工艺验证不充分，实验室方法未确认以及偏差和OOS未彻底调查，FDA发出警告性
WARNING LETTER
The W.S. Badger Company, Inc.
MARCS-CMS 622318 — APRIL 12, 2022
April 12, 2022
Dear Ms. Hamilton and Ms. Schwerin-Whyte:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, The W.S. Badger Company, Inc., FEI 3009946959, at 768 Route 10, Gilsum, NH, from August 30 to September 14, 2021.
美国食品和药物管理局(FDA)于2021年8月30日至9月14日检查了企业位于NH Gilsum, 768 Route 10的药品生产工厂W.S. Badger Company, Inc, FEI 3009946959 。
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).
本警告信总结了药品严重违反现行良好生产规范(CGMP)规定的情况。参见《联邦法规法典》第21篇，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).
由于生产、加工、包装或贮存方法、设施或控制不符合CGMP，企业的药品根据《联邦食品、药品和化妆品法案》(FD&C法案)第501(a)(2)(B)条21 U.S.C. 351(a)(2)(B)属于掺假药品。
We reviewed your September 28, 2021 response to our Form FDA 483 in detail.
FDA详细审查了企业在2021年9月28日对FDA 483表格的回复。
During our inspection, our investigators observed specific violations including, but not limited to, the following:
在FDA的检查过程中，检查人员发现了具体的违规行为，包括但不限于以下:
1. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
1. 未能制订充分的书面生产和工艺控制规程，以保证药品所声称的或表明拥有的成分、规格、质量和纯度。(21 CFR 211.100(a))。
Your firm distributed various over-the-counter (OTC) drug products, but you failed to adequately validate your drug manufacturing processes and lacked adequate process validation studies for multiple products. In multiple batches of your sunscreen products, including those intended for infants, quality control testing yielded out-of-specification (OOS) results. Without process validation, your firm lacks basic assurance that you understand the adequacy of manufacturing inputs and parameters that affect product quality, and can ensure robust operations that reproducibly deliver products that meet specifications. In addition, you lacked adequate cleaning validation.
贵公司销售各种非处方(OTC)药品，但未能充分验证药品生产工艺，并缺乏对多种产品的充分工艺验证研究。在企业的多批防晒产品中，包括婴儿防晒产品，质量控制测试产生了OOS结果。如果没有工艺验证，贵公司就缺乏基本的保证，以确保企业了解影响产品质量的生产输入和参数的充分性，并能够确保稳健的操作，可重复交付符合规格的产品。此外，企业缺乏足够的清洁验证。
During the time period that you lacked adequate process validation, you manufactured, released, and distributed at least (b)(4) batches representing at least 23 unique drug product item codes. This is a repeat violation.
缺乏充分工艺验证的期间，企业生产、放行和分发了至少代表23个独特药品代码的xx批次。这是一次重复违规。
Your response stated that you were working with a consultant to complete your process validation studies, and that your plans were partially complete. You planned on completing your studies by (b)(4). You also stated that you planned to complete cleaning validation by the same date.
回复称企业正在与顾问合作完成工艺验证研究，企业的计划部分完成。计划在xx前完成。企业还表示计划在同一天完成清洗验证。
Your response was inadequate because your proposal to address your missing or inadequate process validation studies did not specify whether you planned to continue distribution of products produced from processes still lacking initial validation studies (process performance qualification (PPQ)). Similarly, your proposal for cleaning validation lacked adequate details. You had committed to performing process and cleaning validation for your products in response to the previous inspection and at a regulatory meeting held with FDA on November 19, 2019. However, from the time since your previous inspection, you had only performed PPQ studies for one of your products (SPF30 Baby Sunscreen), and had not yet completed the validation report for that product. It is difficult for the Agency to have confidence in your current commitments to comply with the FD&C Act when you failed to adhere to previous process and cleaning validation commitments.
企业的回复是不充分的，因为企业针对缺失或不充分工艺验证研究的提案没有明确说明企业是否计划继续分销仍然缺乏初始验证研究(工艺性能确认(PPQ))的工艺生产的产品。同样，企业的清洁验证提案也缺乏足够的细节。企业在2019年11月19日与FDA召开的监管会议上承诺对产品进行工艺和清洁验证，以回应之前的检查。然而，自上次检查以来，企业只对其中一款产品(SPF30婴儿防晒霜)进行了PPQ研究，并且还没有完成该产品的验证报告。当企业未能遵守之前的工艺和清洁验证承诺时，FDA很难对企业目前遵守FD&C法案的承诺有信心。
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.
工艺验证评估一个工艺在整个生命周期中设计的可靠性和控制状态。生产工艺的每个重要阶段都必须进行适当的设计，并确保原料投入、中间体和成品药品的质量。工艺确认研究确定是否建立了初始控制状态。成功的工艺鉴定研究在商业销售前是必要的。此后，对工艺性能和产品质量的持续警惕监督是必要的，以确保企业在整个产品生命周期中保持稳定的生产操作。
In response to this letter, provide the following:
针对本函，请提供：
• 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 sound design, process performance qualification, and ongoing lifecycle monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.
•验证程序以及相关程序的详细总结，以确保整个产品生命周期的受控状态。请描述企业的合理设计、工艺性能确认以及对批内和批间差异的持续生命周期监控的程序，以确保持续的受控状态。
• The latest update and timelines for performing appropriate process performance qualification (PPQ) for each of your marketed drug products. Explain whether your firm plans to further distribute any products for which process validation studies have not yet been completed. Also, include your process performance protocol(s), and written procedures for qualification of equipment and facilities.
对每种上市药品进行适当工艺性能确认(PPQ)的最新更新和时间表。说明贵公司是否计划进一步销售工艺验证研究尚未完成的产品。另外，包括企业的工艺性能协议，以及设备和设施的书面确认程序。
• Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst-case in your drug manufacturing operation. This should include but not be limited to identification and evaluation of all worst-case:
对企业的清洁验证程序进行适当改进，特别强调纳入药品生产操作中确定的最坏情况。这应包括但不限于识别和评估所有最坏情况:
o drugs with higher toxicities
O毒性较高的药物
o drugs with higher drug potencies
O具有较高药效的药物
o drugs of lower solubility in their cleaning solvents
O在清洁溶剂中溶解度较低的药物
o drugs with characteristics that make them difficult to clean
O难以清洗的药物
o swabbing locations for areas that are most difficult to clean
O擦洗最难清洁的区域
o maximum hold times before cleaning
O清洁前最大保持时间
In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.
此外，描述在引入新的生产设备或新产品之前，在企业的变更管理系统中必须采取的步骤。
• A summary of updated procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.
•修订程序的总结，以确保适当的程序用于产品、工艺和设备的清洁程序的验证或确认。
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指南文件《工艺验证:一般原则和实践》，了解FDA认为工艺验证的适当元素的一般原则和方法，网址为https://www.fda.gov/media/71021/download。
2. Your firm failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
2.未能建立并记录检验方法的精确度、灵敏度、专属性、重现性。(21 CFR 211.165(e))
You released finished OTC drug products based on release testing performed by a third-party contract testing laboratory (CTL). The analytical test methods had not been validated for accuracy, specificity, and reproducibility. For example, the zinc oxide release test method that your CTL used was validated for another customer’s zinc-based products, but not for yours. Additionally, these same unvalidated test methods lacked scientific evidence to demonstrate that they were stability-indicating for your specific formulations. FDA initially made you aware of your lack of method validation over two years ago during your previous inspection and since then, you manufactured, released, and distributed numerous batches from multiple product codes without having adequate release and stability method validation data. This is a repeat violation.
企业基于第三方合同检测实验室(CTL)放行检测结果放行OTC药品成品。分析测试方法的准确性、专属性和重现性尚未得到验证。例如，企业的CTL使用的氧化锌放行测试方法在其他客户的锌基产品中得到了验证，但在企业的产品中没有。此外，这些同样未经验证的试验方法缺乏科学证据来证明它们对企业的特定配方具有稳定性。FDA最初在两年前的上次检查中告知企业缺乏方法验证，此后，企业在没有足够的放行和稳定性方法验证数据的情况下，从多个产品生产、放行和分销了大量批次。这是一次重复违规。
Your response stated that you became aware that your CTL was using a method that was not specific for your formulation of OTC zinc-based products during an audit of your CTL on August 10, 2021. You also stated that you only then started working with your CTL to perform the necessary method validation studies for your products.
企业的回复称，在2021年8月10日对CTL进行审核时，意识到企业的CTL使用了一种不适用于企业OTC锌基产品配方的方法。企业还表示那时才开始与CTL合作，对企业的产品进行必要的方法验证研究。
Your response was inadequate because you did not address why it took so long to initiate corrective actions and preventive actions despite having been cited for lack of method validation at your previous inspection. You did not have adequate zinc oxide release and stability test method validations during your May 2019 inspection, and committed to completing method validation at the November 19, 2019 regulatory meeting. It is difficult for the Agency to have confidence in these current method validation commitments when you failed to adhere to your previous commitments.
企业的回复是不充分的，因为没有说明为什么尽管企业在之前的检查中缺乏方法验证而被引用，但却花了这么长时间才开始采取纠正措施和预防措施。企业在2019年5月的检查中没有进行足够的氧化锌放行和稳定性试验方法验证，并承诺在2019年11月19日的监管会议上完成方法验证。没有遵守企业以前的承诺时，FDA很难对这些目前的方法验证承诺有信心。
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. You are responsible for the quality of your drugs regardless of agreements in place with your contract facility. 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.
药品生产必须符合CGMP要求。FDA知道许多药品生产商使用独立的承包商，如生产设施、检测实验室、包装商和标签商。FDA将承包商视为生产商的延伸。企业应该对药品的质量负责，无论企业与合同工厂是否达成协议。企业需要确保药品按照FD&C法案第501(a)(2)(B)条生产，以确保安全性、成分、规格、质量和纯度。参见FDA指南文件《药品合同生产安排:质量协议》https://www.fda.gov/media/86193/download。
In response to this letter, provide the following:
针对本函，请提供：
• A detailed, independent assessment of all test methods to ensure they include specific instructions to ensure repeatability, are supported by adequate validation (or verification, for USP compendial methods) studies, and are appropriate for their intended use. The assessment should also determine whether test methods used in the stability program are stability-indicating. The scope of the assessment should encompass any tests conducted by your firm or its contract laboratories.
对所有测试方法进行详细、独立的评估，以确保它们包括重复性的具体说明，有充分的验证(或确认，对于USP药典方法)研究的支持，并适合其预期用途。评估还应确定稳定性方案中使用的试验方法是否具有稳定性指示性。评估的范围应包括由贵公司或其合同实验室进行的任何测试。
• A status report and timelines for completing validation (or verification, if appropriate) for all analytical test methods.
•所有分析测试方法完成验证(或确认，如果合适)的状态报告和时间表。
• A comprehensive independent review of your entire laboratory system, and a corrective action and preventive action (CAPA) plan that ensures full remediation of the laboratory operation. For example, the review of your laboratory system should include, but should not be limited to, the suitability of all laboratory equipment, a fully remediated calibration program, staff competencies, supervisory oversight, data systems, and other elements of laboratory control. This need for a compliant laboratory system also extends to any laboratory performing testing on your behalf.
对企业整个实验室系统进行全面的独立审核，以及一份纠正措施和预防措施(CAPA)计划，以确保对实验室操作进行全面的整改。例如，对实验室系统的审查应包括但不限于所有实验室设备的适用性、完全修正的校准程序、员工能力、监督检查、数据系统和实验室控制的其他要素。这种对合规实验室系统的需求也延伸到为企业进行检验的任何实验室。
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 analytical method validation at https://www.fda.gov/media/87801/download.
关于FDA认为分析方法验证的适当元素的一般原则和方法，请参阅FDA的指导文件《药物和生物制品的分析程序和方法验证》https://www.fda.gov/media/87801/download。
3. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
3.未能彻底调查批产品或其成分与质量标准的不明原因的差异或不符，不论该批次是否已被放行销售。[ 21 CFR 211.192 ]。
Your investigations were inadequate. You implemented ineffective corrective actions and preventive actions as you repeatedly obtained OOS viscosity and high water activity results. During an approximately two-year time period, you recorded at least 25 OOS results for viscosity. During the same time period, you also recorded at least 45 OOS results for high water activity. If the water activity exceeded your specifications, you would then test for bioburden. Several of these high water activity batches were also OOS for bioburden and failed release. In addition, you have received at least 29 complaints regarding product consistency and at least 129 complaints regarding lack of effect since March 2018. This is a repeat violation.
企业的调查不充分。企业实施了无效的纠正措施和预防措施，因为反复获得OOS粘度和高水活度结果。在大约两年的时间内，企业记录了至少25个粘度OOS结果。在同一时期，企业还记录了至少45个高水活度的OOS结果。如果水的活度超过企业的标准，那么将测试生物负荷。这些高水活度批次中的几个批次也是生物负载和放行失败的OOS。此外，自2018年3月以来，企业收到了至少29起关于产品一致性的投诉，以及至少129起关于缺乏疗效的投诉。这是一次重复违规。
For example, you investigated an instance of OOS high water activity in your SPF30 Baby Sunscreen Cream finished product on June 9, 2020. You determined the root cause to be moisture in the (b)(4), and implemented (b)(4) to achieve greater control of moisture in the (b)(4), subsequently closing the investigation on August 17, 2020. However, even after applying the (b)(4), you observed 30 additional OOS results for high water activity, with some batches later failing for bioburden.
例如，企业在2020年6月9日调查了SPF30婴儿防晒霜成品中OOS高水分活性的实例。企业确定根本原因是xx中的水分，并实施xx以更好地控制xx中的水分，随后于2020年8月17日结束调查。然而，即使在使用xx后，企业仍观察到30个额外的高水活度OOS结果，其中一些批次后来因生物负载而失败。
One of the subsequent 30 high water activity results occurred in your SPF35 Kids Clear Face Sunscreen Stick. Bioburden testing performed after the high water activity result showed the total aerobic microbial count failed specification at 390 cfu/mL. You rejected this lot, but your investigation did not determine the root cause of the microbial failure or extend the investigation to determine if any additional lots may have been affected. It is also concerning that you obtained OOS results for high water activity and failing results for bioburden in a product that does not appear to contain water as a component.
SPF35儿童清洁脸防晒棒含有30种高水分活度结果之一。在高水活度结果后进行的生物负荷测试显示，总需氧微生物计数未达到390 cfu/mL的标准。企业拒绝了该批次，但调查没有确定微生物失效的根本原因，也没有延伸调查以确定是否有其他批次可能受到影响。同样令人担忧的是，企业在一种似乎不含水成分的产品中获得了高水活度的OOS结果和不合格的生物负载结果。
In your response regarding the failing viscosity results, you stated that you do not consider viscosity to be a critical quality attribute. You also stated that you would amend your investigations program to ensure investigations are more thorough.
在关于粘度结果不合格的回复中，企业不认为粘度是一个关键的质量属性。还表示将修改企业的调查程序，以确保调查更加彻底。
Your response was inadequate because it discounted the significance of the viscosity specification without performing an adequate investigation into factors that caused the failures. You did not identify adequate CAPAs to resolve the potential root causes, and you did not sufficiently assess how other batches may have been compromised. Viscosity is a meaningful quality attribute for topical drug products, such as sunscreens and creams. Your range of viscosities varied substantially during the course of batch processing and may have contributed to your product complaints. Viscosity is important to drug product stability and in the application of your drug products to the skin, and should be measured using validated methods, e.g. USP <911> Viscosity.
已的回复是不充分的，因为没有对导致故障的因素进行充分的调查，就降低了粘度规格的重要性。企业没有确保足够的纠正措施来解决潜在的根本原因，也没有充分评估其他批次可能收到的影响。粘度是外用药物产品(如防晒霜和面霜)的一个有意义的质量属性。企业的粘度范围在批处理过程中变化很大，可能导致了企业的产品被投诉。粘度对于药品的稳定性和将药品应用到皮肤上非常重要，应该使用经过验证的方法进行测量，例如USP <911>粘度。
Your response regarding the high water activity results and failing bioburden results acknowledged that the documentation of your investigations was inadequate. You attributed the continued high water activity results to the same root cause of high moisture in your (b)(4) and your follow-up CAPA was to (b)(4) to the (b)(4). You also stated that you would review your investigation procedures to include an assessment of whether the identified issue could have affected other lots.
企业关于高水活度结果和失败的生物负荷结果的回复承认调查文件是不充分的。企业将持续的高水分活度结果归因于企业xx中水分高的同一根本原因，企业的后续CAPA是xx至xx。还表示，企业将审查调查程序，包括评估所发现的问题是否可能影响其他批次。
Your response was inadequate because it lacked suitable impact assessment of your many OOS and failing results on your products on the market within expiry. FDA informed you, more than two years ago, that your investigations were not enabling effective CAPAs. At the time, you made similar commitments to improve your investigation process. However, you failed to adequately improve your investigation process since then. At the time of inspection, you had not yet initiated follow-up CAPAs in response to the excessive water activity and failing bioburden results. At the time, you also stated you were exploring adding (b)(4).
企业的回复是不充分的，因为它缺乏对许多OOS和有效期内上市产品的不合格结果的适当影响评估。FDA在两年多前通知企业，调查无法实现有效的capa。当时，企业也做出了类似的承诺来改进调查流程。然而，从那以后，企业没有充分改进调查程序。在检查时，企业还没有针对过量的水活度和不合格的生物负荷结果启动后续的capa。当时，企业还表示正在探索添加(b)(4)。
In response to this letter, provide the following:
针对本函，请提供以下内容：
• A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for products currently in the U.S. market and within expiry as of the date of this letter and a report summarizing the findings of the analysis, including the following for each OOS:
•对目前在美国市场和截止本函日期仍在有效期的产品的所有无效OOS(包括在制品和放行/稳定性测试)结果进行回顾性、独立的审核，并出具一份总结分析结果的报告，包括每个OOS的以下内容:
o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.
o确定与无效OOS结果相关的科学论证和证据是否确定或非确定地证明了实验室错误是根本原因。
o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.
o对于最终确定实验室根本原因的调查，应提供理由，并确保发现易受相同或类似根本原因影响的所有其他实验室方法进行整改。
o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.
o对于回顾性审核中发现的实验室中不确定或没有发现根本原因的所有OOS结果，包括对生产的彻底审查(例如，批生产记录、生产步骤的充分性、设备/设施的适用性、原材料的可变性、工艺能力、偏差历史、投诉历史、批次失败历史)。为每次调查提供一份潜在生产根本原因的总结，以及任何生产操作的改进。
• A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include but should not be limited to addressing the following:
•对OOS结果调查系统的全面审查和整改计划。CAPA应包括但不应限于解决以下问题:
o Quality unit oversight of laboratory investigations
o质量部门监督实验室调查
o Identification of adverse laboratory control trends
o确认实验室的不利控制趋势
o Resolution of causes of laboratory variation
o实验室变化原因的解决
o Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified
o当实验室原因无法确定时，对可能的生产原因展开彻底调查
o Adequately scoping each investigation and its CAPA
o充分确定每项调查及其CAPA的范围
o Revised OOS investigation procedures with these and other remediations
o修订了包含这些和其他整改措施的OOS调查程序
CGMP Consultant
CGMP顾问
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. 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.
基于FDA发现的违规行为的性质，我们强烈建议聘请一位符合21 CFR 211.34中规定的合格顾问来帮助贵公司满足CGMP要求。使用顾问并不能减轻贵公司遵守CGMP的义务。贵公司的执行管理层仍有责任解决所有缺陷，以确保持续的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 any violations and for preventing their recurrence or the occurrence of other violations.
在这封信中引用的违规行为并不是企业设施中存在的所有违规行为的清单。企业有责任调查和确定任何违规行为的原因，并防止其再次发生或其他违规行为的发生。
Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.
请及时纠正违规行为。未能及时并充分地解决该问题可能会导致无需另行通知的监管或法律行动，包括但不限于扣押和禁令。未解决的违规行为也可能妨碍其他联邦机构授予合同。
Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.
未能解决违规问题还可能导致FDA拒绝签发出口证书。FDA可能会拒绝批准将贵公司列为药品生产商的新申请或补充申请，直到任何违规行为被完全解决，并且FDA确认企业符合CGMP。FDA可能会重新检查，以核实企业是否完成了针对任何违规行为的纠正措施。
This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
这封信告知了FDA的发现，并为企业提供解决上述缺陷的机会。收到此信后，请在15个工作日内书面回复本办公室。说明企业已经采取了何种措施来解决任何违规，并防止其再次发生。在回复这封信时，企业可以提供额外的信息供我们考虑，FDA将继续评估企业的活动和做法。如果企业不能在15个工作日内完成纠正措施，说明延迟的原因和完成计划。
Send your electronic reply to ORAPHARM1_RESPONSES@fda.hhs.gov. Your written notification should refer to Warning Letter #622318 and include FEI number 3009946959.
If you have questions regarding the content of this letter, please contact us through ORAPHARM1_RESPONSES@fda.hhs.gov, and “cc” Compliance Officer Nancy Scheraga (Nancy.Scheraga@fda.hhs.gov).
Sincerely,
/S/
Craig Swanson
Acting Program Division Director/District Director
Office of Pharmaceutical Quality Operations
Division I/New Jersey District
