ERP系统一定要验证吗？
ERP系统一定需要验证吗?这个问题一直是困惑众多制药同行多年。最近这个问题有了较为官方的答案。德国药监局最近在EudoaGMDP数据库上传了一份对Artemis Biotech的GMP不符合报告中,列举了5条主要缺陷,其中一条为:托管GMP相关数据但不在质量管理体系内的ERP系统的安装和执行缺乏QA监管。
这些缺陷如下:
In total 35 observations were made by the inspection team over the course of the inspection.Five of them were categorised as major deficiencies and therefore potentially leading to a risk to the human and veterinary patient when using active pharmaceutical ingredients manufactured at the inspected site.
检查组在检查期间共发现35个缺陷项。其中5个为主要缺陷并且因此可能导致使用该企业所生产的活性药物的病人或动物产生风险。- The installation and execution of an Enterprise Resource Planning System, hosting GMP relevant data but outside of the quality management system, demonstrated a lack of QA oversight.托管GMP相关数据但不在质量管理体系内的ERP系统的安装和执行缺乏QA监管。
- Repackaging operations were conducted without any documentation and QA approval.重新包装操作没有任何文件和QA批准。
- The issuance of labels for raw materials and APIs was found inadequately controlled.原始物料和API标签的发放没有充分的控制。
- Within the instrumental laboratory the Company violated basic principles on data integrity, i.e. 在仪器实验室方面,公司违反数据完整性的基本原则,如
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- manual integration without justification and QA oversight.人工集成而没有论证和QA监管
- - The Company’s approach on the validation of computerised systems (Shimadzu LabSolutions) was considered as not in compliance with the requirements.公司计算机化系统(岛津LabSolutions)的验证方法被认为不符合要求。
问题:对于物料管理,很多企业采用电脑系统管理(ERP/SAP),对于这点在2010年版GMP中没有明确的指导?答:原则是一样的。计算机系统应经过验证。点评:计算机系统验证应证实软件的准确性、完整性、可靠性、安全性以及可追溯性。
问题:请解释“完全计算机化仓储管理系统”的定义,“完全”是否指“ERP”等管理系统?答:“ERP”管理系统可以实现“完全”。“完全计算机化仓储管理系统”指的是物流状态、信息采集、采购、入库、检验、验收、放行、领用、质量信息、追溯信息全部采用封闭的计算机系统管理的系统。
问题:GMP规定,使用完全计算机化仓储管理系统进行识别的,物料、产品等相关信息可不必以书面可读的方式标出。我公司使用的是ERP管理系统,是否属于完全计算机化仓储管理系统?完全计算机化仓储管理系统是一个什么样的系统?答:国内药厂所用的计算机管理系统通常是ERP或SAP系统,该类计算机系统一般由多个模块组成,与企业的仓储管理其他相关的硬件和软件紧密相关,是否属于完全计算机化管理系统应通过企业对该系统的应用广度和深度来识别。GMP的管理原则是防止混淆、差错、污染与交叉污染,这也适用于计算机化仓储管理系统下的物料管理过程。企业如果能够通过计算机自动管理手段(无纸化)来确保物料不出现混淆、差错的可能,则可以被视为完全计算机化仓储管理系统。例如:仓储的货位管理并非依靠人工肉眼来检查,而完全靠计算机处理;物料入库、出库的识别不是依靠操作人员肉眼进行识别,而是依靠条码读取等方式进行的,则基本上属于完全计算机化仓储管理系统。
问题:老师我想咨询一下在对计算机的验证中需要对计算机的编程进行验证吗如果需要能简单说一下如何验证吗谢谢答:对于GMP而言,计算机化系统的验证不必包括计算机的编程。 问题1:ERP系统、空调系统的计算机化系统按你们风险评估的结果的话那是否需要建立数据审计跟踪系统?问题2:2010版GMP附录确认与验证中第九章第五十条“对设施、设备和工艺,包括清洁方法应当进行定期评估,以确认它们持续保持验证状态。”如何进行评估呢?还是说最好是直接进行定期再验证?期待老师您的答复,谢谢!答:1、现阶段,暂时未强制要求ERP系统、空调系统的计算机化系统必须建立数据审计跟踪系统。
2、评估可采用多种方式,定期再验证并不是评估的一种方式,而是评估后采取的措施。
关于这份不符合报告的内容如下:
Nature of non-compliance :
不符合内容
In total 35 observations were made by the inspection team over the course of the inspection.Five of them were categorised as major deficiencies and therefore potentially leading to a risk to the human and veterinary patient when using active pharmaceutical ingredients manufactured at the inspected site. - The installation and execution of an Enterprise Resource Planning System, hosting GMP relevant data but outside of the quality management system, demonstrated a lack of QA oversight.- Repackaging operations were conducted without any documentation and QA approval.- The issuance of labels for raw materials and APIs was found inadequately controlled.- Within the instrumental laboratory the Company violated basic principles on data integrity, i.e. manual integration without justification and QA oversight.- The Company’s approach on the validation of computerised systems (Shimadzu LabSolutions) was considered as not in compliance with the requirements.
检查组在检查期间共发现35个缺陷项。其中5个为主要缺陷并且因此可能导致使用该企业所生产的活性药物的病人或动物产生风险。托管GMP相关数据但不在质量管理体系内的ERP系统的安装和执行缺乏QA监管。重新包装操作没有任何文件和QA批准。原始物料和API标签的发放没有充分的控制。在仪器实验室方面,公司违反数据完整性的基本原则,如,人工集成而没有论证和QA监管,-公司计算机化系统(岛津LabSolutions)的验证方法被认为不符合要求。
Action taken/proposed by the NCA :
NCA(药监机构:National Competent Authorities)所采取的/建议的措施
Recall of batches already released
召回已放行的批次
No immediate recall is needed. Each involved NCA should evaluate, following assessment conducted in conjunction with MAHs, if a potential recall of medicinal product is needed. The risk based evaluation should take in account if there are alternative suppliers and potential risk of shortage. Given the nature of non-compliances, assessment should include a complete retest of all imported batches of active substance.
Prohibition of supply
禁止供应
Due to the nature of non-compliances, prohibition of supply is recommended.
Suspension or voiding of CEP (action to be taken by EDQM)
暂停或收回CEP证书(EDQM来做)
This inspection was carried out as part of the EDQM inspection Programm. The impact of this NCS on the CEPs is to be decided by the EDQM. The concerned CEPs are Simvastatin Butylated Hydroxy Anisole 50 - 150 ppm R1-CEP 2006-091-Rev 00; Simvastatin Butylated hydroxy anisole 0.18-0.22% R1-CEP 2007-155-Rev 01; Simvastatin Antioxidant Butylated Hydroxy Toluene 0.01% R1-CEP 2003-257-Rev 03
Others
其他
This supplier should not be approved in any new/ongoing applications. Each involved NCA should evaluate if the supplier should be removed from existing MAs.
Additional comments :
备注
This inspection was performed in the framework of the CEP dossier for the manufacture of Simvastatin Antioxidant Butylated Hydroxy Toluene 0.01% R1-CEP 2003-257.The company also produces Fumagillin (antibiotic manufactured from fermentation) for the French market. This API was not within the scope of this inspection.
