质量部门、纯化水控制以及药品质量不符合cGMP及法规要求，FDA发出警告信。
WARNING LETTER
Shuzy Rock Inc.
MARCS-CMS 630110 — SEPTEMBER 01, 2022
September 1, 2022
Dear Mr. Stefansky and Mr. Iskowitz:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Shuzy Rock Inc, FEI 3013835844, at 161 Helen Street, South Plainfield, from January 11 to February 14, 2022.
美国食品和药物管理局(FDA)于2022年1月11日至2月14日对企业位于南普莱恩菲尔德海伦街161号的药品生产工厂Shuzy Rock Inc进行了检查，编号为FEI 3013835844。
FDA determined that drug products manufactured at your facility, including “Premium Nature INSTANT HAND SANITIZER”, are adulterated within the meaning of section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic (the FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions.
FDA认定，贵工厂生产的药品，包括“优质天然即食洗手液”，在联邦食品、药品和化妆品(FD&C法案)第501(a)(2)(a)条、21 U.S.C. 351(a)(2)(a)条的意义下是掺假的，因为它们是在不卫生的条件下制备、包装或保存的。
The results of the FDA laboratory testing of batches of these products distributed in the U.S. market also demonstrate that these drug products represented to be manufactured at your facility are adulterated within the meaning of section 501(c) of the FD&C 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.
FDA对经销于美国市场的这些产品批次的实验室检测结果也表明，根据FD&C法案21 U.S.C. 351(c)第501(c)条的含义，贵工厂生产的这些药品存在掺假，即其规格、纯度或质量低于其声称或声称拥有的质量标准。
This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
本警告信总结了成品药严重违反CGMP法规的情况。参见第21篇《联邦法规》(CFR)第210和211部分(第21篇《联邦法规》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 are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
因为企业生产、加工、包装或保存的方法、设施或控制不符合CGMP要求，企业的药品根据FD&C法案第501(a)(2)(B)条、21 U.S.C. 351(a)(2)(B)的含义被认定为掺假。
Additionally, Shuzy Rock Inc is not duly registered with FDA as required by section 510 of the FD&C Act and 21 CFR Part 207. With some limited exceptions, firms that manufacture, prepare, propagate, compound, or process drugs in the United States, or that are offered for import into the United States, must be registered with the FDA (Sections 510(b), (c), (d), and (i) of the FD&C Act, 21 U.S.C. 360(b), (c), (d), and (i)).
此外，Shuzy Rock公司没有按照FD&C法案第510条和21 CFR第207部分的要求在FDA正式注册。除了一些有限的例外，在美国生产、制备、销售、合成或加工药物的公司，或提供进口到美国的药物，必须在FDA注册(FD&C法案第510(b)、(c)、(d)和(i)条，21 U.S.C. 360(b)、(c)、(d)和(i)条)。
Premium Nature INSTANT HAND SANITIZER, Premium Nature INSTANT HAND SANITIZER TRAVEL SIZE, (b)(4) INSTANT HAND SANITIZER GEL, (b)(4) SHAMPOO, and (b)(4) CONDITIONER FOR MEN AND WOMEN are not duly listed with FDA as required by section 510(j) of the FD&C Act. Failure to properly list a drug product is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). 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.
高级自然速溶洗手液，高级自然速溶洗手液旅行号，(b)(4)男性和女性速溶洗手液凝胶，(b)(4)洗发水和(b)(4)护发素没有按照FD&C法案第510(j)条的要求正式向FDA申请。根据《FD&C法案》第301(p)条，21 U.S.C. 331(p)条，不正确提出药品申请是被禁止的，根据《FD&C法案》第502(o)条，21 U.S.C. 352(o)条，将导致药品被错误标识。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州际贸易。下面将更详细地说明这些违反行为。
Insanitary Conditions
不卫生的条件
Your drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, or held under insanitary conditions. FDA investigators observed your facility to be in a state of disrepair, poorly cleaned and maintained as evidenced by refuse on the floors, unaddressed spills, and broken tiles along the base of the wall in the filling room. You do not have adequate controls in place to maintain a clean production environment and prevent cross-contamination of drug products and non-drug products manufactured at your facility.
根据FD&C法案第501(a)(2)(a)条，企业的药品是掺假的，因为它们是在不卫生的条件下制备、包装或保存的。FDA调查人员观察到贵工厂年久失修，清洁和维护不善，地板上的垃圾，未处理的溢出物，以及灌装室墙底的瓷砖破损。企业没有适当的控制来维持清洁的生产环境，并防止贵工厂生产的药品和非药品的交叉污染。
Additionally, you manufactured drug products using nondedicated equipment without adequate, validated cleaning procedures. Your equipment, including filling machines, were found to be soiled during the FDA inspection. FDA analysis of your marketed hand sanitizer drug product found impurities including polymers, silicate type material, and rust-colored particles which may have originated from product cross-contamination on nondedicated equipment and poorly maintained equipment.
此外，企业使用非专用设备生产药品，没有经过充分验证的清洁程序。企业的设备，包括灌装机，在FDA的检查中被发现是脏的。FDA对企业上市的洗手液药品的分析发现了包括聚合物、硅酸盐类物质和铁锈色颗粒在内的杂质，这些杂质可能来自于非专用设备和维护不善设备上的产品的交叉污染。
FDA Tested Samples
FDA检测样品
Adulteration Violations: Subpotency
掺假违规: Subpotency
Premium Nature INSTANT HAND SANITIZER, represented to be manufactured at your facility, is labeled to contain 65% volume/volume (v/v) of the active ingredient alcohol (ethanol). However, FDA laboratory testing of batches of this product distributed in the U.S. market found that the drug product contained a range of 48 – 57% v/v ethanol.
优质天然即食免洗洗手液，由贵工厂生产，标签上注明有效成分酒精(乙醇)的体积/体积(v/v)为65%。然而，FDA对在美国市场销售的该产品批次的实验室检测发现，该药品含有48 - 57% v/v的乙醇。
Additionally, Premium Nature INSTANT HAND SANITIZER, manufactured at your facility, is labeled to contain 70% v/v of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this product distributed in the U.S. market found that the drug product contained 55% v/v ethanol. Therefore, these hand sanitizer drug products are adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the products lower than what is declared on their labeling.
此外，贵公司生产的优质天然免洗洗手液，标注含有70% v/v的活性成分酒精(乙醇)。然而，FDA实验室检测了一批在美国市场销售的该产品，发现该药品含有55% v/v乙醇。因此，根据FD&C法案第501(c)条，这些洗手液药品是掺假的，因为乙醇的有效成分含量低于产品标签上声明的含量。
CDC recommends1 that, if soap and water are not readily available, consumers should 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).
疾控中心建议，如果没有肥皂和水，消费者应该使用含酒精的洗手液，酒精含量不低于60%(乙醇)。这是1994年《卫生保健杀菌药品暂定最终专论》(59 FR 31402)中规定的乙醇的最低活性成分浓度，经《消费用防腐剂的安全性和有效性;非处方人用外用抗菌药物产品;对专著暂定终稿的修改建议;重新开放行政记录”，提案规则81 FR 42912(2016年6月30日)。
On January 7, 2022, FDA held a teleconference with your contract manufacturer, (b)(4). We recommended that they consider removing all of the firm’s Premium Nature hand sanitizer drug product(s) currently in distribution from the U.S. market and within expiry.
2022年1月7日，FDA与企业的合同制造商xx召开了电话会议。我们建议他们考虑将该公司目前在美国市场上销售的所有优质自然洗手液药品(s)从美国市场上撤下。
On January 20, 2022, FDA held a teleconference with you and your counsel. We recommended that you consider removing all of your firm’s hand sanitizer drug products currently in distribution from the U.S. market and within expiry.
2022年1月20日，FDA与企业以及企业的律师举行了电话会议。我们建议企业考虑将贵公司目前在美国市场上销售的所有洗手液药品和在有效期内的产品下架。
On January 24, 2022, FDA notified the public of the subpotency of your hand sanitizer drugs products at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
2022年1月24日，FDA在以下网站上向公众通知了企业洗手液产品的非足效性:https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
In response to this letter, provide:
在回复本函时，请提供:
A detailed investigation into how the hand sanitizer drug product described above, labeled as containing 65% (v/v) ethanol, in fact contained an average of 48 – 57% ethanol and how hand sanitizer product described above, labeled as containing 70% (v/v) ethanol, in fact contained an average of 55% ethanol.
详细调查了上述标注为含有65% (v/v)乙醇的洗手液药品实际上平均含有48 - 57%的乙醇，以及上述标注为含有70% (v/v)乙醇的洗手液产品实际上平均含有55%的乙醇。
A list of all raw materials used to manufacture your hand sanitizer drug products, including the suppliers’ names, addresses, and contact information.
一份用于生产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 distributed in the U.S., and a full reconciliation of all material you distributed.
一份在美国销售的所有批次洗手液药品的清单，以及企业销售的所有材料的完整核对表。
Copies of the complete batch records for all batches distributed in the United States.
在美国销售的所有批次的完整批记录副本。
The subpotency of hand sanitizer drug products represented to be manufactured in your facility demonstrate 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.2
贵工厂生产的洗手液药品的弱效果证明贵工厂的质量保证不符合FD&C法案第501(a)(2)(B)条下的CGMP要求
CGMP Violations
CGMP违规
We reviewed your March 7, 2022, response to our Form FDA 483 in detail. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.
我们详细审查了企业2022年3月7日对我们FDA 483表格的回复。企业的回复是不充分的，因为它没有提供足够的细节或纠正措施的证据，使企业的操作符合CGMP。
During our inspection, our investigators observed specific violations including, but not limited to, the following.
在我们的检查中，我们的调查人员发现了具体的违规行为，包括但不限于以下情况。
1. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
1.企业的质量管理部门没有履行其职责确保所生产的药品CGMP合规并且符合鉴别、规格、质量和纯度的既定标准（21 CFR 211.22）。
Your firm failed to have adequate procedures and personnel with the CGMP responsibilities for oversight for the manufacture of your over-the-counter (OTC) drug products. You could not identify any personnel with the responsibility and authority of the Quality Unit (QU). You could not provide procedures for investigations, recalls, complaint handling, the approval of manufacturing instructions, and the evaluation and approval or rejection of finished drug product batches before release to the market. Likewise, your firm did not have a procedure for the evaluation and approval or rejection of incoming materials. As such, your firm utilized (b)(4) that was not USP grade for the manufacture of your hand sanitizer drug products.
贵公司没有足够的程序和具备CGMP职责的人员来监督企业非处方(OTC)药品的生产。企业无法确定任何具有质量部门(QU)职责和权限的人员。企业未能提供调查、召回、投诉处理、操作规程批准、成品批次在上市前的评估和批准或拒绝的程序。同样，你们贵公司也没有评估、批准或拒绝来料的程序。因此，贵公司在生产洗手液药品时使用了不属于USP级别的xx药品。
The CGMP regulations assign responsibilities to the QU which include approving or rejecting incoming materials, in-process materials, and drug products; ensuring that controls are implemented and completed satisfactorily during manufacturing operations; and reviewing production records and investigating any unexplained discrepancies. You have not demonstrated that you have a QU capable of these responsibilities.
CGMP法规将责任分配给QU，包括批准或拒绝进货物料、中间体和药品;确保控制在生产过程中得到实施和圆满完成;检查生产记录，调查任何无法解释的差异。企业没有证明企业有一个能够承担这些责任的质量管理部门。
See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at: https://www.fda.gov/media/71023/download.
参见FDA指导文件《药品CGMP法规的质量体系方法》，以帮助实施质量体系和风险管理方法，以满足CGMP法规21 CFR，第210和211部分的要求:https://www.fda.gov/media/71023/download。
In response to this letter, provide:
在回复本函时，请提供:
A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
一份全面的评估和整改计划，以确保企业的QU获得有效运作的权力和资源。评估还应包括但不限于:
o A determination of whether procedures used by your firm are robust and appropriate.
o确定贵公司使用的程序是否健全和适当。
o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
o在企业的整个运营过程中，总负责人监督以评估对适当做法的遵守情况的规定。
o A complete and final review of each batch and its related information before the QU disposition decision.
o在QU处置决定之前，对每批产品及其相关信息进行完整和最终的评审。
o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.
o监督和批准所有其他QU职责的调查和履行，以确保所有产品的鉴别、规格、质量和纯度。
A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
对整个生产和实验室操作中使用的文件系统进行完整的评估，以确定文件实践的不足之处。包括详细的纠正措施和预防措施计划，全面纠正贵公司的文件实践，以确保企业在整个运营过程中保留可追溯的、易读的、完整的、原始的、准确的、同步的记录。
2. Your firm failed to establish adequate 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)).
2.未能建立生产和工艺控制的书面程序，以确保药品具有其声称或表明拥有的鉴别、规格、质量和纯度[ 21 CFR 211.100(a) ]。
Inadequate Process Controls
过程控制不充分
Your production instructions and production records were inadequate to ensure consistent manufacture of OTC drug products. Your hand sanitizer manufacturing “recipe” lacked critical parameters such as equipment identification, mixing speeds, component addition rates, filling parameters, and bottle fill volume. Likewise, you failed to provide executed batch records, or any other information recorded during the manufacture of distributed hand sanitizer batches.
企业的生产说明和生产记录不充分，无法保证OTC药品生产的一致性。企业的洗手液生产“配方”缺乏关键参数，如设备标识、混合速度、成分添加率、灌装参数和装瓶容积。同样，企业也未能提供已执行批次记录，或在分布式洗手液批次生产过程中记录的任何其他信息。
Inadequate Cleaning Controls
不适当的清洁控制
Your cleaning procedures were inadequate. For example, your “Clean Production Area” procedure prescribed a “deep clean” of the production room (b)(4) but did not describe this process with sufficient detail. Additionally, you failed to have cleaning instructions for specific manufacturing equipment. Your cleaning schedule was not supported by validation studies and you did not maintain cleaning records. Lastly, your production area was not observed to be in a clean state and your filling equipment was soiled.
企业的清洁程序不充分。例如，企业的“洁净生产区”程序规定了生产车间xx的“深度清洁”，但没有对这一过程进行足够详细的描述。此外，企业没有特定生产设备的清洁说明。企业的清洁计划没有得到验证研究的支持，企业也没有保持清洁记录。最后，企业的生产区域没有被观察到处于清洁状态，企业的灌装设备很脏。
Inadequate Water System Design and Controls
供水系统设计与控制不足
Your water system which is used to generate water used in the manufacture of your drug products is inadequately designed and controlled for its intended use. Your firm uses (b)(4) water without additional treatment, monitoring, or testing. Water is carried through your facility (b)(4) that was observed to be in the same position on January 24, 2022, and January 25, 2022, during the FDA inspection. It did not appear that the (b)(4) was dismantled for cleaning and you failed to provide cleaning procedures or records. The positioning of the (b)(4) within which water could pool and support microbial growth. Your water system design, monitoring plan, and cleaning procedures are inadequate for OTC drug manufacturing.
企业用于生产药品的水系统设计和控制不充分。你们贵公司使用xx水没有进行特殊的处理、监测或检验。FDA检查期间，在2022年1月24日和2022年1月25日观察到的相同位置，水通过贵工厂xx输送。企业似乎没有拆解xx进行清洁，企业也没有提供清洁程序或记录。水可以聚集并在xx的位置有利于微生物的生长。企业的水系统设计、监控计划和清洁程序不适合OTC药品生产。
In response to this letter, provide:
在回复本函时，请提供:
A remediation plan that better assures ongoing management oversight throughout the manufacturing lifecycle of all drug products. Provide a more data-driven and scientifically sound program that identifies sources of process variability, and assures that manufacturing including both production and packaging operations meet appropriate parameters and quality standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step and its controls, and vigilant ongoing monitoring of process performance and product quality.
一项整改计划，以更好地确保在所有药品的整个生产生命周期中进行管理监督。提供更多数据驱动和科学合理的程序，以识别工艺变化的来源，并确保包括生产和包装操作在内的制造满足适当的参数和质量标准。这包括但不限于，评估设备对其预期用途的适用性，确保投入原材料的质量，确定每个制造工艺步骤及其控制的能力和可靠性，以及对工艺性能和产品质量的持续监测。
An assessment of each drug product process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes, and will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.
对每个药品工艺流程进行评估，以确保有一个数据驱动的、科学合理的程序，可以识别和控制所有的可变性来源，从而使企业的生产工艺始终符合适当的规范和生产标准。这包括但不限于，评估设备对其预期用途的适用性，企业的监视和测试系统中可检测性的充分性，输入材料的质量，以及每个制造过程步骤和控制的可靠性。
Timelines for completed process performance qualification for marketed drug products.
已上市药品完成工艺性能鉴定的时间表。
A comprehensive, independent assessment of your water system design, control, and maintenance.
对水系统的设计、控制和维护进行全面、独立的评估。
A thorough remediation plan to install and operate a suitable water system. Include a robust ongoing control, maintenance, and monitoring program to ensure the new system consistently produces water adhering to Purified Water, USP monograph specifications and appropriate microbial limits. Regarding the latter, ensure that your total microbial count limit for water is appropriate in view of the intended use of the products produced by your firm.
安装和运行合适的水系统的彻底修复计划。包括一个稳健的持续控制、维护和监控程序，以确保新系统持续生产符合纯化水、USP各论规范和适当的微生物限度的水。对于后者，鉴于贵公司生产的产品的预期用途，请确保其它的水中微生物总数限制是适当的。
3. 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)).
3.每批药品放行前，未能进行适当的实验室检验，以判定与药品最终质量标准（包括每一活性成份的成分、规格）的完全符合性。 (21 CFR 211.165(a))
Your firm failed to perform adequate drug product testing prior to release to the market. You could not provide a list of tests, specifications, or test procedures used as part of batch release. Likewise, you could not provide release testing results for distributed batches. As noted above, FDA testing found your hand sanitizer products to be subpotent and contaminated with other impurities.
贵公司在药品投放市场前未能进行充分的药品检测。无法提供作为批放行的一部分使用的测试、规范或测试过程的列表。同样，企业不能为上市药品提供放行测试结果。如上所述，FDA检测发现企业的洗手液产品不是足效的，并且被其他杂质污染了。
In response to this letter, provide:
在回复本函时，请提供:
A list of chemical and microbiological specifications, including test methods, used to analyze each lot of your drug products before a lot of disposition decision.
一份化学和微生物规格的清单，包括测试方法，用于分析企业的每个批次的药品，在批次处置决定之前。
o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the U.S. that are within expiry as of the date of this letter.
o对保留样品进行全面的化学和微生物检测的行动计划和时间表，以确定截至本函日期在有效期内分发到美国的所有批次药品的质量。
o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
o每批保留样品的所有测试结果的摘要。如果检测发现药品质量不合格，应迅速采取纠正措施，如通知客户和召回产品。
Establishment Registration and Drug Listing Violations
企业注册和药品上市违规行为
Shuzy Rock Inc manufactures drug products as detailed in an FDA inspection conducted on January 11, 2022. Under section 510(b) of the FD&C Act, 21 U.S.C. 360(b), and 21 CFR 207.17(a), all manufacturers must register each establishment. Additionally, firms must review and update registration information annually or certify that there are no changes in accordance with 21 CFR 207.29. Our query of FDA’s drug registration and listing database showed that Shuzy Rock Inc (FEI: 3013835844) was never registered with FDA. Shuzy Rock Inc is required to submit registration information annually by electronic means for each establishment it owns or operates that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is in commercial distribution in the United States. Shuzy Rock Inc has not fulfilled its registration requirement. Failure to register in accordance with section 510 of the FD&C Act or to provide any information required by section 510(j) is a prohibited act under section 301(p) of the FD&C Act, 21 U.S.C. 331(p). In addition, all drugs manufactured in such establishment not duly registered under section 510 are misbranded under Section 502(o) of the FD&C Act, 21 U.S.C. 352(o).
Shuzy Rock公司生产的药品在2022年1月11日进行的FDA检查中详细说明。根据FD&C法案第510(b)条、21 U.S.C. 360(b)条和21 CFR 207.17(a)条，所有制造商必须注册每个工厂。此外，公司必须每年审查和更新注册信息，或根据21 CFR 207.29证明没有变化。我们查询了FDA的药品注册和上市数据库，发现Shuzy Rock Inc (FEI: 3013835844)从未在FDA注册。Shuzy Rock公司被要求每年通过电子方式为其拥有或经营的每一家从事在美国商业销售的药品的制造、制备、销售、配制或加工的企业提交注册信息。Shuzy Rock公司未达到注册要求。未按照FD&C法案第510条进行注册或未提供第510(j)条要求的任何信息，根据FD&C法案第301(p)条，21 U.S.C. 331(p)，属于禁止行为。此外，所有在该机构生产的没有根据第510条正式注册的药物都是根据FD&C法案第502(o)条(21 U.S.C. 352(o)条)被定义为错标产品。
Under section 510(j)(1) of the FD&C Act, 21 U.S.C. 360(j)(1), and 21 CFR 207.41, all drugs manufactured, prepared, propagated, compounded, or processed for U.S. commercial distribution must be listed with FDA. Premium Nature INSTANT HAND SANITIZER, Premium Nature INSTANT HAND SANITIZER TRAVEL SIZE, (b)(4) INSTANT HAND SANITIZER GEL, (b)(4) SHAMPOO, and (b)(4) CONDITIONER FOR MEN AND WOMEN have never been listed with FDA. Failure to properly list a drug product is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o).
根据FD&C法案第510(j)(1)条，21 U.S.C. 360(j)(1)条和21 CFR 207.41条，所有为美国商业销售而生产、制备、流通、合成或加工的药物都必须在FDA注册。高级自然速溶洗手液，高级自然速溶洗手液旅行号，(b)(4)速溶洗手液凝胶，(b)(4)洗发水和(b)(4)男女护发素从在被FDA注册。根据《FD&C法案》第301(p)条，21 U.S.C. 331(p)条，不正确列出药品是被禁止的，根据《FD&C法案》第502(o)条，21 U.S.C. 352(o)条，以上药品被定义域错误标识。
The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).
根据《FD&C法案》第301(a)条，21 U.S.C. 331(a)款，禁止在州际贸易中引入或交付错标的药物。
Drug Production Ceased
停止生产药品
We acknowledge your written notification that you have ceased manufacturing hand sanitizers as of September 2020, and have no intention of resuming production of hand sanitizers drug products or any other drug product in the future.
我们了解到企业的书面通知，即企业已于2020年9月停止生产洗手液，并无意在未来恢复生产洗手液药品或任何其他药品。
If you plan to resume any manufacturing regulated under the FD&C Act, notify this office prior to resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.
如果你计划恢复任何受FD&C法案监管的生产，在恢复企业的药品生产业务之前通知本办公室。如果企业恢复CGMP活动，企业有责任解决所有缺陷，以确保贵公司有能力持续遵守CGMP。此外，根据我们在贵公司发现的违规行为的性质，企业应该聘请一名符合21 CFR 211.34规定的合格顾问，协助贵公司满足CGMP要求。在企业向FDA寻求解决贵公司的符合性状况之前，有资格的顾问还应对企业的整个操作进行CGMP符合性的全面审计，并评估所有纠正措施和预防措施的完成程度和有效性。
Center for Food Safety and Applied Nutrition Concerns
食品安全和应用营养中心
In addition, we note that some of the products you repack are regulated as cosmetics, as defined in section 201(i) of the Federal Food, Drug and Cosmetic Act (the Act). A cosmetic is adulterated under section 601(c) of the Act [21 U.S.C. 361(c)] if it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. The conditions at your facility, which are described elsewhere in this letter, may cause the cosmetic products you repack to be adulterated. We note that under section 301(a) of the Act [21 U.S.C. 331 (a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic product that is adulterated.
此外，我们注意到，根据《联邦食品、药品和化妆品法》(《法案》)第201(i)条的定义，企业重新包装的一些产品是作为化妆品监管的。根据本法[21 U.S.C. 361(c)]第601(c)条的规定，如果化妆品是在不卫生的条件下制备、包装或保存的，因此可能被污物污染，或可能对健康有害，则该化妆品是掺假的。贵工厂的条件，在本信的其他地方有描述，可能会导致企业重新包装的化妆品掺假。我们注意到，根据该法案[21 U.S.C. 331 (a)]第301(a)条，禁止将掺假化妆品引入州际贸易。
Conclusion
结论
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
本函中所列举的违规行为并不包括贵工厂存在的所有违规行为。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。
Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure, and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.
请及时纠正任何违规行为。未能及时和充分地解决此问题可能导致在没有进一步通知的情况下采取监管或法律行动，包括但不限于扣押和禁令。未解决的违规行为也可能阻止其他联邦机构授予合同。
Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.
未能解决违规也可能导致FDA扣留出口证书的发放。FDA可能会拒绝批准将贵公司列为药品制造商的新申请或补充申请，直到完全解决任何违规问题并确认贵公司符合CGMP。我们可能会重新检查，以确认企业已完成纠正措施，以解决任何违规行为。
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 complete corrective actions 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个工作天内以书面方式回复本办公室。说明企业已经做了什么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。如果企业不能在15个工作日内完成纠正措施，请说明延误的原因和完成的时间表。
Send your electronic response to orapharm1_responses@fda.hhs.gov. Your written notification should refer to Warning Letter CMS # 630110 and include FEI: 3013835844.
If you have any questions, contact Compliance Officer Barbara Wilimczyk-Macri at barbara.wilimczyk@fda.hhs.gov .
Sincerely,
/S/
Nerizza Guerin
Acting Program Division Director
Office of Pharmaceutical Quality Operations Division I
_____________________
1 https://www.cdc.gov/handwashing/hand-sanitizer-use.html
2 In March 2020, the Agency published three guidance documents to provide regulatory flexibility to certain firms to help meet the demand for alcohol-based hand sanitizer during the COVID-19 public health emergency (PHE). Additionally, on December 31, 2021, these guidances were withdrawn, and firms were required to cease distribution, by March 31, 2022, of any remaining hand sanitizer products that were prepared under the temporary policies before or on December 31, 2021. See, 86 FR 56960, October 13, 2021.
2 .2020年3月，该机构发布了三份指导文件，为某些公司提供监管灵活性，以帮助满足COVID-19突发公共卫生事件(PHE)期间对含酒精洗手液的需求。此外，在2021年12月31日，这些指南被撤回，企业被要求在2022年3月31日之前停止销售任何在2021年12月31日之前或当日根据临时政策制备的剩余洗手液产品。见，86 FR 56960, 2021年10月13日。
