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Warning Letter 320-20-47
September 24, 2020
Dear Mr. Willard:
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.
美国FDA于2020年3月2日至6日检查了你们位于加拿大的LEC Custom Products, Inc.生产场所。
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).
本警告信总结了制剂生产严重违反CGMP的行为。参见21CFR第210与211部分。
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug product 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).
由于你们的制剂生产、加工、包装或保存的方法、场所或控制不符合CGMP要求，你们的药品根据FDCA的501(a)(2)(B)以及21 U.S.C. 351(a)(2)(B)被认为是掺假药品。
We reviewed your March 25, 2020, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
我们已详细审核了你公司2020年3月25日对FDA483表的回复，并此告知已收到后续通信。
During our inspection, our investigator observed specific violations including, but not limited to, the following.
检查期间，我们的调查人员发现的具体问题包括但不仅限于以下：
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 CFR211.63). 你公司在生产、加工、包装或保存药品时未使用经过适当设计、具备足够尺寸并适当定位安装的设备，便于其既定用途和清洁与维护（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.
你们生产OTC药品销售给消费者，包括儿童。你们的非无菌药品中的主要成分是XX。你们使用了XX系统来制备XX，用于清洁和生产操作。我们发现有约XX英尺的硬管和软管从该XX系统接出，其中在不使用时会有停滞的XX，可能会滋生生物膜。在2017年FDA检查之后，你们书面承诺会检测你们的XX中的微生物情况。但是在本次检查中我们发现你们仅是在安装新XX接口时检测了XX。另外，你们的检测结果表明你们的XX一直不能符合USP的XX标准。USP的XX标准是25 ºC时不大于XXμS/cm。你们的检测数据显示你们的水平接近XXμS/cm，你们改掉了XX点的XX接口，即使如此检测数据仍显示所制备的XX仍不符合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.
在你们的回复中，你们声称你们制订了你们的XX标准，检测你们的XX中的XX和总菌落计数，并且超过XXμS/cm的XX并未用于药品生产。
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.
你们的回复是不充分的，因为你们的XX不满足USP中的XX要求，你们并未承诺会对XX的微生物属性进行定期检测。另外，由于你们非无菌药品中的主要成分是XX，因此有致病菌污染的潜在风险，例如洋葱伯克氏菌，你们公司并未作为你们XX系统的微生物检测的一部分对其进行检测。
In your response to this letter, provide the following:
在回复本函时请提交以下内容：
• A comprehensive, independent remediation plan for the design, control, and maintenance of the (b)(4) system.
• XX系统的设计、控制和维护的全面独立补救计划
• 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.
• 在所有已识别的设计问题全面纠正，并且所有维护修理完成之后的XX系统验证报告。包括有系统验证方案、完成的测试结果和最终验证报告
• The summary of improvements made to the program for ongoing control and maintenance.
• 持续控制和维护程序的改进摘要
• A procedure for your (b)(4) system monitoring that specifies routine microbial testing of (b)(4) to ensureits acceptability for use in each batch of drug products produced by your firm.
• 你们XX系统的监测程序，在其中写明对XX的日常微生物检测，从而确保其可用于你公司所生产的每个药品批次
• 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.
• 管理你们持续控制、维护和监测的程序，确保经过补救的系统能始终制备出符合XX、USP各论要求以及适当的化学和微生物限度的XX
• 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.
• 证明具备恰当化学属性和微生物总菌落计数的数据，从而确保该系统能制备出适合你们所有产品既定用途的XX
• A detailed risk assessment addressing the potentialeffects 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.
• 一份详细的风险评估，说明你们使用XX对所有当前在美国销售且在有效期内的所有药品的质量的潜在影响。说明你们将要采取的风险评估响应措施，例如通知客户和召回产品
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 purportor are represented to possess (21 CFR 211.100(a)). 你公司未能建立书面生产和工艺控制程序，设计用以确保你们生产的药品具备其理当具备或显示具备的鉴别、含量、质量和纯度（21 CFR 211.100(a)）。
Your firm lacked a process validation program.
你公司缺乏工艺验证程序
A. Inadequate Control of Manufacturing Processes生产工艺控制不足
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，你们告诉我们目前生产的XX OTC药品并未执行工艺验证。你们在上一次FDA检查之后曾书面承诺会执行工艺验证。但是你们并未执行你们所承诺的纠正措施。
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.
工艺验证评估的是工艺生命周期中其设计合理性和受控状态。每个生产工艺的重大阶段均必须进行恰当设计，确保原料输入、中间体和成品的质量。工艺确认研究会确定是否建立初始的受控状态。在商业化销售之前必须完成成功的工艺确认研究。之后，必须持续严格监测工艺性能和产品质量方可确保你们在产品生命周期中维护稳定的生产操作。
See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation athttps://www.fda.gov/media/71021/download.
参见FDA指南文件“工艺验证通则和规范”。
B. Inadequate Control of (b)(4) System XX系统控制不足
(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用作你们药品生产的主要成分。你们对XX系统缺少验证研究。你公司并未能证明你们能够有效设计、控制、维护和监测该系统，从而确保其始终生产出药用级别的XX，最少符合USP各论要求和恰当的化学和微生物限度。
In your response, you stated you initiated process validation protocol activities.
在你们的回复中，你们声称你们已启动了工艺验证方案活动。
Your response cannot be fully evaluated because you didn’t provide sufficient details about your plan regarding process validation activities.
你们的回复并不能进行全面评估，因为你们并未提交足够的详细信息，说明你们工艺验证活动的计划。
In your response to this letter, provide the following:
在你们回复本函时请提交以下内容：
• 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.
• 一份对你们验证计划的详细摘要，确保在产品生命周期中处于受控状态，以及相关的程序。说明你们的工艺性能确认（PPQ）计划，以及对批间和批内波动的持续监测，从而确保持续的受控状态
• A timeline for performing PPQ for each of your marketed drug products.
• 对你们所有已上市药品执行PPQ的时间表
• Include your process performance protocols, and written procedures for qualification of equipment and facilities.
• 提交你们的工艺性能确认方案，和设备与设施确认书面程序
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)).你公司未能以适当时间间隔对设备和工器具进行清洁、维护，以及根据药品特性进行适当消毒和/或灭菌，以防止可能改变药品的安全性、鉴别、含量、质量或纯度使得超出正式或既定要求的故障或污染（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.
你们生产在共用设备上多个OTC药品。在检查期间，你们告诉我们你们的生产和灌装操作并没有清洁验证数据。上次FDA检查之后，你们书面承诺会执行清洁验证活动。但是你们并未执行你们所承诺的纠正措施。
In your response, you stated you initiated cleaning validation activities.
在你们的回复中，你们声称你们已启动了清洁验证活动。
Your response cannot be fully evaluated because youdid not provide sufficient details about your plan regarding cleaning validation activities.
你们的回复无法进行全面评估，因为你们并未提交清洁验证活动计划的详细信息。
In your response to this letter, provide the following:
在回复本函时请提交以下：
• Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identifiedas worst case in your drug manufacturing operation. This should include, but not be limited to identification and evaluation of all worst-case:
• 对你们清洁验证程序的恰当改进，特别要注意结合你们药品生产操作中被识别为最差情形的条件。其中应包括但不仅限于识别和评估所有最差情形：
Drugs with higher toxicities
毒性高的药品
Drugs with higher drug potencies
效价高的药品
Drugs of lower solubility in their cleaning solvents
在其清洁溶液中溶解度低的药品
Drugs with characteristics that make them difficult to clean
因其特性而难以清洁的药品
Swabbing locations for areas that are most difficult to clean
最难清洁位置的擦拭取样点
Maximum hold times before cleaning
清洁之前的最长放置时长
• In addition, describe the steps that must be takenin your change management system before introduction of new manufacturing equipment or a new product.
• 此外，在你们的变更管理系统中说明引入新生产设备或新产品之前所必须采取的措施
• A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.
• 为确保有恰当的程序确认和验证产品、工艺和设备清洁程序而更新后的SOP摘要
4. Your firm failed to establish a 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)). 你公司未建立和遵守足够的书面检测程序，设计用以评估药品的稳定性特性，以及使用稳定性测试结果确定适当的存贮条件和有效期（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.
你公司缺少恰当的稳定性数据来支持你公司药品的XX年有效期。在检查期间，你们告诉我们说没有稳定性试验程序，你们并不了解要如何执行稳定性研究。没有恰当的稳定性数据，你们并不能确保你们的药品符合既定标准，以及在整个药品货架期内符合预定的质量标准。
You committed in writing to establishing a stability program after previous FDA inspections. However, you did not follow through on your promised corrective actions.
你们在上次FDA检查之后曾书面承诺会建立稳定性程序。但是你们并未执行你们承诺的纠正措施。
In your response, you stated you initiated a stability program.
在你们的回复中你们承诺会启动稳定性程序。
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.
你们的回复无法进行全面评估，因为你们并未提交加速研究结果来支持暂时确定的有效期或证明在售药品的质量。
In your response to this letter, provide the following:
在你们回复本函时请提交以下：
• A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:
• 一份全面独立的评估和CAPA计划，确保你们稳定性计划的充分性。你们经过补救的计划应包括但不仅限于：
Stability indicating methods
稳定性指示性方法
Stability studies for each product in its marketed container-closure system before distribution is permitted
允许销售之前，以上市销售方式包装的每种药品稳定性研究结果
An on-going program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid
每种产品每年增加具有代表性批次样品至持续稳定性计划，从而确定所声明的货架期保持有效
Detailed definition of the specific attributes to be tested at each station(timepoint)
对每个时间点要检测的特定属性的详细规定
• All procedures that describe these and other elements of your remediated stability program.
• 说明这些和你们经过补救后的稳定性计划中其它要素的所有程序
• Stability study data for all drug products manufactured for the U.S. market at your facility.
• 在你工厂为美国市场生产的所有药品的稳定性研究数据
• 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.
• 你们药品的所有质量标准，以及每个项标准包括上下限（适用时）的范围论证
5. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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)). 你公司未检测每种组份样品的鉴别和相关项目，确保其符合所有书面的纯度、含量和质量标准。你公司亦未以适当时间间隔验证和建立你们组份供应商的检测分析可靠性(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.
你公司未对OTC药品生产所用进厂组份进行检测，确定其鉴别、纯度、剂量和质量。你公司未建立你们原料供应商确认计划。
Instead, your firm used results from your suppliers’ certificates of analysis (COA) without establishing the reliabilityof 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，你公司使用了来自你们供应商COA的结果，但没有通过恰当的验证来验证你们供应商分析的可靠性，亦没有对每批进厂组份进行至少一项专属性鉴别。根据21 CFR 211.84(d)(2)，你们不能依赖于你们供应商的COA来核查你们组份的鉴别。
Additionally, you manufacture multiple drugs that contain glycerin, yet you did not perform identity testing for diethyleneglycol (DEG) and ethylene glycol (EG). The use of glycerin contaminated with DEG has resulted in various lethal poisoning incidents in humans worldwide.
另外，你们生产多个含有甘油的药品，但你们并未进行DEG和EG鉴别检测。使用被DEG污染的甘油已在全球导致多起中毒致死事件。
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.
参见FDA指南文件“甘油中DEG检测”帮助你们在生产含有甘油的药品时符合CGMP要求。
In your response, you committed to performing identity testing on all of your excipients, including glycerin.
在你们的回复中，你们承诺会对所有你们的辅料包括甘油执行鉴别检测。
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.
你们的回复是不充分的，因为你们并未说明你们对你们组份供应商的确认计划，未说明你们是否检测了所有销往美国药品批次中的DEG和EG。
In your response to this letter, provide thefollowing:
在回复本函时请提交以下：
• 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.
• 一份对你们物料体系的全面独立评估，确定是否所有组份、容器密闭器的供应商均经过确认，并且所有物料均给予了恰当的有效期或复验期。审核还应确定是否所有进厂物料的控制足以防止使用不当组份、容器密闭器
• 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.
• 提交一份使用了未经过充分检测和确认的组份生产的药品的全面风险评估。你们的风险评估应包括在美国仍在效期内的所有产品。采取快速纠正措施和预防措施，详细说明你们未来的措施，确保恰当地选择你们的供应商，持续检查供应链和恰当的进厂批次控制。
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)).未能建立足够的质量部门，未书面制订并遵守质量部门适用职责与程序（21 CFR 211.22(a) 和 (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:
在检查期间，我们的检查员发现你们的QU并未对你们的OTC药品生产进行充分的监管。例如你们QU未能确保以下：
• Review of executed batch production and packaging records, including testing performed by your external laboratories, was performed before releasing your drug products for distribution.
• 审核已执行批生产记录和包装记录，包括你们内部实验室在药品放行销售之前执行检测
• Sampling, testing, and release of your drug product containers and closures was performed before use in manufacturing.
• 你们药品容器密闭器在用于生产之前进行了取样检测和放行
• Logs for deviations and out-of-specifications (OOS) were maintained as required by your procedures.
• 按你们程序要求维护偏差和OOS登记本
• An adequate complaint procedure was developed thatrequires maintaining a record of drug product complaints.
• 建立足够的客户投诉程序，要求保存药品投诉记录
In your response, you submitted numerous corrective actions, including hiring a Quality Manager, to address your QU failures.
在你们的回复中，你们提交了大量纠正措施，包括聘用质量经理，来解决你们的QU问题。
Your response is inadequate. You failed to reviewthe 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.
你们的回复是不充分的。你们未能审核你们QU缺陷范围，提交证据证明你们起始和实施的程序能够确保对你们的药品生产工艺进行充分控制。你们亦未说明你们缺少质量监管对你们所生产且仍在效期内药品质量的潜在影响。
In your response to this letter, provide the following:
在回复本函时请提交以下：
• 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:
• 一份全面独立的评估和补救计划，确保你们的QU被赋予了权力和资源有效展开工作。评估还应包括但不仅限于：
A determination of whether procedures used by your firm are robust and appropriate
确定你们公司所用程序是否稳健恰当
Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
QU监管所有操作评估其是否遵守恰当规范的条款
A complete and final review of each batch and its related information before the QU disposition decision
在QU处置决定之前对每个批次及其相关信息进行全面最终审核
Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
监管和批准调查，履行所有其它QU职责，确保所有产品的鉴别、剂量、质量和纯度
Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality 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 athttps://www.fda.gov/media/71023/download.
你公司的质量体系是不足的。参见FDA指南文件“药品CGMP法规的质量体系方法”来帮助实施质量体系和风险管理方法从而符合CGMP法规要求。
Repeat Observations and Cessation of Manufacturing 重复缺陷和停产
In your August 19, 2020, correspondence you indicated that you have ceased drug manufacturing at Kenview Boulevard (Brampton site, formerly the Burlington site) and moved all of your drug production operations to your facility located at 2300 Drew Road (Mississaugasite). Based on repeat observations and your failure to follow through with written commitments to perform various corrective actions at the Brampton and Burlington sites, you do not have adequate executive management oversight and control over the manufacture of drugs.
在2020年8月19日你们的函件中，你们说你们已停止Kenview Boulevard（Brampton 场所,之前的Burlington场所）的药品生产，并将你们所有药品生产操作转移至你们位于2300 Drew Road （Mississauga 场所）的工厂。基于重复缺陷情况，以及你们未能遵守在Brampton 和Burlington工厂执行各种纠正措施的书面承诺，我们认为你们并没有足够的高级管理人员监管和控制药品生产。
If you plan to resume manufacturing drugs for theU.S. market at the Brampton site, notify this office prior to resuming your operations and include written confirmation that the corrective actions from your March 25, 2020, response to the Form FDA 483 observations have been implemented.
如果你们计划恢复在Brampton场所生产美国市场的药品，请在恢复运作之前通知本办公室，在其中放入书面确认，确认已实施了2020年3月25日回复给FDA483表的纠正措施。
In your response to this letter provide the change control documents related to any equipment relocations to the Mississauga site.Additionally, provide documentation to demonstrate that all CGMP concerns detailed above were evaluated at the Mississauga site and you are operating in compliance with CGMP at the Mississauga site. FDA plans to verify the implementation of corrective actions and production change control related todrug manufacturing at the next Mississauga site inspection.
在你们对本函的回复中，请提交一份Mississauga场所重新定位所有设备的相关变更控制文件。另外，请提交文件证明所有CGMP相关的详细信息均已在Mississauga场所经过了评估，并且你们在Mississauga的运行是符合CGMP的。FDA计划在下次去Mississauga检查期间核查纠正措施的执行情况，以及与药品生产有关的生产变更控制。
CGMP Consultant Recommended CGMP顾问建议
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.
鉴于我们在你公司所发现的违规情况，我们强烈建议你们使用一位有21 CFR 211.34所述资质的顾问来协助你们公司符合CGMP要求。我们亦建议该具备资质的顾问对你们整体运营情况进行药品CGMP合规情况全面审计，并由其在你们寻求满足FDA合规要求之前对你们CAPA的完成情况和有效性进行评估。
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.
你们使用顾问并不能解除你们公司符合CGMP的义务。你们公司的高级管理层仍负有义务全面解决所有缺陷，确保持续CGMP符合性。
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.
此函中所引用的违规并不是全部。你们有责任对这些偏差进行调查，确定原因，防止其再次发生，防止你们设施内其它偏差的发生。
In addition, we note that some of the OTC drug products you manufacture may also be regulated as cosmetics, as defined insection 201(i) of the FD&C Act. A cosmetic may be deemed adulterated under section 601(c) of the FD&C Act, 21 U.S.C. 361(c), if it has been prepared, packed,or held under unsanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. Some of the sanitation conditions that cause the OTC drug products you manufacture to be adulterated may also cause the products to be adulterated cosmetics. We note that under section 301(a) of the FD&C 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，我们注意到你们所生产的有些OTC药品可能亦要按FDCA第201(i)规定作为化妆品监管。化妆品的生产、包装或保存条件如果不卫生，可能受到脏物污染，或者对健康产生危害，则根据FDCA第601(c)条21 U.S.C. 361(c)亦认为是掺假品。有些导致你们生产的OTC药品成为掺假药品的卫生条件亦会使得化妆品成为掺假品。我们提醒根据FDCA第301(a)条21 U.S.C. 331 (a)，掺假化妆口是禁止引入或在州间交易的。
FDA placed your firm on Import Alert 66-40 on July14, 2020.
FDA已于2020年7月14日将你公司置于进口禁令66-40中。
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.
在贵公司未能完成所有偏差纠正并且由我们确认你们符合CGMP之前，FDA可能会搁置所有将你公司列为药品生产商的新申报和增补申报的批准。
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).
未能纠正这些偏差可能还会导致FDA依据FDCA第801(a)(3)条和21 U.S.C. 381(a)(3)拒绝接受在上述地址生产的产品进入美国。
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.
在收到此函后，请在15个工作日内回复至本办公室。在回复中说明自从检查后，你们做了哪些工作来纠正你们的偏差，防止其再次发生。如果不能在15个工作日内完成纠正措施，说明延迟的原因以及完成计划。
If you believe that your products are not inviolation of the FD&C Act (or you have complied with FDA regulations),include your reasoning and any supporting information for our consideration.
如果你们认为你们的产品并未违反FDCA（或者你们是符合FDA法规的），请说明你们的理由和并提交支持性信息给我们参考。
Send your electronic reply toCDER-OC-OMQ-Communications@fda.hhs.gov.
Please identify your response with FEI 3004737602and ATTN: Kevin Maguire.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
Cc: (b)(4)
文章来源：允咨GMP制药技术
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