200瓶灌装线图块
目录
1.前言............................................................................................................................................. 1
1.1背景...................................................................................................................................1
1.1.1指南说明.................................................................................................................1
1.1.2法规背景.................................................................................................................1
1.1.3技术背景.................................................................................................................1
1.2范围...................................................................................................................................2
2.质量管理...................................................................................................................................... 4
3.人员........................................................................................................................................... 34
3.1无菌药品生产对人员的基本要求和原则.......................................................................34
3.1.1人员的培训...........................................................................................................34
3.1.2人员卫生...............................................................................................................35
3.1.3人员监测计划.......................................................................................................36
3.1.4实验室人员...........................................................................................................37
3.2关键区域人员的良好行为规范......................................................................................37
3.3无菌区着装和更衣确认..................................................................................................39
4.厂房设施.................................................................................................................................... 44
4.1设计和布局......................................................................................................................44
4.2功能区设计.......................................................................................................................52
4.2.1无菌操作区............................................................................................................52
4.2.2气锁........................................................................................................................53
4.2.3无菌准备区和辅助区............................................................................................59
4.3.4传递区域................................................................................................................60
4.2.5仓贮区....................................................................................................................60
4.3建筑设计与房间装饰.......................................................................................................60
4.3.1建筑设计................................................................................................................60
4.3.2房间装饰................................................................................................................62
5.公用系统.................................................................................................................................... 63
5.1概论.................................................................................................................................63
5.1空调净化系统（HVAC）.................................................................................................63
5.2水系统..............................................................................................................................69
5.3气体系统..........................................................................................................................71
5.3.1压缩空气...............................................................................................................71
5.3.2氮气.......................................................................................................................73
5.4无菌产品生产的电力系统..............................................................................................74
6仪器设备..................................................................................................................................... 75
6.1设备的选型与设计...........................................................................................................78
6.1.1净化、清洗和灭菌的要求....................................................................................78
6.1.2材质、外观和安全设计要求................................................................................78
6.1.3结构设计要求........................................................................................................79
6.1.4在线监测、控制和验证的要求............................................................................79
6.1.5对公用工程的要求................................................................................................79
6.2仪器、仪表......................................................................................................................80
6.2.1仪器、仪表和计量................................................................................................80
6.2.2仪器、仪表的设计、性能、定位........................................................................80
6.2.3仪器仪表的周期校准............................................................................................82
6.2.4仪器仪表校准的内容............................................................................................83
6.3设备维修...........................................................................................................................83
目录无菌制剂GMP实施指南
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6.4电脑系统...........................................................................................................................83
6.4.1概述........................................................................................................................83
6.4.2计算机验证...........................................................................................................84
7物料............................................................................................................................................ 86
7.1无菌药品生产对物料的基本要求和原则......................................................................92
7.2无菌药品物料的风险控制..............................................................................................95
8生产管理..................................................................................................................................... 98
8.1工艺流程...........................................................................................................................99
8.2过程控制.........................................................................................................................100
8.2.1计划管理..............................................................................................................101
8.2.2时限管理..............................................................................................................101
8.2.3内毒素控制..........................................................................................................102
8.2.4批次划分..............................................................................................................106
8.2.5.清场管理..............................................................................................................107
8.2.6取样......................................................................................................................108
8.2.7物料平衡..............................................................................................................110
8.3生产管理控制要点的实例分析.....................................................................................110
8.3.1药液称量配制......................................................................................................111
8.3.2制袋管理..............................................................................................................111
8.3.3灭菌管理..............................................................................................................111
8.3.4灭菌后样品的传输..............................................................................................112
8.3.5粉体分装..............................................................................................................112
8.3.6阻隔膜包装..........................................................................................................112
8.3.7产品检漏..............................................................................................................112
9清洗和准备............................................................................................................................... 113
9.1胶塞...............................................................................................................................115
9.1.1胶塞的清洗和准备.............................................................................................115
9.1.2胶塞清洗机.........................................................................................................119
9.2玻璃容器........................................................................................................................122
9.2.1玻璃容器的清洗和准备.....................................................................................122
9.2.2洗瓶机.................................................................................................................125
9.2.3隧道烘箱.............................................................................................................127
9.3塑料容器.........................................................................................................................129
9.4颗粒杂质........................................................................................................................130
9.5传递................................................................................................................................131
10药液的配制............................................................................................................................. 133
10.1起始物料.......................................................................................................................135
10.2溶液的配制...................................................................................................................138
10.3微生物污染水平控制...................................................................................................143
10.4除菌过滤......................................................................................................................146
10.5药液配制设备..............................................................................................................160
11灌装......................................................................................................................................... 167
11.1 C级下大容量灌装........................................................................................................169
11.2小容量灌装..................................................................................................................172
11.2.1 A/B级下小容量灌装.........................................................................................172
11.2.2 A/C级下小容量灌装.........................................................................................175
11.3粉针剂的分装..............................................................................................................176
11.4灌装设备......................................................................................................................180
12冻干......................................................................................................................................... 184
12.1冻干流程......................................................................................................................184
12.2冻干工艺的验证...........................................................................................................189
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12.3冻干机.........................................................................................................................197
12.3.1设备技术要求...................................................................................................197
12.3.2设备确认...........................................................................................................200
13轧盖......................................................................................................................................... 205
13.1轧盖工序......................................................................................................................206
13.2轧盖的环境要求..........................................................................................................207
13.3轧盖机.........................................................................................................................209
14灭菌方法................................................................................................................................. 212
14.1灭菌概述......................................................................................................................212
14.2湿热灭菌.......................................................................................................................213
14.2.1湿热灭菌概述...................................................................................................214
14.2.2湿热灭菌程序的开发........................................................................................221
14.2.3湿热灭菌确认与验证........................................................................................228
14.2.4灭菌系统的日常维护.......................................................................................230
14.3干热灭菌.......................................................................................................................231
14.3.1干热灭菌概述....................................................................................................232
14.3.2干热灭菌确认与验证.......................................................................................236
14.3.3干热灭菌设备日常管理要点...........................................................................243
14.4辐射灭菌......................................................................................................................243
14.4.1辐射灭菌概述...................................................................................................244
14.4.2辐射灭菌的确认和验证...................................................................................246
14.4.3辐射灭菌的日常管理要点...............................................................................249
14.5环氧乙烷灭菌..............................................................................................................257
14.5.1环氧乙烷灭菌概述...........................................................................................258
14.5.2环氧乙烷灭菌的确认和验证............................................................................261
14.6过滤除菌工艺...............................................................................................................268
14.6.1除菌级过滤器的验证/细菌截留......................................................................268
14.6.2完整性检测........................................................................................................ 276
14.6.3过滤器的选择和特性描述................................................................................287
15无菌药品的最终处理............................................................................................................. 295
15.1密封完整性测试...........................................................................................................295
15.2颗粒/可见异物和其它缺陷检查................................................................................302
15.3半成品的灯检、贴签和包装......................................................................................309
16无菌工艺模拟试验................................................................................................................. 311
16.1无菌工艺模拟试验方法...............................................................................................312
16.2无菌工艺模拟试验的实施...........................................................................................316
16.3无菌工艺模拟试验结果解读.......................................................................................321
17清洁和消毒............................................................................................................................. 326
17.1概述..............................................................................................................................326
17.2清洁消毒体系建立......................................................................................................329
17.3清洁消毒效果...............................................................................................................334
18环境监控................................................................................................................................. 342
18.1污染来源.......................................................................................................................342
18.2洁净区级别的划分......................................................................................................343
18.3监测方案......................................................................................................................345
18.3.1限度...................................................................................................................346
18.3.2监测方法和设备................................................................................................349
18.3.3取样计划............................................................................................................354
18.3.4取样点及取样量的设置....................................................................................355
18.4超标处理......................................................................................................................358
18.5数据分析......................................................................................................................360
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18.6环境微生物的鉴别......................................................................................................360
19无菌检查................................................................................................................................. 362
19.1参数放行法..................................................................................................................362
19.2无菌检查的环境条件..................................................................................................365
19.3方法描述......................................................................................................................371
19.4检验数量和检验量......................................................................................................372
19.4.1检验数量............................................................................................................372
19.4.2样品量（检验量）...........................................................................................373
19.5培养基出现浑浊时的处理程序...................................................................................375
19.6观察和评价..................................................................................................................375
19.7培养基.........................................................................................................................377
19.7.1培养基种类........................................................................................................377
19.7.2培养基控制（培养基的适用性检查）............................................................378
19.8方法验证.......................................................................................................................381
20吹-灌-封技术.......................................................................................................................... 383
20.1工艺流程.......................................................................................................................384
20.2设备设计和气体质量...................................................................................................386
20.2.1设备设计............................................................................................................386
20.2.2气体质量............................................................................................................387
20. 3验证和确认..................................................................................................................388
20.4批监测和控制...............................................................................................................389
21隔离技术................................................................................................................................. 391
21.1隔离技术的要求及应用...............................................................................................391
21.2隔离系统的验证...........................................................................................................405
21.3隔离系统的维护体系...................................................................................................412
22 EHS .......................................................................................................................................... 415
22.1环境——空气..............................................................................................................415
22.1.1废气排放...........................................................................................................415
22.1.2 VOC's（可挥发性有机化合物），异味.............................................................416
22.1.3消耗臭氧层物质...............................................................................................417
22.2环境——废水..............................................................................................................418
22.2.1污水处理...........................................................................................................418
22.2.2预防措施...........................................................................................................419
22.2.3应急措施...........................................................................................................419
22.2.4废水分质处理...................................................................................................420
22.2.5回收与废物最小化...........................................................................................420
22.3环境——噪音..............................................................................................................421
22.3.1外界噪音...........................................................................................................421
22.3.2噪音敏感区域...................................................................................................422
22.3.3噪声治理...........................................................................................................422
22.4环境——固体废物......................................................................................................423
22.4.1管理要求...........................................................................................................423
22.4.2垃圾填埋地.......................................................................................................424
22.4.3废物运输...........................................................................................................425
22.4.4焚烧处理...........................................................................................................425
22.4.5废物的回收利用...............................................................................................426
22.5健康和安全..................................................................................................................426
22.5.1危险物质和有毒产物.......................................................................................426
22.5.2工作环境中的噪音...........................................................................................427
22.5.3健康体检...........................................................................................................427
22.5.4物料控制...........................................................................................................428
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22.5.5表面和安全通道...............................................................................................429
22.5.6防火..................................................................................................................429
22.5.7设施防护...........................................................................................................430
22.5.8电气安全和静电危害.......................................................................................431
22.5.9压力系统的安全性...........................................................................................431
22.5.10粉尘爆炸.........................................................................................................432
22.6厂址选择......................................................................................................................432
22.6.1环境空气洁净度...............................................................................................432
22.6.2供水..................................................................................................................433
22.6.3环境敏感区.......................................................................................................433
22.6.4选址的其它问题...............................................................................................434
22.7能源供应......................................................................................................................434
22.7.1热能..................................................................................................................434
22.7.2燃料储存...........................................................................................................434
22.7.3电力供给...........................................................................................................435
22.7.4能源节约...........................................................................................................435
22.8监测和管理措施..........................................................................................................436
22.8.1环境现状公示...................................................................................................436
22.8.2环境影响评价...................................................................................................436
22.8.3排污注册与申报...............................................................................................437
22.8.4应急预案...........................................................................................................438
22.8.5管理体系...........................................................................................................438
22.9信息安全......................................................................................................................439
22.9.1技术保密...........................................................................................................439
22.9.2文件存放...........................................................................................................439
22.9.3标签存放...........................................................................................................440
22.9.4资料与物品销毁...............................................................................................440
附录：无菌药品生产风险控制实例........................................................................................... 441
附1.1注射剂质量风险分析与质量风险控制...................................................................441
附1.2注射剂车间风险评估实例.......................................................................................448
参考资料....................................................................................................................................... 474
词汇表.......................................................................................................................................... 475
术语表.......................................................................................................................................... 479
关键词列表................................................................................................................................... 487
400瓶灌装线图块
冻干PM图20110417
10平方固定式自动进出料冻干机
20平方固定式自动进出料冻干机
20平方移动式自动进出料冻干机
40平方移动式自动进出料冻干机
