1、2012 年中国医疗器械企业 FDA 警告信一览表2012/8/16 updatedDate Company1 01/13/20122 02/14/20123 02/23/20124 03/20/20125 03/27/20126 05/09/20127 06/18/20128 06/27/20129 06/27/201210 7/16/12注：2011 年收到 FDA 警告信约 7 家, 其中台湾 2 家，香港 1 家信息系统及技术调研系统，01/13/2012 对照南京微创做的不足之处，及改进措施只有部分灭菌柜进行了过程确认且 PQ 报告中的要求和常规要求不一致方案中要求放置一定数量的xx
2、 而实际未放置1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process is validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). For example:当过程结果不能通过后
3、续检验或测试来验证的过程需要确认，过程确认要依据批准的相关程序进行，例如： Your facility has (b)(4) chambers, of which (b)(4) are currently operational, for sterilization of syringe products. The annual sterilization process validation, conducted in 2011, was conducted only on chamber (b)(4) No validations were conducted on the remaini
4、ng chambers. Your firm provided a performance qualification report for the sterilization process. This report indicates that the process flow for the sterilization cycle for the sterilization validation conducted in 2011 requires (b)(4) in a (b)(4) for (b)(4) The (b)(4) actual time was (b)(4) Furthe
5、rmore, the (b)(4) was not yet operational at the time of the inspection.你们公司目前用于注射器灭菌使用的灭菌柜，仅有(b)(4) 灭菌柜在 2011 年进行年度灭菌过程确认，但其它灭菌柜没有进行灭菌确认。你们公司提供了灭菌过程性能确认报告，报告中显示(b)(4) 灭菌柜的灭菌确认周期，但实际上，未在要求的时间内进行确认。 The annual sterilization validation protocol that your firm used for the sterilization validation cond
6、ucted in 2011 requires the placement of (b)(4) and (b)(4) in each of the loads when performing the sterilization validation. Only (b)(4) and (b)(4) were placed in the load for the sterilization validation cycles run in 2011.你们公司 2011 年的年度灭菌确认方案中，要求在进行灭菌确认时放置一定数量的 XX，而实际上未放置CAPA, 几份capa 报告上说明有效，但无相关文
7、件证明2. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, your CAPA No.s 1101 -01, 1102-01, 1103-01, 1107-01, and 1108-01 were all marked as effective, but there was no documentation to show that co
8、rrective and preventive actions had been implemented.没有建立和维护适当的纠正预防措施实施程序，例如：你们 5 份 CAPA 报告都说明是有效的，但是没有文件证明，纠正预防措施已被实施。无设计变更程序3. Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes be
9、fore their implementation, as required by 21 CFR 820.30(i). For example, your firm did not have procedures for design changes.没有建立和维持设计变更程序，确保在实施变更前，进行识别，记录，确认或验证，评审和批准设计的变更。例如：你们公司没有设计变更程序。未能确保设备得到校准、检查和维护4. Failure to adequately establish and maintain procedures to ensure that equipment is routine
10、ly calibrated. Inspected, checked, and maintained, as required by 21 CFR 820.72(a). For example: (b)(4)没有建立和维持适当的程序以确保设备得到校准、检查和维护。例如：(b)(4) 灭菌柜审核计划包括xx，但实际未包含5. Failure to adequately conduct quality audits to assure that the quality system is in compliance with the established quality system requir
11、ements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firms audit plan for 2011 includes requirements for auditing the production area for requirement numbers 8.2.3, 7.5.4, and 7.5.5. The audit of the production area, conducted on September
12、2011, did not include coverage of areas 8.2.3, 7.5.4 or 7.5.5, which were identified in the audit plan as being required.没有进行适当的质量审核以确保质量体系是符合已建立的质量体系的要求，并确质量体系的有效性。例如：你们公司 2011 年审核计划中要求在 2011 年 9 月审核生产区域，其审核项包含 XX条款，但实际上审核时未包含 XX 条款。DHR 未包括或者引用证明器械按照DMR 和标识生产的可接受记录尤其缺失标识记录和追踪表上表明完成所有记录6. Failure to
13、 adequately maintain procedures to ensure that device history records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the requirements of this part, as required by 21 CFR 820.184. For example, the
14、 DHRs for your firms Disposable 3-part Syringe do not include or refer to the location of documentation of the acceptance records which demonstrate that device is manufactured in accordance with the DMR and the primary identification label and labeling used for each production unit. Specifically, th
15、e DHRs for lot numbers 20110608 and 21000325 lack documentation of the labeling used on the devices and documentation to show that all of the records identified on the trace list were completed.没有建立和维持适当的程序以确保 DHR 记录器械每个批、批号或单元，以证明器械是按照DMR 要求进行生产的。例如：你们公司一次性使用的注射器没有接受记录以证明器械是按照DMR 要求进行生产的。DHR 中尤其缺少器
16、械的标识记录和追踪表上表明已完成的所有记录。DMR 文件不合适如某 DMR 文件没包括 xx型号7. Failure to adequately maintain DMRs for each type of device which include or refer to the location of all the information required by 820.181, as required by 21 CFR 820.181(a). For example:DMR 文件不充分，没有包括每一种型号的信息。例如： The DMR (b)(4) which your firm us
17、es to control the production of the Disposable 3-part Syringe, does not reference the 2 ml, 2.5 ml or 60 mL sizes.DMR 引用的质量控制程序和企业所用不同规范缺少 xx型号你们公司用于控制一次性注射器生产的 DMR，没有包括 XX 规格。 The procedure that your firm uses to control the quality control process is the (b)(4) procedure, SC/QS02387. However, the
18、DMR references the following procedures for control of the quality control processes: (b)(4)你们公司用于质量控制的程序与 DMR 引用的质量控制程序不同。 The specifications for the (b)(4) operations lack specifications for the 2.0 ml, 2.5 mL, 30 ml, and 60 ml syringe sizes.操作说明书中缺少注射器 XX 规格。MDR 程序不合适不能及时和有效识别、交流和评价可能需要提交 MDR的事件。
19、定义和 803 不符没有说明实施完整的调查和评价事件的起因没有规定谁向FDA 报告没有确保及时提交报告的流程，如 5 天内提交Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17(a). For example, after reviewing your firms MDR procedure entitled, (b)(4) File number SC/QP 10.0-01, Edition/time: A/0, effective
20、 date 2011/10/25, the following issues were noted:没有适当地维持和实施书面的 MDR 程序。例如：审核你们公司 MDR 程序文件，有如下问题：1. SC/QP 10.0-01 does not establish a process that provides for the timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:没有建立一个
21、程序，确保及时有效的进行识别、沟通和评估事件是否符合 MDR 的要求。例如： The definition of “MDR event“ is not consistent with 21 CFR Part 803.3. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, your firms procedure should include definitions based on 21 CFR Part 803.3 for th
22、e terms: “become aware,“ “caused or contributed,“ and “MDR reportable event,“ and definitions for the terms “reasonably known and reasonably suggests,“ found respectively in 21 CFR 803.50(b) and 803.20(c)(1).DMR 事件的定义与 21 CFR Part 803.3 不一致。为了便于报告事件的正确解释，以及确保提交的 MDR 质量，你们公司的 MDR 程序应该包括 21 CFR Part 8
23、03.3 条款的定义。2. SC/QP 10.0-01 does not establish a process that provides a standardized review or procedure to determine when an event meets the criteria for reporting under this part. For example: There are no instructions for conducting a complete investigation of each event and evaluating the cause
24、 of the event.没有建立一个过程确保提供标准化评审程序来确定，当事件符合条件时，如何处理。例如：没有说明对每个事件实施完整的调查以及评估事件的起因。 The procedure, as written, does not specify who makes the decision for reporting events to FDA.书面程序中没有规定是谁负责向 FDA 报告。3. SC/QP 10.0-01 does not establish a process that provides for the timely submission of complete medi
25、cal device reports. Specifically, the following are not addressed: Circumstances under which an event must be submitted as a 5-day report, and Circumstances under which your firm must submit initial, supplemental, or follow-up reports and the requirements for such reports.没有建立一个程序以确保 MDR 提交的及时性。尤其是没
26、有解决如下问题：5 天内必须提交 MDR 报告；在任何情况下，你们公司必须提交最初的、补充的、后续的报告，以及 MDR 报告的要求If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:http:/www.fda.gov/Forlndustrv/FDAeSubmitter/ucm107903.htm1If your firm wishes to discuss MDR reportability cri
27、teria or to schedule further communications, it may contact the MDR Policy Branch at 301-796-6670 or by email at MDRPolicyfda.hhs.gov.如果你的公司希望提交 MDR 通过电子方式提交的报告，它可以按照指示按以下 URL：http:/www.fda.gov/Forlndustrv/FDAeSubmitter/ucm107903.htm1如果你的公司希望讨论 MDR 可报告准则或安排进一步的沟通，联系的 MDR 政策科 301-796-6670 或发送电子邮件至 MD
28、RPolicyfda.hhs.gov。02/14/2012客户抱怨 (b)(4) for PCB Model no. 8705WM dated October 5, 2011; and (b)(4) for PCB Model no. 8705WM dated October 8, 2011.检查你公司从 2011 年 10 月 4 号17 号的过程抽样检查，表明有几批的抽样数量使用错误。例如：如下批号的抽样量使用错误： (b)(4) for PCB 型号是.7117E 日期是 2011.10.4; (b)(4) for PCB 型号. 8705WM 日期是 2011.10.5; and (b
29、)(4) for PCB 型号是. 8705WM 日期是2011.10.8.We reviewed your firms response and conclude that it is not adequate. For those PCB lots that were accepted using the wrong sample size, your firm did not provide evidence to indicate that a correction was implemented to re-sample the lots according to the estab
30、lished sampling procedure. In addition, your firm did not provide information to indicate that all PCB sampling inspection records were evaluated to determine whether any more PCB lots were accepted with improper sample size.我们评估了一下你们公司的回复并且认为它不充分。这些使用了错误的抽样数量的 pcb，你公司并没有提供证据表明根据已经建立的抽样检验程序，执行了再次抽样的
31、措施。并且你公司没有提供信息表明所有的 pcb 抽样检查的记录得到确认用来确定是否有批次使用了不恰当的抽样数量。4. Failure to establish and maintain procedures to ensure that Device History Records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the Device Master Record, as required by
32、21 CFR 820.184. For example, your firms Department Manager of Regulatory Affairs stated that this facility has yet to establish a written DHR procedure. Also, (b)(4), (b)(4), and (b)(4), for the blood pressure monitor model number HEM-6052-Z do not include or refer to the location of the primary ide
33、ntification label and labeling used for each production unit.根据 21 CFR 820.184 的要求，没有建立和维护程序用来确保每个批次或者每个产品的 DHR 得到维护，以此用来证明按照 DMR 进行了生产。例如，你公司的法规事务经理指明已经建立了DHR 程序，型号为 HEM-6052-Z 的血压测量仪没有包含在里面或者没有指明原始的识别标签和每个产品标识的场所。We reviewed your firms response and are unable to determine its adequacy. It is uncle
34、ar whether a procedure is being established to ensure that all required information is being maintained in a DHR. You did not provide a copy of the new procedure for our review to verify that DHRs contain or make reference to all required documents.我们评估了一下你公司的回复，认为回复的证据不够充分。不能表明是否有程序被建立用来确保所有的要求的信息都
35、涵括在一个 DHR 中。你们没有提供一份经过我们评估的新程序的复印件，用来确认 DHR 中包含或者制作引用了所有要求的文件。Our inspection also revealed that your firms devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by
36、or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:在 502(t)(2) of the Act, 21 U.S.C. 352(t)(2)中，我们审核发现你公司的器械存在贴错标签的情况，在 519 of the Act, 21 U.S.C. 360i 中和 21 CFR Part 803 中，你公司没有成功或者拒绝
37、提供材料或者信息对器械进行重新检验，严重违反了，但是不局限于此：Failure to develop, maintains, and implements written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17.根据 21 CFR 803.17 的要求，没有建立，维护和执行所有写的 MDR 程序。For example, your firm does not have a procedure for identification, evaluation, and communication
38、of events that may be subject to MDR requirements.例如，你公司没有程序用来识别，评估和沟通事件，这个是 MDR 要求的主题。The adequacy of your firms response cannot be determined at this time. Your firm indicated that a corporate level complaint handling procedure is being established by the parent company located in Kyoto, Japan; ho
39、wever, a copy was not submitted for our review.你公司在这个时候没有合适的回复。你公司指明一个集团水平的客户抱怨处理程序正在日本东京建立和执行，但是根据你的答复，新的程序并没有提交。U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additio
40、nally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to th
41、e subject devices have been corrected.美国联邦机构给这个器械发布一个警告信，便于他们将这个信息放进报告。此外，III 类的上市前的审批申请将不会得到申请直到这些得到纠正。国外政府的证书请求不会得到批准知道这些得到纠正。02/23/2012软件确认1. Failure to establish and maintain adequate procedures for validating the device design, as required by 21 CFR 820.30(g). For example, upon request by the i
42、nvestigator, no documentation was provided to demonstrate that the display module and controller software used in the IPL Systems and accessories was validated to ensure that it conformed to defined user needs and intended uses.根据 21 CFR 820.30(g)的要求，没有对设计确认建立或者维护适当的程序。例如，根据研究者的要求，没有证据证明显示模块和使用在 IPL
43、 系统和附件上的软件得到确认，用来确保它符合用者的需求和预期用途。We reviewed your response and conclude that it is not adequate. You did not provide data to demonstrate that the IPL Systems software has been adequately validated. In addition, your response does not identify objective steps taken to address IPL Systems manufactured
44、 with software that was not properly validated.我们评估了你的回答，认为它是不充分的。你没有提供数据证明 IPL 系统上的软件得到了适当的确认。另外，你的回答并不能证明具体的步骤已经实施了用来表明带软件的 IPL 系统的生产。2.设计变更2. Failure to establish and maintain adequate procedures for the identification, documentation, validation, verification, review, and approval of design chang
45、es before their implementation, as required by 21 CFR 820.30(i). For example, upon request by the investigator, no objective evidence was provided to verify that IPL Systems and accessories design changes (IPL-HS-300 chassis) made on April 16, 2008, were documented. 根据 21 CFR 820.30(i)的要求，没有建立和维护适当的
46、程序对设计变更进行控制，在实施前没有进行识别，记录，确认，验证，评审以及批准等过程。例如，根据审核员的要求，没有证据证明在 2008.4.16 制作的 IPL 系统以及其附属的设计变更(IPL-HS-300 底盘)没有进行设计验证，We reviewed your response and conclude that it is not adequate. Your response does not include evidence that these design changes were documented. Also, the response does not address s
47、teps taken to ensure that employees are properly trained to facilitate implementation of adequate design change procedures.我们评估了你的回答，认为它是不充分的。你的回答没有包含设计变更进行评估的证据。另外，你的答复中没有包含对操作者的培训，以便操作人员更好地执行设计变更。客户抱怨&事故报告3. Failure to establish and maintain adequate procedures for receiving, reviewing, and evalua
48、ting complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, Complaint Procedure QP8201, version A/1, effective September 28, 2008, is inadequate because of the following: 根据 21 CFR 820.198(a)的要求，没有建立适当的程序对客户抱怨的接受，评审以及评估进行控制。例如，客户抱怨程序 QP8201，A/1 版本，2008.9.28 发行，内容是不充
49、分，见如下：A. The complaint procedure failed to include an assessment to determine whether the complaint represents an event that is required to be reported to the FDA under part 820.198(a).抱怨程序中没有包含对抱怨的评估，确定抱怨是否需要向 FDA 上报，根据 820.198(a)的要求。B. The complaint procedure failed to define a complaint as any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of the device after release for distribution.客户抱怨的程序中对抱怨的定义没有定义清楚，抱怨是任何以书面、口头、电讯的形式宣称，已经投放市场的
