又一中国药企被FDA挂网警告

据药智新闻记者获悉河南康迪药械有限公司在2019年12月3日收到了FDA的警告信，河南康迪药械有限公司是一家专做膏药、贴剂等药械类产品的生产厂家。信中指出该公司在美国销售的关节止痛膏（Capsicum Plaster HOT）和利多卡因贴（1st Medx-Patch With 4% Lidocaine.）未经过FDA批准，并且对生产药品的原料监管不严。近日FDA官网挂出了警告信全文。

FDA官网挂出的警告信具体内容如下：

December 3, 2019

Warning Letter 320-20-09

Dear Mr. Qi Lei:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Henan Kangdi Medical Devices Co. Ltd., 3009271465, at SME Pioneer Park, No. 4, 2nd Area, Zhoukou, Henan, from March 4 to 7, 2019.

美国食品药品监督管理局（FDA）于2019年3月4日至7日检查了河南康迪药械有限公司。

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.

本警告函汇总了成品药CGMP法规的重大违规。详见美国联邦法规第21卷，第210和211章。

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).

因为你们的方法、设施、生产工艺、包装或者储存的方式不符合CGMP法规，你们的药品根据《联邦食品、药品和化妆品法》（FD&C）第501(a)(2)(B)章节，《美国法典》第21卷第351(a)(2)(B)节被认定为违规。

Your firm manufactures "Capsicum Plaster HOT" and " 1st Medx-Patch With 4% Lidocaine." These products are unapproved new drugs in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d). These violations are described in more detail below.

贵公司生产的关节止痛膏和利多卡因贴。这些产品是未经批准的新药，违反了FD&C法案。根据法典，禁止将此类产品引入美国市场。下面将更详细地描述这些违规行为。

We reviewed your March 22, 2019, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

我们详细审查了你们于2019年5月22日对FDA 483文件的回复，并确认收到你们之后的回复。

During our inspection, our investigator observed specific violations including, but not limited to, the following.

在检查期间，我们的检查员发现的具体违规包括但不限于如下。

1. 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)).

你们公司未能对每批药品在出厂前进行适当的实验室测定，以确定其是否符合药品的最终规格，包括每种活性成分的特性和强度。

Your firm manufactures and distributes various over-the-counter (OTC) transdermal patch drug products such as "Capsicum Plaster HOT" pain relieving and " (b)(4) for the United States market. Our inspection found that you did not test your finished drug products to determine whether each batch met identity and strength specifications before being released to the U.S. market. Complete testing of each batch before release is an essential part of determining if a drug product batch meets its specifications.

贵你们公司为美国市场生产和销售各种非处方（OTC）透皮贴剂，如关节止痛膏等一些产品。FDA检查发现，在投放到美国市场之前，公司没有对药品成品进行检验，以确定每批产品是否符合特性和强度规格。每批药品在放行前的完整测试是确定一批药品是否符合规格的重要步骤。

The quality unit must be empowered to make final quality decisions. It is essential that the quality unit be enabled to provide timely oversight of all laboratory and manufacturing data that could impact product quality, whether or not lots have already been distributed. When making batch disposition decisions, the quality unit must be provided with all batch production and control records, including all deviations and test data, to enable a fully informed and appropriate decision regarding suitability for distribution. The quality unit must assure that drug products are fully tested for all critical attributes prior to release.

质量部门必须有权做出最终的质量决定。无论批次是否已经销售，质量部门必须能及时监督所有可能影响产品质量的实验室和生产数据。在做出批量处理决定时，质量部门必须提供所有批次生产和控制记录，包括所有偏差和试验数据，以便就是否适合销售作出充分知情和适当的决定。质量部门必须确保药品在出厂前经过所有关键属性的全面测试。

In your response, you stated that you will search for a third-party testing laboratory with adequate capabilities. Additionally, you committed to test for the active ingredient in each batch of finished drug products sold within the U.S. market to ensure product specifications are met.

在你们的答复中，表示将寻找一个有足够能力的第三方检测实验室。此外，还承诺检测在美国市场销售的每批产品中的有效成分，以确保产品符合规范。

Your response is inadequate because you did not include information about your third-party testing laboratory including name and location, methods, or a detailed description of the tests they will conduct (e.g., identity, strength and purity). Furthermore, you did not provide how you will evaluate the capability of your third party to perform the intended tests. Additionally, you provided no testing documentation for finished drug product batches currently in the U.S. market.

你们的回复是不充分的，因为没有提供第三方检测实验室的信息，包括名称和位置、检测方法，或他们将进行的检测的详细描述（例如特性、强度和纯度）。此外，也没有提供如何评估第三方实验室执行测试的能力和目前在美国市场上的产品批次的测试文件。

In response to this letter, provide:

针对本函，请提供：

· A comprehensive and independent review of your laboratory practices, procedures, methods, equipment, and analyst competencies. Based on this review, provide a detailed corrective action and preventive action (CAPA) plan to fully remediate your laboratory system. Your plan should also include the procedures you will use to evaluate the effectiveness of the implemented CAP A plan.

对实验室测试、程序、方法、设备和分析能力进行全面和独立的审查。在此审查的基础上，提供详细的修正措施和预防措施（CAPA）计划，以完全纠正实验室测试系统。计划还应包括将用于评估已实施的CAP A计划的有效性的程序。

· A list of all analytical test methods and specifications used to analyze each batch of your drug products before making the batch disposition decision. Include associated written procedures.

所有分析测试方法和规格的列表，用于在作出批次处理决定之前分析每批药品。包括相关的书面程序。

· A summary of test results obtained from retrospective testing of retain samples of all drug product batches currently in distribution in the U.S. Include test results for identity and strength of active ingredients, and all other appropriate chemical and microbial quality attributes. If you released any batch that was out of specification, indicate the corrective actions you will take, such as customer notifications and product recalls. Provide a timeline for completing this testing expeditiously.

对目前在美国销售的所有药品批次的保留样品进行回顾性测试，包括活性成分的特性和强度的测试结果，以及所有其他适当的化学和微生物质量属性。如果销售了任何超出规格的批次，请说明将采取的纠正措施，如客户通知和产品召回。提供快速完成测试的时间表。

· A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture. Your summary should include, but not be limited to, your procedure to ensure that any test methods performed by a contract testing laboratory on your behalf are properly validated prior to use for batch analysis. Additionally, include the procedure to evaluate the capability of your third party to accomplish the testing they are contracted to perform.

一个计划摘要，用于鉴定和监督测试你生产药品的实验室设施。摘要应包括但不限于以确保合作测试实验室代表康迪执行的任何测试方法在用于批量分析之前得到正确验证的资料。此外，还应包括评估第三方完成合同规定的测试能力的资料。

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier's test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

康迪未能进行至少一次检验以验证药品的每一种成分的属性。也未能在适当的时间间隔内验证和确定原料供应商测试分析的可靠性。

You failed to test incoming active pharmaceutical ingredients (API) and other raw materials (e.g., (b)(4)) used to manufacture your drug products to determine their identity, purity, strength, and other appropriate quality attributes. Instead, our investigator observed your firm released API and other materials for use in manufacturing based solely on a visual inspection of the contents of material containers and a review of component suppliers analyses reports. You did not retain these suppliers' analysis reports, but discarded them after review. Additionally, you did not establish the reliability of your suppliers' analyses through appropriate validation. Your firm did not ensure that at least one specific identify test was conducted for each lot of your incoming materials. This violation was also observed during the December 2016 inspection, after which you committed to test incoming raw material.

你们未能测试用于生产药品的原料药（API）和其他原材料以确定其特性、纯度、强度和其他适当的质量属性。相反，FDA调查员观察到贵公司发布的原料药和其他用于制造的材料报告，仅仅是基于对材料容器内容物的目视检查和对部分供应商的审查分析，且没有保留这些供应商的分析报告，在审查后将其丢弃。此外，公司也没有通过适当的验证来确定供应商分析的可靠性，没有保证每批来料都至少进行一次鉴定试验。在2016年12月的检查中也发现了这一违规行为，之后承诺对来料进行测试。

In your response, you stated your intent is to find a qualified third-party testing laboratory, revise your procedure for incoming material, and send to the third-party laboratory each lot of active ingredient used in drug products for U.S. supply.

在你们的回复中，声明你们想找到一个合格的第三方检测实验室，改正来料手续，并将用于美国供应的药品中的每批活性成分提供给第三方实验室。

Your response is inadequate because you did not commit to cease manufacturing drugs until the required testing of drug components is in place, and you did not conduct a risk assessment for products already in distribution in the United States. Furthermore, your response did not include the testing of raw materials, other than active ingredients, used in your finished drug products. Additionally, you failed to address how you will establish the reliability of your suppliers' analyses, and provided no documentation to support your CAPA plan.

对此你们的回复是不充分的，因为回复中没有承诺在药物成分的必要检测到位之前停止生产药物，而且没有对已经在美国销售的产品进行风险评估。此外，回复还不包括对成品药中使用的原料药（活性成分除外）的检测。此外，也没有说明如何建立供应商分析的可靠性，也没有提供支持CAPA计划的资料。

In response to this letter, provide:

针对本函，请提供：

· A comprehensive, independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified, assigned appropriate expiration or retest dates, and have incoming material controls adequate to prevent use of unsuitable components, containers, and closures.

对原材料进行全面、独立的审查，以确定每个供应商的所有容器、密封件和成分是否充分合格，是否指定了适当的有效期或重新测试日期，以及是否有足够的来料控制措施，以防止使用不合适的组件、容器和密封件。

· The chemical and microbiological quality control specifications you will use to determine disposition of each incoming lot of components before use in manufacturing.

将使用的化学和微生物质量控制规范来确定每批来料在制造前的存放。

· A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any testing results on your suppliers' certificates of analysis (COA) in lieu of testing each component

lot for purity, strength, and quality, specify how you will first establish the reliability and consistency of your suppliers' test results for these attributes through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.

描述如何测试每批原料是否符合所有适当的特性、强度、质量和纯度规范。如果您打算接受供应商分析证书（COA）上的任何测试结果，而不是测试每批原料的纯度、强度和质量，指定如何通过初始验证和定期重新验证，首先应建立供应商对这些属性的测试结果的可靠性和一致性。此外，还应承诺始终对每批进厂原料进行至少一次特定的测试。

· A summary of test results obtained from full testing of all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.

对所有原料进行全面测试，以评估各原料供应商提供的COA可靠性的测试结果汇总。包括描述COA验证程序的标准操作程序。

3. Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).

康迪未能保证该药品的有效期是通过适当的稳定性试验而确定的。

Your firm has not established an adequate stability program to support the (b)(4) expiration date assigned to your drug products. You lack sufficient data to demonstrate that the chemical and microbiological properties of your drug products will remain acceptable throughout their labeled expiry period.

康迪尚未制定足够的稳定性计划来支持贵公司给药品指定的有效期。缺乏足够的数据证明你方药品的化学和微生物特性在标签有效期内是有效的。

In your response, you committed to conduct stability testing on your drug products under accelerated conditions, and to ensure such testing are on samples held under appropriate temperature and humidity control.

在你们的回复中，承诺加速对药品进行稳定性测试，并确保在适当的温度和湿度控制下对样品进行此类测试。

Your response is inadequate because you failed to provide stability protocols, including all relevant quality attributes and acceptance criteria, and you did not provide assurance that your test methods will be adequate to assess drug stability. In addition, you did not clarify whether your stability testing will be conducted under real time conditions to support your OTC drug product expiry. Furthermore, you did not indicate any actions to ensure that all distributed drug product batches maintain their quality attributes through their labeled expiry.

对此回复是不充分的，因为没有提供稳定性方案，包括所有相关的质量属性和验收标准，并且没有提供保证测试方法将足以评估药物稳定性。此外，没有说明是否会在实时条件下进行稳定性测试，以支持非处方药产品的有效期，也没有指出任何措施来确保所有销售的药品批次在其标记的有效期内保持其有效性。

Based upon the lack of material testing, finished testing, and stability testing, there is minimal assurance that your drug manufacturing operations are capable of operating in a state of control.

由于缺乏原材料测试、成品测试和稳定性测试，因此无法保证药品生产操作在受控状态下运行。

In response to this letter, provide:

针对本函，请提供：

· A comprehensive, independent assessment and CAP A plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:

全面、独立的评估和CAPA计划，以确保稳定计划的充分性。补救计划应包括但不限于：

o Stability indicating methods

o Stability studies for each drug product in its marketed container-closure system before distribution is permitted

o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid

o Detailed definition of the specific attributes to be tested at each station (timepoint)

稳定性指示方法。

允许销售前每种药品在市场上的容器密封系统中的稳定性研究。

每年将每种产品的代表性批次添加到计划中，以确定保质期索赔是否有效。

每个时间点要测试的特定属性的详细定义。

· All procedures that describe these and other elements of your remediated stability program.

描述这些和修正稳定性计划的其他要求的所有过程。

· A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.

一份详细的步骤，用于设计、验证、维护、控制和监控每个制造过程，包括对批次内和批次间变化的警惕性监控，以确保持续的控制状态。另外，包括设备和设施的鉴定计划。

· A description how top management will support quality control, quality assurance, and reliable operations, including but not limited to timely provision of oversight and resources to proactively address deficiencies in laboratories and manufacturing in order to support robust operations.

说明管理层将如何支持质量控制、质量保证和可靠运营，包括但不限于及时提供监督和资源，以主动解决实验室和制造业的缺陷，从而支持稳健运营。

Quality Unit Authority质量主管部门

Significant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. 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.

本函中的重大发现表明康迪的质量部门未充分行使其权力和职责。康迪公司必须为质量部门提供适当的权力和充足的资源，以履行其职责，并始终如一地确保药品质量。参见FDA的指导文件《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法规要求。

Repeat Observations at Facility设施重复观测

In a previous inspection, dated December 12 to 14, 2016, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

在2016年12月12日至14日的前一次检查中，FDA发现了类似的观察结果。康迪在答复中对这些意见提出了具体的补救措施。屡次失败的结果表明，康迪对药品生产的行政管理监督和控制是不够的。

Use of Contract Manufacturers使用合同制造商

Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.

药品必须按照CGMP生产。FDA知道许多药品制造商使用独立的承包商，如生产设施、测试实验室、包装商和贴标商。FDA认为承包商是制造商的延伸。

You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA's guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.

无论与制造商达成什么协议，康迪都要对药品质量负责。必须确保药品是按照FD&C法案生产的，以确保安全、特性、强度、质量和纯度。参见FDA的指导文件《药品合同制造安排：质量协议》

CGMP Consultant Recommended CGMP顾问推荐

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 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.

根据我们在康迪公司发现的违法行为的性质，如果康迪打算恢复为美国市场生产药品，FDA强烈建议聘请一名符合要求的顾问，协助康迪满足CGMP的要求。FDA还建议合格的顾问对CGMP合规性的整个操作进行全面审计，并建议顾问在寻求解决康迪合规状况之前，评估纠正措施和预防措施的完成情况和有效性。

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.

使用顾问并不代表不用遵守CGMP的义务。康迪的执行管理层仍然负责解决所有缺陷和系统缺陷，以确保持续的CGMP合规性。

Unapproved New Drug Charges未经批准的新药

"Capsicum Plaster HOT" and "1st Medx-Patch With Lidocaine 4%"

"Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" 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 the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or as defined by 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 external analgesics.

关节止痛膏和利多卡因贴是FD&C法案内定义的药物，它们用于诊断、治疗、缓解、治疗或预防疾病，和/或《美国法典》内定义的药物，它们意在影响身体的结构或任何功能。具体来说，这些产品是作为外部镇痛剂使用的。

Examples of claims observed on the product labeling that establish the intended uses (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:

在产品标签上观察到的确定产品预期用途的示例包括但不限于：

"Capsicum Plaster HOT" Label Claims

"For long lasting relief of Rheumatism, Lumbago, Notalgia, and Sciatica, Arthralgia, Stiff Shoulder and Muscle Pain."

关节止痛膏标签声称

用于长期缓解风湿、腰痛、痛、坐骨神经痛、关节痛、肩关节僵硬和肌肉疼痛

"1st Medx-Patch With Lidocaine 4%" Labeling Claims

"For the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, sprains, muscle soreness and stiffness."

利多卡因贴标签声称

暂时缓解与关节炎、单纯背痛、劳损、扭伤、肌肉酸痛和僵硬有关的肌肉和关节的轻微疼痛

OTC drug products such as "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" that are intended for external analgesic indications such as the relief of pain are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-The-Counter Human Use (48 FR 5852, February 8, 1983). Pending the promulgation of a final rule, FDA generally does not intend to pursue regulatory action against products marketed in accordance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1 unless a particular product poses a public health concern. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the "new drug" procedures of the FD&C Act (section 505). However, "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" do not meet these conditions for the reasons explained below.

非处方药产品，如关节止痛膏和利多卡因贴，用于止痛等外部适应症，正在作为非处方药审查的一部分进行评估。根据用于非处方人类使用的外部止痛药物的暂定定论（TFM），这些药物被认为是公认的安全有效的，并且没有品牌错误。在最终条例颁布之前，FDA一般不打算对根据TFM中提出的条件和每个一般条件销售的产品采取监管行动，除非特定产品引起公众健康问题。然而，此类营销可能会面临这样的风险，即最终规定可能需要通过FD&C法案的“新药”程序重新制定、重新标记或FD A批准。然而，关节止痛膏和利多卡因贴不符合这些条件，原因如下。

The formulation for "Capsicum Plaster HOT" includes capsicum in a concentration that exceeds what has been proposed in the External Analgesic TFM (see 48 FR 5852 at 5868, February 8, 1983). "Capsicum Plaster HOT" is labeled to contain Capsicum Extract 2.89%, while the External Analgesic TFM allows Capsicum in a concentration of 0.025% to 0.25%. Additionally, the product label for "Capsicum Plaster HOT" includes indications such as "long lasting relief of rheumatism, lumbago, notalgia, and sciatica" that are not proposed under this rulemaking or any rulemaking being considered under the OTC Drug Review.

关节止痛膏的配方包括浓度超过外部镇痛剂TFM中提议的浓度，关节止痛膏标示含有2.89%的辣椒提取物，而外部镇痛剂TFM允许浓度在0.025%到0.25%的浓度范围内。此外，关节止痛膏的产品标签包括本规则制定或OTC药物审查中考虑的任何规则制定中未提出的“风湿、腰痛、痛和坐骨神经痛的长期缓解”等适应症。

The formulation for "1st Medx-Patch With Lidocaine 4%" includes lidocaine but this product is considered a counterirritant under the External Analgesic TFM because it is labeled for the temporary relief of minor aches and pains of muscles and joints. Lidocaine is not proposed as a counterirritant active ingredient in the External Analgesic TFM nor does the TFM propose the combination of anesthetic ingredients, such as lidocaine, with counterirritant ingredients (48 FR 5852 at 5868, February 8, 1983).

利多卡因贴的配方中包括利多卡因，但该产品被视为外部镇痛剂中的一种抗刺激剂，因为它被标记为用于暂时缓解肌肉和关节的轻微疼痛。利多卡因不作为外部镇痛剂中的抗刺激活性成分，TFM也不建议麻醉成分（如利多卡因）与抗刺激成分的组合。

Furthermore, we are not aware of any adequate and well controlled clinical trials in the published literature that support a determination that "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" are generally recognized as safe and effective for their labeled indications. Additionally, we are not aware of similar OTC products as formulated and labeled that were available in the United States market on or before the inception of the OTC Drug Review.

此外，FDA还不知道在已发表的文献中有任何充分且控制良好的临床试验支持关节止痛膏和利多卡因贴对于其标记适应症通常被认为是安全和有效的。此外，FDA不知道在非处方药审查开始时或之前在美国市场上有类似的处方和标签的非处方药产品。

"Capsicum Plaster HOT" and "1st Medx-Patch With Lidocaine 4%," as labeled, are therefore new drugs within the meaning of section 201 (p) of the FD&C Act because they are not generally recognized among scientific experts as safe and effective for the drug uses described in its labeling. "New drugs" may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug.

关节止痛膏和利多卡因贴因此属于FD&C法案所指的新药，因为它们在科学专家中并不被公认为对其标签中所述的药物用途安全有效除非根据FD&C法案FDA批准的申请对新药有效，否则新药不得引入或交付用于美国贸易。

"Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" are not the subject of approved new drug applications; therefore, marketing these products in the United States is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d) and violates section 505 of the FD&C Act.

关节止痛膏和利多卡因贴不属于批准的新药申请；因此，根据《联邦食品药品监督管理法》、《美国法典》禁止在美国销售这些产品，并违反了《联邦食品药品监督管理法》第505条。

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 these violations and for preventing their recurrence or the occurrence of other violations.

这封信中列举的在康迪工厂内的违规行为并不止一个。您负责调查和确定这些违规行为的原因，并防止其再次发生或发生其他违规行为。

FDA placed your firm on Import Alert 66-40 on October 25; 2019.

食品和药物管理局于2019年10月25日将贵公司置于进口警报66-40。

Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new drug applications or supplements listing your firm as a drug manufacturer.

在康迪完全纠正所有违规行为并且FDA确认康迪遵守CGMP之前，FDA可能会拒绝批准任何新的药物申请或将您的公司列为药物制造商的补充厂商。

Failure to correct these violations may also result in the FDA continuing to refuse admission of articles manufactured at Henan Kangdi Medical Devices Co. Ltd., SME Pioneer Park, No. 4, 2nd Area, Zhoukou, Henan into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381 (a)(3). Articles under this authority may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

如果不纠正这些违规行为，FDA可能会继续拒绝河南康迪医疗器械有限公司生产的药品进入美国。本授权药品可能会被拒绝入境，因为其制造过程中使用的方法和控制措施不符合CGMP。

After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to [e-mail] or mail your reply to:

Joseph Lambert, Pharm.D.

Compliance Officer

U.S. Food and Drug Administration

White Oak Building 51 , Room 4235

10903 New Hampshire Avenue

Silver Spring, MD 20993

USA

Please identify your response with FEI 3009271465.

Sincerely,

/S/

Francis Godwin

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research