Lovastatin Tablets 20mg Cleaning Validation ProtocolÅ·ÃËÇå½àÑéÖ¤·½°¸

8/13/2019 Lovastatin Tablets 20mg Cleaning Validation ProtocolÅ·ÃËÇå½àÑéÖ¤·½°¸

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Subject

Lovastatin Tablets 20mg Cleaning Validation Protocol

Table of contents

1. Responsibility

2. Purpose3. Frequency

4. Relevant SOP’s

5. Equipment

. !est "et#o$

%. &cceptance 'riteria

(. Ris) &nalysis

*. Samplin+ Plan

1,. &ction ta)en -#en outo/limit result /oun$

12. Revali$ation

13. 'leanin+ 0ali$ation Eecutive Recor$

14. 'onclusion

&ttac#ments

ritten by 制者： ate 日期：

Revie-e$ by 核者：复 ate 日期：

&pprove$ by 批准者： ate 日期：

&pprove$ by 批准者： ate 日期：



1. Responsibilit

& is responsible /or plan t#e cleanin+ vali$ation.

' is responsible /or samplin+ an$ analysis. Pro$uction epartment is responsible /or per/ormin+ cleanin+ pro$uction equipment.

2. Purpose!#e purpose o/ t#is cleanin+ vali$ation protocol is to $emonstrate t#at t#e cleanin+ proce$ure use$

to clean 67825,9 #i+# s#ear mier : +ranulator; t#ree－$imensional mier ，'!'2 7ot &ir

'irculatin+ rier ， 68F4,, +ranulators < mill =orsc# P73,,3 !ablet Press，9>15, #i+#

e//iciency coatin+ mac#ine an$ PP25,9 blister pac)a+in+ mac#ine can e//ectively remove resi$ues o/

t#e pro$ucts manu/acture$ in 8S5, 0orte Oscillator:'ompact Sieve，67825,9 #i+# s#ear mier :

+ranulator; t#ree－$imensional mier ，'!'2 7ot &ir 'irculatin+ rier ， 68F4,, +ranulators < mill

=orsc# P73,,3 !ablet Press，9>15, #i+#e//iciency coatin+ mac#ine an$ PP25,9 blister

pac)a+in+ mac#ine to a pre$etermine$ level t#at $oes not raise any sa/ety concerns.

!. "re#uenc

!#e cleanin+ vali$ation stu$y is per/orme$ a/ter t#ree consecutive ma?or cleanin+s o/ 8S5, 0orte

Oscillator:'ompact Sieve，67825,9 #i+# s#ear mier : +ranulator; t#ree－$imensional mier ，'!'

2 7ot &ir 'irculatin+ rier ， 68F4,, +ranulators < mill =orsc# P73,,3 !ablet Press，9>15,

#i+#e//iciency coatin+ mac#ine an$ PP25,9 blister pac)a+in+ mac#ine a/ter t#e manu/acture o/@ovastatin !ablets.

$. Relevant S%P&s

SOPP3,4,, 'leanin+ proce$ure /or7@S>3,,7i+# Spee$ "ier:>ranulator

7@S>3,,

SOPP3,4,,'leanin+ proce$ure /or@F12,E-B airpillow-dry Granulator LF120E-B

SOPP31,,, 'leanin+ proce$ure /or 8P43 7i+# Spee$ rotary tablet press

SOPP3,%,,'leanin+ proce$ure /or HLD-1000B Hopper type of blender

7@1,,,9

SOPP3,,,'leanin+ proce$ure /or A=1, +ranulators

A=1,

SOPP311,,'leanin+ proce$ure /or 9>3,,E #i+#e//iciency coatin+ mac#ine

9>3,,E

SOPP313,,'leanin+ proce$ure /orP713,、 PP25,9 blister pac)a+in+ mac#ine

P713,、PP25,

ESS0,,% 0ali$ation +ui$eline B cleanin+

ESS0,11 Sur/ace samplin+ /or cleanin+ vali$ation

ESS0,14 Selection o/ t#e -orst case in cleanin+ vali$ation

SOP'1,%5

ESS>", "icrobe !est



5. Equipment

'.1 List of (#uipment

!#e list o/ Equipment use$ in t#e manu/acture o/ @ovastatin !ablets

1．7@S>3,, #i+# s pee$ mier : +ranulator

2. L"120()* airpillo+)dr ,ranulator

3. 8P43!ablet Press 8P43 !ablet Press4. "E!&@ E!E'!OR

5. 7@1,,,97@1,,,9 7opper type o/ blen$er

. A=1,+ranulators

%. P713,CPP25,blister pac)a+in+ mac#ine P713,、

(. 9>3,,E#i+#e//iciency coatin+ mac#ine

!able 1

'.2 Validation Scope

7@S>3,, #i+# s#ear mier : +ranulator

L"120()* airpillo+)dr ,ranulator

8P43!ablet Press

"E!&@ E!E'!OR

7@1,,,9 !ranule mier

A=1, +ranulators

P713,、PP25, blister pac)a+in+ mac#ine

9>3,,E#i+#e//iciency coatin+ mac#ine

-. Test et/od!#e cleanin+ vali$ation stu$ies are base$ on t#e s-abbin+ tec#nique an$ rinsin+ samplin+. !#e

selecte$ s-abs s#oul$ be c#aracteriDe$ /or t#eir suitability an$ a recovery test s#oul$ be per/orme$

prior to t#e vali$ation stu$ies. !#e vali$ation stu$ies inclu$e s-abbin+ o/ t#e main sur/ace area as-ell as t#e #ar$toclean locations. S-abbin+ an$ rin+in+ is carrie$ out /or t#e active in+re$ient.

o. (#uipment

o.

(#uipment ame Product Contact Surface

rea

m23

1 7@S>3,, #i+# s pee$ mier : +ranulator 2.(1

2 @F12,E9 airpillow-dry Granulator 5.*,

3 8P43!ablet Press

4 METAL DETECTOR ,.3

5 7@1,,,9HLD-1000B Hopper type of

blender 5.25

6 A=1,+ranulators ,.3%

7 P713,CPP25, blister pac)a+in+ mac#ine 1.,

8 9>3,,E#i+#e//iciency coatin+ mac#ine (.43

!otal Pro$uct 'ontact Sur/ace &rea m2 **.2



Samplin+ "et#o$S-ab Samplin+

Rin+in+ samplin+

4. cceptance Criteria Visual 5nspection

− cceptance Criteria

!#ere is no visible resi$ue in equipment sur/ace a/ter cleanin+. cceptance Criteria of microbe

- For s-ab samples

icrobes 2 C"67cm2 ， '0 C"6 7 2' cm2

- For rinsin+ samples :icrobes 100 C"67ml

cceptance Criteria of assa

ctive 5ngredient see ttac/ment 2-3

MC m+:s-ab G HHHH,.,(43H HHHHHH

&ctive

For rinsin+ samples

MC m+:@ G HHHH,.,(4H HHHHHH &ctive

Test fre#uenc

!#e cleanin+ vali$ation stu$ies are con$ucte$ a/ter t#ree consecutive ma?or cleanin+s o/

Iour)rin !ablets.

8. Ris9 nalsis

!#e resi$ues o/ t#e pro$ucts are not $istribute$ uni/ormity; so t#e ris) analysis s#oul$

be $one be/ore cleanin+ vali$ation samplin+. !#e 'ritical location -ill be $etermine$ at ris)

analysis. Ris) analyses are summariDe$ in &ttac#ment 1an$ &ttac#ment 1(.

:. Sampling Plan

"or active ingredient

:.1 S+ab sampling

!#e /ollo-in+ location -ill be sample$ as ris) analysis

:.1.17@S>3,,#i+# s#ear mier:+ranulator

!otal are % samples

!able 3

Part ame Sampling Location Sampling o.S+ab rea Ss

cm23

Pan Si$e 7@S>3,,1 2,,

Jn$ersi$e 7@S>3,,2 2,,Knner sur/ace 7@S>3,,3 2,,

Rim area un$er t#e seal 7@S>3,,4 2,,



7@S>3,,5 2,,

7@S>3,,

7@S>3,,% 2,,

:.1.! 8P43!ablet Press

!otal are ( samples

!able 5


cm23

P>1、8P431 2,,

P>1、8P432 2,,

P>1、8P433 2,,

P>1、8P434 2,,

P>1、8P435 2,,

P>1、8P43 2,,

P>1、8P43% 2,,

P>1、8P43( 2,,

:.1.$ 7@1,,,9HLD-1000B Hopper type of blender

!otal are 3 samples

!able


cm23

!" #$内 6S7,,1 2,,

6S7,,2 2,,%!" #$内 6S7,,3 2,,

:.1.- ;<")$00 granulators = mill

!otal are samples

!able (


cm23

&' #$内 68F4,,1 2,,

#$内 68F4,,2 2,,() $内 68F4,,3 2,,

*+内 68F4,,4 2,,

%!" #$ 68F4,,5 2,,

#$ 68F4,, 2,,

:.1.4 >PP)2'0* blister pac9aging mac/ine

!otal are 4 samples!able *


cm23

PP25,91 2,,

PP25,92 2,,

PP25,93 2,,

PP25,94 2,,



:.1.8 (TL >(T(CT%R

!otal are 4 samples

!able 1,


cm23

!, - $ "1 2,,

. $ "2 2,,

%!, #$内 "3 2,,

/%" #$内 "4 2,,

:.1.: *,>)1'0> /ig/)efficienc coating mac/ine

!otal are ( samples

!able 11


cm23

0! + 9>15,1 2,,

$ 9>15,2 2,,

*+ 9>15,3 2,,

$ 9>15,4 2,,

*+ 9>15,5 2,,

+ 9>15, 2,,

9>15,% 2,,

9>15,( 2,,

:.2 Rinsing sampling

9>15, #i+#e//iciency coatin+ mac#ine

Sampling location

T/ree－dimensional mi?er 7@1,,,9

Sampling location4 +5 体

"or icrobes

7894 :

:.!.1 ;@<25,9 #i+# s#ear mier:+ranulator67825,9;< =制>?湿

!otal are % samples

@% :个

!able 12 # 12

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm23

4 $

Pan

制>

Si$e $ 67825,9& 25

Jn$ersi$e*$ 67825,99 25

%!" Knner sur/ace #$内 67825,9' 25& Rim area un$er t#e seal

&B

67825,9 25

#$内 67825,9E 25



> / 67825,9F 25

.#$ 67825,9> 25

:.!.2 8S5, 0orte Oscillator:'ompact Sieve

8S5, F!otal are 5 samples

@5 :个

!able 13 # 13

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm23

4 $

-& #$内 8S5,& 25

网 -#$ 8S5,9 25

%!" #$内 8S5,' 25

GHI #$内 8S5, 25() #$内 8S5,E 25

:.!.! =orsc# P73,,3 !ablet Press

=ORS'7 P73,,3 J K /?

!otal are ( samples

@( :个

!able 14 # 14

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm234 $

.!, #$内 P73,,3& 25

! #$ P73,,39 25

P73,,3' 25

%/) #$内 P73,,3 25

N) #$内 P73,,3E 25

$ P73,,3F 25

*$ P73,,3> 25

P #$内 P73,,37 25

:.!.$ T/ree－dimensional mi?er

7@1,,,9Q!,KS? U V清!otal are 3 samples

@3 :个

!able 15 # 15

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm23

4 $

!" #$内 6S7,,& 25

6S7,,9 25

%!" #$内 6S7,,' 25

:.!.' CT)C)2 7ot &ir 'irculatin+ rier CT)C)2Q W XY

!otal are 1, samples

@1, :个



!able 1 # 1

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm234 $

X #$ '!'2& 25

$内 '!'29 25

Y体 Z '!'2' 25

[ '!'2 25

+ '!'2E 25

'!'2F 25

\ ]^'!'2> 25

'!'27 25

Y #$内 '!'2K 25

GH条 '!'26 25

:.!.- ;<")$00 granulators = mill

;<")$00Q_>、O`?

!otal are samples

@ :个

!able 1% # 1%

Part ame

部件名称Sampling Location4 5A

Sampling o.4 :

S+ab rea Ss

cm23

4 $

&' #$内 68F4,,& 25

#$内 68F4,,9 25

() $内 68F4,,' 25

*+内 68F4,, 25

%!" #$ 68F4,,E 25

#$ 68F4,,F 25

:.!.4 >PP)2'0* blister pac9aging mac/ine

>PP)2'0*Qabcd e1 ?!otal are 4 samples

@4 :个

!able 1( # 1(

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Ss

cm23

4 $

!, $ PP25,91 25

*+ PP25,92 25

f!g #$ PP25,93 25

g #$ PP25,94 25

:.!.8 (TL >(T(CT%R

h i



!otal are 4 samples

@4 :个

!able 1* # 1*

Part ame

部件名称

Sampling Location

4 5A

Sampling o.4 :

S+ab rea Ss

cm23

4 $!, - $ "& 25

. $ "9 25

%!, #$内 "' 25

/%" #$内 " 25

:.!.: *,>)1'0> /ig/)efficienc coating mac/ine

12?

!otal are ( samples

@( :个

!able 2, # 2,

Part ame

部件名称

Sampling Location

4 5A

Sampling o.

4 :

S+ab rea Sscm23

4 $

0! + 9>15,& 25

$ 9>15,9 25

*+ 9>15,' 25

$ 9>15, 25

*+ 9>15,E 25

+ 9>15,F 25

9>15,> 25

9>15,7 25

:.$ Ringing samplingjkl4

9>15, #i+#e//iciency coatin+ mac#ine12?

Sampling location 取部位： "" " ""硅管、

T/ree－dimensional mi?er 7@1,,,9 Q!,KS? U V清

Sampling location4 +5 体

10. ction ta9en +/en out)of)limit result found

mnS3opqB rst4Buv

L, Knspect t#e process o/ operation

V

1. Knspect t#e equipment o/ assay fwsxB )

2. Knspect t#e step o/ operation y

#. Knspect t#e process o/ samplin+ z V

L1 &，' an$ t#e pro$uction $epartment calculate -it# t#e results o/ inspect.

&，' { + r |

L2 "o$i/y t#e vali$ation planM revali$ate t#e items; -#ic# are not applicable be/ore.

}~ ， mnSB • |€ 划

11. Revalidation



‚

Revali$ation s#oul$ be consi$ere$ un$er t#e /ollo-in+ circumstances

"""""""""""""""""在下列情况生，必考 !" #$ ：

− 'leanin+ met#o$ c#an+e$: " " " " " "清 % & '

− 'leanin+ $eter+ents c#an+e$: """" "清 '− Pro$uct c#an+e$:" "" "( '

12. Cleaning Validation (?ecutive Record

V

ƒ„ 11( Ris) &nalysis !able fw#

ƒ„ 1* 0isual Knspection an$ Samplin+ /or &ctive Kn+re$ient • …

ƒ„ 2, 0isual Knspection an$ Samplin+ /or "icrobes • …

ƒ„ 21 &nalytical Results /or &ctive Kn+re$ient fw r

ƒ„ 22 &nalytical Results /or "icrobes fw r

ƒ„ 23 Samplin+ Recovery !est †‡ˆ

ƒ„ 24 S-ab '#acteriDation /or 'leanin+ 0ali$ation

k ‰ Š‹ Œ清 )

ƒ„ 25 S-ab Samplin+ /or 'leanin+ 0ali$ation k ‰ 清

ƒ„ 2 'alculation /or &cceptance 'riteria opqB

14. C%CL6S5%

!#e results obtaine$ s#oul$ not ecee$ t#e calculate$ contamination limit. !#e cleanin+ proce$ure /or

all pieces o/ pro$uction equipment e//ectively removes resi$ues o/ @ovastatin !ablets manu/acture$ in

t#is equipment an$ is t#ere/ore $eeme$ vali$ate$. "icrobes limit comply -it# t#e requirement.

rmŽ %B p. B V‘’“”< N –， ”<清清 *

9pqnS—˜



ttac/mentƒ„ 1A Ris9 nalsis Table for active ingredient fw#A

Equipment Iame ™称 67825,9 7i+# S#ear "ier : >ranulator ate 日期

67825,9 ;< =制>?湿

1 2 ! $

1.1 1.2L 2.1

'ritical

+

3.1

Ris) /or Process

Step

3.2

Eval.

o/ ris)

,

3.3

Follo-up

o/ ris)

š›-

”

4.1

Possible cause

’cBœ

4.2

0ali$ation

measur

uv

4.3

0ali$ation

plan

划

4.4

ate

日期

4.5

Responsibl

e person

ž

Io.

‘.

'omponent

Iame

+„™称

Sam. Io.

+

'ontact&rea

#/

$

Aes

š

Io

›

Aes

š

Io

›

1

2

3

4

5

制>

%!"

&

>

Knner sur/ace

#$内

#$内

#$内

#$

#$

N

N

N

N

Possibility o/

contamination

-it# previous

pro$uctŸ批 ¡0

¢B’c‹

itto

£-

itto

£-

itto£-

"

"

"

7

7

N

N

'leanin+

proce$ure o/

SOP is not

e//icient ¤=m¥清

”<

itto

£-

itto

£-

itto

£-

'#ec) cleanin+

result at $e/ine$

location¦ §+

r清

itto

£-

itto

£-

itto

£-

See

vali$ation

protocol

清

¤¨

1.2L Sample Io. see t#e seven samplin+ points on !able3. +： @ % :个 # !.

"ormat

B*



ttac/mentƒ„ 2 A Ris9 nalsis Table for active ingredient fw#A

Equipment Iame ™称 8S5, 0orte Oscillator:'ompact Sieve ate 日期

8S5, F

1 2 ! $

1.1 1.2 2.1

'ritical

+

3.1

Ris) /or Process

Step

3.2

Eval.o/ ris)

,

3.3

Follo-upo/ ris)

š›-

”

4.1

Possible cause

’cBœ

4.2

0ali$ationmeasure

uv

4.3

0ali$ation plan

划

4.4

ate

日期

4.5

Responsible person

ž

I

o

‘

.

'omponent

Iame

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L

Sam.

.Io.

+

'ontact

&rea

#/

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Aes

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Io

›

Aes

š

Io

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1

2

3

4

5

12

网

%!"

GHI

()

Knner sur/ace

#$内

Sur/ace

#$

Sur/ace

#$内

#$内

#$内

Possibility o/

contamination -it#

previous pro$uctŸ批 ¡ ¢0

B’c‹

itto

£-

itto

£-

itto£-

itto

£-

@

7

7

"

"

N

'leanin+

proce$ure o/

SOP is not

e//icient ¤=m¥清

”<

itto

£-

itto

£-

itto

£-

itto

£-

'#ec) cleanin+

result at $e/ine$

location¦ §+

r清itto

£-

itto

£-

itto

£-

itto

£-

See

vali$ation

protocol 清

¤¨

1.2 L Sample Io. see /ive samplin+ points on !able 4. +：@ 5 :个 # $.

ttac/mentƒ„ !A Ris9 nalsis Table for active ingredient fw#A

"ormat

B*



Equipment Iame ™称 =orsc# P73,,3 !ablet Press ate 日期

=ORS'7 P73,,3 J K /?

1 2 ! $

1.1 1.2L 2.1

'ritical

+

3.1

Ris) /or Process

Step

3.2

Eval.

o/ ris)

,

3.3

Follo-up

o/ ris)

š›-

”

4.1

Possible cause

’cBœ

4.2

0ali$ation

measur

uv

4.3

0ali$ation

plan

划

4.4

ate

日期

4.5

Responsibl

e person

ž

Io.

‘

.

'omponent Iame

+„™称

Sam.

Io.

+

'ontact

&rea

#/

$

Aes

š

Io

›

Aes

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Io

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1

2

3

4

5

%

(

7opper

.!,

"34

567

897

"6:;<

… P= =

P

Knner sur/ace

#$内

#${

#$

#$内

#$

#$

#$内

#$内

N

N

N

N

N

N

N

N

Possibility o/contamination

-it# previous

pro$uctŸ批 ¡0

¢B’c‹

itto

£-

itto

£-

itto

£-

"

7

"

"

@

"

@

7

N

N

N

N

N

'leanin+ proce$ure o/

SOP is not

e//icient ¤=m¥清

”<

itto

£-

itto

£-

itto

£-

itto

£-

'#ec) cleanin+result at $e/ine$

location¦ §+

r清

itto

£-

itto

£-

itto

£-

itto

£-

Seevali$ation

protocol

清

¤¨

1.2L Sample Io. see t#e ei+#t samplin+ points on !able5. +： @ ( :个 # '.

ttac/mentƒ„ $A Ris9 nalsis Table for active ingredient fw#A

"ormat

B*



Equipment Iame ™称 !#ree－$imensional mier ate日期

7@1,,,9 Q!,KS? U V清

1 2 ! $

1.1 1.2L 2.1

'ritical

+

3.1

Ris) /or Process

Step

3.2

Eval.

o/ ris)

,

3.3

Follo-up

o/ ris)

š›-

”

4.1

Possible cause

’cBœ

4.2

0ali$ation

measur

uv

4.3

0ali$ation

plan

划

4.4

ate

日期

4.5

Responsibl

e person

ž

Io.

‘

.

'omponent Iame

+„™称

Sam.

Io.

+

'ontact

&rea

#/

$

Aes

š

Io

›

Aes

š

Io

›

1

2

3

!"

%!"

体

Knner sur/ace

#$内

Knner sur/ace

#$内

Knner sur/ace

#$内

N

N

N


-it# previous

pro$uctŸ批 ¡0

¢B’c‹

itto

£-

"

"

7


SOP is not

e//icient ¤=m¥清

”<

itto

£-

itto

£-


location¦ §+

r清

itto

£-

itto

£-

Seevali$ation

protocol

清

¤¨

1.2L Sample Io. see t#e t#ree samplin+ points on !able . +： @ 3 :个 # -.

ttac/mentƒ„ 'A Ris9 nalsis Table for active ingredient fw#A

"ormat

B*



Equipment Iame ™称 '!'2 7ot &ir 'irculatin+ rier ate 日期

'!'2 Q W XY

1 2 ! $

1.1 1.2L 2.1

'ritical

+

3.1

Ris) /or Process

Step

3.2

Eval.

o/ ris)

,

3.3

Follo-up

o/ ris)

š›-

”

4.1

Possible cause

’cBœ

4.2

0ali$ation

measur

uv

4.3

0ali$ation

plan

划

4.4

ate

日期

4.5

Responsibl

e person

ž

Io.

‘

.

'omponent Iame

+„™称

Sam.

Io.

+

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Remar)s HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

Si+nature HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH ate HHHHHHHHHHHHHHHHHHHHHH

™ 日期



ƒ„ 1: V5S6L 5SP(CT5% > SPL5,

• …4





+„™称 •


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2.

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4.

5.

.

%.

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11.



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• …4





+„™称 •


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1.

2.

3.

4.

5.

.

%.

(.

*.

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™ 日期



ƒ„ 1: V5S6L 5SP(CT5% > SPL5,

• …4


Equipment HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 9atc# Io 批. HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH


+„™称 •


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%.

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*.

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• …4





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• …4





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%.

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• …4





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%.

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ƒ„ 20 V5S6L 5SP(CT5% > SPL5,• …4





+„™称 •

'lean Jnclean "icrobes

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1.

2.

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4.

5.

.

%.

(.

*.

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• …4





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• …4





+„™称 •

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3.

4.

5.

.

%.

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• …4





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1.

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4.

5.

.

%.

(.

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ƒ„ 20 V5S6L 5SP(CT5% > SPL5,

• …4




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4.

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%.

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• …4





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ƒ„ 21 LT5CL R(S6LTS

fw r

Product ameA *atc/ o.A (#uipmentA

™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11

Si+nature HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH ate HHHHHHHHHHHHHHHHHHHHHHHH ™ 日期




fw r


™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11





fw r


™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11





fw r


™ 批.

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+5

ctive 5ngredient

mg7s+ab3

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mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

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+5

ctive 5ngredient

mg7s+ab3

«‹¬f

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11





fw r


™ 批.

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+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11

Si+nature HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH ate HHHHHHHHHHHHHHHHHHHHHHHH

™ 日期




fw r


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 日期




fw r


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 日期




fw r


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 批.

(#uipment Part

+5

icrobes C"6 7s+ab3

789

Pass

S®

"ail

mS®

1

2

3

4

5

%

(

*

1,

11


™ 日期



ƒ„ 23

Hisun Pharmaceuticals Co., Ltd.

¯°

E$ition Io.

±²：

Sampling Recover Test

4 †‡ˆ

0ali$ation Jnit

³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期：

uality &ssurance

¶· +

Pa+e 1 o/ 3

Safet

¸¹

• ear po-$er/ree +loves an$ +o++les.

º» ¼½…¸¹¾ .

• Jse a /ume cupboar$ -#ile -or)in+ -it# or+anic solvents.

¿x”?ÀÁ —xÂ .

(#uipment and aterials

…9!

Equipment

• Stainless steel sur/ace ma$e o/ t#e same material as t#e equipment construction material -#ic# s#oul$ be

sample$.

Ã£Ä Bm ÅÆ

• S-ab use$ as t#e sample$ location in t#e equipment Iame HHHHHHHHHHHHH

‰ ： ™称 HHHHHHHHHHHHH

• Suitable +lass Erlenmeyer /las)s.

(¶@.

• Po-$er/ree +loves

» ¼½

• 'lean pincers

'清

Materials

9!

• Etractin+ solvent /or active material samplin+

x«‹¬fÇBÀÈ

'#oose t#e appropriate solvent ta)in+ into consi$eration t#e solubility o/ t#e contaminant active in+re$ients in

it. !#e toicity o/ t#e solvent s#oul$ also be consi$ere$. Fluvastatin So$ium selects t#e -ater to etract activematerial.

É BÀ ，Ê Ë «‹¬fBÀÌ‹…Í‹ Î xl U Ç A B

• %5 alco#ol /or cleanin+ a+ents samplin+.

x清 %5ÏÐÑÀÈ.• &ctive in+re$ient o/ t#e pro$uct to be vali$ate$ /or cleanin+.

Ò«‹¬fÓ k清

Procedure

V‘

!#e aim o/ t#is test is to $etermine t#e reliability o/ t#e samplin+ met#o$; an$ to ta)e into account loss $ue to samplin+

limitation.

Ô B•Bš § ¤=B’ ‹C D ; £ Ê Õ p制Ö¬B ×.

!#is test is to be per/orme$ /or t#e pre$etermine$ active in+re$ient in accor$ance -it# t#e speci/ic protocol /or t#e

equipment. | Ø §B Ù¨ÃÆÚB«‹¬fB- 0 .



ƒ„ 23


¯°

E$ition Io.

±²：

Sampling Recover Test4 †‡ˆ

0ali$ation Jnit

³

Superse$es´µ

Pro$uction +

E//ective ate

|日期：

uality &ssurance

¶· +

Pa+e 2 o/ 3

Method for Active Ingredient

«‹¬f4 ¤=

1. Jsin+ t#e appropriate solvent #ere usin+ -ater; prepare a stoc) solution calculate$ to yiel$ t#e approimate

amount o/ t#e active in+re$ient as calculate$ /or t#e maimal allo-able contamination level but not more t#an 3 o/

t#e calculate$ value per ,.5ml.

¿xÉ BÀA Î xl0制œ!ÀÈ， q šÛ*§¶pÜšmcÝ pqBÞßà ,.5ml.

2. &pply a measure$ amount o/ t#e stoc) solution to t#e test sur/ace 1, 1,cm an$ $ry it in an oven 3%°.

0制áâ qBÀÈ，ã ä Å-E 1, 1,cm ，Xå 3%°.

3. &llo- t#e sample to cool at room temperature.

æ ç èéF .

4. ear +loves an$ ta)e samples /rom t#e test sur/aceM every 1, 1, cm sur/ace #as one sample an$ ta)e at least 2

s-ab samples in every sur/ace usin+ ne- +loves an$ a $i//erent s-ab -ette$ -it# t#e etractin+ solution.

º¼½ êë#$G 个 1, 1, cm ³B ìf H ; àíxîï ð‰ êë¿xñB¼½… ”ÇÈI

B‰.

5. !rans/er eac# s-ab into a suitable labele$ +lass Erlenmeyer /las) an$ protect it /rom eternal contamination. !#e

samplin+ must be complete as quic)ly as possible to prevent solvent evaporation an$ contaminant re$eposition ont#e sample$ sur/ace.

ò‰ ó ôB(¶ Ò，õö÷ ¢@ B . ø ùú¬“öÀ … ¢9 ó #$J K .

. Submit t#e labele$ seale$ +lass Erlenmeyer /las) to t#e analytical laboratory imme$iately alon+ -it# t#e blan)sample one s-ab -ette$ -it# t#e etractin+ solvent an$ t#e appropriate analytical request /orm.

fwû ， ôBGHB (¶ …üý þÇ B‰ ÿófw çLM @ 湿 .

%. !#e samplin+ recovery value is t#e ratio bet-een t#e measure$ values an$ t#e epecte$ values.

†‡ˆš 准 …期望之比.

cceptance Criteria

’ 准

• !#e overall samplin+ yiel$ value o/ s-abs s#oul$ be not less t#an %,.

¹+‰ †‡ˆm³ %,.

• Kn cases -#ere lo- results are obtaine$ in a repro$ucible manner; t#e sample sur/ace area may be sample$ a+ain

usin+ a secon$ s-ab an$ t#e results obtaine$ /rom bot# s-abs summe$ up.

如r³ %,，’“ ÷Æ只‰ ¦£Æ $ € “-U，者之…复 %,



ƒ„ 23


¯°

E$ition Io.

±²：Sampling Recover Test

4 †‡ˆ

0ali$ation Jnit

³Superse$es

´µ

Pro$uction

+

E//ective ate

|日期：

uality &ssurance

¶· +

Pa+e 3 o/ 3

Test Result

†‡ˆ rA

S-ab samplin+ test results

m Å 1,,cm2 ìêë r：H

Select area

ìH!est active

in+re$ient amount

Ž ¶þu+ÿ

S-ab percent

†‡ˆþÏÿ

"ean s-ab percent

平ã†‡ˆþÏÿ

RSþÏÿ

%5 alco#ol

%5ÐÑ

1

2

3

4

5



ƒ„ 24


¯°

E$ition Io.±².

S+ab C/acteriDation for

Cleaning Validation

‰ Š‹ Œ

0ali$ation Jnit ³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 1 o/ 3

Safet

¸¹

• ear po-$er/ree +loves an$ +o++les.

º» ¼½…¸¹¾ .

• Jse a /ume cupboar$ -#ile -or)in+ -it# or+anic solvents.

¿x”?ÀÁ —xÂ


…9!

• S-abs to be teste$.

x‰

• &nalytical instrumentation.

fw )

• Pincers.

'

• >lass Erlenmeyer /las)s.(¶@.

• Puri/ie$ -ater.

化l.

• Solvent to be use$ to saturate s-ab.

‰ 浸透È.

• Solvent to be use$ to etract t#e s-ab accor$in+ to t#e speci/ic cleanin+ vali$ation protocol.

‰ ÇÈ

Procedure

V‘

Sa! a!sorption capacit"

‰ 吸 ‡c 力

1. Kn$ivi$ually -ei+# 1, unuse$ $ry s-abs.

f ¶称 1, å燥B‰ €¶个 .

2. Soa) eac# s-ab in t#e puri/ie$ -ater.

‰ 浸ó 化lÒN .

3. Jsin+ pincers; remove t#e s-ab /rom t#e -ater; #ol$ it until $rippin+ stops; an$ place it imme$iately on t#e balance pan.

x ' ‰ %，直óm‚滴落ÀÈ 止，立 ‰ 放ó天平 -N ON .

4. Kn$ivi$ually -ei+# t#e 1, saturate$ s-abs an$ calculate t#e s-ab solvent absorption capacity.

f ¶称 1, ”ÀÈB‰ ， ‰ B吸‡c力个I .



ƒ„ 24


¯°

E$ition Io.±².


Cleaning Validation

‰ Š‹ Œ

0ali$ation Jnit ³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 2 o/ 3

Sa! interference

‰ å

1. Place on unuse$ $ry s-ab in Erlenmeyer /las)s; -#ic# eac# containin+ one o/ t#e /ollo-in+ solvents.

¦ 形 Ò放入å燥B未¿xB‰ ，à 形含”Æ .列À@ 个 @ P

• Puri/ie$ -ater

化l

• S-ab etractin+ solvent to be use$ in t#e analytical test met#o$

fw B‰ ÇÈ

2. S#a)e /or 5 minutes.

F 5 f .

3. !est t#e etraction solvent by t#e analytical met#o$s to be use$ to $etermine t#e active in+re$ient; respectively; an$

calculate t#e s-ab inter/erence response; to be ta)en into account in t#e analytical $etermination. «‹¬fB‰ ÇÈ， ‰ å 影

cceptance criteria

’ 准

!#e s-ab suitability is base$ on t#e /ollo-in+ consi$erations

‰ BÉx‹š建立¦.列Ê 之-

• Io c#an+e in s-ab appearance an$ color.

‰ B÷ … 色 ”~Q .

• S-ab $urability -it#out si+ns o/ $isinte+ration; /ibers or se$iments.

‰ 久耐x， ” 落{ 淀 Q R K .

• ater absorption capacity is not less t#an t#e volume o/ solvent or -ater nee$e$ to $issolve t#e calculate$

amount o/ resi$ual active in+re$ient; respectively.

lB吸‡c力mcï需—ÀÌ«‹9 –B* 体 .



ƒ„ 24


¯°

E$ition Io.±².


Cleaning Validation

‰ Š‹ Œ

0ali$ation Jnit ³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 3 o/ 3

!est results

r：

Purified +ater l

1 2 ! $ ' - 4 8 : 10

ry s-ab -ei+#t

å‰ €þ+ÿ

et s-ab -ei+#t

‰ €þ湿 +ÿ

&bsorption -ei+#t

‰ 吸l¶þ+ÿ



ƒ„ 25


¯°

E$ition Io.

±²S+ab Sampling for Cleaning

Validation ‰ 4

0ali$ation Jnit

³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 1 o/ 4

Safet

¸¹

ear po-$er/ree +loves an$ +o++les.

º» ¼½…¸¹¾


…œ!

• S-ab Jse approve$ s-abs; suc# as !e-ipe or #atman paper.

‰ ¿xÓ核准B‰

• Solvent For t#e active in+re$ient; use t#e solvent prescribe$ in t#e speci/ic cleanin+ vali$ation protocol.

À ： x Ù¨Ò§BÀ «‹¬f 清

Samplin+ /rame For /lat sur/aces; use a 1, cm 1, cm stainless steel /rame -it# a #an$le.

：平!#$ 1,1, cm，m

• Pincers.

'

• >lass Erlenmeyer /las)s.

(¶@

Procedure

V‘

oteA Etreme care s#oul$ be ta)en to prevent s-ab contamination $urin+ #an$lin+.

- A "õöUÒ‰ Ó ¢.

Active ingredients

« ¬

1. Jsin+ clean pincers soa) t#e s-ab in t#e solvent an$ #ol$ it until $rippin+ stops.

‰ 浸ó§BÀÈÒ， …# ÀÈ滴$，直óm‚滴落止N N .

2. Rub t#e saturate$ s-ab manually over t#e sample sur/ace area $esi+nate$ in t#e equipment $ia+ram appearin+ in t#e

speci/ic cleanin+ vali$ation protocol. For /lat sur/aces; use t#e stainless steel /rame. For smaller sur/aces an$ #ar$

toreac# locations; rub t#e -#ole sur/ace.

x¼%&‰ ，¦'Ø ô$ B #$x力ã Bêë，平!#$êëm ， ³B#$…m划 E

ôêëB#$，—êë_ #$个 .

S-abbin+ is per/orme$ in a controlle$ /as#ion by stri)in+ t#e sample sur/ace area as in$icate$ in t#e Fi+ure 12.1.

êë¤K Ê.S 1.

3. !rans/er t#e s-ab into a labele$ +lass Erlenmeyer /las) an$ seal t#e /las).

êëôB‰ 放ó ôB(¶ Ò，&-&'N @



ƒ„ 25


¯°

E$ition Io.


Validation

‰ 4

0ali$ation Jnit

³

Superse$es

´µ

Pro$uction

+E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 2 o/ 4

4. Repeat t#e proce$ure /or eac# location in$icate$ on t#e equipment $ia+ram an$ recor$ t#e samplin+ on t#e samplin+

/orm o/ t#e cleanin+ vali$ation protocol.

s”B | ，V‘£-

5. Submit samples /or analysis.

(óN ' 化

cceptance Criteria

’ 准

See &ttac#ment 2.

ƒ„2.

'leanin+ vali$ation protocol samplin+ /orm

Ù¨清

"igure 1. S-ab Samplin+ ‰



ƒ„ 25


¯°

E$ition Io.


Validation

‰ 4

0ali$ation Jnit

³

Superse$es

´µ

Pro$uction

+E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 3 o/ 4

'leanin+ vali$ation test results

fw r清

67825,9 #i+# s#ear mier:+ranulator

67825,9;< =制>?湿

8S5, 0orte Oscillator:'ompact Sieve

8S5, F

Select area

ìH

!est active in+re$ient

amount Ž ¶

þm+:s-abÿ

"'

m+:s-ab

RS

%5

alco#ol

%5ÐÑ

1

2

3

4

5

%



Select area

ìH


amount Ž ¶

þm+:s-abÿ

"'m+:s-ab

RS

%5alco#o

l

%5ÐÑ

1

2

3

4

5



ƒ„ 25


¯°

E$ition Io.


Validation ‰ 4

0ali$ation Jnit

³

Superse$es

´µ

Pro$uction

+

E//ective ate

|日期

uality &ssurance

¶· +

Pa+e 4 o/ 4

=orsc# P73,,3 !ablet Press

=ORS'7 P73,,3 J K /?

Select area

ìH


amount Ž ¶

þm+:s-abÿ

"'

m+:s-ab

RS

%5 alco#ol

%5ÐÑ

1

2

3

4

5

%

(



&ttac#mentƒ„ 2

'alculate /or &cceptance 'riteria opqB

Calculations3

& G )/，1,, m+

&llopurinol !ablets 1,, m+

9 G Û* ®B þorst 'ase Pro$uctÿ

"or llopurinol Tablets 100 mg

@o-est stren+t#

Pro$uct Q&m+

9atc# siDe

Pro$uct Q9 tablet

&rea s-abbe$

cm2

,.,,1

Re$uction

'riterion

,.,,1 N1,,

N4,,;,,, N 2,, G2.,1

4 **2,, S-ab

"aimum $aily

osa+ePro$uct

Q9 tablet

Pro$uct contact

Sur/ace &rea cm2

9atc# siDe Pro$uct

Q9 m+

&rea s-abbe$

cm2

1,PP"

'riterion

1,N

42,,(,,, N 2,, G,.,(431,,,,,, **2,, S-ab

Pro$uct contact

Sur/ace area cm

2

T/e 0.001 reduction criterion is 2010ug7s+ab

T/e 10 PP reduction criterion is 8$.!ug7s+ab

T/erefore for Lovastatin Tablets 20 mg t/e calculated acceptance value for all pieces of e#uipment used is 8$.!

ug 7s+ab of Lovastatin Tablets.

Documents

Lovastatin Tablets 20mg Cleaning Validation ProtocolÅ·ÃËÇå½àÑéÖ¤·½°¸