【FDA警告信】 320-18-46 墨西哥Degasa

翻江鼠

警告信编号	320-18-46
检查公司	墨西哥Degasa
检查时间	2017年9月4-8日
缺陷项
1.      Your firm does nothave, for each batch of drug product, appropriate laboratory testing, as necessary, of each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(b)). 你公司为对每批药品进行适当的化验室检测，必要时，检测需要无致病菌的药品(21 CFR 211.165(b))。 Your firm failed to implement adequate microbial testing for your drug products. For example, your povidone-iodine antiseptic products are intended for significant indications such as “(b)(4),”“preparation of skin prior to surgery,” “prevent infection in minor cuts,scrapes, and burns,” “(b)(4),” and “helps to reduce bacteria that can potentially cause skin infection.” You lacked testing of these products for microbial attributes, including absence of objectionable microbial contamination, or sterility, where appropriate. 你公司未能对你们的药品执行充分的微生物检测。例如，你们的聚维酮碘抗菌药品用于严重症状如“XX”、“外科手术前皮肤消毒”、“防止小刀口、擦伤和烧伤引发的感染”、“XX”以及“帮助减少可能导致皮肤感染的细菌”。你们对这些产品缺少微生物特性检测，包括无致病菌污染或无菌性（适当时）。 It is essential that your drug products are producedin a manner that is suitable for their intended uses and that each batch is tested for conformance to appropriate microbial quality specifications. 你们的药品生产方式应适合其既定用途，每个批次应检测其是否符合适当的微生物质量标准。 In your response to this letter, address the following: 在你们对此函的回复中，请提交以下内容： An action plan for promptly testing retain samples of all batches in the U.S. market that are still within expiry to determine their microbial quality. These tests should be performed and results provided to the FDA within 30 days of receipt of this letter. Include complete analytical records for each of these tests, and full information on the name and location of the testing laboratory performing the analyses. If any test results reveal that you released drug products that did not meet appropriate microbial specifications, specify the corrective actions you have taken or will take, including notifying customers or recalling products. 一份行动计划，立即检测所有仍在美国市场且在有效期内的批次留样以确定其微生物质量。应在收到此函30日内即执行这些检测，并将结果提交给FDA，并包括这些检测的完整分析记录，以及实施检测的实验室名称和位置。如果所有检测结果揭示出你们所放行的药品不符合适当的微生物标准，请说明你们已采取或将要采取的纠正措施，包括通知客户或召回产品。 For each of your drug products, provide microbiological test methods and finished product release specifications for microbiological quality. Include tests for either microbial limits (i.e., total counts and objectionable microbes) or sterility, depending on the intended use of the product. 请提交每种药品的微生物检测方法和药品放行的微生物质量标准，包括微生物限度（即总计数和致病菌）或无菌性检测，依药品既定用途而定。 Provide validation studies for each microbiological testing method (e.g., microbial limits, sterility, antimicrobial effectiveness) used for your drug products. 提交你们药品所用每个微生物检测方法的验证研究（例如，微生物限度、无菌性、抗菌效果）。 Provide an independent, comprehensive assessment of the manufacturing operations used to manufacture each of your topical drug products, with special emphasis on material inputs, enhanced bioburden controls, and contamination prevention. 提交一份用于生产每个局部用药生产所用生产操作的独立全面评估，特别要强调物料输入、增强的生物负载控制和污染防止。 2.      Your firm failed toensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards(21 CFR 211.194(a)). 你公司未能确保化验室记录中包括从所有必须检测中生成的完整数据，以确保其符合既定规格和标准(21 CFR 211.194(a))。 Your firm was unable to provide complete raw data related to the qualification of your “(b)(4)” water system. You lacked basic information (including missing sanitization data) to assess water system performance. According to your employee, half the data you generated over ayear was lost. 你公司未能提供与你们的XX水系统确认相关的完整原始数据。你们缺少基本信息（包括缺失消毒数据）以评估水系统性能。根据你们员工的说法，你们生成的一年多数据中有一半都丢失了。 Your laboratory also lacked data such as weight of samples, test methods, records of calculations performed, standards used for release of final products, and water monitoring data. 你们化验室还缺少数据如样品重量、检测方法、所执行的计算记录、放行最终产品所用标准和水监测数据。 Our inspection also indicated that your water systemis not suitable for its intended use. Specifically, our findings indicate that your water system was not appropriately designed, controlled, and maintained to consistently produce high-purity water. 我们的检查还显示你们的水系统并不适合其既定用途。具体来说，我们发现的缺陷显示你们的水系统未经适当设计、控制和维护以持续产出高纯水。 Water is a major ingredient in your drug products. Itis essential that you employ a water system that is robustly designed, and that you effectively control, maintain, and monitor the system to ensure it consistently produces water suitable for pharmaceutical use that conforms tothe USP monograph for purified water and appropriate microbial standards. 水是你们药品中的主要成分。你们使用经过良好设计的水系统、对其进行有效控制、维护和监测以确保其持续产出适合药用符合USP纯化水和适当微生物标准的水是很重要的。 We acknowledge your commitment to update your procedure for laboratory records. However, you did not address how you will assure that procedures are appropriate, properly implemented, and followed. You also did not adequately address the impact of your insufficient data on decisions made by your firm regarding manufacturing and product quality. 我们知晓你们承诺要更新你们化验室记录的程序。但是，你们并未说明要如何确保该程序会恰当地实施和被遵守。你们亦未充分说明你们不充分的数据对生产和产品质量方面所做决策的影响。 In your response to this letter, provide the following: 在回复此函时，请提交以下内容： A comprehensive independent evaluation of the water system design, including a thorough corrective action and preventive action plan (CAPA) to install and validate a suitable water system. 一份全面独立的水系统设计评估，包括一份安装和验证适当的水系统的彻底的CAPA。 An effective program for ongoing control, maintenance, and routine monitoring that ensures the remediated system consistently produces water that meets USP Purified Water monograph specifications and appropriate microbial limits. Regarding the latter, your topical products necessitate significantly tighter total count action limits than those currently used by your firm. 一份有效的持续控制、维护和日常监测的有效计划，确保所弥补的系统会持续产出符合USP纯化水各论质量标准和适当的微生物限度的水。关于后者，你们的局部用药需要比你们公司目前所用总计数行动限严的多的限度。 Investigation of the missing water system data, including root causes, and your CAPA plan. Include a risk assessment of the impact on product quality of using water from this system in the manufacture of your drug products. 缺少水系统数据的调查，包括根本原因和你们的CAPA计划。包括一份在你们药品生产中使用该系统中产出水对产品质量影响的风险评估。 A retrospective review of both in-process and finished product test results to determine where product quality may have been compromised due to your practice of not maintaining complete analytical data. 一份对中控和成品检测结果的回顾性审核，以确定是否因为你们未维护完整分析数据的做法导致了产品质量受损。 A comprehensive assessment of the documentation systems used throughout your manufacturing and laboratory operations to determine where else you lack complete records. Include a detailed CAPA plan with systemic remediations to assure your facility maintains complete records. The CAPA should include, but not be limited to, revised procedures, training, and systemic actions implemented to assure integrity of all CGMP records. 一份生产和检测所用全面文件体系的评估，以确定你们还有其它方面是否缺少完整的记录。包括一份系统性补救的详细CAPA计划，确保你们工厂保持完整的记录。CAPA应包括但不仅限于修订程序、培训、所实施的系统性措施以确保所有CGMP记录的完整性。 Quality Unit Authority 质量部门权力 Significant findings in this letter indicate that your quality unit is not able to fully exercise its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority, sufficient resources, and staff to carry out its responsibilities and consistently ensure drug quality. 本函中的严重缺陷显示你们质量部门未能全面履行其权力和/或职责。你们公司必须为质量部门提供恰当的权力、足够的资源和人员来履行其职责，持续确保药品质量。

本文摘自 OurGMP

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