Data Integrity and Validation Issues identified during GMP Inspection

GMP 检查期间发现的数据完整性和验证问题

Following FDA´s August 2019 inspection of a Canadian manufacturer of over-the-counter (OTC) drug products, the Agency now issued a Warning Letter due to non-compliance with cGMP.

在 FDA 于 2019 年 8 月对一家加拿大非处方药 （OTC） 制造商进行检查后，由于不符合 cGMP，FDA发出了警告信。

Data Integrity issues

数据完整性问题

The FDA inspectors found discrepancies between HMI (human machine interface) data and batch records and practices of operators not following batch instructions. Therefore the agency requires to provide

FDA 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，FDA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。

Validation issues

验证问题

The agency observed a lack of process validation and, in addition, a lengthy bulk hold time prior to filling 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，此外，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 therefore requests

因此，该机构要求：

• a detailed summary of the validation program for ensuring 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，

• associated procedures including process performance protocol(s), and written procedures (and a program) for qualification of equipment and facilities;

• 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, controlling and monitoring of manufacturing 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，以确保持续受控状态。

Particles and OOS Results

粒子（异物）和OOS结果

According to FDA, the company failed to adequately investigate and document the presence of particles in a 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 of units of this lot. However, this CA did not expand to 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. 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）。制造商得出结论，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。此外，该公司没有对OOS测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程序进行独立评估和补救计划，

• a comprehensive assessment and remediation plan to ensure that the QU (Quality Unit) is given the authority and resources to effectively function.

• 全面的评估和补救计划，以确保 QU（质量部门）获得有效运作的权力和资源。