4月20日，FDA官网公布了一封针对国内企业（厚福生物科技江苏有限公司）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70％的活性成分乙醇，但实际平均乙醇含量为45％，因此被视为掺假药品。FDA随后建议该公司从美国市场上召回所有洗手液，但并未得到公司的响应。
图：4月20日，FDA官网公布对厚福生物科技的警告信
Warning Letter 320-21-42
April 12, 2021
Dear Mr. Wu:
警告信320-21-42
2021年4月12日
吴先生：
Your firm was recently registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of a consumer antiseptic hand rub drug product (also referred to as a consumer hand sanitizer) labeled as PANROSA Instant Hand Sanitizer. This drug product was declared to be manufactured at your facility, Hou Fu Biotech (Jiangsu) Co., Ltd., FEI 3015089546, at Building 5 South of Floor 3, Shengming Jiankang Industries Park, Nantong, Jiangsu, China. Following an attempt to import PANROSA Instant Hand Sanitizer into the United States, it was detained and refused admission at the border.
你们公司最近注册为人药生产商。美国FDA对一种消费者手部免洗杀菌药品(洗手液)进行了检验，其标签标识为“PANROSA即用洗手液”。该药品声称为在你们的工厂生产，即厚福生物科技江苏有限公司，FEI 3015089546，位于中国江苏省南通市生命健康产业园5号楼3楼南。PANROSA即用洗手液试图进口到美国时被扣留，并拒绝在边境入境。
图：PANROSA即用洗手液标签（图片来源于网络）
The results of 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) of the FD&C Act (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。
In addition, PANROSA Instant Hand Sanitizer is an unapproved new drug introduced or delivered for introduction into interstate commerce in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a), and is misbranded under sections 502(a), (f)(2), and (ee) of the FD&C Act, 21 U.S.C. 352(a), (f)(2), and (ee). Introduction or delivery for introduction of these products into interstate commerce is prohibited under sections 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a). These violations are described in more detail below.
此外，PANROSA即用洗手液是未经批准的新药，你们公司生产、引入或交付用于州际贸易的，违反了FD＆C法案505(a)条，即21 USC 355(a)条；根据502条502(a)，(f)(2)和(ee)，即21 USC 352(a)，(f)(2)和(ee)，该产品也属于标识错误。根据FD＆C法案301(d)和(a) 条，即21 USC 331(301) (d)和(a) 条，禁止将此类产品引入州际贸易。这些违规行为，将在下文中详细介绍。
掺假的违法项
Adulteration Violation
PANROSA Instant Hand Sanitizer, declared to be manufactured at your facility, is labeled to contain 70% volume/volume (v/v) of the active ingredient 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 45% v/v ethanol. 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，被标识为含有70％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45％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 recommends 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 November 12, 2020, FDA held a teleconference with you and Registrar Corp, your registered U.S. Agent. We recommended you consider removing all of your firm’s hand sanitizer drug products currently in distribution from the U.S. market. However, as of the date of this letter you have yet to initiate a recall.
2020年9月8日，FDA与你们和你们在美国注册代理商Registrar Corp举行了电话会议。我们建议你们考虑从美国市场上撤回你们公司目前正在分销的所有洗手液药品。但是，截至本函发出之日，你们尚未发起召回。
On November 13, 2020, FDA notified the public of subpotency of your hand sanitizer drug product at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use.（
https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use.）
https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use.）2020年11月13日，FDA在以下网站上将你们洗手液药品的含量不足通知了公众：（网址略）。
In response to this letter provide the following:
在对本函的回复中，请提供：
• A detailed investigation into how the hand sanitizer drug product described above, which was labeled as containing 70% ethanol, in fact contained an average of 45% ethanol.
•对上述洗手液药品进行详细调查，该产品被标识为含有70％的乙醇，实际上却含有45％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。
• 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。
The subpotency of hand sanitizer drug products declared to be manufactured in 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。
未经批准的新药和标识错误的行为（略）
CGMP顾问推荐
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 December 3, 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12月3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，而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 FD&C 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FD&C法案的要求。这包括FDA考虑对你们工厂进行检查，确定已解决掺假问题。
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，请要求召开监管会议，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。
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov
将您的电子回复发送至邮件（略）。
Please identify your response with FEI 3015089546 and ATTN: Towanda Terrell.
在回复中，请标记信息FEI 3015089546和ATTN：Towanda Terrell。
Sincerely,
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
此致
弗朗西斯 戈德温
生产质量办公室主任
合规办公室，CDER
CC:
Registered US Agent
Registrar Corp David Lennarz
144 Research Drive
Hampton, VA 23666
抄送：
美国注册代理商（略）
Ref.: WARNING LETTER. Hou Fu Biotech - Jiangsu Co., Ltd. MARCS-CMS 611644 — APRIL 12, 2021. FDA.
