Beruflich Dokumente
Kultur Dokumente
2554
( FTA )
Good Manufacturing Practice
(GMP PIC/S)
(practice guidance)
..
GMP
-
()
GMP PIC/S
GMP
2
/
/
3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
19
GMP PIC/S
1
1
2
3
4
15
15
15
16
17
19
19
21
22
24
30
38
45
61
69
82
93
97
99
100
103
108
116
120
156
161
..2546
.. 2554
..2554
1.
(Good Manufacturing Practice)
Pharmaceutical Inspection Co-operation Scheme (PIC/S)
2.
3.
..2554 Pharmaceutical
Inspection Co-operation Scheme (PIC/S) Guide to Manufacturing Practices for Medicinal Products
PE 009-9 1 September 2009
3
1
(Site Master File)
2 / (GMP
Certificate)
/
3
..2554
()
(Critical deficiency) (Major deficiency)
(Minor deficiency)
..2554
..2554 3
1. (Critical deficiency)
2. (Major deficiency)
3. (Minor deficiency)
1. ..2534
2
2. ..2535
3. ..2535
4. ..2535
5. ..2535
6. ..2540
7. ..2540
8. ..2540
9. ..2540
10. ..2546
11. (Product Development Recommendation for
Semisolid Dosage Forms) ..2546
12. (Guide to
Pharmaceutical Process Validation of Solid Dosage Forms) ..2546
13. (Guide to Cleaning Validation)
..2543
14. (Guide to
Validation of Heat Sterilization Process) ..2546
internet web site http://www.fda.moph.go.th
download
1.
1.1 ( ) ()
1.2 (validity)
1.3 ()
1.3 ( 1.6 )
3
1.4 24
1.4
1.4.1
1.4.2
1.4.3 24
1.5 ()
( (campaign
basis))
1.5
1.5.1
1.5.2 cytostatic
campaign basis
1.5. 3
1.6 (
())
1.7
1.7.1
1.7.2
1.7.3
1.7.4
1.7.5
1.7.6
part time (full time)
1.8
( 7)
4
1.8
1.8.1
1.8.2
1.8.3
1.8.4 100
A4
1.9 (Quality Management System)
1.9.1
1.9.2
1.9.3 (audit programme)
1.9.4
( 6.1.2 )
1.9.5 ISO 9001 9004
//
1.9.6
excipients
1.9.7
2. (500 A4)
2.1 (Organization Chart)
( 1.9.2 )
2.1
senior manager supervisors
2.2 (key personnel)
2.2
2.3
2.3
2.3.1 identify
2.3.2 GMP
2.3.3
2.3.4
2.3.5 identify
2.3.6
2.4
2.4
2.4.1
2.4.2
2.4.3
2.4.4
2.4.5 (clean room) A-D
2.5
2.5
2.5.1
2.5.2
2.5.3
3.
3.1 (
)
3.1
3.1.1
3.1.2
3.1.3 A4 A3
3.1.4
3.2
6
3.2 ( 500 A4)
3.2.1 (critical
area)
3.2.2
3.3 (Ventilation System)
(critical area) (airborne contamination)
( schematic drawing of the system)
3.4 3.1
3.5 ( schematic drawing of the system)
3.5.1 schematic
3.5.2
3.5.3
3.5.4 (specification)
3.5.5
7
3.5.6
a.
b. (conductivity)
c.
3.5.7
3.5.8 (sanitation)
3.6 ( (preventive
maintenance) )
3.6.3
3.6.4
3.7 (
)
3.7 ( 250
A4)
3.7.1 ( AISI Grade 316 stainless steel
)
3.7.2 ( polypropylene
, PVC non reactive plastic material )
3.7.3
3.7.4
lot no. exp.date freeze drier
3.7.5 pH meter, Chromatography,
GLC, HPLC ,
3.7.6 incubator (),
LAL, , antibiotic assay
3.7.7
3.8 ( (preventive
8
maintenance) )
3.8.3 (routine)
3.8.4
1.
2. ()
3.8.5
3.9 (Qualification) (calibration)
3.9
( 750 A4)
3.9.1 (prospective,
retrospective)
3.9.2 (critical equipment)
3.9.3 process validation 5.4
3.9.4 development and validation batch
3.9.5
software
3.9.6 ( 4.2.9)
3.10
3.10 (Sanitation) (
250 A4)
3.10.1
3.10.2
3.10.3
3.10.4
3.10.5
4.
4. ( 500 A4)
4.1
4.1
4.1.1
4.1.2
4.1.3 (Master document)
4.1.4 (standard format)
1. (Product specification) (process specification)
2.
3.
4.
5.
6.
7. QA
4.1.5
4.1.6
4.1.7
4.2 (
)
4.2
4.2.1 /
4.2.2 (specification for disposables)
4.2.3 SOP
4.2.4 (QC procedures)
4.2.5
4.2.6
4.2.7
4.2.8 ( 3.9.5)
4.2.9 ( 3.9, 5.4)
10
4.2.10 (reconciliation)
printed material
4.2.11
5.
5.1 flow charts parameter
()
5.2
5.2.1 (supplier)
5.2.2
5.2.3
5.2.4
5.2.5
5.2.6
5.2.7
5.2.8 bulk manufacture
1.
(filter integrity test)
2.
3.
4.
5.2.9
1. bulk
2. line clearance
3.
5.2.10
5.2.11 Authorized Person
5.3 reprocessing rework
11
5.3 reprocess rework
5.4 (rejected material and products)
5.4
5.4.1 (/)
5.4.2
5.5 process validation
6.
6.1
6.1
6.1.1
6.1.2
6.1.3
QC ( 1.9.4)
6.1.4
( 1.9 4
)
7.
7.1 (audit)
GMP
7.1
GMP
8.
8.1
8.1
12
8.1.1
8.1.1.1
8.1.1.2
8.1.1.3
8.1.1.4
8.1.1.5 ,
8.1.1.6
8.1.1.7 First in First out lot
8.1.2
8.2
8.2
8.2.1
8.2.1.1
8.2.1.2
1.
2.
3.
8.2.1.3
8.2.1.4
8.2.1.5
8.2.2
8.2.2.1
1.
2.
3.
4.
5.
8.2.2.2
8.2.2.3
8.2.2.4
8.2.2.5
9.
9.1 ( 1.9.3)
9.1
13
9.1.1
9.1.2
9.1.3 (follow
up)
9.1.4
9.1.5
************************
14
1.
3. / (GMP Certificate)
4. 1
commercial batch size 3
(Process Validation)
5. 2
GMP
1. GMP
1.1
1.2
1.3
GMP
2.
..2546
.. 2554
3
/
PIC/S (Good Manufacturing
Practice for Medicinal Products) 4
1. (Routine lnspection)
..2554
1.1
1.2
1.3
15
2. (Follow-up lnspection)
3. (Concise Inspection)
4. (Special lnspection)
4.1
4.2
4.3 GMP
1.
10
2.
3. 30
16
1.
1.1
1.1.1
1.1.2
1.1.3
1.1.4
1.1.5
1.1.6 ()
1.2
1.2.1
1.2.2
1.2.3
1.2.4
1.2.5 ()
2.
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
2.10
2.11
2.12
2.13 ()
3. ()
3.1 ()
3.2
3.2.1 ()
3.2.2 ()
3.2.3 ()
17
3.2.4 ()
3.2.5 ()
3.2.6 ()
3.3 ()
3.4 ()
3.5 ()
3.6 ()
4. ......
5. ......
6.
6.1
6.2
6.3
6.4
6.5
6.6
7.
7.1
7.1.1
7.1.2
7.1.3
7.1.4
7.1.5
7.1.6
7.1.7
7.1.8
7.1.9
7.1.10
7.1.11
7.1.12
7.1.13 ()
7.2
8. ()
18
(GMP Certificate)
(Risk Assessment)
..2554
..2554
(Routine lnspection) (Follow-up lnspection)
(Concise Inspection) (Special lnspection)
/ (GMP Certificate)
1.
2.
3.
4.
1
5.
/ (GMP Certificate)
/
(GMP Certificate)
1.
(Critical deficiency) (Critical deficiency)
/ (GMP Certificate)
19
15
( GMP)
(Major deficiency)
15
/
(Critical
deficiency) /
(GMP Certificate)
2.
2.1 (Critical deficiency)
(Critical deficiency) /
(GMP Certificate)
15
/ (GMP Certificate)
GMP
20
/
/
1.
(Critical deficiency)
GMP GMP
(GMP Certificate)
60
2. (Critical deficiency)
GMP
GMP
3. (Major deficiency)
60 (
)
90
21
(//)
..2546
..2554
(Critical deficiency) (Major deficiency)
(Minor deficiency)
/
..2510
95
96 14 48
1. (Critical defect)
(GMP)
1.1
1.2
1.3
14
2. (Major defect)
(GMP)
22
2.1
15
2.2
2.3 2
2.4
3
2.5 4
14
23
..2554
----------------------------- 2 5 6(9) (10) 7(4)
..2546 ..2510
29
32 33 41 43 45
1
..2546
2 90
3
(Worst case)
(Quarantine)
(Change control)
(Quality control)
(In-process control)
24
(Return)
(Recall)
(Production)
(Qualification)
(Process validation)
(Cleaning validation)
(Re-validation)
(Prospective validation)
25
(Concurrent validation)
(Retrospective validation)
(Reconciliation)
(Infected)
(Reprocessing)
(Reworking)
(Recovery)
(Packaging)
(Cross contamination)
(Quality assurance)
(Manufacture)
(Risk analysis)
(Calibration)
(Bracketing design)
26
(Matrixing design)
(Specification)
(Action limit)
(Alert limit)
(Sterility)
6
10
(Dead-leg)
(Bioburden)
(Contained area)
(Controlled area)
D
(Clean area)
/ (Clean/ Contained area)
(Record)
(Simulated product)
27
(Medicinal products)
(Veterinary medicinal products)
(Bulk product)
(Intermediate product)
(Finished product)
(Authorised person)
(Manufacturer)
(Media fill)
Simulated product fills, broth trials, broth fills
(Standard operating procedure)
(System)
(Computerised system)
/ (Batch or lot)
(Manufacturing date)
(Expiry date)
(Starting material)
(Packaging material)
28
(Procedures)
(Self-contained facilities)
(Dedicated facilities)
(Biological agents)
(endoparasites)
(Pre-mix for medicated feeding stuffs)
(Air lock) 2
-
4 ..1 ..2 ..3 ..4 ..5 ..6 ..7 ..8
..9 ..10 ..11 ..12
29
30
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(1)
(2)
31
(3)
()
()
()
()
()
()
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(1)
1 8 4
(2)
1 9-10 5 138 12 255-261
(3) 2, 3, 5 6
(4) /
4, 5 6
(5) 2 17-21
(6)
4 79-80, 89-90, 92, 97 100-101 6 175-176 7
32
(7.3)
1 4 80 6 174
(8)
(9) 3 47 52 5 166 8
223-230
(10) 3 47 52 5
166 8 215-222
(1)
(2)
(3)
(4)
(5)
(6)
33
(7)
(8)
5 160 6 169
(1) 3 30-34, 55-58 62-73 4
94-96 99 6 171-173 177
(2) 6 177-180 10 234-238
(3) 4 98 6 181
(4)
4 79-80, 92, 97 100-101 6 175-176 182-183 7 212
11 241 4 81
19
(7) 5 160 6 169
(8) 6 178-180 11
239-254
(dosage form)
1 (3.75 )
/ 500
1
34
(1)
(3)
(4)
(5)
(1)
(2)
(3)
(4)
(5)
(6)
3
(7)
(8)
(9)
(10)
(11)
(12) (technical agreements)
35
3
high risk, medium risk low risk
High risk , cytotoxic drugs sustained release preparations
1
Medium risk potent drugs 2 mg unit dose
penicillins, cephalosporins, carbapenems Beta-lactam ring
2 2
Low risk 4
3
(dosage form)
10
(1)
(2)
11
(qualification)
// 3
1
// 3 /
1
// 3
1
/
12
(job description)
(2)
(3) (job description)
/
37
(organization chart)
(job description)
13
14
(1)
(2)
(3)
(4)
(5)
(6)
38
15
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
16
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
2 16 (1-11)
17
39
(1)
(2)
(2.1) 80%
(2.2)
(2.3)
(2.4)
1
(3)
GMP
1
2
(1)
/ 5
(2)
GMP 1
18
GMP
(on the job training)
2
17
40
19
20
21
22
41
(1)
(2)
14 350
(3)
(4)
23
1
X-ray [
(SGOT SGPT tests)
]
(1) clarity test
1
42
24
25
14 349-352
26
27
43
28
29
44
30
31
(1)
(2)
32
(1) 200-300
500-1,000
(2)
45
(3)
(4)
33
(1)
(2) air lock
(3)
(4) (pest
control)
(5)
(6)
(7)
(5)
34
(1)
(2)
(3)
46
security card
35
(Biological preparation)
(Cross contamination)
(Campaign)
(Pesticides) (Herbicides)
(1)
penicillins, cephalosporins, , sex hormone, cytotoxic drug anticancer
(distribution loop)
campaign
(2) potent drugs anti-inflammatory steroid cross contamination
product
(campaign) cleaning validation,
environmental monitoring
/ (campaign)
(campaign)
47
36
37
(1)
(2)
38
( )
(1)
(2)
(3) epoxy insulated sandwich panel
(6) epoxy
(7)
48
39
(1)
(2)
(3)
(low level return)
(4)
40
(2)
(3) sanitization
41
(1) HVAC
Filter Pre-Filter,medium Filter HEPA Filter
(2)
batch record , environmental monitoring viable monitoring (settling plate, air
sampler)
(3) air lock
49
environmental monitoring
()
42
(1)
dispensing booth
43
(1)
(2) HVAC
(3)
44
(1)
(2) (primary packaging)
50
45
(1) 200-300
500 - 1000 1
46
(1)
(2)
(3)
(1) (2)
47
(1)
log book
48
(1)
(2)
51
49
(1)
(2)
(compressed air)
(3)
50
(1)
location control by computer
(2)
51
(1)
dispensing booth laminar air flow
(2)
52
52
(1) /
/
log book
(2)
53
(1)
log book
(2)
(1)
54
(1)
/
(2) / lot number
(1) (2)
55
53
56
(1)
split type hood
safety shower eye wash
HVAC sterility test
(class A B)
log book
(2)
(3)
(4) /
(5)
toxicity (safety)
-
biohazard safety cabinet
-
- Pass box
microbial limit test
-
- LAF (laminar air flow)
- grade D
endotoxin LAL
- microbial limit test
-
- pass box
- grade A/B
- sterile grade B
- isolator grade D
54
pyrogen
-
- 3
- -
-
-
- 3
- 3
-
- 25
-
-
(1) Electrical
stabilizer
58
55
59
60
(1)
2 ... ..2535 ()
1-15
1
1
1
16-40
2
2
2
41-80
3
3
3
50 1
15
(2)
(3) /
- 1) 2)
-
-
- (
)
(2)
56
61
62
63
64
(1)
65
57
(1) (dead leg)
(3)
(4) punch dies mould
(5)
cleaning validation 12 289-295
validate
66
(1)
(2) (janitor room)
(3)
(4) clean compressed air
67
(1)
58
68
69
(1)
70
(1)
(master calibration program)
(2) log book daily weight checking ,
operating, cleaning and calibration calibration record
(3) .
ASTM
(4)
. ASTM
(5) impact assessment
- (calibrate)
1 ( calibrate 3 /
daily check) calibrate (reference)
- pH meter
- 3 daily check
- UV-visible spectrophotometer 1
- HPLC 1 system suitability
59
- 1
71
72
(1) sanitization
sanitizing method
(2) alert limit, action limit (trend analysis)
(1)
(2)
(3)
(laminar flow asepitic process,
saturated steam autoclave)
60
74
75
76
(1)
(2)
(3)
(1)
(2)
77
(1)
(2)
(3) 3
61
78
79
80
1
81
(
19)
82
83
62
(1)
()
()
() ( )
()
(2)
(3)
(4)
(5)
84
85
(1) ()
(2)
(3)
(4)
(5)
(6) ()
(7)
63
86
(1)
(2)
(3)
(4) ()
87
(1)
(2)
(3)
(4)
(5)
()
(6)
88
(1)
(2) ()
(3)
(4)
(5)
(6)
(7)
(8)
()
64
(active ingredient)
(inactive ingredient)
89
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
90
65
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
91
92
(1)
(2) ( (1))
(3)
(4)
(5)
66
(6)
(7)
(8)
93
94
6 177
10
95
96
97
67
98
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
99
100
101
(log book)
(log book)
68
102
(1) 2 11
(2)
(1)
(2) 2 11
103
104
105
106
107 (Intermediates) (Bulk products)
108
(1) (instruction)
(2)
69
(3)
109
(1)
(2)
110
111
112
113
114
70
115
116
(change control)
117
118
119
71
120
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(.. 2531)
(.. 2536) (.. 2543)
72
120 (1)
121
121
122
123
124
125
12
12
126
127
73
(1)
(2)
128
5 103-108
5 103-108
129
(1)
130
(1) ()
(1)
(2)
(3)
74
(1)
(2)
131
132
133
134
135
75
136
(area clearance)
137
(1)
/
138 12
(1)
139
(1)
(2)
140
76
141
5 126-135
142
Lot No./Control No.
-
143
(1)
(version )
144
(1)
/
77
145
146
147
148
149
150
145-150
151
152
153
154
78
155
(1)
(2)
(3)
(4)
(5)
156
(1)
156
157
158
157 158
159
79
160
161
162
162
163
1632
164
165
80
166
81
167
2 11 13
2 11 13
168 2
169
82
169
170
171
172
7
173
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(2) - (8)
174
1
5
83
(validation document)
(qualification document) (stability study
document)
174
175
(trend analysis)
quality control chart
176
6 174
(laboratory notebook) / (record) 5
176
177
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
10
84
178
11
179
180
1
( )
2
11
181
(1) (official
monograph) / (verification)
accuracy, precision linearity
(2) (official
monograph) /
(validation) ASEAN guidelines for validation of analytical procedures guidelines
(3) (non-official
monograph) / (dosage form)
(validation) ASEAN guidelines for validation of analytical
procedures guidelines
85
(4)
(validation) ASEAN guidelines for validation of analytical procedures guidelines
(5) (validation)
(
)
181
182
183
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(4)
certificates of analysis supplier
(7)-(8)
2 13
184
86
185
(1) (
)
(2)
volumetric solutions volumetric
solutions
(3) positive/negative control
(4)
(5)
()
volumetric solutions
volumetric solutions
volumetric solutions
(positive/negative control)
certificate of analysis ( )
supplier
186
187
()
/
188
genus species
( mice)
189
88
(program)
( )
()
190
191
192
4
89
3
12
()
193
(1) ()
(2)
(3)
(4)
(5)
(6)
(7)
()
(1) 10
(5)
seal
(7) ASEAN guidelines for
stability study of drug product
194
90
195
1
(trend analysis) 1
5 5
3
ICH Topic Q1D Bracketing and Matrixing designs for
stability testing of drug substances and drug products
196
197
91
( 2 13 )
( 7)
198
199
92
200
201
202
203
204
/
/
93
205
206
207
208
209
210
211
212
213
214
94
(1)
(2) /
(2.1) (GMP PIC/S)
(2.2)
(2.3)
/
(2.4) /
/
(2.5)
(3)
(3.1) (master formula)
(3.2)
4
(4)
(4.1)
1 5-8 6
(4.2)
(4.3)
(4.4)
95
(4.5)
(4.6)
(5)
(6)
8
(7)
12 296-297
96
215
216
217
218
219
220
221
222
215-222
223
97
224
225
226
227
228
229
230
(1) Flow chart
(2)
24
(3)
(4)
(5)
98
231
232
233
()
(corrective action)
(1)
(2)
(3)
(4)
(5) /
/ 1
(6) ()
(7)
/
99
10
6 177 180
234
(1)
(2)
(3)
(4)
(5)
234 ( 1 6)
235
Near-infrared spectrophotometer
2 10 236
100
236
(1)
(2)
(3)
(4)
(1)
PIC/S, US
FDA, TGA, ISO 9001
Annex 4
WHO guidelines for sampling of pharmaceutical products and related materials (TRS No 929, 2005)
237
Annex 4 WHO guidelines for sampling
of pharmaceutical products and related materials (TRS No 929, 2005)
101
238
(1)
(2)
(3)
(4)
(5)
ISO 2859-1, BS
6001-1, ANSI/ASQCZ 1.4-1993 5
102
11
(1)
(2)
(1)
(2) (
) 2
2 2
103
239
240
(Pharmacovigilance
report)
241
242 1
243 ( )
2
2
Jan 2000 Jan 2003
104
- Feb 2000
Feb 2002
- Feb 2001
Jan 2003
- Feb 2002
Jan 2003
244
- 2
1
- 2
1
245
246
105
247
1
248
- 25OC 252OC 605
249
7
250
251
244 246
106
252
253
254
107
12
255
256
257
(1)
(2)
(3)
(4)
(5)
(6)
(7)
258
257
108
259
260
261
262
263
264
265
(1)
(2)
(3)
(4)
109
265
266
267
(1)
(2)
268
267
269
270
(1)
(2)
271
270
272
110
273
274
275
276
277
(1)
(2)
(3)
(4)
111
(5)
(6)
(7)
(8)
(9)
(10)
(11)
278
3
279
(industrial scale batches)
280
277
281
282
283
112
284
285
286
287
288
10 30
286
10
289
290
291
113
292
293 3
294
295
296
297
114
298
115
13
299
(1)
(2)
HVAC coarse filter, medium filter and final HEPA filter AHU
(3) HVAC qualification
(4) (Environmental Monitoring) Air sampler,
settling plate
(HVAC)
300
(1)
ferrules & clamps
pump sanitary pump clean in
place
(2)
116
cleaning validation
(3) (dead legs) baffle
ball valve sanitary ball valve butterfly valve
valve
(4) cleaning validation
cleaning
(5)
301
(1)
302
sanitization
303
304
(1)
(2)
305
306
(2)
process validation
307
119
14
(Pyrogen)
308
//
HVAC
309
(Terminally sterilised)
(Conducted aseptically)
(1)
(2)
120
(3) layout
310
4
A
(Laminar Air Flow)
0.36 0.54 /
C D
311 EN/ISO
14644-1
121
(at rest)
(in operation)
0.5
5.0
0.5
5.0
A
B
C
D
3,520
3,520
352,000
3,520,000
20
29
2,900
29,000
3,520
352,000
3,520,000
20
2,900
29,000
312
A
1
A ISO 4.8
5.0
B () (0.5 5.0 )
ISO 5
C () ISO 7
ISO 8
D () ISO 8
EN/ISO 14644-1
(1) D
(2)
EN ISO 14644-1 ( (confidence interval)) appendix B 6.2 EN ISO 14644-1
EN ISO 14644
.
313
5.0
(Isokinetic sample heads)
(1) 1.5
(2) central
122
( 5 )
(inox or polymer) on site
isokinetic probe 318
(3) isokinetic head
314
EN/ISO 14644-2
- B 6
-
315
(1) (clean air device) laminar air flow, isolator restricted access
barrier system (RABS)
(2)
/
316 A
A
5.0
(1)
(3) A
A
B
B
(1) B
laminar air flow lyophilization
(2) manifold system B
124
B (in operation)
318
(1) sedimentation
5 ( S 1.5 5
30%)
0.5 5
319
(1) 1
- ()
-
1 ( 30 )
A
320 A B 5.0
5.0
125
321
15 20 (Clean up period)
(1)
clean up period
322 C D
15 20 (Clean up
period)
(1)
( GMP Annex 20)
(re-qualification)
(2)
323
126
324
A
C
D
A
C
D
325
(Swabs)
(1) A
4 4
(2) false negative
1
127
326
()
(
(
55 )
90 )
/
()
/4
<1
<1
<1
A
10
5
5
B
100
50
25
C
200
100
50
D
()
()
4
5
/
<1
5
-
(1)
327
(1)
329
(Laminar)
330
D
331
(validation)
332
(3)
333
A C
A B
129
D
334
(4)
(5)
(Clean-in-place) (Sterile-in-place)
(6)
(7)
(8)
333 334
335 D
335
336
C
336
337
2 3
A C
(Emulsions)
C
130
337
338 D
A B
338
339
C A
B
C
A B
340
A B
340
341
A B
B
( 423-427)
(1)
( 427)
grade A air supply
grade A air supply
131
(2) D
(3)
(vial stopper combination),
,
, ,
341
342 (Emulsions)
A
B
342
343
344
(1) training
(2)
(3) aseptic personnel qualification
program , basic microbiology, aseptic practice
proficiency, demonstrate gowning proficiency 3 , participation in a process
132
training
345
346
347
347
348
(1)
(2)
(3)
(4) ISO 14644-5:2004(E) Annex C (informative) Personnel
133
349
(1)
(2)
autoclave
(3)
350
D
C
2
A B
350
351
B C
A B
351
352
134
(1)
(2)
(3) drinking water
non-sterile
353
354
355
356
353-356
357 A B
A B
357
358
135
358
359 (Interlock)
360
10 15
(1) 10 15 0.04-0.06
10 15
361
(1)
136
(2) 2
Aseptic process
363 A B
A B
364
365
(1)
/
365
366
70
70 endotoxin
70
367
(1) 12
aseptic process
terminal sterilization /
aseptic process
368
(1)
(2)
(3)
369
A B
138
(1)
(2) A B
autoclave
A B
370
(1)
(2)
(3)
(4) vaporized hydrogen peroxide, formalin
Formalin
371
372
(1)
139
373
374
375
PI 007 PIC/S Recommendation on the validation of aseptic
processes 3
376
(1) 5,000
(2) 5,000 10,000
() 1
() 2
(3) 10,000
() 1
() 2
376
140
377
(1)
(2)
(3)
378
(14)
,
bioindicator
379
(Endotoxin)
141
380
(1)
(2) 25
381
(8)
382
383
384
(1)
385
142
(1) holding time
386
387
(Overkill
sterilization)
(Parametric release)
(Endotoxin)
(1) bioburden
bioburden
(sterility assurance level, SAL = 10-6) bioburden (
terminal sterilization overkill cycle) rapid micro-methods
(2)
Terminal sterilization: F0
overkill
sterilization
bioburden
388
389
390
(Simple aqueous or oily solution)
(1)
144
(2) ( 12)
(3) overkill cycle development (cycle design)
(4)
(5) (simple aqueous or oily solution)
1, 2 3
391
(Biological indicators)
(1)
(2)
(3) 1
392
393
(1)
145
(1)
(2)
395
396
397
(1)
data logger, multirecorder
(2) cold spot
146
398
(1)
399
(1) (heat
up time) load pattern
(review batch release)
400
(1) laminar
(2)
0.2 micron filter leak test
(
aseptic)
(
aseptic)
(
terminal sterilization)
(
terminal sterilization)
401
147
402
403
purified water
404
(HEPA filter)
(Pyrogen) (Endotoxin)
148
405
18
406 (Indicator)
407
408
409
(Radiation-sensitive colour disk)
410
149
411
412
413
414 (Biological
indicators)
415
416
150
417
0.22
(1) 0.22
(2) 0.22
(3)
418
(1) 0.22
419
420
(Bubble point test)
(Diffusion flow test) (Pressure hold test)
151
(1)
421
422
423
A
424
425
152
426
427
A
A
153
428
429
(1) restricted access barriers
system (RABS)
(2)
430
431
154
432
(4)
(5) PIC/S Recommendation on Guidance on Parametric Release PI 005-3 25
September 2007
434
(9)
(2)
155
19
510
(1)
511
(prospective validation)
(retrospective validation)
156
512
513
(
)
514
515
516
517
157
518
(double check)
519
520
521
158
522
4 81
523
524
525
526
159
527
7
528
160
GMP PIC/S
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
.()
.
.
.
.
.
.
.
.
.
.
.
.
.
..
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
161
GMP PIC/S
32
34
35
36
37
38
39
40
41
42
43
44
45
46
47
.
.
.
.
.
.
.
.
.
.
.
..
.
..
162