今天是:

实验室资讯网

FDA发布警告信强调质量部权力

实验室资讯网时间:2018-02-11 点击: 百度搜索

【导读】近日,FDA发布警告信谴责某公司的质量部门 没有全面履行其权力和/或职责 。并 要求公司必须为质量部门提供适当的权力、足够的资源和人员来履行其职责,持续确保药品质量 。 该公司缺陷......
TAG标签: FDA 警告信 强调质量部权力 质量部

近日,FDA发布警告信谴责某公司的质量部门没有全面履行其权力和/或职责。并要求公司必须为质量部门提供适当的权力、足够的资源和人员来履行其职责,持续确保药品质量。 

 

该公司缺陷还包括如下:

·        未对偏差/稳定性失败进行调查

·        工艺还在摸索,但已进行商业生产并放行

·        工艺验证不充分

·        未分析工艺波动的来源

·        仅仅用一批工艺确认来证实工艺,未证实工艺重现性

·        稳定性失败但是未采取适当的措施

·        质量部门权力不足

 

警告信相关缺陷摘译如下:

 

1.      Your firm failed tothoroughly investigate any unexplained discrepancy or failure of a batch or anyof its components to meet any of its specifications, whether or not the batchhas already been distributed (21 CFR 211.192).  

你公司未能彻底调查所有已放行和未放行的批次或其成分任何不明原因的不合格或异常(21 CFR211.192)。 

 

You failed tothoroughly investigate release and stability testing failures concerning twobatches of your (b)(4) drug products. These product failures includedviscosity and appearance. During stability testing, you also identifiedpackaging defects. You did not initiate investigations for each of these drugquality issues. When you did investigate, you failed to adequately evaluate themanufacturing process and associated records, identify root causes, andimplement effective corrective actions and preventive actions (CAPA). 

你未能彻底调查2批XX药品的放行和稳定性测试失败。这些产品失败包括粘度和外观。在稳定性测试中,你们还发现了包装缺陷。你们未对这些药品的所有质量问题发起调查。在你们调查时,你们未能充分评估生产工艺和相关记录,识别出根本原因,以及实施有效的纠正措施和预防措施(CAPA)。 

 

For example, youfound tubes swelling at the 3-month stability time point. You did not investigatethis significant defect, which can be indicative of microbial growth andspoilage. Notably, your packaging stability specification requires “no change inpackaging.” 

例如,你们在3个月稳定性时间点发现管膨胀。你们未调查此重大缺陷,这可能是微生物滋生和腐败的现象。尤其是你们的包装稳定性标准要求“包装不得发生变化”。 

 

In response to ourfindings, your customer recalled the remaining in-date batch of this product onNovember 28, 2017.

在回复此缺陷时,你们的客户于2017年11月28日召回了当时剩余的该药品。 

 

For more informationabout handling failing, out-of-specification, out-of-trend, or other unexpectedresults and documentation of your investigations, see FDA’s guidance document, InvestigatingOut-of-Specification (OOS) Test Results for Pharmaceutical Production, athttps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070287.pdf. 

关于处理不合格、OOS、OOT和其它非预期结果以及记录你们调查的更多信息,参见FDA指南文件“药品生产中OOS结果调查”。 

 

2.      Your firm failed toestablish adequate written procedures for production and process controldesigned to assure that the drug products you manufacture have the identity,strength, quality, and purity they purport or are represented to possess (21CFR 211.100(a)).  

你公司未能为生产和工艺控制建立书面程序,以确保你们生产的药品具备其鉴别、含量、质量和纯度(21 CFR211.100(a))。 

 

The processes used tomanufacture your (b)(4) drug products have not been shown to beconsistent and reliable, and consequently batches of your drug products arelikely to significantly vary in strength, quality, and purity. 

用于生产你们的XX药品的工艺未显示出其一致性和可靠性,你们药品的后续批次可能会在含量、质量和纯度方面有重大变异。 

 

For example, you lackedadequate process validation studies. Your validation report summarized aretrospective analysis of a single process qualification batch, (b)(4).You manufactured and released this batch in 2015.Notably, testing of this batchfound stability failures of multiple quality attributes, including appearanceand viscosity. Your validation report was approved on March 17, 2017, shortlybefore we inspected your facility. You lack evidence of process validationbecause you have not addressed all potential sources of variation that must becontrolled to consistently yield drugs of uniform character and quality, andhave not demonstrated that the process is reproducible. 

例如,你们缺乏足够的工艺验证研究。你们的验证报告总结了对XX单个工艺确认批准的回顾性分析。你们在2015后生产放行了该批次。特别是对该批次的检测发现多个质量属性稳定性失败,包括外观和粘度。你们的验证报告于2017年3月17日批准,就在我们检查你们工厂前不久。你们缺乏工艺验证证据,因为你们未说明所有潜在的波动来源,这些必须受控以持续产出均一属性和质量的药品,且未证明工艺是可重复的。 

 

Senior managementstated that your firm has struggled with manufacturing this drug product, andthat you were still conducting research to gain better product and processunderstanding. Although you acknowledged a lack of understanding to assureconsistent quality, you still commercially distributed (b)(4) drugproducts to consumers. 

高级管理人员称你们公司在为该药品生产而努力,你们仍在进行研究以获得更好的产品和工艺了解。尽管你们知道在如何确保一致质量方面还缺乏了解,但你们还是商业化销售了XX药品给消费者。 

 

Each significantstage of a manufacturing process must be designed to assure that raw materialinputs, in-process materials, and finished drugs meet their quality attributesand specifications. Process validation evaluates the soundness of design andstate of control of a process throughout its lifecycle. Process qualificationstudies provide a determination whether an initial state of control has beenestablished. Successful process qualification studies are required prior tocommercial distribution. Thereafter, ongoing vigilant oversight of processperformance and product quality is essential to ensure you maintain a stablemanufacturing operation throughout the product lifecycle. 

生产工艺的每个重大阶段都必须设计以确保原料输入、中间体和制剂成品符合其质量属性和标准。工艺验证评估一个工艺在其生命周期内的设计合理性和受控状态。工艺验证研究能确定是否已建立起初始的受控状态。在商业化销售之前要求有成功的工艺确认研究。之后,对工艺性能和产品质量要有持续的警惕监管,以确保你们在产品生命周期中维持稳定性的生产操作。 

 

See FDA’s guidance document, ProcessValidation: General Principles and Practices, for general principles and approaches that FDA considers appropriate elements of process validation, athttps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070336.pdf. 

参见FDA指南文件“工艺验证:通则和规范”。 

 

3.      Your firm failed tofollow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR211.166(a)).  

你公司未能遵守充分的书面检测程序,以评估药品的稳定性特性,并使用此类稳定性测试结果来确定适当的存贮条件和有效期(21 CFR211.166(a))。 

 

You did not haveadequate stability data to demonstrate that the chemical and physicalproperties of your (b)(4) drug products remain acceptable throughout thelabeled (b)(4) expiry period. Two lots reviewed during our inspectionfailed on stability at various tests and time points. You distributed these twolots of (b)(4) drug products to the U.S. 

你们没有足够的稳定性数据证明你们XX药品的理化特性在标示的XX有效期内保持可接受。在我们检查期间所审核的2批稳定性试验多个检测和时间点失败。你们将XX药品的这2批销往了美国。 

 

Batch (b)(4)failed for viscosity at multiple time points, and you terminated the stabilitystudy for batch (b)(4) after you identified phase separation in allsamples at the 9-month time point. 

批次XX在多个时间点粘度不合格,你们在发现所有样品在9个月时间点都有相分离现象时终止了批次XX的稳定性研究。 

 

At the time of theinspection, you had not taken appropriate action on these batches, such asnotifying your customer or recalling products from the market. 

在检查期间,你们未对这些批次采取适当的措施,例如通知你们的客户或从市场上召回产品。 

 

Inadequate Response  

回复不充分 

 

Your April 13, 2017,response to FDA’s inspectional observations wasinadequate. You did not provide sufficient evidence that you are takingcorrective actions to bring your operations into full compliance with CGMP. Inresponse to this letter, provide the following: 

你们于2017年4月13日提交针对FDA检查缺陷的回复是不充分的。你们未提交充分的证据证明你们正在采取纠正措施使得你们的操作全面符合CGMP要求。在回复此函时,请提交以下: 

 

A summary of the actions you     have taken to comprehensively remediate your investigation process, and an     improved procedure. 

你们已采取的全面弥补你们调查流程和改进程序的措施摘要

 

Your investigations, using your revised procedures, for all drug quality related failures. A detailed summary of your review of all test results, root causes of specification failures, affected batches distributed to the U.S. market, and related CAPA.

采用你们修订后的程序对所有药品质量相关失败进行的调查。你们对所有检测结果、不合格根本原因、受影响销往美国的批次和相关CAPA的审核摘要

 

A data-driven and scientifically sound process validation program that appropriately identifies sources of variability, and ensures oversight of intra-batch and inter-batch variation on an ongoing basis throughout the product lifecycle.

数据驱动的科学合理工艺验证计划,适当识别差异来源,确保在产品生命周期中对批内和批间差异的持续监管

 

Timelines for performing prospective process qualification for your drug products.

对你们药品实施前瞻性工艺确认的时间表

 

A procedure describing your stability program.

描述你们稳定性试验计划的程序

 

Data for (b)(4) batches successfully manufactured as part of prospective qualification     studies, to demonstrate that these batches are stable over the shelf life.

作为前瞻性确认研究的一部分的XX批次成功生产的数据,以证明这些批次在货架期内是稳定性

 

The disposition of (b)(4) batch (b)(4), including whether you plan to distribute it in the     U.S.

对XX批XX的处置,包括你们是否计划在美国销售

 

Data to demonstrate that your (b)(4)Test–BP method used to test drug products marketed in the U.S.is equivalent to, or better than, the current USP (b)(4)Test.

证明你们用于检测销往美国的药品的XX测试-BP方法等同于或优于当前USP的XX检测的数据

 

A thorough assessment of your adherence to CGMP requirements, and a CAPA plan to assure full remediation. 

对你们遵循CGMP要求的彻底评估,以及确保全面弥补的CAPA计划

 

You shouldcomprehensively address each of these items in your written response. 

你应在书面回复中全面说明每个项目。 

 

Quality UnitAuthority  

质量部门权力 

 

Significant findingsin this letter indicate that your quality unit is not fully exercising itsauthority and/or responsibilities. Your firm must provide the quality unit withappropriate authority, sufficient resources, and staff to carry out itsresponsibilities and consistently ensure drug quality. 

在此函中的重大缺陷显示出你们质量部门没有全面履行其权力和/或职责。你公司必须为质量部门提供适当的权力、足够的资源和人员来履行其职责,持续确保药品质量。 

 

Responsibilities as acontractor  

作为合同商的职责 

 

Drugs must bemanufactured in conformance with CGMP. FDA is aware that many drugmanufacturers use independent contractors, such as production facilities,testing laboratories, packagers, and labelers. FDA regards contractors asextensions of the manufacturer. 

药品生产必须符合CGMP。FDA明白许多药品生产商使用独立的合同商,例如生产场所、检测实验室、包装商和贴标商。FDA认为合同生产商是生产商的延伸。 

 

You and yourcustomer, (b)(4), have a quality agreement for the manufacture of (b)(4)drug products. You are responsible for the quality of drugs you produce asa contract facility, regardless of agreements in place with product owners. Youare required to ensure that drugs are made in accordance with section501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, andpurity. See FDA’s guidance document, ContractManufacturing Arrangements for Drugs: Quality Agreements, at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM353925.pdf. 

你和你的客户XX有XX药品生产的质量协议。虽然你们与药品所有者签有协议,但作为合同场所,你们对你们所生产的质量负有责任。你们应确保药品生产符合FDCA第501(a)(2)(B)部分对安全性、鉴别、剂量、质量和纯度的要求。参见FDA指南文件“药品合同生产安排:质量协议”。

(本文来源:GMP办公室 )

(责任编辑:Labtoday)

引用地址:

TAG标签: FDA 警告信 强调质量部权力 质量部
顶一下
(1)
100%
踩一下
(0)
0%
免责声明: 除标明《实验室资讯网》原创外,本网部分文章转载自其它媒体,转载目的在于传递更多信息, 并不代表本网赞同其观点和对其真实性负责,且不承担此类作品侵权行为的直接责任及连带责任。 如其他媒体、网站或个人从本网下载使用,自负版权等法律责任。如涉及作品内容、版权和其它问题, 请在30日内与本网联系,我们将在第一时间删除内容!
------分隔线----------------------------
发表评论
请自觉遵守互联网相关的政策法规,严禁发布色情、暴力、反动的言论。
评价:
表情:
用户名: 验证码:点击我更换图片
栏目列表
推荐内容