翻译：JULIA 来源：Julia法规翻译
ViaUPS Warning Letter 320-17-44
Return Receipt Requested
August 2, 2017
Mr. John Chilver
President
Cellex-C International Inc.
9 New St. Toronto, Ontario M5R 1P7, Canada
Dear Mr. Chilver:
The U.S. Food and Drug Administration (FDA) inspectedyour drug manufacturing facility, Cellex-C International Inc. at 9 New Street,Toronto, from January 16 to 19, 2017.
美国FDA于2017年1月16-19日检查了你们位于加拿大多伦多的Cellex-C制剂生产场所。
This warning letter summarizes significant violationsof current good manufacturing practice (CGMP) regulations for finishedpharmaceuticals. 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 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).
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21 U.S.C. 351(a)(2)(B)被认为是掺假药品。
We reviewed your February 7, 2017, response in detail.
我们详细审核了你们公司2017年2月7日的回复。
During our inspection, our investigator observedspecific 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 tohave, for each batch of drug product, appropriate laboratory determination ofsatisfactory 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)).
你公司在药品放行之前，没有适当的化验室检测并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 CFR211.165(a)）。
You released your (b)(4) drug products withouttesting any of them for conformance to specifications, including identity andstrength.
你们没有检测XX药品确定其符合质量标准，包括鉴别和剂量，就放行了药品。
Your response indicated that you will have a contractlaboratory test all finished drugs for active ingredients. Your response isinadequate because it lacks sufficient detail about the selection, qualification,and oversight procedures you will use to engage your contract testinglaboratory. You also have not provided your action plan and timelines forconducting tests to determine the identity and strength of active ingredientsin all drug products within expiry that you previously released withoutperforming such testing.
你们的回复说你们有一个合同化验室，检测所有制剂的活性成分。你们的回复是不充分的，因为其缺乏足够的细节说明你们将用来管理你们合同检验化验室的选择、确认和监管程序。你们也没有提供你们检测所有之前未检测而放行但仍在有效期内的药品，以确定其中活性成分鉴别和剂量的行动计划和时间表。
2. Your firm failed totest samples of each component for conformity with all appropriate writtenspecifications for identity, purity, strength, and quality (21 CFR 211.84(d)(1),(2)).
你们公司未能检测样品中每种成分，确定其鉴别、纯度、剂量和质量是否符合所有恰当的书面质量标准（21 CFR211.84(d)(1), (2)）。
You failed to test incoming active pharmaceuticalingredients and other components you use in manufacturing (b)(4) drugproducts to determine their identity, purity, strength, or other appropriatespecifications.
你们未能检测进厂活性药物成分和其它你们用以生产XX药品的成分，确定其鉴别、纯度、剂量或其它适当的质量标准。
Your response claimed that because it is not feasiblefor you to perform component identification testing, you would instead rely onyour supplier’s certificate of analysis (COA) for the identity of each incomingcomponent. Your response is inadequate for two reasons. First, you must conductat least one specific identity test to analyze all incoming components. You maynot rely on your supplier’s COA to verify the identity of your components. Yourresponse was also inadequate because you did not indicate how you would addressyour failure to test all incoming components for specifications other thanidentity.
你们的回复声称由于你们自己检测成分鉴别是不现实的，因此你们依赖于你们供应商的COA来鉴别每种进厂成分。你们的回复是不充分的，理由有二。第一，你们必须执行至少一种专属性鉴别测试，分析所有进厂成分。你们可以依赖于你们供应商的COA来核对你们成分的鉴别。你们的回复不充分还因为你们没有指明你们要如果解决你们没有检测所有进厂成分除鉴别以外的其它成分是否符合质量标准。
3. Your firm failed toestablish written responsibilities and procedures applicable to the qualitycontrol unit (21 CFR 211.22(d)).
你们公司未能建立质量部门的书面职责和程序(21 CFR211.22(d))。
Your firm lacked critical procedures to ensure thatyour quality unit has the appropriate authority to carry out itsresponsibilites. You lacked, for example, procedures to handle complaints andreview production records.
你们公司缺乏关键程序用以确保你们质量部门有适当的权限履行其职责。例如，你们缺乏程序处理投诉和审核生产记录。
According to your response, you will establish aquality procedure with “clear job descriptions.” Your response is inadequatebecause you failed to provide this proposed written procedure, and because youhave not demonstrated how establishing “clear job descriptions” will ensurethat your firm has appropriate written responsibilities and proceduresapplicable to the quality control unit.
根据你们的回复，你们将建立质量程序写明“清楚的岗位描述”。你们的回复是不充分的，因为你们未能提供此所所占书面程序，也没有说明要如何建立“清楚的岗位描述”来确保你们公司具备适当的质量部门用书面职责和程序。
4. Your firm failed toestablish adequate written procedures for production and process controldesigned to assure that the drug products you manufacture have the identity,strength, quality, and purity they purport or are represented to possess (21CFR 211.100(a)).
你们公司未能建立足够的书面生产和工艺控制程序设计以确保你们生产的药品具备既定应有的鉴别、质量和纯度(21 CFR211.100(a))。
You have not validated the manufacturing processes foryour drug products. You lack assurance that your manufacturing processes resultin batch uniformity, integrity, and consistent drug quality.
你们没有验证你们药品的生产工艺。你们缺乏让你们的生产工艺保证批均一度、完整性和持续的药品质量的保障。
In your response, you committed to validating themanufacturing processes for your drug products. Your response is inadequatebecause you did not provide an action plan and timelines for validating yourdrug manufacturing processes.
在你们的回复中，你们承诺要验证你们药品的生产工艺。你们的回复是不充分的，因为你们没有提供你们药品生产工艺验证的行动计划和时间表。
5. Your firm failed toprepare batch production and control records with complete information relatingto the production and control of each batch of drug product produced (21 CFR211.188).
你们公司未能制订批生产和检验记录，在其中包括与所生产每批药品生产和检验有关的完整信息。
Your batch production records were incomplete. Theylacked information regarding critical steps in your filling and packagingoperations.
你们的批生产记录是不完整的，其中缺乏与你们灌装和包装操作关键步骤的信息。
According to your response, you have revised yourmanufacturing formulation worksheet. Your response is inadequate. Theworksheets you provided still omitted information about your manufacturingprocesses, such as identification of all critical equipment used duringmanufacturing, descriptions of the final drug product containers and closures,and details about in-process and finished product sampling.
根据你们的回复，你们已修订了你们的生产配方工作表。你们的回复是不充分的。你们提供的工作表仍然忽略了关于你们生产工艺的信息，例如，所有生产中所用的关键设备的识别信息，最终成品容器密闭器的描述，中控和成品取样的详细信息。
CGMP consultant recommended CGMP顾问建议
Based upon the nature of the violations we identifiedat your firm, we strongly recommend engaging a consultant qualified as setforth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. Youruse of a consultant does not relieve your firm’s obligation to comply withCGMP. Your firm’s executive management remains responsible for fully resolvingall deficiencies and ensuring ongoing CGMP compliance.
根据我们在你们公司所发现的违规情况，我们强烈建议你们聘请具备21CFR211.34中所述资格的顾问，协助你们公司符合CGMP要求。你们聘用顾问并不解除你们公司符合CGMP的义务。你们公司的执行管理层仍负有全面解决所有缺陷和确保持续CGMP符合性的义务。
Conclusion 结论
Violations cited in this letter are not intended as anall-inclusive list. You are responsible for investigating these violations, fordetermining the causes, for preventing their recurrence, and for preventingother violations.
在本函中所引的违规情况并非全部清单。你们有责任调查这些违规情况，确定其原因，防止其再次发生，防止其它违规情况。
FDA placed your firm on Import Alert 66-40 on June 2,2017.
FDA已于2017年6月2日发布你们公司进口禁令。
Until you correct all violations completely and weconfirm your compliance with CGMP, FDA may withhold approval of any newapplications or supplements listing your firm as a drug manufacturer.
在你们完全纠正所有违规情况，并由我们确认你们符合CGMP要求之前，FDA可能会搁置所有将你公司列为药品生产商的新申报和增补。
Failure to correct these violations may also result inFDA continuing to refuse admission of articles manufactured at Cellex-CInternational Inc., 9 New Street, Toronto, into the United States under section801(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 andcontrols used in their manufacture do not appear to conform to CGMP within themeaning 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 officein writing within 15 working days. Specify what you have done since ourinspection to correct your violations and to prevent their recurrence. If youcannot complete corrective actions within 15 working days, state your reasonsfor 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:
请将你们的电子回复发送至上述邮箱或邮件发至以下地址：
Daniel W. Brisker
Consumer Safety 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 3003525539.
Sincerely,
/S/
Thomas J. Cosgrove
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
