抗菌凝胶等产品主要成分被替代，FDA发出警告信。
WARNING LETTER
Frozen Wheels, LLC
MARCS-CMS 619443 — DECEMBER 20, 2021
Mr. Halwani:
尊敬的Halwani先生:
Your firm was registered as a drug repacker. The U.S. Food and Drug Administration (FDA) conducted testing of consumer antiseptic hand rubs (also referred to as a consumer hand sanitizers) labeled as “Greenfrog HAND SANITIZER,” “Cleansepure,” and “Antibacterial Gel, 70% Ethanol Concentration.” Following an attempted import into the United States, “Greenfrog HAND SANITIZER,” “Cleansepure,” and “Antibacterial Gel, 70% Ethanol Concentration” were detained and refused admission at the border. The three drug products listed above were among the many shipments of consumer antiseptic hand sanitizers you attempted to import into the United States for interstate commerce between April 2020 to June 2020.
贵公司注册为药品再包装商。美国食品和药物管理局(FDA)对标有“Greenfrog洗手液”、“清洁液”和“70%乙醇浓度的抗菌凝胶”的消费者消毒洗手液(也被称为消费者洗手液)进行了测试。在试图进口到美国之后，“绿蛙洗手液”、“清洁液”和“70%乙醇浓度的抗菌凝胶”在边境被扣留并拒绝入境。上述三种药品是企业在2020年4月至2020年6月期间试图进口到美国用于州际贸易的多批杀菌洗手液中的一批。
The results of FDA laboratory testing of batches of “Greenfrog HAND SANITIZER,” “Cleansepure,” and “Antibacterial Gel, 70% Ethanol Concentration” drug products detained at the border demonstrate that these drug products are adulterated within the meaning of section 501(d)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act), 21 U.S.C. 351(d)(2), in that a substance was substituted wholly or in part therefor.1 Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.
FDA对在边境被扣留的“Greenfrog洗手液”、“清洁液”和“70%乙醇浓度抗菌凝胶”药品批次的实验室检测结果表明，这些药品在《联邦食品、药物和化妆品法》(FD&C法或本法案)第501(d)(2)条的含义范围内定义为掺假，21 U.S.C. 351(d)(2)，即物质被全部或部分替代。根据《FD&C法》第301(a)条，21 U.S.C. 331(a)，禁止将此类产品引入或交付于州际贸易。下面将更详细地说明这些违反行为。
Introduction or Delivery for Introduction of Adulterated Drugs
引进或交付掺假药品
1. Greenfrog HAND SANITIZER
1.Greenfrog洗手液
Import and invoice records reviewed indicated that you attempted to import Greenfrog HAND SANITIZER, a drug product. Greenfrog HAND SANITIZER is labeled to contain 70% volume/volume (v/v) of the active ingredient alcohol (ethyl alcohol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug you attempted to import contained an average of 0% ethyl alcohol and 54% of methanol v/v. The Greenfrog HAND SANITIZER drug product you attempted to introduce into interstate commerce is adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient of ethyl alcohol was substituted wholly or in part with methanol, a dangerous chemical when in contact with human skin or ingested.
经审查的进口和发票记录表明，企业试图进口一种药品Greenfrog洗手液。Greenfrog洗手液被标记为含有70%体积/体积(v/v)的有效成分酒精(乙醇)。然而，FDA对在边境扣留的一批该产品的实验室检测发现，企业试图进口的药物平均含有0%的乙醇和54%的甲醇v/v。根据FD&C法案第501(d)(2)条，企业试图引入州际商业的Greenfrog洗手液含有掺假成分，因为有效成分乙醇的全部或部分被甲醇取代，甲醇当与人体皮肤接触或摄入时是一种危险的化学物质。
2. Cleansepure
2.清洁剂
Import and invoice records reviewed indicated that you also attempted to import Cleansepure, another drug product. Cleansepure is also labeled to contain 70% volume/volume (v/v) of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug you attempted to import contained an average of 9.6% ethyl alcohol and an average of 58% of methanol v/v. Therefore, the Cleansepure hand sanitizer drug product you attempted to introduced into interstate commerce is also adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient of ethyl alcohol was substituted wholly or in part with methanol, a dangerous chemical when in contact with human skin or ingested.
经审查的进口和发票记录表明，企业还试图进口另一种药品Cleansepure。清洁液也被标记为含有70%体积/体积(v/v)的活性成分酒精(乙醇)。然而，FDA对在边境扣留的一批该产品的实验室检测发现，企业试图进口的药物平均含有9.6%的乙醇和平均58%的甲醇v/v。因此，根据FD&C法案第501(d)(2)条，企业试图引入州际商业的Cleansepure洗手液产品也存在掺假行为，因为乙醇的有效成分全部或部分被甲醇取代，甲醇是一种与人体皮肤接触或摄入时的危险化学物质。
3. Antibacterial Gel, 70% Ethanol Concentration
3.抗菌凝胶，70%乙醇浓度
Import and invoice records reviewed indicated that you attempted to import Antibacterial Gel, 70% Ethanol Concentration, a drug product. Antibacterial Gel, 70% Ethanol Concentration is labeled to contain 70% volume/volume (v/v) of the active ingredient alcohol (ethyl alcohol). However, FDA laboratory testing of this product detained at the border found that the drug you attempted to import contained < 0.25% of ethyl alcohol and instead was comprised of 63% isopropanol. Therefore, the Antibacterial Gel, 70% Ethanol Concentration hand sanitizer drug product you attempted to introduce into interstate commerce is adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient of ethyl alcohol was substituted wholly or in part with (b)(4), an undeclared active ingredient.
经审查的进口和发票记录表明，企业试图进口一种药品为70%乙醇浓度的抗菌凝胶。抗菌凝胶，70%乙醇浓度标记为含有70%体积/体积(v/v)的活性成分酒精(乙醇)。然而，FDA对该产品在边境被扣留的实验室检测发现，企业试图进口的药物中酒精含量低于0.25%，而由63%的异丙醇组成。因此，根据FD&C法案第501(d)(2)条，企业试图引入州际商业的70%乙醇浓度抗菌凝胶洗手液药品存在掺假行为，因为乙醇的活性成分全部或部分被未申报的活性成分(b)(4)所取代。
On August 3, 2020 and September 11, 2020, FDA notified the public of the methanol contamination in Greenfrog HAND SANITIZER and Cleansepure at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
2020年8月3日和9月11日，FDA在以下网站上通知公众Greenfrog洗手液和清洁液中的甲醇污染:https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
In response to this letter provide the following:
在回复本函时，提供以下资料:
A list of all suppliers for your hand sanitizer drug products, including the suppliers’ names, addresses, and contact information.
企业的洗手液药品的所有供应商的名单，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 imported into the United States by your firm, and a full reconciliation of all material you distributed.
一份贵公司进口到美国的所有批次洗手液药品的清单，以及企业分发的所有材料的完整核对表。
Copies of the drug supply chain custody information for all drug product batches distributed to the U.S.
分发给美国的所有药品批次的药品供应链监管信息副本。
Conclusion
结论
Violations in this letter are not intended as an all-inclusive list of violations. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
本函中的违规行为并非包括企业所有违规行为。企业有责任调查和确定任何违规行为的原因，并防止其再次发生或其他违规行为的发生。
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.
这封信通知企业我们的发现，并为企业提供了一个解决上述缺陷的机会。收到本函后，请于15个工作日内以书面方式回复本办公室。说明企业已经采取了什么措施来解决任何违规行为，并防止其再次发生。在回复本函时，企业可以提供额外的信息供我们考虑，因为我们将继续评估企业的活动和实践。如未能在15个工作日内办理，请说明延误的原因及完成手续的时间表。
Your written notification should refer to case # 619443.
企业的书面通知应参照第619443号案例。
Please electronically submit your reply, on company letterhead, to Mark W. Rivero, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to mark.rivero@fda.hhs.gov.
请用带公司抬头的信纸将答复以电子方式提交给合规官Mark W. Rivero，邮箱:ORAPHARM2_RESPONSES@fda.hhs.gov。此外，请将企业的回复提交到mark.rivero@fda.hhs.gov。
If you have questions regarding the contents of this letter, you may contact NAME via phone at (504) 846-6103 or email at mark.rivero@fda.hhs.gov.
如对本函内容有任何疑问，可通过电话(504)846-6103或电子邮件(mark.rivero@fda.hhs.gov)与NAME联系。
Sincerely,
/S/
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
Division II
_________________________________
1. Due to an increased demand for alcohol-based hand sanitizers during the COVID-19 pandemic, FDA published the Guidance for Industry: Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) on March 19, 2020, and subsequently updated the guidance several times, most recently on February 10, 2021. This guidance communicates the Agency’s temporary policy that we do not intend to take action against firms for CGMP violations under section 501(a)(2)(B) of the FD&C Act if such firms prepare alcohol-based hand sanitizers for consumer use (or for use as a health care personnel hand rub) during the public health emergency, provided certain circumstances described in the guidance are present. These circumstances include preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. As detailed below, a review of the hand sanitizer products you attempted to import into the United States indicate that these products are not prepared consistent with FDA’s temporary policy set forth in the guidance.
1、由于COVID-19大流行期间对含酒精洗手液的需求增加，FDA于2020年3月19日发布了《行业指南:在突发公共卫生事件(COVID-19)期间制备某些含酒精洗手液产品的临时政策》，随后多次更新该指南，最近一次是在2021年2月10日。本指南传达了FDA的临时政策，即我们不打算根据FD&C法案第501(a)(2)(B)条对违反CGMP的企业采取行动，如果此类企业在公共卫生紧急情况下为消费者使用(或作为医护人员洗手液使用)准备含酒精的洗手液，前提是指南中描述的某些情况存在。这些情况包括只使用指南中规定的成分和配方制备洗手液产品。如下所述，对企业试图进口到美国的洗手液产品的审查表明，这些产品的制备不符合FDA指南中规定的临时政策。
