GMP检查期间发现的数据完整性和验证问题

1、GMP检查期间发现的数据完整性和验证问题Data Integrity issues数据完整性问题The FDAinspectors found discrepancies between HMI (human machine interface) data and batch records and practices of operators not following batch instructions. Therefore the agency requires to provideFDA检验员发现HMI (人机界面)数据与批记录数据存 在差异，并且操作人员未按批指令操作。因此， FD

2、A要求提供：a comprehensive investigation into the extent of the inaccuracies in data records and reporting;全面调查数据记录和报告不准确的程度results of the data review for drugs distributed together with a detailed description of the scope and root causes of the data integrity lapses.已放行药品的数据审核结果，以及数据完整性失效的范 围和根本原因的详细描述。

3、Validation issues验证问题The agency observed a lack of process validationand, in addition, a lengthy bulk hold time prior tofilling drug products without assuring that this practice does not impact the chemical and microbiological quality.该机构注意到未执行工艺验证，止匕外，漫长的待灌装产 品保持时间未能确保这种做法不会影响化学和微生物质量。The agency th

4、erefore requests因此，该机构要求：a detailed summary of the validation program forensuring a state of control throughout the product lifecycle,用以确保在整个产品生命周期中处于受控状态的验证计划的详细摘要，associatedproceduresincludingprocessperformance protocol(s), and written procedures (anda program) for qualification of equipment and f

5、acilities;相关程序，包括工艺性能方案，以及设备和设施确认的书面程序（和计划）a detailed program for designing, validating,maintaining,controllingand monitoringofmanufacturing processes that includes monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control.生产工艺设计、验证、维护、控制和监测的详细程序, 包括监测批次内和批次间变异，以确保持续受

6、控状态。Particles and OOS Results粒子（异物）和OOS吉果According to FDA, the company failed to adequately investigate and document the presence of particles ina product. The manufacturer concluded that the particles were from a broken belt on the filling line, and the corrective action （CA） was to reject a number

7、 of units of this lot. However, this CA did not expandto cover batches that were previously filled at the same line or a preventative maintenance plan to prevent recurrence of similar incidents. In addition, the company failed to conduct an adequate investigation into an OOS test result for content.

8、 The FDA therefore requests to provide据FDA称，该公司未能充分调查和记录产品中是否存在 颗粒（异物）。制造商得由结论，颗粒（异物）来自灌装线 上断裂的传送带，纠正措施（CA）是拒绝此批次产品。但是，此CA未扩展到涵盖以前在该生产线上灌装的批次，也 没有用以防止类似事件再次发生的预防性维护计划。止匕外， 该公司没有对OOSM试结果进行充分调查。因此，FDA要求提供a comprehensive, independent assessment of the overall system for investigating deviations, discrepancies, complaints, OOS results, and failures,对偏差、差异、投诉、OOS和不合格结果调查的整个系统进行全面、独立的评估，an independent assessment and remediation plan for the CAPA program,对CAPA序进行独立评估和补救计划，a comprehensive assessment and remediation pla