FDA警告信：江西某企业，药品含量不合格

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2月9日，FDA官网公布了一封针对国内企业（上饶市春宇科技有限公司）的警告信，该公司生产免洗消毒洗手液，在美国按照非处方药品进行管理。FDA对此产品进行检验表明，该产品标识含有75％的活性成分乙醇，但实际平均乙醇含量为58％，因此被视为掺假药品。FDA随后要求该公司提供CGMP的相关信息，但FDA认为公司提供的资料存在问题，该公司的质量保证不能按照CGMP要求运行。

Warning Letter 320-21-24

February 3, 2021

Dear Mr. Suer:

警告信320-21-24

2021年2月3日

苏尔先生：

Your firm is registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of a consumer antiseptic rub drug product (also referred to as a consumer hand sanitizer), labeled as Instant – Hand Sanitizer – Moisturizing. This drug product was declared to be manufactured at your facility, Shangrao Chunyu Technology Co., Ltd., FEI 3015958566, at Xuri Zone, Shangrao Economic-Technical Development Area, Shangrao, Jiangxi 334100, China. Following an attempt to import Instant – Hand Sanitizer – Moisturizing into the United States, it was detained and refused admission at the border.

你们公司已注册为人药生产商。美国FDA对免洗消毒液药品(洗手液)进行了检验，其标签标识为“快速手部消毒液”(Instant – Hand Sanitizer – Moisturizing)。此药品声明为在你们工厂生产，即上饶市春宇科技有限公司，FEI 3015958566，位于江西省上饶市上饶经济技术开发区徐日区，邮编为334100。该洗手液试图进口到美国时被扣留，并拒绝在边境入境。

The results of the FDA laboratory testing of a batch of this product detained at the border demonstrate that this drug product declared to be manufactured at your facility is adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act or Act), 21 U.S.C. 351(c), in that its strength, purity, or quality falls below that which it purports or is represented to possess. In addition, this product is adulterated within the meaning of section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)), in that the subpotency demonstrates that the quality assurance within your facility is not functioning in accordance with Current Good Manufacturing Practice (CGMP) requirements.

对于边境扣留的一批产品，FDA进行了实验室检验，结果表明：声明在你们工厂生产的该药品属于《联邦食品、药物和化妆品法》(FD&C法案)第501(c)条(21 USC 351(c)条)所规定的掺假产品，因为其强度、纯度或质量低于其声称或表示拥有的标准。此外，按照第501(a)(2)(B)节(21 USC 351(a)(2)(B))，本产品也是视为掺假的，这是因为其含量不足，证明你们设施内的质量保证是不能按照CGMP要求运行的。

掺假的违法项

Adulteration Violation

Instant – Hand Sanitizer – Moisturizing, declared to be manufactured at your facility, is labeled to contain 75% of the active ingredient alcohol ethyl alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug product contained an average of only 58% ethanol volume/volume. This hand sanitizer drug product is adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the product lower than that which is declared on its label.

你们工厂生产的产品，被标记为含有75％的活性成分酒精(乙醇)。但是，对于在边境扣留的一批该产品，FDA实验室检验发现该药品平均仅包含58％的乙醇（体积/体积）。根据FD＆C法案第501(c)条的规定，这种洗手液药品视为掺假，原因是产品中乙醇的活性成分含量低于标签上声明的含量。

CDC recommends1 that, if soap and water are not readily available, consumers use an alcohol-based hand sanitizer that contains not less than 60% alcohol (ethanol). This is the minimum active ingredient concentration of ethanol specified in the 1994 Tentative Final Monograph for Health-Care Antiseptic Drug Products (59 FR 31402), as further amended by “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016).

疾病预防控制中心建议，如果不容易获得肥皂和水，则消费者应使用酒精含量不低于60％的酒精(乙醇)洗手液。这是1994年《杀菌药物暂定最终专论》(59 FR 31402)中指定的最低乙醇有效成分浓度，并进一步在以下修订文件中确立：“消费者杀菌产品的安全性和有效性；人用局部抗菌非处方药；暂定最终专论的拟议修订；重新开放行政记录”拟议规则，81 FR 42912(2016年6月30日)。

On September 8, 2020, FDA held a teleconference with you and Pragmatic Compliance, LLC, your registered U.S. Agent. We requested additional information concerning your CGMP operations, including test methods for your finished product. In your response, you provided your test method for release of finished hand sanitizer products. The method you submitted uses a (b)(4) that is unsuitable for the testing of finished hand sanitizers that contain materials other than ethanol and water in their (b)(4). The use of this unsuitable device to test your finished hand sanitizer products violates CGMP requirements (see 21 CFR 211.160(b)(requiring the use of scientifically sound and appropriate test procedures to, among other things, assure that drug products conform to appropriate standards of identity, strength, quality, and purity).

2020年9月8日，FDA与你们和你们在美国注册代理商Pragmatic Compliance, LLC举行了电话会议。我们要求提供有关你们CGMP操作的其它信息，包括成品的检验方法。在答复中，你们提供了放行成品洗手液产品的检验方法。你们提交的方法使用了XX，不适合检验包含乙醇和水以外物料的成品洗手液。使用此不合适的仪器检验成品洗手液产品，你们违反了CGMP要求(请参阅21 CFR 211.160(b)(要求使用科学合理且适当的检验程序，来确保药品符合鉴别、强度、质量和纯度的适当标准)。

In response to this letter, provide the following:

对此信件，提供如下答复：

• A detailed investigation into how the hand sanitizer drug product described above, which was labeled as containing 75% ethanol, in fact contained 58% ethanol.

•对上述洗手液药品进行详细调查，该产品被标记为含有75％的乙醇，实际上却含有58％的乙醇。

• A list of all raw materials used to manufacture all of your hand sanitizer drug products, including the suppliers’ names, addresses, and contact information.

•用于生产你们所有洗手液药品的所有原材料的清单，包括供应商的名称、地址和联系信息。

• A list of all batches of any hand sanitizer drug products shipped to the United States by your firm, and a full reconciliation of all material you distributed.

•你们公司运往美国的所有洗手液药品的所有批次的清单，以及你们分发的所有物料的完整清单。

• For all batches distributed to the U.S., provide a third-party analysis using validated test methods for ethanol content. For out-of-specification (OOS) batches, provide your action plan to address any product quality or patient safety risks for your drug products in U.S. distribution, including potential customer notifications and recalls.

•对于所有分发给美国的批次，使用已验证的乙醇含量检验方法，提供第三方分析结果。对于不合格(OOS)批次，请提供你们行动计划，就在美国经销药品，解决任何质量或患者安全风险，包括潜在的客户通知和召回。

• Copies of the complete batch records for all batches distributed to the U.S.

•就分发给美国的所有批次，提供完整批记录的副本。

• A complete, comprehensive, and independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

•就实验室操作、程序、方法、设备、文档和分析人员能力，进行完整、全面和独立的评估。在此审查的基础上，提供详细计划，以补救和评估实验室系统的有效性。

The subpotency of a drug product declared as manufactured at your facility demonstrates that the quality assurance within your facility is not functioning in accordance with CGMP requirements under section 501(a)(2)(B) of the FD&C Act.

在你们工厂生产的药品含量不足，这表明你们工厂的质量保证未按照FD＆C法案第501(a)(2)(B)节中的CGMP要求运行。

推荐使用CGMP顾问

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified, as set forth in 21 CFR 211.34, to evaluate your operations and to assist your firm in meeting CGMP requirements, if your firm intends to resume manufacturing drugs for the U.S. market. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and that the consultant evaluates the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

如果你们公司打算恢复生产面向美国市场的药品，根据我们发现的违规行为的性质，我们强烈建议聘请符合21 CFR 211.34规定的合格顾问，来协助你们公司满足CGMP要求。我们还建议合格的顾问对你们整个操作过程进行全面审计，以确保其符合CGMP要求，并建议在你们寻求公司与FDA的合规性解决方案之前，顾问对你们CAPA的完成情况和有效性进行评估。你们聘用顾问并不能免除公司遵守CGMP的义务。你们公司的执行管理层仍然负责解决所有缺陷和系统性缺陷，以确保持续符合CGMP。

结论

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations associated with your drug products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

本信函中引用的违规行为并非旨在列出与你们产品相关的所有违规行为。你们有责任调查和确定这些违规的原因，并防止其再次发生或发生其它违规情况。

Note that FDA placed all drugs and drug products manufactured by your firm on Import Alert 66-78 on November 6, 2020, as the methods used in and controls used for the manufacture, processing, packing, or holding of these products do not appear to conform to current good manufacturing practices within the meaning of section 501(a)(2)(B) of the FD&C Act. Drugs and drug products that appear to be adulterated or misbranded may be detained or refused admission without physical examination.

请注意，FDA于2020年11月6日将你们公司生产的所有药品置于进口警报66-78上，因为生产、加工、包装或仓储这些产品所用的方法和控制措施不符合cGMP，cGMP在FD＆C法案第501(a)(2)(B)条中规定。视为掺假或标识错误的药品，可在未经物理检查的情况下被扣留或拒绝入境。

All drugs and drug products manufactured by your firm may remain listed on this import alert, until there is evidence establishing that the conditions that gave rise to the appearance of a violation have been resolved, and the Agency has confidence that future entries will be in compliance with the Act. This may include an inspection prior to the Agency considering the appearance of adulteration to be addressed.

你们公司生产的所有药品都可能会保留在此进口警报中，直到有证据表明导致违法行为的条件得到解决，并且FDA相信将来将符合该法案的要求。这包括FDA考虑对你们工厂进行检查（基于掺假问题）。

If you decide you want to manufacture drugs for the United States in the future, request a Regulatory Meeting to discuss corrective actions.

如果你们决定将来要为美国生产药品，请要求召开法规会议，讨论纠正措施。

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot do so within 15 working days, state your reasons for delay and your schedule for completion.

这封信通知你们我们的发现，并为你们提供解决上述缺陷的机会。收到这封信后，请在15个工作日内以书面形式答复FDA办公室。说明你们为解决任何违规行为、并防止其再次发生所采取的措施。在回信中，当我们继续评估你们活动和做法时，你们可以提供其它信息供我们考虑。如果你们无法在15个工作日内这样做，请说明延误原因和完成时间表。

Ref.: WARNING LETTER- ShangRao Chunyu Technology Co., Ltd. MARCS-CMS 610194 — FEBRUARY 03, 2021. FDA.

gao7869

我认为可能包装出了问题，挥发了，含量低了。

syhorchid

涉及掺假问题吗？