1

2
7
1 6
1 9
1 9

HEPA .24

2 8
3 2
3 3
3 5
3 5
3 7
4 1
4 2
4 4
4 9
4 9
5 2
5 4
5 6
5 8
6 3
A

64

6 8
7 0

FED-STD-209 ISO14644-1

FED-STD-209

FED-STD-209

HEPA

0.3 mDOP
99.972.541
0.249 kPa

HEPA
80

10 3 g/0.3 mDOP
10 5


1.5 m/min5 ft/min
6.4 mm0.25 in
Laskin

Dioctyl phthalate (DOP)Laskin

DOPCount Mean DiameterCMD0.3
Geometric Standard DeviationGSD1.5
Mass Mean DiameterMMD0.7 m

25-300 ft/min

DOP

28.3 L/min1.0 ft3/min

14

HEPA
2.5 cm1 in

20

Laminar Flow Cabinet

LAFC

SMACNA

3
0-3

90%

0.5 m 2%
59%10 m

1.

10

2.

1
234

1.

ASHRAE AFI TEST

2.

Am
erican Society of Heating, Refrigerating, and Air-Conditioning

EngineersASH

RAE 52-68

11

3.

DOP
DOP

1.

2.

3.

HEPA

HEPA 0.3 m HEPA

0.1 m

HEPA

12

HEPA
HEPA

1.

DOP
100

2.
5-12 fpm 0.0001-0.001 grains/ ft3
750

3.

4. HEPA

30%

13

5. 9 15

HEPA HEPA

R.H.

60 234
1

Class100
60 234

60 234

PTP

234

234

14

Class
100

10,000

100,000

100,000

885

15

1,2,3
1,2,3
1,2,3
1,2,3
OPT
OPT

HEPA

1,2

1,2

1,2

1,2,3

1,2,3

1,2,3

1,2,3

1,2,3

1,2,3

16

1,2

N/A

OPT( 1,2)

OPT

OPT

OPT

OPT

OPT

OPT

OPT

OPT

OPT

OPT

OPT

OPT

N/A
1
2
3
OPT

17

1.
2.HEPA
3.
4.
5.

1.
2.
3.

18

4.

1.

2.

19

3.

1.

30 cm12 in

2
10.37 m4
ft2

35

2.
HEPA

20

20.37 m24 ft2

15 cm6 in

3.

2L/secft 3 /min

1.

2.
1m/secft/min

21

2
3

100%

3.

1
L/secft3/min
2
3

100%

4.
1
2L/secft 3 /min

22


1.Laminar flow 9020

2.

5%

3.15

ACR

ACR=

( m 3 / s ) 3600
m 3

HEPA
3600
1020

23

HEPA

HEPA

HEPA
M3.5Class 100FED-STD-209

10 g/L
Laskin
310 10 droplets/m 3 10 9 droplets/ft 3

24

Laskin
28 m 3 /min1000 ft 3 /min138
kPa20 lb/in 2 2.7 ft 3 /min75 L/min

1130 m 3 /min40,000 ft 3 /min

50

1.
2.28.3 L/min1.0 ft 3 /min
3.

25

1.

2.

100 g/L1020
1020 g/L

100

26

3.

2.5 cm1 in
1.2 in 1.2 in3 m/min10 ft/min
0.093 m2/min1.0 ft 2 /min

1.0.03

2.0.03

HEPA
1.3

27

2.3.8 cm1.5 in

1.Terminal
HEPA filter/ Laminar Flow Unit HEPA99.97DOP Test

2.

FED-STD-209ISO14644-1

0.1,0.2,0.3,0.5 mFED-STD-209ISO14644-1

28


1.
2.
3.
4.

1.

2.

FED-STD-209
ISO14644-1

FED-STD-209

29

FED-STD-209

100,000
M6.5
10,000
M5.5
1,000
M4.5
100
M3.5

9.3
100
33
6
64
2.52.5
1.5
16
1.21.2
0.4
4
0.60.6

1010
88
44
22

3.

FED-STD-209ISO14644-1

4.

1
2

5 m
30

10 m

1.

12345

2.

95%
FED-STD-209

0.5um Class 100,000

Class 10,000
Class 100

3,530,000's/m3
100,000's/ft3
353,000's/m3
10,000's/ft3
3,530's/m3
100's/ft3

31

1.

2.

3.

2.5 Pa0.25 mm0.01 inw.g.

32

10 Pa
(1mm)

1.

2.
3.
4.

33

1.3 m x 3 m10 ft
x 10 ft0.9 m3 ft

2.

3.

4.

5.

6.35

7.

1.

34

2.
3.1422.5 cm9 in90
cm36 in

14

35

1.

1/ T
0.1

210%-95%
1%

2.

124

3.

36

4.

1
2
3
z
z
z
z
z
5.

37

1.

10.05
0.163.2%15

210%-95%
0.1%

2.

124

38

42

3.

39

4.

2
z
z
z
z
z
z

3%

z
z
z

40

6%

5.

100

1.

2.28.3 L/min.1.0 ft3/min

0.5 m

41

1.3.5106
particles/m31105 particles/ft3

2.5-10 cm2-4 in

3 m/min10 ft/min

3.0.3-3 m1-10 ft

10-3

42

1.

2.28.3 L/min.1.0 ft3/min

0.5 m

1.

2.

3.

43

HEPA

44

5 m

0.12 m

1.

2.

3.

4.""

45

()

5.

6.

7.

8.

9.4

10.

46

1.

1
AC BC
= Particles / cm
ACW

AC=""
BC=""
ACW=

3
AC BC
ACA = Net . particles / cm
ATW

ACA=
ATW=

47

48

90 mm
64 cm2cfu

49

( )

HEPA

1./
2.

cGMP

1.
2.

//

3.//

50

4.
5.
6.

7.
8.

170%

2
3

9.

1
2

51

Class 100,000
Class 10,000
Class 100

cfu/4hrs cfu/1hr
90mm 90mm
100
20
50
5
5
1

1.

52

2.

1000 L1 m3

53

1.
2.
3.
4.
5.
6.

Class 100,000
Class 10,000
Class 100

100 cfu/m3
20 cfu/m3
3 cfu/m3

1.
2.

54

3.
4.

90 mm55 mm
Class100Class10,000
Class100
Class10,000

//

Class100

1.
2.

3.

4.

5.
6.

55

 5 /
cfu/

< 1Class100
< 5Class10,000

RODACreplicate organism detection and counting

1.
2.
3.
4.
5.
6.

56

Class100

Class10,000

Class100,000

/
//
( /
)
(
) Class100

cGMP

1.
2.

//

3.
4.

57

5.
6.

7.

8.
9.
10.//
11.

Class 10,000
Class 100

cfu/plate
5
3

USP25 <1116>

5 cm x 5 cm

58

1.

0.9

2.

Class100

/
//
(/
)

Class10,000

(
) Class100

59

Class100,000

(
)

1.10 ml0.9

5 cm x 5 cm /
/
2.

//
2
3

410 ml0.9

50.5 ml

60

6
7

30

8
9
70%
10
11

12

3.

61

1
2

cfu/plate

Class 10,000
Class 100

5
3

USP25 <1116>

62


-, 88 .
-, 89 .
-, 88 .
-GMP, 74
.
IES CONTAMINATION CONTROL DIVISION RECOMMENDED PRACTICE
006.2, Testing cleanrooms.

SASSIG, Guidelines on test methods for environmental monitoring for aseptic

dispensing facilities, 1999.

VALIDATION OF ASEPTIC PHARMACEUTICAL PROCESSES, Validation of air

systems used in parenteral drug manufacturing facilities.

FEDERAL STANDARD, Airborne particulate cleanliness classes in cleanroom and

clean zone, 1992.

ISO/TC209 (ISO STD14644), 2001.

USP25 <1116> Microbiological evaluation of clean rooms and other controlled
environments.

63

90%
95%
99%

{x1,x2,, xn}

64

X =

1
n

i =1

( Xi X )

i =1

S =

D = min x upperbound , x lowerbound

C ra =

n 1

D
S ( k confidence

(n)

Kconfidence(n)A1upperboundlowerbound
70(2)
upperbound=72, lowerbound=68

Cra > 1

95%Cra=1.02

A1- k

4
5
6
7
8
9
10
11-20
21

k90
2.6
2.4
2.2
2.1
2.0
2.0
1.9
1.8
1.7

k95
3.6
3.0
2.8
2.6
2.5
2.4
2.4
2.2
2.0

K99
6.5
5.0
4.4
4.0
3.7
3.5
3.4
3.1
3.0

65

n
n

70(2) 10
1
71.2

2
70.8

3
70.2

4
69.8

5
69.7

6
70.1

7
71

8
68.9

9
69.5

10
71.8

X = 70 .3; S = 0.886 ; D = 1.7

A1 K90(10)=1.9 Cra=1.01 90%

n
n n

20(1)
14
1
20.5

2
20.2

3
20.8

4
19.6

5
19.5

6
19.8

7
19.7

10

11

12

13

14

66

20.3

20.3

20.1

19.4

20.0

20.2

20.5

X = 20 . 06 ; S = 0 . 416 ; D = 0 . 936

95%

A1 K95(14)=2.2 Cra=1.02

95%
99%A1 K99(14)=3.1 Cra=0.73
99%

67

Uniformity
Entrance plane
Work zone
Calibrated equipment
Air-generated aerosol
Parallel airflow
Uniform airflow
Antimicrobial
Viable particle
Regulatory limitations
Air handling system
Aerosol photometer
Spatial Uniformity
Nonunidirectional airflow cleanroom
Anemometer
Airflow volume
Confidence levels
Threshold
As-built cleanroom (facility)
Temporal Uniformity
Disinfction
High efficiency particulate air filter
Finger dab plate
Controlled work space
Controlled environment
Probing or scanning
Contact plate
Mixed airflow cleanroom
Petri dish
As-rest cleanroomfacility
Unidirectional airflow cleanroom
Residual activity
Closed-cell neoprene
No controlled environment
Isokinetic smoke generator
Colony forming unit
Transfer device
Temperature control zone
Isolator
Electronic micromanometer
Resistance temperature devices (RTDs)

68

Designated leak
Standard leak penetration
Clean air device
Cleanroom
Clean zone
Thermal anemometer
Heat sinks
Operational cleanroom (facility)
Discrete-particle counter
Critical work zone
Critically controlled environment

69


Aerosol photometer
Airflow volume
Air handling system
Air-generated aerosol
Anemometer
Antimicrobial
As-built cleanroom (facility)
As-rest cleanroomfacility
Calibrated equipment
Clean air device
Clean zone
Cleanroom
Closed-cell neoprene
Colony forming unit
Confidence levels
Contact plate
Controlled environment
Controlled work space
Critical work zone
Critically controlled environment
Designated leak
Discrete-particle counter
Disinfction
Electronic micromanometer
Entrance plane
Finger dab plate
Heat sinks
High efficiency particulate air filter
Isokinetic smoke generator
Isolator
Mixed airflow cleanroom
No controlled environment
Nonunidirectional airflow cleanroom
Operational cleanroom (facility)
Parallel airflow
Petri dish
Probing or scanning
Regulatory limitations
Residual activity
Resistance temperature devices (RTDs)

70

Spatial Uniformity
Standard leak penetration
Temperature control zone
Temporal Uniformity
Thermal anemometer
Threshold
Transfer device
Unidirectional airflow cleanroom
Uniform airflow
Uniformity
Viable particle
Work zone

71