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近日，FDA发布了对中国药企BBC Group Limited的警告信，为其恢复国外现场检查以来首次基于现场检查发布的对中国药企的警告信，缺陷包括如下：
FDA要求审查气相色谱仪(GC)的分析数据。然而，该公司表示，在检查开始之前大约一个月，所有2018年至2020年的检验数据都已丢失。这些数据已不可恢复。
该公司仅保留实验室记录的静态副本(即纸质记录)进行审查，FDA认为这是不够的，因为它们没有保留完整色谱的动态记录格式来支持测试结果，并且它们不包括完整原始记录的一部分的系统适应性记录。
FDA检查人员发现GC相关的计算机系统和软件缺乏访问限制。例如，使用GC执行药品分析的实验室员工都以“系统管理员”身份登录，不需要密码，并具有完全的系统管理权限。此外，没有启用GC上的审计追踪。
FDA发现该公司的黏度计和紫外线-可见光度计是能够在产品/物料测试过程中保存数据的。尽管有这种能力，但该公司分析人员未能保存完整的动态测试数据。
该公司还使用电子表格进行稳定性试验数据输入。但是，这些电子表格不受控，也没有保护措施来防止数据操纵、覆盖或删除。
分析测试方法没有得到充分验证。具体来说，没有系统适应性性要求，也没有确定对照标准。
FDA检查人员在生产现场发现设备产品接触表面上的锈迹，随后要求查看设备维护日志。这些文件仅提供中文。FDA翻译后发现所提供的文件与检查期间要求的设备不同。
翻译文章来源：药融圈
2021年8月10日，FDA对福建漳州BBC Group Limited就数据完整性、交叉污染和缺乏文件问题出具警告信。详细情况如下：
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, BBC Group Limited, FEI 3010165327, at Yangxia Development Zone, Pumei Town, Yunxiao County, Zhangzhou, China, from March 22 to March 26, 2021.
2021年3月22日至3月26日，美国食品和药物管理局（FDA）检查了贵公司即BBC集团有限公司，FEI 301065327，位于中国漳州云霄县浦梅镇阳下开发区的药品生产设施。
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).
本警告信总结了严重违反成品药品现行良好生产规范（CGMP）规定的情况。见标题21《联邦法规》（CFR）第210和211部分（21 CFR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 Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
由于您的生产、加工、包装或储存的方法、设施或控制不符合CGMP，因此您的药品根据《联邦食品、药品和化妆品法案》（FD&C法案）21 U.S.C.351（a）（2）（B）第501（a）（2）（B）节被认为掺假。
In addition, your firm manufactures L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER products that are unapproved new drugs 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 are misbranded under sections 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of such 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，贵公司还生产L.O.L. SURPRISE! (西瓜、草莓和樱桃）香味洗手液产品是未经批准的新药，但在州际贸易中进货或交货，违反《联邦食品和药品法》第21 U.S.C.355（a）节的规定，并且根据《联邦食品和药品法》第502（ee）节的规定，并且根据《联邦食品和药品法》第21 U.S.C.352（ee）的502(ee)节，标签错误。FD&C Act, 21 U.S.C. 331(d) 和 (a)节禁止此类产品在州际贸易中进货或交货。下文将更详细地描述这些违规行为。
We reviewed your April 13, 2021 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.
我们详细审查了您于2021年4月13日对我们的FDA 483表格的回复。您的回复不充分，因为它没有提供足够的细节或纠正措施的证据，以证明您的运营符合CGMP。
During our inspection, our investigator observed specific violations including, but not limited to, the following.
在我们的检查期间，我们的检查员观察到了具体的违规行为，包括但不限于以下内容。
CGMP Violations
CGMP违规
1. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
1. 贵公司未能对计算机或相关系统实施适当控制，以确保只有授权人员才能对主生产和控制记录或其他记录进行更改（21 CFR 211.68（b））。
Your firm manufactures over-the-counter (OTC) drug products, including alcohol-based hand sanitizers[1]. During the inspection of your facility, our investigator attempted to review analytical data from your gas chromatograph (GC) supporting the release of drug products distributed to the United States. However, your firm stated that all testing data from 2018 to 2020 was lost approximately one month prior to the initiation of our inspection. The GC is used to analyze the identity and strength of active ingredients and impurities contained in your OTC drug products, as well as other critical parameters. According to firm management, the data is unrecoverable. While your firm retained a static copy of laboratory records for review (i.e., paper record), they were inadequate as they did not preserve the dynamic record format of the full chromatographs to support test results and they did not include system suitability documentation that are part of the complete, original record.
Additionally, our investigator observed that the computerized system and software associated with your GC lacked restricted access. For example, your laboratory employees who used the GC to perform analyses of drug products all logged in as “System Administrator,” which does not require a password, and had full system administration rights. In addition, audit trails on your GC were not enabled.
贵公司生产非处方（OTC）药品，包括含酒精的洗手液[1]。在检查您的设施期间，我们的调查员试图检查来自您的气相色谱仪（GC）的分析数据，这些数据对销售到美国的药品提供支持。然而，贵公司表示，2018年至2020年的所有测试数据在我们开始检查前大约一个月丢失。GC用于非处方药产品中所含活性成分和杂质的鉴别和强度分析，以及其他关键参数。根据公司管理层的说法，这些数据是无法恢复的。虽然贵公司保留了实验室记录的静态副本以供审查（即纸质记录），但这些记录并不充分，因为它们没有保留完整色谱仪的动态记录格式以支持测试结果，并且不包括作为完整原始记录一部分的系统适用性文档。
此外，我们的调查人员观察到，与您的GC相关的计算机化系统和软件缺乏受限访问。例如，使用GC进行药品分析的实验室员工都以“系统管理员”身份登录，不需要密码，并且拥有完整的系统管理权限。此外，未启用GC上的审计追踪。
Furthermore, you did not retain all original, dynamic records, obtained during the course of testing on other laboratory equipment. Your viscometer and UV-Vis spectrophotometer had the capability to save data from product/material testing. Despite having this capability, your analysts failed to save the complete, dynamic testing data, and therefore the data was not available for review by the FDA investigator. The viscometer is used to measure the viscosity of finished drug products during release testing and the UV-Vis spectrophotometer is used to measure ethanol content during raw material testing.
此外，您没有保留在其他实验室设备测试过程中获得的所有原始动态记录。您的粘度计和紫外可见分光光度计能够保存产品/材料测试的数据。尽管具备此功能，但您的分析员未能保存完整的动态测试数据，因此FDA检查员无法对数据进行审查。在释放试验期间，粘度计用于测量成品的粘度，紫外-可见分光光度计用于测量原料的乙醇含量。
Your firm also utilizes electronic spreadsheets to input data for your stability program. However, these spreadsheets are not controlled and there is no protection to prevent data manipulation, overwriting, or erasure.
贵公司还利用电子表格为稳定性项目输入数据。但是，这些电子表格不受控制，并且没有保护数据以防止被操纵、覆盖或擦除。
In your response, you indicated that you purchased and/or installed additional equipment to address this violation, including, but not limited to, an uninterrupted power source, remote hard drive, electrical equipment, and new software. Your response also states that you have updated and developed associated procedures, created individual accounts for all personnel that utilize laboratory equipment, and conducted accompanying trainings. However, your response is inadequate because it lacked supporting documentation, including evidence to support that the computer security controls were effective at preventing data and document manipulation. Additionally, you did not perform a retrospective risk assessment into how system vulnerabilities may have impacted data integrity.
在您的回复中，您表示您购买和/或安装了其他设备以解决此违规问题，包括但不限于不间断电源、远程硬盘驱动器、电气设备和新软件。您的回复还表明，您已经更新和制定了相关程序，为所有使用实验室设备的人员创建了个人账户，并进行了相应的培训。但是，您的答复不充分，因为它缺少支持文档，包括支持计算机安全控制有效防止数据和文档被操纵的证据。此外，您没有对系统漏洞如何影响数据完整性进行回顾性风险评估。
Your firm does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/97005/download.
贵公司没有充分确保数据的准确性和完整性，以支持您生产的药物的安全性、有效性和质量。请参阅FDA的指导文件《数据完整性和药物CGMP合规性》，以获取关于建立和遵循CGMP合规数据完整性实践的指导，网址为https://www.fda.gov/media/97005/download.
We strongly recommend that you retain a qualified consultant to assist in your remediation. In response to this letter, provide the following:
我们强烈建议您聘请一名合格的顾问协助您进行补救。针对本函，提供以下内容：
A comprehensive investigation into the extent of the inaccuracies in data records and reporting including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.
对数据记录和报告中的不准确程度进行全面调查，包括对向美国销售的药物的数据审查结果。包括对数据完整性失效的范围和根本原因的详细描述。
A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.
对检查到的（数据完整性）失效对药物质量的潜在影响的风险评估。您的评估应包括对因数据完整性失效而受影响的药物释放对患者造成的风险的分析，以及对正在进行的操作构成的风险的分析。
A management strategy for your firm that includes the details of your global corrective action and preventive action plan. The detailed corrective action plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm including microbiological and analytical data, manufacturing records, and all data submitted to FDA.
贵公司的管理战略，包括全面的的纠正措施和预防措施计划的细节。详细的纠正措施计划应说明您打算如何确保贵公司生成的所有数据的可靠性和完整性，包括微生物和分析数据、生产记录以及提交给FDA的所有数据。
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 (CAPA) 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过程中使用的文件系统进行全面评估，以确定文件实行的不足之处。包括详细的纠正措施和预防措施（CAPA）计划，全面纠正贵公司的文件实行方法，以确保在整个运营过程中保留可追溯、清晰、完整、原始、准确的同期记录。
A comprehensive, independent assessment and CAPA plan for computer system security and integrity. Include a report that identifies design and control vulnerabilities, and appropriate remediations for each of your laboratory computer systems. This should include, but not be limited to：
计算机系统安全性和完整性的全面、独立评估和CAPA计划。包括识别设计和控制漏洞的报告，以及针对每个实验室计算机系统的适当补救措施。这应包括但不限于：
A list of all hardware that includes all equipment, both standalone and network, in your laboratory.
所有硬件的列表，包括实验室中的所有设备，包含独立设备和网络设备。
Identification of vulnerabilities in hardware and software, encompassing both networked and non-networked systems.
识别硬件和软件中的漏洞，包括网络和非网络系统。
A list of all software configurations and versions, details of all user privileges, and oversight responsibilities for each of your laboratory systems. Regarding user privileges, specify user roles and associated user privileges (including the specific permissions allowed for anyone who has administrative rights) for all staff who have access to the laboratory computer systems, and their organizational affiliations and titles. Also describe how you will ensure laboratory staff are not given administrative rights, or other permissions that compromise data retention or reliability.
所有软件配置和版本的列表，所有用户权限的详细信息，以及每个实验室系统的监督责任。关于用户权限，请为所有有权访问实验室计算机系统的员工及其组织从属关系和职务指定用户角色和相关用户权限（包括任何具有管理权限的人员所允许的特定权限）。另外，请描述您将如何确保实验室工作人员不被授予管理权限或其他损害数据保留或可靠性的权限。
System security provisions, including, but not limited to, whether unique user names/passwords are always used, and their confidentiality safeguarded.
系统安全规定，包括但不限于是否始终使用唯一用户名/密码，以及保护其机密性。
Detailed procedures for robust use and review of audit trail data, and current status of audit trail implementation for each of your systems.
耐用和审查审计追踪数据的详细规程，以及每个系统的审计追踪实施的当前状态。
Interim control measures and procedural changes for the control, review, and full retention of laboratory data.
实验室数据控制、审查和完全保留的临时控制措施和程序变更。
A detailed summary of your procedural updates and associated training, including but not limited to system security control to prevent unauthorized access, appropriate user role assignments, secondary review of all analyses, and other system controls.
程序变更和相关培训的详细总结，包括但不限于防止未经授权访问的系统安全控制、适当的用户角色分配、所有分析的二次审查以及其他系统控制。
Provisions for oversight by QA managers, executives, and internal auditors with appropriate information technology (IT) expertise (e.g., to evaluate infrastructure, configuration, network requirements, data management practices, and segregation of duties including administrator rights).
规定由具有适当信息技术（IT）专业知识的QA经理、执行官和内部审计师进行监督（例如，评估基础设施、配置、网络要求、数据管理实践以及职责分配，包括管理员权利）。
A remediated program for ensuring strict ongoing control over electronic and paper-based data to ensure that all additions, deletions, or modifications of information in your records are authorized, and all data is retained. Include a full CAPA plan and any improvements made to date.
补救计划，用于确保对电子和纸质数据进行严格的持续控制，以确保对记录中信息的所有添加、删除或修改都得到授权，并且所有数据都得到保留。包括完整的CAPA计划和迄今为止所做的任何改进。
An independent, thorough retrospective assessment into the impact of laboratory system design, control, and staff practices on your data accuracy, completeness, and retention since January 1, 2018.
自2018年1月1日起，对实验室系统设计、控制和员工实践对数据准确性、完整性和保留的影响进行独立、彻底的回顾性评估。
A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedure(s) to ensure changes are justified, reviewed, and approved by your quality unit. Your change management program should also include provisions for determining change effectiveness.
对您的变更管理系统进行全面、独立的评估。该评估应包括但不限于您的规程，以确保变更得到质量部门的证明、审查和批准。您的变更管理计划还应包括确保变更有效性的规定。
2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
2. 贵公司未能建立实验室控制，包括科学合理和适当的质量标准、标准品、取样计划和检测规程，以确保成分、药品容器、包装、中控材料、标签和药品符合适当的标识、强度、质量，和纯度标准（21 CFR 211.160（b））。
Your analytical test methods were not adequately validated, including those for the active ingredient ethanol, which is used to manufacture your alcohol-based hand sanitizers, and analysis for the impurity (b)(4). Specifically, no system suitability requirements were present and reference standards were not identified. Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy, sensitivity, specificity, and reproducibility and are suitable for their intended purpose.
您的分析测试方法未经过充分验证，包括用于生产酒精洗手液的活性成分乙醇，以及杂质（b）（4）的分析。具体而言，没有体现系统适用性要求，也未经对照品鉴定。必须提供数据，以确定试验中使用的分析程序符合准确度、灵敏度、专属性和再现性的适当标准，并适合其预期用途。
In your response, you indicated that you updated test methods, established method validation protocols, and completed test method evaluation. However, your response is inadequate for the following reasons.
在您的回复中，您表示您更新了测试方法，建立了方法验证方案，并完成了测试方法评估。但是，您的答复不充分，原因如下。
The response lacked information on the analyte reference standards used for the method validation.
该回复缺少用于方法验证的分析物对照品的信息。
The response lacked method validation details on identity of the tested analytes, system suitability, method specificity data, preparations of the analyte stock solutions, and accuracy and precision data from spike and recovery experiments at different concentration levels.
该回复缺少关于被测分析物的鉴定、系统适用性、方法专属性数据、分析物储备溶液的制备以及不同浓度下加标和回收实验的准确度和精密度数据的方法验证细节。
The response lacked an assessment of drug products manufactured utilizing the deficient methods.
该回复缺乏对使用缺陷方法生产的药品的评估。
In response to this letter, provide the following:
针对本函，提供以下内容：
A comprehensive, 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.
对您的实验室实践、规程、方法、设备、文件和分析员能力进行全面、独立的评估。基于此审查，提供详细的计划，以补救和评估实验室系统的有效性。
An independent assessment of all test methods and data review procedures used by your firm to ensure they have appropriate instructions, method suitability criteria, and validation to determine whether they are fit for intended purposes.
对贵公司使用的所有测试方法和数据审查程序进行独立评估，以确保它们具有适当的说明、方法适用性标准和验证，以确定它们是否适合预期用途。
Your test results, using an adequately validated test method, of retains for all finished drug products, within expiry. You should test all appropriate quality attributes of each batch that you distributed into U.S. commerce to ensure that your drug products conform to appropriate standards of identity, strength, quality, and purity. If testing yields an OOS result, indicate the corrective actions you will take, including notifying customers and initiating recalls.
使用经过充分验证的测试方法，对所有成品药在有效期内的留样进行测试。您应该测试发运到美国市场的每批药品的所有适当的质量属性，以确保您的药品符合适当的鉴别、强度、质量和纯度标准。如果测试产生OOS结果，说明您将采取的纠正措施，包括通知客户和发起召回。
See FDA’s guidance document Analytical Procedures and Methods Validation for Drugs and Biologics for general principles and approaches that FDA considers appropriate elements of method validation at: https://www.fda.gov/media/87801/download.
关于FDA认为适当的方法验证要素的一般原则和方法，请参见FDA的指导文件《药物和生物制品分析程序和方法验证》，网址：https://www.fda.gov/media/87801/download.
3. Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).
贵公司未能按照药品的性质，在适当的时间间隔清洁、维护和/或消毒设备和器具，以防止可能改变安全性、特性、强度和质量的故障或污染，或药品纯度超过官方或其他既定要求（21 CFR 211.67（a））。
During our inspection, the investigator observed rust on (b)(4) and product contact surfaces of four of the (b)(4) used to manufacture drug products, including the manufacture of your OTC hand sanitizers. Upon request, you provided our investigator with manufacturing equipment maintenance logs for the aforementioned (b)(4). These documents were only available in Chinese. After the conclusion of the inspection, the FDA had the document translated and found that the document provided was for equipment identified as “liquid washing pan” with serial number WJB-001, which is located in Workshop (b)(4) on the (b)(4) floor, and not the (b)(4) with equipment ID’s 12 through 15 located in Workshop (b)(4) on the (b)(4) floor that were observed with rust. FDA is concerned that you provided maintence records for different equipment than those requested during the inspection.
在我们的检查过程中，检查员观察到用于制造药品（包括OTC洗手液）的四种（b）（4）和产品接触面生锈。根据要求，贵方向我方检查员提供了上述（b）（4）的生产设备维护日志。这些文件只有中文版本。检查结束后，FDA对文件进行了翻译，发现提供的文件适用于编号为WJB-001的“液体清洗盘”设备，该设备位于（b）（4）层的（b）（4）车间，而不是位于（b）（4）地板上的车间（b）（4）中的设备ID为12到15的（b）（4），这些设备被发现生锈。FDA认为您提供的维护记录与检查期间所要求的不同。
In your response, you indicated that you replaced all the (b)(4) in your (b)(4). However, your response failed to address the rust documented in other parts of the (b)(4). Additionally, your response is inadequate as you failed to revise your cleaning and maintenance procedures to prevent recurrence of this issue, you failed to perform a risk assessment of drug products manufactured in the four (b)(4) that contained rust, and you did not determine the root cause of why employees who perform (b)(4) inspections of manufacturing equipment did not observe the rust in the (b)(4).
在您的回复中，您表示您替换了（b）（4）中的所有（b）（4）。然而，您的回复未能解决（b）（4）中其他部分记录的锈蚀问题。此外，您的回复不充分，因为您未能修改清洁和维护程序以防止该问题再次发生，您未能对四个（b）（4）中生产的含锈药品进行风险评估，您没有弄清对生产设备（b）（4）进行检查的员工没有观察到（b）（4）中的锈迹的根本原因。
In response to this letter, provide the following:
针对本函，提供以下内容：
Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.
您的CAPA计划对设施和设备实施日常、警戒的运营管理监督。除其他事项外，该计划应确保及时发现设备/设施性能问题，有效执行维修，遵守适当的预防性维护计划，及时对设备/设施基础设施进行技术升级，并改进持续管理审查系统。
Your plan for continued manufacture of drug products in the aforementioned (b)(4)containing rust. Our inspection observed rust on and around the (b)(4) and other parts of the (b)(4).
贵方在上述含锈（b）（4）中继续生产药品的计划。我们的检查发现，（b）（4）和（b）（4）的其他部分及其周围生锈。
A risk assessment for drug products manufactured in the four (b)(4) that contained rust to determine if a market action is warranted.
对四个（b）（4）生产的含有铁锈的药品进行风险评估，以确定是否需要采取市场行动。
Unapproved New Drug and Misbranding Violations
未经批准的新药和品牌错误违规行为
L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER products are “drugs” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are intended for use as a consumer topical antiseptic.
L.O.L. SURPRISE! (西瓜、草莓和樱桃）香味洗手液产品是《美国联邦食品和药品法》21 U.S.C.321（g）（1）（B）第201（g）（1）（B）节定义的“药物”，因为它们旨在用于疾病的诊断、矫正、缓解、治疗或预防，和/或根据《美国联邦食品和药品法》21 U.S.C.321（g）（1）（C）第201（g）（1）（C）节，因为它们旨在影响身体的结构或任何功能。具体而言，这些产品旨在用作消费者的局部抗菌剂。
Examples of claims observed on the L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER product label and labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:
在L.O.L. SURPRISE! (西瓜、草莓和樱桃）香味洗手液产品上观察到的声明实例，标签和提供产品预期用途（如21 CFR 201.128所定义）证据的标签包括但不限于以下内容：
“HAND SANTIZER. . .Drug Facts. . .Uses. . . to decrease bacteria on the skin that could cause disease. . . Direction – rub a dime sized drop into hands.”
“洗手液…实际是药品…使用…减少皮肤上可能导致疾病的细菌…说明–将一个一角硬币大小的液滴涂抹到手中。”
This topical antiseptic product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. New drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a), unless they are lawfully marketed under Section 505G of the FD&C Act (which is not the case for this product, as further described below) or other exemptions not applicable here. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for these drug products, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER drug products are GRASE for use under the conditions suggested, recommended, or prescribed in its labeling. Accordingly, these products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).
这种局部防腐剂产品是FD&C Act, 21 U.S.C. 321(p)第201（p）节所指的“新药”，因为在其标签中规定、推荐或建议的条件下使用它通常不被认为是安全有效的（GRASE）。未经FDA事先批准，不得在州际贸易中进货或交货，如FD&C Act, 21 U.S.C. 355（a）节所述，除非其根据FD&C Act第505G节合法销售（本产品并非如此），如下文所述）或此处不适用的其他豁免。既没有根据FD&C Act, 21 U.S.C. 355第505节，经FDA申请批准该药品是有效的，我们也不知道在已发表的文献中有任何充分且受控的临床研究支持您的L.O.L. SURPRISE!(西瓜、草莓和樱桃）香味洗手液药品是在其标签中建议、推荐或规定的条件下使用是安全有效的。因此，这些产品是未经批准的新药，销售时违反了FD&C Act, 21 U.S.C. 355(a) and 331(d)的第505(a)和301(d)章节。
We note that over-the-counter (OTC) topical antiseptic products have been the subject of rulemaking under FDA’s OTC Drug Review. In particular, such products were addressed in a tentative final monograph (TFM) entitled “Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Health-Care Antiseptic Drug Products,” Proposed Rule, 59 FR 31402 (June 17, 1994) (1994 TFM), 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)(Consumer Antiseptic Rubs Proposed Rule). Over the course of these rulemakings, three active ingredients (benzalkonium chloride, ethyl alcohol (ethanol), and isopropyl alcohol) were classified as Category III for use in consumer antiseptic rub products, meaning that additional safety and effectiveness data are needed to support a determination that a drug product containing one of these active ingredients would be GRASE for use in a consumer antiseptic rub.
我们注意到，根据FDA的OTC药物审查，非处方（OTC）局部抗菌产品一直处于规则制定下。特别是，这类产品在题为“非处方人类使用的局部抗菌药物产品”的暂定最终专著（TFM）中进行了论述；《医疗保健抗菌药物产品的暂定最终专论建议规则》，59 FR 31402（1994年6月17日）（1994年TFM），进一步修订为《消费者抗菌产品的安全性和有效性；非处方人类使用的局部抗菌药物产品；暂定最终专著修正案；行政程序重启》；拟议规则，81 FR 42912（2016年6月30日）（消费者抗菌涂抹拟议规则）。在这些规则制定过程中，三种活性成分（苯扎氯铵、酒精（乙醇）和异丙醇）被归类为第三类，用于消费类抗菌产品，这意味着需要更多的安全性和有效性数据来支持确定含有这些活性成分之一的药物产品将被用于消费者抗菌涂抹。
Section 505G of the FD&C Act, addresses nonprescription drugs marketed without an approved application. Under 505G(a)(3) of the FD&C Act, drugs that were classified as Category III for safety or effectiveness in a TFM that is the most recently applicable proposal or determination for such drug issued under 21 CFR Part 330 – and that were not classified as Category II for safety or effectiveness – are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM, including the active ingredient, and comply with all other applicable requirements.
FD&C Act第505G节规定了未经批准申请而销售的非处方药。根据FD&C Act 505G（a）（3）条，根据21 CFR Part第330部分发布的TFM中被分类为安全性或有效性第三类的药物-且未被分类为安全性或有效性第二类的药物-无需根据第505节获得批准申请只要它们符合适用TFM中概述的相关使用条件（包括活性成分），并符合所有其他适用要求，即可上市。
However, L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER products do not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rule, nor any other TFM, proposed rule, or final rule, and do not meet the conditions under section 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505.
然而，L.O.L. SURPRISE! (西瓜、草莓和樱桃）香味洗手液产品不符合1994年TFM（经2016年消费者抗菌涂抹建议法规进一步修订），也不符合任何其他TFM、建议法规或最终法规，未根据第505节批准申请，不符合FD&C Act第505G（a）（3）节规定的营销条件。
According to the product label, L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, and CHERRY) SCENTED HAND SANITIZER products contain the active ingredient “chloroxylenol 0.015%.” Chloroxylenol is not permitted as an active ingredient for use as a consumer antiseptic hand rub drug product under the 1994 TFM.[2] Such products do not conform with the TFM, nor are they consistent with the formulations described in FDA’s temporary policies for hand sanitizers during the COVID-19 public health emergency.[3]
根据产品标签，L.O.L. SURPRISE! (西瓜、草莓和樱桃）香味洗手液产品含有活性成分“氯二甲酚0.015%”。根据1994年TFM，氯二甲酚不允许作为有效成分用于消费者抗菌擦手药品。此类产品不符合TFM，它们也不符合FDA在新冠病毒-19突发公共卫生事件期间对洗手液的临时政策中所述的配方。
Additionally, these products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee) because L.O.L. SURPRISE! (WATERMELON, STRAWBERRY, CHERRY) SCENTED HAND SANITIZER products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and is not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.
此外，这些产品根据FD&C Act, 21 U.S.C. 352(ee)第502（ee）节规定，标签错误。因为根据FD&C Act, 21 U.S.C. 355h第505G 章节规定，L.O.L. SURPRISE! (西瓜、草莓、樱桃）香味洗手液产品属于非处方药，但不符合该节下的营销要求，并且不是按照FD&C Act, 21 U.S.C. 355第505节批准的申请的项目。
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).
FD&C Act 21 U.S.C.331（a）第301（a）节禁止将标签错误的药物引入州际商业。
文章来源：允咨GMP制药技术
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