Warning Letter 320-19-10 January 29,2019
Mr. Ma Xing Fa
General Manager, Hangzhou Sunking Nonwovens Co.,Ltd.
No. 888 Chongchao Rd., Chongxian Industrial Area, Hangzhou, Zhejiang, 311108 China
Dear Mr. Ma:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility Hangzhou Sunking Nonwovens Co.,Ltd., at No. 888 Chongchao Rd., Chongxian Industrial Area, Hangzhou, Zhejiang, from August 7 to 9, 2018.
美国FDA于2018年8月7日至9日检查了你们位于浙江省杭州市余杭区崇贤街道崇超路888号的杭州申皇无纺布用品有限公司生产场所。
This warning letter summarizes significant violations of current good manufacturing practice (C
GMP) 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 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 response, received on September 24, 2018, in detail.
我们详细审核了你们2018年9月24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 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)). 你公司未能在放行之前对每批药品进行适当的实验室检测，确保其符合药品的最终质量标准，包括每种活性成分的鉴别和剂量（21 CFR 211.165(a)）。
Your firm released over-the-counter (OTC) (b)(4) drug products without appropriate quality control release testing, including but not limited to, the identity testing of (b)(4) active ingredient.
你公司未进行适当的质量控制放行检测就放行了OTCXX药品，包括但不仅限于XX活性成分的鉴别检测。
In addition, we have concerns about the validity of test results for your finished drug product. Reports from your contract laboratory included strength test results of (b)(4) active ingredientand microbial test results (total bacterial and total fungal counts) that were identical for (b)(4) batches of your (b)(4) drug product that were shipped for distribution to the U.S. market.
另外，我们对你们成品检测结果的有效性有所担忧。来自你们合同实验室的报告包括有XX活性成分的剂量检测结果和微生物检测结果（总细菌和总真菌计数）显示你们发往美国的XX批次XX药品检测结果是一样的。
2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)). 你公司未执行至少一项检测来验证药品的每种成分的鉴别。你公司亦未以恰当的时间间隔验证和建立你们成分供应商的检测可靠性（21 CFR 211.84(d)(1) and (2)）。
Your firm lacked testing of incoming raw materials,used in the manufacturing of your drug product, including active pharmaceutical ingredients and other components, for their identity, strength, and other quality attributes. Your firm also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of the suppliers’ analyses through appropriate validation.
你公司缺乏对你们药品生产所用进厂物料的检测，包括活性药物成分和其它组份的鉴别、剂量和其它质量属性。你公司还依赖于你们供应商的COA，却并未通过适当的验证建立这些供应商的分析可靠性。
3. Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)). 你公司未能确保药品具备受到适当稳定性试验支持的有效期（21 CFR 211.137(a)）。
Your firm has not established a stability program,including written procedures. Your firm also did not have stability data to support the (b)(4) expiration dates assigned to your OTC drug product. Without stability data, you cannot assure the quality of your drug products throughout their labeled shelf lives.
你公司未建立稳定性程序，包括书面程序。你公司亦没有稳定性数据支持赋予你们OTC药品的XX有效期。在没有稳定性数据时，你们不能确保你们的药品在其所标示的货架期内的质量。
4. Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)). 你公司未制订生产和工艺控制书面程序，设计用于确保你们生产的药品具备其理当具备的鉴别、剂量、质量和纯度（21 CFR 211.100(a)）。
Your firm has not validated the processes used tomanufacture your drug products. Your firm did not perform process qualification studies and lacks an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
你公司未验证你们药品生产所用工艺。你公司未进行工艺确认研究，缺乏工艺持续监控计划用以确保稳定的生产操作和持续的药品质量。
参见FDA指南文件“工艺验证通则”。
5. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)). 你公司未建立足够的质量控制部门，使其具备批准或拒收所有组份、药品容器密闭器、中间体、包材、标签和药品成品的职责和权力（21 CFR 211.22(a)）。
Your firm lacks an adequate quality unit. You have not established written procedures for numerous functions of the quality unit,including but not limited to, quality unit operations, batch release, change control, complaints, supplier qualification, recalls, and annual product reviews. During the inspection, you indicated that your firm lacks a quality agreement describing the roles, responsibilities, and procedures to be followed by you and your contract laboratory regarding component and final product testing.
你公司缺少足够的质量部门。你们未建立书面程序规定质量部门的大量职责，包括但不仅限于质量部门运作、批放行、变更控制、投诉、供应商确认、召回和年度产品回顾。在检查期间，你们说你们公司缺乏质量协议描述你和你们合同实验室在组份和成品检测方面的角色与职责，以及要遵守的程序。
Use of Contract Laboratories使用合同实验室
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers.FDA regards contractors as extensions of the manufacturer. As such, you are responsible for making final release decisions.
药品生产必须符合CGMP。FDA了解许多药品生产商使用独立的合同方，如生产设施、检验实验室、包装商和贴标商。FDA认为合同商是生产商延伸。因此你们有义务做出最终放行决策。
You are responsible for the quality of drugs you produce, regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA’s guidance document
, Contract Manufacturing Arrangements for Drugs: Quality Agreements, at:
https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf.无论你们与合同场所是否有协议，你们都对你们生产的药品质量负有责任。你们应确保药品生产符合FDCA的第501(a)(2)(B)条款，确保其安全性、鉴别、剂量、质量和纯度。参见FDA指南文件“药品委托生产安排：质量协议”。
Quality Systems Guidance 质量体系指南
你公司的质量体系是不充分的。建立和遵守符合CGMP要求的质量体系，参见FDA指南文件Q8（R2）药品开发、Q9质量风险管理和Q10药品质量体系。
Inadequate Response 回复不充分
Your response to the FDA inspection did not provide sufficient details or evidence that your firm will remediate your operations to ensure compliance with CGMP.
你们对FDA检查的回复未提供足够详细的内容或证据证明你公司将对你们操作进行补救以确保其符合CGMP要求。
In response to this letter, provide the following:
在回复此函时请提交以下：
• The test methods and specifications you use to analyze each batch of drug product prior to release, including both chemical and microbial quality attributes. Include asummary of all test results obtained from testing of all batches of drug products intended for the U.S. market within expiry. Include your procedures that will ensure you test each batch of finished drug product, prior to release, according to batch release specifications.
• 你们用于分析每批药品并放行所用的检验方法和质量标准，包括化学和微生物质量属性。包括一份对准备销往美国市场且在有效期的所有批次药品进行检测所得的所有检测结果的总结。包括你们将确保你们会对每批成品在放行之前根据批放行标准进行检测的程序。
• Your plan for testing retains of all drug products distributed to the U.S. market within expiry for identity and strength of active ingredients, and microbial quality, including total count and objectionable microorganisms. If you released any batch that were out of specification (OOS), indicate the corrective actions you will take, such as customer notifications and product recalls.
• 你们对所有已销往美国且在有效期内的所有药品留样的活性成分鉴别和剂量以及微生物质量，包括总计数和致病菌的检测计划。如果你们放行的批次中有OOS批次，请说明你们将采取的纠正措施，如通知客户和召回产品。
• Batch release specifications for all incoming components including the (b)(4). Includeyour procedures for analyzing each batch of incoming components and the procedure that requires testing of components prior to release and use.
• 所有进厂组份的批放行标准，包括XX。包括你们分析每批进厂组份的程序，以及要求在放行使用之前对组份进行检测的程序。
• Provide a risk assessment of all drug products distributed to the U.S. market within expiry,to determine the impact of not testing components, such as the (b)(4).
• 提交一份对所有已销往美国且在有效期内药品的风险评估，确定未检测组份的影响，如XX。
• Your plan, with timelines, to develop and implement a complete drug stability program. This plan should include an assessment of stability by testing retain samples of your drug product in the U.S. market within expiry. Indicate the correctiveactions you will take, including notifying customers, if OOS results are found.
• 你们制订和实施一份完整的药品稳定性试验程序的计划和时间表。该计划应包括对你们在美国市场上且在有效期内药品的留样检测的稳定性的评估。说明如果发现OOS结果你们将采取的纠正措施，包括通知客户。
• A risk assessment of the drug products distributed to the U.S. market within expiry that were not supported by adequate stability testing.
• 一份对销往美国且在有效期内但没有充分稳定性试验支持的药品的风险评估。
• Process performance qualification for your drug products. Provide a detailed summary of your approach for routinely monitoring intra-batch and inter-batch variation.
• 你们药品的工艺性能确认。提交一份你们如何日常监控批间和批内波动的详细总结。
• Your corrective and preventive action (CAPA) plan for establishing an effective quality control unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. Include newly established and updated procedures.
• 你们建立有效质量部门使其具备适当权力和足够资源履行其职责并持续确保药品质量的CAPA。包括新建立和更新的程序。
CGMP Consultant Recommended CGMP顾问建议
Based upon the nature of the violations we identified at your firm, 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.
鉴于我们在你们公司发现的违规情况，我们强烈建议你们聘请符合具备21CFR 211.34所述资质的顾问来协助你们公司符合CGMP要求。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 in your facility.
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 December 13, 2018.
FDA已于2018年12月13日将你公司置于进口禁令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。
Failure to correct these violations may also resultin FDA continuing to refuse admission of articles manufactured at Hangzhou Sunking Nonwovens Co., Ltd., No. 888 Chongchao Rd., Chongxian Industrial Area,Hangzhou, Zhejiang 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).
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 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.
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。
Cesar E. Matto
Senior Policy Advisor
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
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发表于 2019-2-22 13:38:54
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