FDA指南-无菌工艺生产无菌药品-cGMP

潇湘子

I. INTRODUCTION.............................................................................................................1
II. BACKGROUND...............................................................................................................2
A. Regulatory Framework.................................................................................................................2
B. Technical Framework....................................................................................................................2
III. SCOPE...............................................................................................................................3
IV. BUILDINGS AND FACILITIES....................................................................................4
A. Critical Area – Class 100 (ISO 5).................................................................................................5
B. Supporting Clean Areas................................................................................................................7
C. Clean Area Separation..................................................................................................................7
D. Air Filtration..................................................................................................................................8
1. Membrane........................................................................................................................................8
2. High-Efficiency Particulate Air (HEPA).........................................................................................8
E. Design............................................................................................................................................10
V. PERSONNEL TRAINING, QUALIFICATION, & MONITORING........................12
A. Personnel.......................................................................................................................................13
B. Laboratory Personnel..................................................................................................................15
C. Monitoring Program....................................................................................................................15
VI. COMPONENTS AND CONTAINER/CLOSURES..........................................................15
A. Components..................................................................................................................................16
B. Containers/Closures.....................................................................................................................17
1. Preparation....................................................................................................................................17
2. Inspection of Container Closure System........................................................................................18
VII. ENDOTOXIN CONTROL.................................................................................................19
VIII. TIME LIMITATIONS......................................................................................................20
IX. VALIDATION OF ASEPTIC PROCESSING AND STERILIZATION..................20
A. Process Simulations.....................................................................................................................20
1. Study Design.................................................................................................................................21
2. Frequency and Number of Runs....................................................................................................22
3. Duration of Runs............................................................................................................................22
4. Size of Runs....................................................................................................................................23
5. Line Speed......................................................................................................................................23
6. Environmental Conditions.............................................................................................................24
7. Media............................................................................................................................................24
8. Incubation and Examination of Media-Filled Units......................................................................24
9. Interpretation of Test Results.........................................................................................................26
B. Filtration Efficacy........................................................................................................................27

C. Sterilization of Equipment, Containers, and Closures.............................................................28
1. Qualification and Validation.........................................................................................................29
2. Equipment Controls and Instrument Calibration..........................................................................30
X. LABORATORY CONTROLS......................................................................................31
A. Environmental Monitoring.........................................................................................................32
1. General Written Program.............................................................................................................32
2. Establishing Levels and a Trending Program...............................................................................33
3. Disinfection Efficacy......................................................................................................................34
4. Monitoring Methods......................................................................................................................34
B. Microbiological Media and Identification.................................................................................35
C. Prefiltration Bioburden...............................................................................................................36
D. Alternate Microbiological Test Methods...................................................................................36
E. Particle Monitoring......................................................................................................................36
XI. STERILITY TESTING..................................................................................................37
A. Microbiological Laboratory Controls........................................................................................38
B. Sampling and Incubation............................................................................................................38
C. Investigation of Sterility Positives..............................................................................................39
XII. BATCH RECORD REVIEW: PROCESS CONTROL DOCUMENTATION........42
APPENDIX 1: ASEPTIC PROCESSING ISOLATORS.......................................................44
APPENDIX 2: BLOW-FILL- SEAL TECHNOLOGY..........................................................49
APPENDIX 3: PROCESSING PRIOR TO FILLING AND SEALING OPERATIONS....52
REFERENCES............................................................................................................................54
RELEVANT GUIDANCE DOCUMENTS...............................................................................55
GLOSSARY.................................................................................................................................56

zdlxcb

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巴西木

都是英文的吗？谢谢楼主分享

jjb2005

感谢分享，英文的看着吃力，中文的又不给力！两难呀！

liuqygood2005

多谢分享。

smalltrees

等待中文的

红茶.

这么快已经成斑竹推荐了。

苗苗

值得学习，就是全英文的看起来太费劲了

胜利者

x谢谢分享

youngzhou

多谢分享。

/dx_雪中晴

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Summer-

有没有中文的？中英文对照着看会好些。

心若谷

英文的？

jgm123654

下载必谢！

hhq13816599836

水平有限，望！

wqx5219

谢谢分享！

兔小白糖糖

非常感谢，找到了需要的

曾祥敏

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