your expiration date.

贵司没有稳定性数据来支持你们的有效期。

Use of (b)(4) 某原料的使用

During the inspection, we determined that your raw material qualificationprocess was inadequate for your drug products. Specifically, you used (b)(4)in your (b)(4) and (b)(4) products.  

在检查期间，我们确定你们的原料确认工艺对于你们的药品来说是不充分的。你们在你们的某药品中使用了某原料。

(b)(4), results in the drugbeing deemed adulterated.

某原料用于药品中，该药被认定为掺假药。

CGMP consultant recommended 建议聘请CGMP顾问

Your March 18, 2016 response was inadequate.  Although you committedto establish written procedures for quality unit responsibilities and stabilitystudies, your response lacked details. You did not include a retrospectivereview of CGMP deficiencies on the quality of your products already in UnitedStates distribution.  

你们在2016年3月18日的回复是不充分的。尽管你们承诺建立书面的质量部门职责和稳定性试验程序，你们的回复缺少详细信息。你们没有包括对已在美国销售的药品质量方面CGMP缺陷的回顾性审核。

Based upon the nature of the violations we identified at your firm, westrongly recommend engaging a consultant, qualified as set forth in 21 CFR211.34, to assist your firm in meeting CGMP requirements.  Your use of aconsultant does not relieve your firm’s obligation to comply with CGMP. Yourfirm's executive management remains responsible for fully resolving all deficienciesand for ensuring ongoing CGMP compliance.  

基于我们在贵公司发现的违规情况，我们强烈建议你们聘请一位顾问，根据21CFR211.34进行确认，协助你们公司符合CGMP要求。贵司使用顾问并不会解除贵公司符合CGMP的义务。贵司高级管理层仍对全面解决所有缺陷和确保持续CGMP符合性承担全面责任。

Conclusion

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

FDA placed your firm on Import Alert 66-40 on July 15, 2016.

Until you completely correct all violations and we confirm your compliancewith CGMP, FDA may withhold approval of any new applications or supplementslisting your firm as a drug product manufacturer.

Failure to correct these violations may also result in FDA continuing torefuse admission of articles manufactured at Lima & Pergher Industria eComercio at Rua Engenheiro Diniz 2069, B. Martins, Uberlandia,  into theUnited 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, inthat the methods and controls used in their manufacture do not appear toconform 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 15working days. Specify what you have done since our inspection to correct your violationsand to prevent their recurrence. If you cannot complete corrective actionswithin 15 working days, state your reasons for delay and your schedule forcompletion.

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

William Yang, Ph.D.

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 3004364074.

Sincerely,

/S/

Francis Godwin

Acting Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

zysx01234

贵公司未能建立足够的质量控制部门书面职责和程序——这样的药厂真不应该再让其生存下去。职责文件要具体到位，文件也要复审的吧，那平时自检呢都发现不了问题吗，平时做事的人都没有具体职责瞎做事的喽，这样的管理水平太low了:@

zysx01234

基于我们在贵公司发现的违规情况，我们强烈建议你们聘请一位顾问，根据21CFR211.34进行确认，协助你们公司符合CGMP要求。贵司使用顾问并不会解除贵公司符合CGMP的义务。贵司高级管理层仍对全面解决所有缺陷和确保持续CGMP符合性承担全面责任。——这是啥意思嘛
可能人家企业的管理就行现在的民进党蔡英文当局

jinxing0561

很详细的审核额，但都是相似的管理问题，为啥做不好呢？

wopan2012

学习了解，支持一下

北重楼

学习了解一下，有则改之无则加勉