FDA警告信：承诺的CAPA，为何不执行？

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10月6日，FDA公布一封针对加拿大企业的警告信。主要的违规项涉及：设备系统存在问题、未能执行工艺和清洁验证，缺乏适当的稳定性数据，未能验证供应商CoA的可靠性。

在该警告信中， FDA特别指出：

• 此前FDA已经对该公司进行了检查，公司承诺进行多项纠正措施。
  但在本次检查中，FDA发现该公司并未执行。
• 该公司生产了多种含有甘油的药物，但尚未对二甘醇(DEG)和乙二醇(EG)进行鉴别测试。
  FDA说明，使用受DEG污染的甘油，已导致全世界发生多种致命的中毒事件。
  
  
  

Warning Letter 320-20-47

September 24, 2020

Dear Mr. Willard:

警告信320-20-47

2020年9月24日

亲爱的威拉德先生：

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, LEC Custom Products, Inc., 3004737602, at 7 Kenview Boulevard, Brampton, Ontario, from March 2 to 6, 2020.

2020年3月2日至6日，美国FDA检查了你的药品生产设施LEC Custom Products Inc. (FEI 3004737602)，位于加拿大安大略省布兰普顿市。

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 210 and 211).

该警告信总结了严重违反制剂CGMP规定的情况。请参阅21CFR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).

由于你用于生产、加工、包装或储存的方法、设施或控制措施不符合CGMP，因此根据FD＆C法案501(a)(2)(B)条及21 U.S.C.351(a)(2)(B) 条的规定，你的药品被认为是掺假。

We reviewed your March 25, 2020, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

我们详细审查了你2020年3月25日对FDA 483表格的答复，并确认收到你的后续信件。

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

在我们的检查过程中，调查员发现了具体的违规行为，包括但不限于以下行为。

设备问题

1. Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).

1.公司未在生产、加工、包装或保存药品过程中，使用设计合理、尺寸适当且位置合适的设备，以实现预期用途及清洁和维护操作(21 CFR 211.63) )。

You manufacture over-the-counter (OTC) drug products marketed for consumers, including children. The main component in your non-sterile drug products is (b)(4). You used an (b)(4) system to generate (b)(4), for cleaning and production operations. We observed approximately (b)(4) feet of hard piping and hoses coming from this (b)(4) system that holds stagnant (b)(4) when not in use and can harbor biofilm. Following a 2017 FDA inspection, you committed in writing to testing your (b)(4) for microbial attributes. However, during the current inspection we observed you only tested (b)(4), when you installed a new (b)(4) skid. In addition, your testing results demonstrated your (b)(4) consistently fails to meet United States Pharmacopeia (USP) specifications for (b)(4). The USP (b)(4) specification for (b)(4) is not more than (b)(4) μS/cm at 25 oC. Your test data showed your levels approached (b)(4) μS/cm at 25 oC, at which point you changed the (b)(4) skid, even though the test data showed the (b)(4) produced was already failing USP requirements.

你生产面向消费者(包括儿童)的非处方(OTC)药品。你的非无菌药品的主要成分是XX。你使用XX系统生成XX，以进行清洁和生产操作。我们观察到，在该XX系统中，大约XX英尺的硬管和软管在不使用时，内部含有停滞不动的XX，这可能会导致生物膜的产生。在2017年FDA检查之后，你以书面形式承诺要对XX的微生物属性进行测试。然而，目前的检查中，我们观察到，当你安装一个新的XX设备后你只测试XX。此外，你的测试结果表明，你的XX始终未能满足美国药典(USP)。在USP XX质量标准为25oC不超过XXμS/厘米。测试数据显示，在25oC时，水平达到XXμS/ cm ，测试数据表明未能达到USP要求。

In your response, you stated that you established your (b)(4) specifications, tested your (b)(4) for (b)(4) and total plate count, and (b)(4) above (b)(4) μS/cm was not used in drug production.

在答复中，你表示：已经建立了XX质量标准，测试了XX的XX和微生物总计数，以及XX超标时并未用于药物生产。

Your response is inadequate because your (b)(4) failed USP requirements for (b)(4), and you did not commit to routinely testing microbial attributes of your (b)(4). Additionally, because the main component in your non-sterile drug products is (b)(4), there is a potential risk of objectionable microbial contamination, such as Burkholderia cepacia (B. cepacia), which your firm did not test for as part of your microbial testing of the (b)(4) system.

你的回应是不够的，因为你没有达到USP的要求；对于微生物属性XX，你没有进行日常检验。此外，由于你的非无菌药品的主要成分是XX，因此存在潜在的有害微生物污染风险，例如洋葱伯克氏菌，你的公司未对此进行检测。

In your response to this letter, provide the following:

针对此信，请提供：

• A comprehensive remediation plan for the design, control, and maintenance of the (b)(4) system.

•有关XX系统的设计、控制和维护的综合补救计划。

• Validation report for the (b)(4) system obtained after all identified design issues have been fully corrected and any maintenance repairs have been completed. Include the system validation protocol, the complete test results, and the final validation report.

• 在完全纠正所有已识别的设计问题、并且完成所有维护维修之后，获得XX系统的验证报告。包括系统验证草案、完整的检验结果和最终的验证报告。

• The summary of improvements made to the program for ongoing control and maintenance.

•改进摘要：对程序进行持续控制和维护。

• A procedure for your (b)(4) system monitoring that specifies routine microbial testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm.

•XX系统监控程序：说明常规微生物检验XX，以确保公司生产的每批产品使用时的可接受性。

• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces (b)(4) that meets the (b)(4), USP monograph specifications and appropriate chemical and microbial limits.

•控制、维护和监控的管理程序：确保已修复的系统，可以一致地产生XX，符合USP专着质量标准、和适当的化学和微生物限度。

• Data demonstrating appropriate chemical attributes and microbial total count to ensure this system produces (b)(4) suitable for the intended uses of each of your drug products.

•数据：证明适当的化学属性和微生物总计数，以确保该系统产生适合药品预期用途的XX。

• A detailed risk assessment addressing the potential effects of the (b)(4) you use on the quality of all drug product lots currently in U.S. distribution and within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.

•详细的风险评估：解决你使用XX情况下，对目前在美国分销和效期内的所有药品批次质量的潜在影响。说明你将对风险评估采取的措施，例如客户通知和产品召回。

生产和过程控制

2. Your firm failed to establish 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.公司未建立用于生产和过程控制的书面程序，以确保你所生产的药品具有其声称或代表拥有的鉴别、强度、质量和纯度(21 CFR 211.100(a))。

Your firm lacked a process validation program.

你的公司缺少工艺验证程序。

A. Inadequate Control of Manufacturing Processes

A.对生产过程的控制不足

During our inspection, you informed us there was no executed process validation for the (b)(4) OTC products you currently manufacture. You committed to performing process validation activities in writing after previous FDA inspections. However, you did not follow through on your promised corrective actions.

在我们检查期间，对于你当前生产的XX OTC产品，你告知我们没有执行过工艺验证。在此前的FDA检查后，你承诺以书面形式执行工艺验证活动。但是，你没有遵循此前承诺的纠正措施。

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.

工艺验证评估整个流程生命周期中设计的合理性和控制状态。生产过程的每个重要阶段都必须进行适当的设计，并确保原材料输入，在制品和成品药品的质量。工艺确认研究确定是否已建立初始控制状态。商业放行之前，必须进行成功的工艺确认研究。此后，有必要对工艺性能和产品质量进行持续的监督，以确保你在整个产品生命周期中，保持稳定的生产运营。

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.

请参阅FDA的指南《工艺验证：一般原则和实践》，以获取FDA认为工艺验证适当要素的一般原则和方法。

B. Inadequate Control of (b)(4) System

B.对XX系统的控制不足

(b)(4) was used as the main component in the manufacture of your drug products. You lacked validation studies for your (b)(4) system. Your firm did not demonstrate that you could effectively design, control, maintain, and monitor the system, so it consistently produced pharmaceutical grade (b)(4) that, met the USP monograph for (b)(4) and appropriate chemical and microbial limits at a minimum.

XX被用作你的药品生产中的主要成分。你缺少XX系统的验证研究。你的公司没有证明你可以有效地设计、控制、维护和监视该系统，确保该公司始终生产药品等级的XX，并符合USP关于XX的专论、以及适当的化学和微生物要求最低限度。

In your response, you stated you initiated process validation protocol activities.

在你的答复中，你表示已启动工艺验证草案活动。

Your response cannot be fully evaluated because you didn’t provide sufficient details about your plan regarding process validation activities.

由于你没有提供有关工艺验证活动的计划的足够详细信息，因此无法完全评估你的答复。

In your response to this letter, provide the following:

在答复中，提供以下信息：

• A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.

•有关确保整个产品生命周期中的控制状态的验证程序的详细摘要，以及相关过程。描述你的程序以进行工艺性能确认(PPQ)，并持续监控批内和批间变化，以确保持续的控制状态。

• A timeline for performing PPQ for each of your marketed drug products.

•对每种上市药品执行PPQ的时间表。

• Include your process performance protocols, and written procedures for qualification of equipment and facilities.

•包括你的工艺性能草案，以及书面的设备和设施确认程序。

清洁验证问题

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)).

3.你的公司未能按适当的时间间隔清洁、维护设备和器具，其进行消毒和/或灭菌，防止改变安全性、鉴别、强度、质量或纯度的故障或污染，导致超出官方或其他既定要求(21 CFR 211.67(a))。

You manufacture multiple OTC drug products on shared equipment. During the inspection, you informed us no cleaning validation data was available for your manufacturing and filling operations. You committed in writing to performing cleaning validation activities after previous FDA inspections. However, you did not follow through with your promised corrective actions.

你在共享设备上生产多种OTC药品。在检查过程中，你告知我们没有用于生产和灌装操作的清洁验证数据。在此前的FDA检查后，你承诺以书面形式执行清洁验证活动。但是，你没有遵循此前承诺的纠正措施。

In your response, you stated you initiated cleaning validation activities.

在答复中，你表示已启动清洁验证活动。

Your response cannot be fully evaluated because you did not provide sufficient details about your plan regarding cleaning validation activities.

由于你没有提供有关清洁验证活动的计划的足够详细信息，因此无法完全评估你的答复。

In your response to this letter, provide the following:

针对此信，请提供：

•对清洁验证程序进行了适当的改进，特别着重于纳入在药品生产过程中确定为最差情况的条件。最差情况的识别和评估，应包括但不限于：

o products with higher toxicities

o products with higher potencies

o products of lower solubility in your cleaning solvents

o products with characteristics that make them difficult to clean

o swabbing locations for areas that are most difficult to clean

o maximum hold times before cleaning

o具有较高毒性的

o产品具有较高活性的

o产品在清洁溶剂中溶解度较低的产品

o具有使其难以清洁的特性的产品

o 清洁最困难区域的擦拭位置

o清洁前的最长放置时间

In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.

另外，描述在引入新的生产设备或新产品之前，变更管理系统必须采取的步骤。

• A summary of updated SOPs that ensure an appropriate program is in place to verify and validate cleaning procedures for products, processes, and equipment.

•更新的SOP的摘要，以确保制定适当的程序，来验证和确认产品、工艺和设备的清洁程序。

稳定性问题

4. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

4.你的公司未能建立并遵循适当的书面检验程序，以评估药品的稳定性特征；未能使用稳定性检验结果，来确定适当的储存条件和有效期(21 CFR 211.166(a))。

Your firm lacked appropriate stability data to support your firm’s (b)(4)-year expiration date for your drug products. During our inspection, you informed us there was no stability program and that you were not aware of how a stability program is executed. Without appropriate stability data, you cannot ensure your drug products meet established specifications and all pre-determined quality criteria throughout the drug product’s assigned shelf-life.

公司缺乏适当的稳定性数据，来支持你公司药品的有效期。在我们检查期间，你告知我们没有稳定性程序，并且你不知道如何执行稳定性程序。没有适当的稳定性数据，你的药品在指定的产品效期内，你将无法确保符合既定的质量标准和所有预定的质量要求。

You committed in writing to establishing a stability program after previous FDA inspections. However, you did not follow through on your promised corrective actions.

在此前的FDA检查后，你承诺以书面形式建立稳定性程序。但是，你没有遵循此前承诺的纠正措施。

In your response, you stated you initiated a stability program.

在答复中，你说你启动了一个稳定程序。

Your response cannot be fully evaluated because you did not include accelerated studies to support the tentative expiry dates or justification for the quality of the product that remains on the market.

你的回应无法得到充分评估，因为你没有进行加速研究，以支持暂定的有效期，或支持市场上产品的质量。

In your response to this letter, provide the following:

针对此信，请提供：

• A comprehensive, independent assessment and CAPA 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，以确保你的稳定性计划是充分的。你的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)

o稳定性指示方法

o在分销之前，对市售容器密闭系统中的每种药物进行稳定性研究

o正在进行的计划，每年将每种产品的代表性批次添加到其中，以确定有效期声明是否仍然有效

o每个点(时间点)要检验的特定属性的详细定义

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

•针对稳定性补救计划的这些以及其它元素，其所有相关的描述性程序。

• Stability study data for all drug products manufactured for the U.S. market at your facility.

•对于为美国市场生产的所有药品，提供稳定性研究数据。

• All of your specifications for your drug products and your justification for the ranges for each specification including the upper and lower levels, where applicable.

•药品的所有质量标准，以及每种质量标准范围的合理性，包括上下限(如适用)。

入厂检验问题

5. 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)).

5.你的公司未进行至少一项检验，来确认药品中每种成分的鉴别。你的公司也未能在适当的时间间隔内，验证并确定组分供应商检验分析的可靠性(21 CFR 211.84(d)(1)和(2))。

Your firm failed to test incoming components used in manufacturing your finished OTC drug products to determine identity, purity, strength, and quality and your firm did not establish a vendor qualification program for any of your raw material suppliers.

公司未能测试用于生产OTC药品的入厂组分，以确定其鉴别、纯度、强度和质量，并且未为你供应商，建立供应商资格认证计划。

Instead, your firm used results from your suppliers’ certificates of analysis (COA) without establishing the reliability of your suppliers’ analyses through appropriate validation and without conducting at least one specific identity test on each incoming lot of components. Under 21 CFR 211.84(d)(2), you may not rely on your suppliers’ COA to verify the identity of your components.

相反，你的公司使用了供应商的分析证书(COA)的结果，而没有通过适当的验证来确定供应商分析的可靠性，也没有对每个入库的组分进行至少一项特定的鉴别测试。根据21 CFR 211.84(d)(2)，你不能依赖供应商的COA，来确认组分的鉴别。

Additionally, you manufacture multiple drugs that contain glycerin, yet you did not perform identity testing for diethylene glycol (DEG) and ethylene glycol (EG). The use of glycerin contaminated with DEG has resulted in various lethal poisoning incidents in humans worldwide.

此外，你生产了多种含有甘油的药物，但尚未对二甘醇(DEG)和乙二醇(EG)进行鉴别测试。使用受DEG污染的甘油，已导致全世界发生多种致命的中毒事件。

See FDA’s guidance document Testing of Glycerin for Diethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing glycerin at https://www.fda.gov/media/71029/download.

请参阅FDA的指南“甘油的DEG测试”，以帮助你在生产含有甘油的药物时达到CGMP要求，网址为https://www.fda.gov/media/71029/download。

In your response, you committed to performing identity testing on all of your excipients, including glycerin.

在答复中，你承诺对所有辅料(包括甘油)进行鉴别测试。

Your response is inadequate because you did not address your plans for qualification of your component suppliers and whether your firm tested all lots of drug product that you distributed to the United States for DEG and EG.

你的答复不充分，因为你没有阐述组分供应商资格认证计划；对于分发给美国的所有批次的药品，也没有阐述公司是否测试了DEG和EG。

In your response to this letter, provide the following:

针对此信，请提供：

• A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.

•对物料系统进行全面、独立的审查，以确定所有组分、容器和密封件供应商是否有资质，且为物料指定适当有效期或再验日。对于入厂物料的控制措施，审查还应确定是否足以防止使用不合适的组分、容器和密封件。

• Provide a full risk assessment for drug products manufactured using components that were not adequately tested and qualified. Your risk assessment should address all products within expiry and distributed within the United States. Take prompt corrective actions and preventive actions, and detail your future actions to ensure appropriate selection of your suppliers, ongoing scrutiny of their supply chain, and appropriate incoming lot controls.

•对使用未经充分测试和确认的组分生产的药品进行全面风险评估。你的风险评估应针对有效期内的所有产品并在美国范围内进行分销。采取及时的纠正措施和预防措施，并详细说明你将来的措施，以确保适当选择供应商，对供应链进行持续审查以及适当的来料控制。

质量单元问题

6. Your firm failed to establish an adequate quality unit and the responsibilities, and procedures applicable to the quality control unit were not in writing and fully followed (21 CFR 211.22(a)&(d)).

6.贵公司未能建立适当的质量单元，对于质量控制单元的职责和程序，没有文件化、且未严格遵循(21 CFR 211.22(a)＆(d))。

During the inspection, our investigator observed that your quality unit (QU) did not provide adequate oversight for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:

在检查过程中，我们的调查员发现你的质量单元(QU)没有为你的OTC药品生产提供充分的监督。例如，你的QU无法确保以下各项：

• Review of executed batch production and packaging records, including testing performed by your external laboratories, was performed before releasing your drug products for distribution.

•在放行药物、进行分销之前，已执行了批生产和包装记录的审查，包括由外部实验室进行的测试。

• Sampling, testing, and release of your drug product containers and closures was performed before use in manufacturing.

•在生产中使用之前，对药品容器和密封件进行了取样、测试和放行。

• Logs for deviations and out-of-specifications (OOS) were maintained as required by your procedures.

•已按照你的程序，要求维护了偏差和OOS日志。

• An adequate complaint procedure was developed that requires maintaining a record of drug product complaints.

•已制定适当的投诉程序，保留药品投诉记录。

In your response, you submitted numerous corrective actions, including hiring a Quality Manager, to address your QU failures.

在你的答复中，你提交了许多纠正措施，包括雇用质量经理来解决你的QU失败问题。

Your response is inadequate. You failed to review the scope of your QU deficiencies and provide evidence that you drafted and implemented procedures that ensure adequate control over your drug manufacturing processes. You also failed to address the potential effects of your lack of quality oversight on the quality of drugs you manufactured, and which remain within expiry.

你的回应不充分。你没有检查QU缺陷的范围，也没有提供证据证明：你已起草并实施了确保对药品生产过程进行充分控制的程序。你还没有解决：由于缺乏质量监督而对生产的药品质量造成的潜在影响（这些药品仍在有效期内）。

In your response to this letter, provide the following:

针对此信，请提供：

• A comprehensive, independent assessment and remediation plan to ensure your QU is given authority and resources to effectively function. The assessment should also include, but not be limited to:

•提供全面的评估和补救计划，以确保你的QU拥有有效行使职责的授权和资源。评估还应包括但不限于：

-A determination of whether procedures used by your firm are robust and appropriate.

确定贵公司使用的程序是否健全和适当。

-Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.

整个运营过程中，对QU监督规定的评估，已确定对良好实践的遵守情况。

-A complete and final review of each batch and its related information before the QU disposition decision.

在QU决定处置之前，对每批产品及其相关信息进行完整和最终审查。

-Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.

进行监督和批准，调查并履行所有其他QU职责，以确保所有产品的鉴别、强度、质量和纯度。

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

请参阅FDA指南《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，满足CGMP法规21 CFR第210和211部分的要求，网址为https://www.fda.gov/media/71023/download

CGMP顾问推荐

Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations and to assist your firm in meeting CGMP requirements. 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.

根据我们在贵公司发现的违规行为的性质，我们强烈建议聘请有资格的顾问来评估你的业务，并协助贵公司满足CGMP要求。我们还建议合格的顾问对整个运营过程进行全面审核，以确保其符合CGMP要求，并建议顾问在你寻求公司与FDA的合规性解决方案之前，评估CAPA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.

你聘用顾问并不能免除公司遵守CGMP的义务。你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

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.

本信函中引用的违规行为并非旨在列出与你产品相关的所有违规行为。你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。

FDA placed your firm on Import Alert 66-40 on July 14, 2020.

FDA于2020年7月14日将你的公司列入了Import Alert 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.

在你完全纠正所有违规行为、且我们确认你遵守CGMP之前，对于新药申请或补充申请，FDA可能会拒绝批准将你的公司列为药品生产商。

Failure to correct these violations may also result in the FDA continuing to refuse admission of articles manufactured at LEC Custom Products, Inc., located at 7 Kenview Boulevard, Brampton, Ontario 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).

根据FD＆C法案21 801(a)(3)条与USC 381(a)(3) 条，不纠正这些违规行为也可能导致FDA拒绝接纳该工厂生产的产品，无法进入美国。对于该法案授权下的产品，可能会被拒绝入境，因为其生产使用的方法与控制不符合CGMP，CGMP是在FD＆C法案21(501)(a)(2)(B) 条与USC 351(a)(2)(B) 条中被要求的。

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.

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。说明自我们检查以来，你所做的事情，以纠正你违规行为，并防止其再次发生。如果你无法在15个工作日内完成纠正措施，请说明延误原因和完成时间表。

If you believe that your products are not in violation of the FD&C Act (or you have complied with FDA regulations), include your reasoning and any supporting information for our consideration.

如果你认为你产品未违反FD＆C法案(或你已遵守FDA法规)，请提供你理由和任何支持信息，以供我们考虑。

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zysx01234

看样子国内外都差不多，应该说人的思想都是差不多的，先对付过去再说。老天绕过谁

wgx1979

关注关注，学习学习

lilian2007177

这家公司怎么感觉啥都没有，平常的官方检查也对付不过去吧

隐月

感谢分享

安捷伦

是人干的，都是差不多
差异可能就是在管理上面。

wsx

所以对OTC产品还是要加强监管，包括上市前的许可检查。

guaika

挺及时的，慢慢看，要坚持