2015年FDA检查趋势官方总结

julia朱玉姣

2015年FDA检查趋势总结

本内容来自FDA网站公开内容，演讲片附上。

其中对2014年度和2015年度的检查数据进行了对比，其中也提到了数据完整性问题。

对照表

SN	条款编号	2015数量	年度排名	2014数量	年度排名	备注	条款说明
1	211.22(d)	159	1	330	1	保持第一，数量减少	The responsibilities and procedures applicable to the quality control  unit are not in writing or fully followed    质量控制部门适用职责和程序没有书面写就，或没有全面遵守。
2	211.160(b)	138	2	253	2	保持第二，数量减少	Laboratory controls do not include the establishment of scientifically  sound and appropriate specifications, standards, sampling plans, and test  procedures    实验室控制没有包括科学合理和适当的质量标准、取样计划和检验方法的建议。
3	211.192	118	3	231	3	保持第三，数量减少	Failure to thoroughly review any unexplained discrepancy or the failure  of a batch or any of its components to meet any of its specifications whether  or not the batch has been already distributed    未能彻底审核所有无法解释的差异或批不合格，或其成分不符合其质量标准。无论是否放行。
4	211.113(b)	103	4	188	5	上升一位，数量减少	Procedures designed to prevent microbiological contamination of drug  products purporting to be sterile are not established, written or followed.    没有建立、书面写就或遵守防止无菌药品微生物污染的程序
5	211.100(a)	100	5	195	4	下降一位，数量减少	There are no written procedures for production and process controls  designed to assure that the drug products have the identity, strength,  quality, and purity they purport or are represented to possess.    用以确保药品具备既定鉴别、剂量、质量或纯度的生产或工艺控制没有书面程序
6	211.42(c)(10)(iv)	88	6	144	7	上升一位，数量减少	Aseptic processing areas are deficient regarding the system for  monitoring environmental conditions    无菌加工区域的环境条件监测系统有缺陷
7	211.165(a)	75	7	153	6	下降一位，数量减少	For each batch of drug product, there shall be  appropriate laboratory determination of satisfactory conformance to final  specifications for the drug product, including the identity and strength of  each active ingredient, prior to release. Where sterility and/or pyrogen  testing are conducted on specific batches of shortlived radiopharmaceuticals,  such batches may be released prior to completion of sterility and/or pyrogen  testing, provided such testing is completed as soon as possible.    每个药品批次在放行前均应有适当的化验室检测，确定其符合药品最终质量标准，包括每种活性成分的鉴别和剂量。对于寿命较短的放射性药品，其特定批次的无菌和/或热源测试在完成之前，可以放行，但此检测需要尽快完成。
8	211.68(a)	68	8	NA	NA	新增	Routine calibration, inspection and checking of automatic, mechanical  and/or electronic equipment is not performed according to a written program  designed to assure proper performance.    对自动、机构和/或电子设备的日常校正、验看和检查没有根据确保其性能适当的书面程序执行。
9	211.42(c)(10)(v)	68	9	NA	NA	新增	Aseptic processing areas are deficient regarding the system for  cleaning and disinfecting the room and equipment to produce aseptic  conditions.    无菌加工区域用于产生无菌条件的房间和设备的清洁和消毒系统有缺陷。
10	211.100(a)	68	10	130	10	保持第十，数量减少	There shall be  written procedures for production and process control designed to assure that  the drug products have the identity, strength, quality, and purity they  purport or are represented to possess. Such procedures shall include all  requirements in this subpart. These written procedures, including any  changes, shall be drafted, reviewed, and approved by the appropriate  organizational units and reviewed and approved by the quality control unit.    应有书面程序规定生产和工艺控制，用以确保药品具备其既定的鉴别、剂量、质量和纯度。此类程序在其子部分包括所有要求。此类书面程序，包括所有变更，均应经过适当的部门起草、审核和批准，由质量部门审核和批准。
11	211.67(a)	NA	NA	137	8	跌出前十	Equipment and utensils shall be cleaned, maintained, and, as  appropriate for the nature of the drug, sanitized and/or sterilized at  appropriate intervals to prevent malfunctions or contamination that would  alter the safety, identity, strength, quality, or purity of the drug product  beyond the official or other established requirements.    设备和工器具应清洁、维护，适当时要适合药品的特性按适当的周期进行消毒和/或灭菌，防止可能会改变药品的安全性、鉴别、剂量、质量或纯度的故障或污染，使其超出官方或其它既定的要求。
12	211.67(b)	NA	NA	132	9	跌出前十	Written procedures shall be established and followed for cleaning and  maintenance of equipment, including utensils, used in the manufacture,  processing, packing, or holding of a drug product. These procedures shall  include, but are not necessarily limited to, the following:    应建立和遵守药品生产、加工、包装或保存的设备，包括工器具清洁和维护程序。这些程序应包括但不必限于以下：    (1) Assignment of responsibility for cleaning and maintaining  equipment; 将设备的清洁和维护职责进行分配    (2) Maintenance and cleaning schedules, including, where appropriate,  sanitizing schedules; 维护和清洁计划，包括适当时，消毒计划    (3) A description in sufficient detail of the methods, equipment, and  materials used in cleaning and maintenance operations, and the methods of  disassembling and reassembling equipment as necessary to assure proper  cleaning and maintenance; 用于清洁和维护操作的方法、设备和物料，以及拆卸和装配设备的详细描述，以确保适当的清洁和维护    (4) Removal or obliteration of previous batch identification; 之前批次清除和除去的确认    (5) Protection of clean equipment from contamination prior to use; 保护清洁后的设备在使用前不受污染    (6) Inspection of equipment for cleanliness immediately before use. 使用前设备清洁状态的检查

其中分析了趋势影响因素，概括为以下几项：

l  法规成熟度（监管方和受检企业）

l  检查人员背景和专业经验

l  公司文化和管理层监管

l  受检公司的地理位置---是否具备所需的专家

2015度，由于CGMP检查引发的进口禁令（66-40）为26个（工厂地址），由于拒绝检查引发的进口禁令（99-32）为5个（工厂地址），警告信21封（其中原料药12封，制剂13封，有些工厂兼原料药和制剂）。

由于数据完整性引发的警告信原料药有7封（其中80%是海外公司），制剂有6封（其中40%是海外公司），合计13个厂址。这说明美国所用原料药大部分是依赖进口的。

之后，重点针对数据完整性进行了说明。其中也提到了新出版的问答中的三个问题：是否能共用用户名登录计算机系统？不能。母生产和检验记录是否可以使用电子签名？可以。是否可以使用实测样品做系统适用性？不可以，不鼓励符合性导向测试。

zysx01234

呵呵，都是些常见的缺陷，感觉有些很不可思议

lzjxqt

学习下，多谢分享！

道路漫长黑暗

就个人感觉来说这个缺陷才是合理的，如果老是写这个记录没写那个记录不规范之类的才有问题了。

kc1711422001

Thanks for sharing

kevin1196

感谢分享