翻译： JULIA来源： Julia法规翻译
Warning Letter 320-18-62 July 5, 2018
Amish Vyas
Managing Director, Baxter(Claris Injectables Ltd.)
Nr. Parimal Railway Crossing Ellisbridge, Ahmedabad- 380006 Gujarat, India
Dear Mr. Vyas:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Claris Injectables Ltd. at Ahmedabad, from July27, 2017 to August 4, 2017.
美国FDA于2017年7月27日至8月4日检查了你们印度的Claris Injectables Ltd.生产场所。
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
本警告信总结了制剂生产严重违反CGMP的行为。参见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).
由于你们的药品生产、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21U.S.C. 351(a)(2)(B)被认为是掺假药品。
We reviewed your August 25, 2017 response in detail and acknowledge receipt of your subsequent correspondence.
我们已详细审核了你公司2017年8月25日的回复。在此告知你们后续通信亦已收悉。
During our inspection, our investigators 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 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). 你公司未能彻底调查已销售和未销售产品批次或其组份所有未能解释的与质量标准的差异或不符合质量标准的情况(21 CFR 211.192)。
Your firm invalidated out-of-specification (OOS) results without adequate investigation and scientific justification. Examples include:
你公司未经充分调查和科学论证即宣布OOS结果无效。例如：
a. In January, 2017, you obtained OOS results for the (b)(4) impurity during stability testing of (b)(4) injection batches (b)(4). Your OOS investigation reports stated that the postulated cause was “poor column efficiency,” although no chromatographic abnormalities were noted and system suitability criteria were met. During the inspection, your lab management indicated that retention times, the oreticalplates, and tailing factor appeared appropriate and no specific root cause had been demonstrated. You repeated the analyses, obtained passing results, and invalidated the OOS results.
2017年1月，你们在XX注射液批号XX的稳定性测试期间得到XX杂质OOS结果。你们的OOS调查报告说假定原因是“柱效太差”，但并未注意到有色谱异常，系统适用标准也是符合的。在检查期间，你们化验室管理人员说保留时间、理论塔板数和拖尾因子显示正常，并未证明有具体的根本原因。你们重新进行了检验，得到了合格结果，并且宣布OOS结果无效。
In March, 2017, you obtained OOS results for the (b)(4) impurity during stability testing of (b)(4) injection batches (b)(4).You suspected the analyst may have incorrectly rinsed the HPLC vials. New samples prepared and tested by a second analyst using both the original column and a new column, as well as old and new vials, also yielded OOS results.Although you lacked sufficient evidence, your investigation concluded that the OOS results were due to sample vial contamination. You invalidated the OOS results after obtaining passing results from testing retain samples.
2017年3月，你们在XX注射液批号XX的稳定性测试期间得到XX杂质OOS结果。你们怀疑是化验员淋洗HPLC进样瓶错误。第二个化验员制备了新样品，使用原始柱和一支新柱，还有原始瓶与一支新进样瓶，分别进行了检测，也得到了OOS结果。尽管你们缺乏足够的证据，你们的调查仍给出结论说OOS结果是因为进样瓶污染。你们在对留样进行检验得到合格结果之后宣布了OOS结果无效。
After the conclusion of the inspection you initiated a voluntary recall of five batches of (b)(4) drug product due to failing (b)(4) levels, superpotent assays, and (b)(4), all obtained during stability testing and including batches (b)(4).
在检查出结论之后，你们启动了5批XX药品主动召回，原因是XX水平不合格、含量过高以及XX，这些都是在稳定性研究期间得到的结果，涵盖有批次XX。
Notably, you informed FDA that the apparent root cause ofthe (b)(4) assay failures was excessive (b)(4) from your (b)(4).However, the investigation lacked an adequate assessment of all other batches distributed to the U.S. and within expiry that may be potentially affected by (b)(4).
值得注意的是，你们通知FDA说XX含量不合格的明显根本原因是XX高出你们的XX。但是，该调查缺乏对所有其它可能受XX影响、已销往美国且仍在效期内的批次进行的足够评估。
b. Your OOS investigation of the failureof (b)(4) batches (b)(4) to meet the (b)(4) specifications under accelerated stability conditions was also inadequate. You obtained OOS results of (b)(4)% and (b)(4)%, respectively (specification Not More Than (b)(4)%). While the investigation lacked a demonstrated assignable root cause in the laboratory, you obtained passing results during repeat analysis and invalidated the OOS without a Phase II production investigation.
你们对XX批次XX在加速稳定性条件下不符合XX质量标准的OOS调查是不充分的。你们得到的OOS结果分别是XX%和XX%（标准为不得过XX%）。调查并未证明化验室内可归结根本原因，你们在复测中得到了合格结果，然后未进行第二阶段生产调查即宣布了OOS结果无效。
After the inspection, you recalled eight batches of (b)(4) due to superpotent assay and (b)(4) results obtained during stabilitytesting. While use of substandard (b)(4) that allow excessive (b)(4) again appears to have caused the specification failures, your response lacked sufficient relevant information on the root cause and scope of this major problem.
在检查之后，由于稳定性研究期间含量超高和XX结果，你们召回了8个XX批次。你们使用了不合标准的XX使得重复出现XX超出，导致了不符合质量标准的情况出现。你们的回复缺乏足够的根本原因方面关联信息，没有此重大问题的范围界定。
In both of the above instances, you failed to expand your OOS investigations in a timely fashion to address potential manufacturing causes. When an investigation lacks conclusive evidence of laboratory error, athorough investigation of potential manufacturing causes must be performed. Your acceptance of the passing results from testing a new set of samples basedon an unproven hypothesis was insufficient to conclude the investigations.
在上述两起事件中，你们均未能及时扩大你们的OOS调查，说明潜在的生产原因。当一个调查缺乏结论性证据证明化验室错误时，必须对潜在的生产原因进行彻底调查。你们根据一个未经证实的假设，重新检测了一套新的样品，接受了其合格结果，这样做出调查结论是不充分的。
Your response stated that you will revise your OOS Management procedure and perform a retrospective review of your OOS investigations.Your response was inadequate because it lacked identification of root causesand implementation of effective corrective actions and preventive actions (CAPA). It also failed to address inadequacies in the (b)(4) you received from your supplier(s), and whether they are still considered qualifiedfor use by your firm.
你们的回复说你们会修订你们的OOS管理程序，对你们的OOS调查实施回顾性审核。你们的回复是不充分的，因为它缺乏对根据原因的识别，以及实施有效的CAPA。它也没有解决你们从供应商处收到的XX中的不充分的情况，以及你们公司是否仍将其作为合格供应商可以使用。
Notably, your firm has had a worrisome history of recalls dueto substandard (b)(4). In 2017, you recalled (b)(4) parenteral drug products due to recurring(b)(4) complaints. In 2010, your firm conducted a Class I recall of all lots of four parenteral products due to loss of (b)(4) integrity and non-sterility.
值得注意的是，你们公司已经有过因低标准XX而召回的不良历史。在2017年，你们召回了XX注射药品，原因是重复发生的XX投诉。在2010年，你们公司对4个注射药品所有批次执行了I级召回，原因是XX完整性失败和无菌问题。
Also, while your firm has discussed adding a (b)(4) as a corrective action for (b)(4), it would not resolve ongoing issues relating to quality of container-closure raw materials or (b)(4) fabrication. Durability and quality of your large volume parenteral container-closure systems is critical to ensure their robustness until administration at a clinical facility, who will remove (b)(4), and cantemporarily store and then transfer the (b)(4) within the facility before use. Your response lacks a commitment to thoroughly review your (b)(4) dependability with respect to both container-closure raw material quality and (b)(4) fabrication process weaknesses.
还有，虽然你们公司已经讨论了增加一个XX作为XX的纠正措施，但这并不能解决持续发生的与容器密闭器原料或XX制造的质量有关问题。你们大容器注射剂容器密闭器系统的耐用性和质量对于确保其稳固性直到在临床设施里被使用是至关重要的。在临床场合，XX会被移除，可以临时存贮，然后转移至设施内的XX里直至使用。你们的回复缺乏进行对你们容器密闭器原料和XX制造工艺弱点的独立性进行彻底审核的承诺。
In response to this letter, provide:
回复此函时请提交：
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A retrospective, independent review of all invalidated OOS (in-process and finished testing) results obtained for products on the U.S. market. Assess whether the scientific justification and evidence was conclusive. For investigations that conclusively establish laboratory root cause, determine adequacy of the CAPA, and ensure that other laboratory methods vulnerable to the same root cause are identified for remediation. For any OOS results with 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, raw materials, process capability, deviation history, batch failure history).
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一份对来自在销往美国的药品检测中所有宣布无效的OOS（中控和成品检测）结果的独立的回顾性审核，评估这些科学论证和证据是否具有结论性。对于调查能得出化验室根本原因的情况，检查确定CAPA的充分性，确保识别出其它受相同根本原因影响的化验室方法并加以补救。对于所有不具有结论性的OOS结果或者是在化验室未识别出根本原因的OOS结果，包括一份对生产（例如，批生产记录、生产步骤的充分性、原料、工艺能力、偏差历史、批不合格历史）情况的深入审核。
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Provide a summary report of the retrospective review of all OOS investigations for product that remain within expiry. Include a CAPA plan that identifies manufacturing root causes and specifies meaningful improvements. Include the product name, date of the original result, initial and retest OOS results, detailed rationale for invalidating the OOS result, and the outcome of your thorough reassessment. Also, include any additional market actions you intend to initiate because of the retrospective review.
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提交一份对仍在效期内产品的所有OOS调查的回顾性审核总结报告。包括有一份CPAA计划，在其中识别出生产根本原因，指出有意义的改进，包括品名、初始结果日期、初始和复测OOS结果、详细的OOS结果调查理由，以及你们深入重新评估的结果。还有，在其中包括你们因回顾性审核而有意启动的任何其它市场措施。
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A fully remediated OOS investigation procedure, including but not limited to modifications to ensure investigations expand to manufacturing operations when a root cause is not conclusively identified in the laboratory.
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一份全面的修补过的OOS调查程序，包括但不仅限于当在化验室识别的根本原因不具有结论时，修改以确保调查扩展至生产操作。
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Updated investigation into the root cause of container-closure system failures leading to increased (b)(4).
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对容器密闭器系统失败导致XX增加根本原因调查的更新
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Testing of retain samples of batches of all drug products within expiry in the U.S. market that used the (b)(4) suppliers (i.e., raw materials, fabricators) associated with excessive (b)(4).
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所有使用了与XX超标有关的XX供应商（即原料和制造商）销往美国仍在效期内的所有药品的留样批次的检测
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A comprehensive, independent assessment of the quality of all (b)(4) container-closure raw materials (parts such as (b)(4), etc.) and adequacy of all sites who perform (b)(4) fabrication processes. This thorough assessment should also include an evaluation of the adequacy of your qualification program for suppliers of container-closure raw materials ((b)(4) part suppliers) and manufacturers of both (b)(4) and (b)(4).
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一份对所有XX容器密闭器原料（部件如XX等）质量，以及执行XX制造工艺的所有场所的充分性的全面独立评估。该深入评估还应包括一份对你们容器密闭器原料供应商（XX部件供应商）以及XX和XX生产商的确认程序的充分性的评估。
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A full description of your (b)(4) material sourcing process and (b)(4) manufacturing process for both (b)(4) and (b)(4). Include the roles and responsibilities of all parties involved in the (b)(4) supply chain and production. Specifically, for all lot of (b)(4) produced since July 1, 2015, provide a detailed summary of all suppliers and manufacturers that you used for your (b)(4) materials, and vendor lot numbers. In each case describe who performed the (b)(4) formation, fabrication, and final assembly (including the specific nature of any in-house operations, such as use of (b)(4) operations). Include any subcontractors or other parties involved with material supply or fabrication.
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一份对你们XX和XX的XX原料来源工艺和XX生产工艺的全面描述，包括XX供应链与生产中涉及的各方职责。特别是自2015年7月1日以来生产的所有批次，需要提交一份你们XX原料所用所有供应商和生产商的详细汇总，以及供应商批号。在每条信息中写明是谁执行了XX成型、制造和最终组装（包括所有内部操作的特定属性，如使用XX操作）。包括所有物料供应或制造所涉及的分包商或其它各方。
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Vendor-generated Certificates of Analysis (COA) for (b)(4) part manufacturers and suppliers, as well as (b)(4) fabricators and assemblers.
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中间商为XX部件生产商和供应商制作的COA，以及XX制造商和装配商。
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An assessment of your overall system for investigations into deviations, discrepancies, complaints, OOS results, and failures. Your CAPA plan should include, but not be limited to, improved rigor in reviewing the sources of variation in your operation that may cause deviations, failures, or defects, as well as an extensive remediation of your capabilities to ensure CAPA effectiveness.
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一份对你们偏差调查、不符合调查、投诉调查、OOS结果调查和失败市井的整体系统的评估。你们的CAPA计划应包括但不仅限于提高可能引发偏差、失败、或缺陷的操作波动来源审核的严格程序，以及对在扩大范围内对你们能力进行补救，从而确保CAPA有效性。
2. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).你公司未能制订批生产和批检验记录，在其中放入与所生产的每批药品生产和检验有关的完整信息（21 CFR 211.188）。
Our investigator observed an operator recording unreliable data. Specifically, on July 27, 2017, our investigator observed your operator entering datain your Visual Inspection Test(VIT) For (b)(4) Line document for (b)(4) injection,USP, batch (b)(4) a day after the operation was completed. The document stated that the visual inspections were performed on July 26, 2017. In responseto our question regarding how portions of the documentation had been completed without corresponding data, a senior manager at your site could not provide an explanation.
我们的调查人员发现一名操作工正在记录不可靠的数据。具体情况是，2017年7月27日，我们的调查人员发现你们的操作工在操作结束之后一天进入你们XX注射剂USP批号XX的XX文件中灯检（VIT）数据。在回答我们关于文件端口在没有相应数据情况下是如何结束的问题时，你们工厂的一位高级经理无法做出解释。
We acknowledge your efforts to update SOPs and retrain personnel. However, your response is inadequate because you did not perform a retrospective assessment into other possible events in which data were not reported accurately or contemporaneously.
我们了解你们努力更新SOP并重新培训了员工。但是，你们的回复是不充分的，因为你们并未对其它可能存在的未准确或未同步报告数据事件进行回顾性评估。
In response to this letter, provide:在回复此函时请提交：
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A comprehensive, independent risk assessment of production records including but not limited to your visual inspection documentation to determine the completeness, consistency, and accuracy of reported data. Indicate how you determined that the data you used to release product was attributable, legible, contemporaneously recorded, original or a true copy, and accurate. Include a re-examination of retain samples.一份对生产记录的完整独立风险评估，包括但不仅限于你们目视检查文件记录以确定所报告数据的完整性、一致性和准确性。说明你们是如何确定你们用于放行产品的数据是可追溯、清晰、同步记录、原始或真实副本，以及准确的。要包括对留样的复检。
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Provide a complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates documentation practices, and ensures you retain complete, contemporaneously prepared, and accurate records.请提交一份在你们生产和化验室操作中所用的文件记录体系的完整评估，以确定哪些文件记录做法是不充分的。包括一份详细的全面补救文件记录做法的CAPA计划，并且确保你们会保存完整的、同步制作和准确的记录。
3. Your firm failed to maintain buildings used in the manufacture, processing, packing or holding of drug products in a good state of repair (21 CFR 211.58).你公司未能维护用于药品生产、加工、包装或存贮的建筑物使其处于良好的修理状态(21 CFR 211.58)。
Our investigators observed significant evidence of waterdamage in your facility, including warped ceiling panels, puddles of water, and water stains. For example, water damage was evident over the (b)(4), and in sky lights, vents, and ceilings above the finished drug product packaging area and in the personnel corridor outside the Quality Control laboratory.
我们的调查人员在你们的工厂发现了严重的水损证据，包括有天花板变形、水洼和水渍。例如，水损痕迹到处都是：XX上面、天窗、排气和制剂包装区域的天花板以及QC化验室外面的人员通道。
In addition, our investigators observed ceiling panels overthe personnel corridor and (b)(4) that were not sealed, allowing ingress of air from the building’s plenum into post-sterilization areas.
此外，我们调查人员还发现人员通道上的天花板以及XX并未密封，使得空气可以从建筑气窗进入至已灭菌的区域。
It is essential that your plant management maintains the facility in a good state of repair to ensure ongoing suitability for drug manufacturing.
你们工厂的管理人员有必要维护设施使其处于良好的维护状态，以确保其持续适合用于药品生产。
In your response, you attribute the water damage to monsoon rains that fell in the days prior to the inspection. However, the observed staining, rusting pipes, and warping of walls and ceiling panels appeared to indicate the presence of longer-term water and humidity problems in somecases.Your response focuses on water leak repairs and some enhanced preventive measures. However, it does not adequately address production management’s daily responsibilities to promptly address facility damage and the potential for fungal contamination to persist in the facility due to moisture problems.
在你们的回复中，人们将水损归咎于检查之前多日雨季降雨。但是，所发现的脏污生锈的管道，以及墙面和天花板变形说明在多处均长期存在有水，还有湿度问题。你们的回复关注于漏水维修，以及一些加强维护的措施。但是，这并不能充分解决生产管理的日常职责问题，未能积极解决工厂毁坏问题以及由于湿气问题导致的工厂内可能顽固存在的霉菌污染问题。
In response to this letter, provide:
在回复此函时请提交：
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A comprehensive, independent review of your preventive maintenance program(s) for both facilities and equipment, and a CAPA plan to ensure its effectiveness. Your plan should include but not be limited to contingencies for expected seasonal fluctuations in rainfall.一份对你们设施和设备预防性维护计划的全面独立的审核，以及一份确保其有效性的CAPA计划。你们的计划应包括但不仅限于预期雨季发生时的偶然季节波动
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A CAPA plan that formalizes routine, vigilant production management oversight of facility conditions to assure prompt detection of issues, execution of repairs, and other appropriate actions.一份CAPA计划，其中将对设施状态的日常警戒生产管理监管形成正式文件，以确保积极发现问题、执行修理以及其它适当的措施
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Your plan to monitor and control humidity levels in the facility to prevent major environmental control issues due to fungi and other microbial contaminants, which were associated with past product recalls by your firm. Also, explain how your will ensure prompt detection of fungi in the facility.你们对设施中湿度水平的监测和控制计划，以防止由于霉菌和其它微生物污染引起重大环境控制问题，这曾经导致过去你们公司执行产品召回。还有请解释你们要如何确保对工厂内霉菌的主动发现。
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Your plan to requalify the facility after remediating the water damage, including your environmental qualification strategy.在修复水损之后，你们重新确认设施的计划，包括你们的环境确认策略
Data Integrity Remediation数据完整性弥补措施
Your quality system does not adequately ensure the accuracyand integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. In response to this letter provide the following.
你们的质量体系不能充分确保数据的准确性和完整性，无法支持你们生产的药品的安全性、有效性和质量。在回复此函时请提交以下资料：
A. A comprehensive investigation into the extent ofthe inaccuracies in data, records, and reporting, including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.一份对数据记录和报告不准确性程度的全面调查，包括销售至美国的药品数据审核的结果，包括对你们数据完整性问题范围与根本原因的详细描述。
B. A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should nclude analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations.对你们药品质量中所发现的不合格情况的潜在影响的当前风险评估。你们的评估应包括由于受到数据完整性问题影响的药品放行导致的患者风险的分析，以及持续运营所具有的风险。
C. A management strategy for your firm that includesthe details of your global corrective action and preventive action plan. The detailed corrective action plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm, including microbiological and analytical data, manufacturing records, and all data submitted to FDA.你们公司的管理策略，包括你们全球CAPA计划详细情况。详细的纠正措施计划应说明你们准备如何确保你们公司产生的所有数据的可靠性和完整性，包括微生物和分析数据、生产记录，以及所有提交给FDA的数据。
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 as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. We also recommend that the qualified third party perform a comprehensive audit of your entire operation for CGMP compliance, and evaluate the completion and effectiveness of any corrective actions and preventive actions.
依据我们在你们工厂发现的违规情况，我们强烈建议你们使用一位有资质的顾问来协助你们公司符合CGMP要求。我们还建议具备资质的第三方对你们的所有操作进行一次全面的CGMP合规审计，并且评估所有CAPA的有效性和完成情况。
Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
你们使用顾问并不解除你们公司符合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。
Repeat Violations at Facility and Meeting With FDA工厂重复违规以及与FDA的会议
FDA cited similar CGMP violations in a previous warning letter (WL 320-11-003) of November 1, 2010. You proposed specific remediationfor these violations in your response. The repeated serious violations at your facility demonstrate that your facility’s oversight and control over the manufacture of drugs is inadequate.
FDA在以前2010年11月1日的警告信（WL320-11-03）中引用了类似的CGMP违规情况。你们在回复中对这些违规行为拟定了具体的弥补措施。在你们工厂发现的重复的严重违规证明你们工厂对药品生产的监管和控制是不充分的。
In particular, our warning letters discuss the history of recurring serious defects in your marketed (b)(4) products, including but not limited to non-sterile(b)(4) with visible contamination, (b)(4),and other evidence of lost integrity, and most recently quality issues relatingto assay, impurities, and (b)(4). These issues have been exacerbated bythe lack of prompt identification and appropriate remediation, and FDA intervention has generally been necessary for your firm to adequately investigate and remove the defective products from distribution
尤其是我们的警告信讨论了你们上市的XX药品中重复发生的严重缺陷历史，包括但不仅限于非无菌XX的可见污染，XX，以及其它完整性缺失的证据，和大多数据最近发生的与含量、杂质和XX有关的质量问题。这些问题已经由于缺乏积极识别和适当弥补而更加严重，并且FDA的干预通常对于你们公司充分调查和从销售中清除有缺陷的药品是很有必要的。
FDA is aware that Baxter acquired this facility the same day the inspection started. We request that you contact Tramara Dam, by e-mail atTramara.Dam@fda.hhs.gov, within five days of receipt of this letter to schedulea regulatory meeting. Please come prepared to discuss Baxter’s comprehensive remediation plans for this facility.
FDA了解百特于检查开始日正好收购了此工厂。我们要求你们在收到此函5日内通过电子邮件Tramara.Dam@fda.hhs.gov联络TramaraDam，安排一次法规会议。请做好准备来讨论百特对此工厂的全面补救计划。
Conclusion 结论
Violations in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing 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。
If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests thatyou contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effectiveway to bring your operations into compliance with the law. Contacting the DrugShortages Staff also allows you to meet any obligations you may have to reportdis continuances or interruptions in your drug manufacture under 21 U.S.C.356C(b) and allows FDA to consider, as soon as possible, what actions, if any,may be needed to avoid shortages and protect the health of patients who dependon your products.
如果你们在考虑要采取的措施可能会导致你们工厂所生产的药品供应中断，FDA要求你立即联系CDER药品短缺负责人员，这样FDA可以与你们一起采用最为高效的方式引导你们的操作符合法规要求。联系药品短缺负责人员还能让你满足依据21U.S.C. 356C(b)你可能必须报告你们药品中止或中断的义务，让FDA尽快考虑是否需要采取何种措施来避免短缺，保护依赖于你们药品的患者健康。
Until you correct all violations completely and we confirmyour compliance with CGMP, FDA may withhold approval of any new applications orsupplements 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的新申报和增补申报的批准。
Failure to correct these violations may also result in FDArefusing admission of articles manufactured at Claris Injectables Ltd. atAhmedabad, into the United States under section 801(a)(3) of the FD&C Act,21 U.S.C. 381(a)(3). Under the same authority, articles may be subject torefusal of admission, in that the methods and controls used in theirmanufacture 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 inwriting within 15 working days. Specify what you have done since our inspectionto correct your violations and to prevent their recurrence. If you cannotcomplete corrective actions within 15 working days, state your reasons fordelay and your schedule for completion.
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。
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:
Carlos M. González, PhD
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Please identify your response with FEI 3004610460.
Sincerely,
/S/
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Jose E. Almeida
Chairman, President and Chief Executive Officer
Baxter International Inc.
One Baxter Parkway
Deerfield, IL 60015
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