【正文】 int 27 ― 3 3 3 27 uneven temperature distribution 45 ― 3 5 3 45 : Failure Mode Effects Analysis (FMEA) Based on Takayoshi Matsumura, Esai Co. EXAMPLE RPN: Risk Priority Number = S*P*D Annex I: Methods amp。 not an official policy/guidance July 2022, slide 34 ICH Q9 QUALITY RISK MANAGEMENT 當(dāng) RPN大于 40采取措施 當(dāng)嚴(yán)重性超過 5時(shí)采取措施 采取措施后保留關(guān)鍵參數(shù) 。 Tools prepared by some members of the ICH Q9 EWG for example only。nninger, Roche S e v e rit y ( C ons e que nc e s ) : 3 : h igh P r e d ic t e d t o c a u s e s ign i f i c a n t i m p a c t t o q u a l it y ( f a il u r e t o m e e t s p e c i f ic a t ion s ) 2 : m o d e r a t e P r e d ic t e d t o c a u s e mi n o r i mpa c t t o q u a li t y ( f a il u r e t o m e e t s p e c i f i c a t i o n s ) 1 : mi n o r P r e d ic t e d t o c o u ld h a v e m ino r i m p a c t o n q u a li t y o f t h e p r o d u c t ( q u a li t y w it h in s p e c if i c a t ion s ) P ro ba b i l i t y 4 : r e g u lar f a i lur e s E x p e c t e d t o h a p p e n f r e q u e n t ly 3 : r e p e a t e d f a il u r e s C o u ld h a p p e n o c c a s ion a l ly 2 : o c c a s ion a l f a il u r e s E x p e c t e d t o h a p p e n infre q u e n t ly 1 : f a i lur e i s u n li k e ly U n li k e ly t o h a p p e n D e t e c t a bi l i t y 3 : p r o b a b ly n o t d e t e c t e d M a y o v e r loo k a f a u lt o r f a il t u r e p o s s ibly c a n n o t b e d e t e c t e d ( n o t e c h n ic a l s o lu t ion u p t o n o w ) 2 : o c c a s ion a ly n o t d e t e c t e d Fa il t u r e may b e mi s s e d ( man u a l c o n t r o l, r o u t ine ly w o r k w it h s t a t i s t i c a l c o n t r o l) 1 : d e t e c t a b le Fa il t u r e c a n a n d w il l b e d e t e c t e d ( e . g . u s ing s t a t i s t i c a l t o o l s ) Annex I: Methods amp。 not an official policy/guidance July 2022, slide 36 ICH Q9 QUALITY RISK MANAGEMENT : 失效模式效應(yīng)分析 (FMEA) ? 分析制粒工藝步驟因?yàn)閮H僅很少的參數(shù)可以調(diào)整，手工操作許多問題都可能發(fā)生。nninger, Roche S e v e rit y ( C ons e que nc e s ) : 3 : h igh P r e d ic t e d t o c a u s e s ign i f i c a n t i m p a c t t o q u a l it y ( f a il u r e t o m e e t s p e c i f ic a t ion s ) 2 : m o d e r a t e P r e d ic t e d t o c a u s e mi n o r i mpa c t t o q u a li t y ( f a il u r e t o m e e t s p e c i f i c a t i o n s ) 1 : mi n o r P r e d ic t e d t o c o u ld h a v e m ino r i m p a c t o n q u a li t y o f t h e p r o d u c t ( q u a li t y w it h in s p e c if i c a t ion s ) P ro ba b i l i t y 4 : r e g u lar f a i lur e s E x p e c t e d t o h a p p e n f r e q u e n t ly 3 : r e p e a t e d f a il u r e s C o u ld h a p p e n o c c a s ion a l ly 2 : o c c a s ion a l f a il u r e s E x p e c t e d t o h a p p e n infre q u e n t ly 1 : f a i lur e i s u n li k e ly U n li k e ly t o h a p p e n D e t e c t a bi l i t y 3 : p r o b a b ly n o t d e t e c t e d M a y o v e r loo k a f a u lt o r f a il t u r e p o s s ibly c a n n o t b e d e t e c t e d ( n o t e c h n ic a l s o lu t ion u p t o n o w ) 2 : o c c a s ion a ly n o t d e t e c t e d Fa il t u r e may b e mi s s e d ( man u a l c o n t r o l, r o u t ine ly w o r k w it h s t a t i s t i c a l c o n t r o l) 1 : d e t e c t a b le Fa il t u r e c a n a n d w il l b e d e t e c t e d ( e . g . u s ing s t a t i s t i c a l t o o l s ) Annex I: Methods amp。 not an official policy/guidance July 2022, slide 37 ICH Q9 QUALITY RISK MANAGEMENT R i s k A s s e s s m e nt R i s k R e duc t i onS ub S t e pE v e nt( Fa i l ur e m ode )E f f e c tSeverity (S)[123]Probability (P)[1234]Detectability (D)[123]Risk factor (S*P*D)A c t i ons :R i s k re duc t i on s t ra t e gySeverity (S)[123]Probability (P)[1234]Detectability (D)[123]Risk factor (S*P*D)Risk reductionC om m e nt sW e t s e v ing D r y ing Te m p e r a t u r en o t m e e t s p e c if ic a t ion o f degradat i on2 4 1 8 im p lem e n t 2 t e m p e r a t u r e m e a s u r e s 1 1 1 1 7a u t o m a t ic a ll y inte r r u p t ion b y n o t m e e t ing r a n g e 。 t im e c o n s u m ingh u m idit y m e a s u r e m e n t in t h e e x a u s t ing a ir2 1 2 4 2ind ire c t m e a s u r m e n t 。 d e p e n d ing o n p o w e r c o n s u m p t ion 。 u s e o f d o s a g e p u m p s3 2 1 6 21t o g e t f ine a p p r o p r iate g r a n u lateP r e m ix ing Gr a n u lati o n m a n n e r o f a d d ing w a t e rn o t m e e t s p e c if ic a t ion o f d is o luti o n a n d d e s inte g r a t ion3 1 1 3 ins t a ll s p r a y n o z z les 1 1 1 1 2t o g e t f ine a p p r o p r iate g r a n u lateGr a n u lati o n Qu a li t y o f E x c ipie n t sa ll p a r a m e t e r s h a v e t o b e r e e v a lua t e d3 4 3 36A d a p t inte r n a l s p e c if ic a t ion o f p h y s ic a l p a r a m e t e r s ( e . g . d e n s it y , m e t a b il it y w e t a b il it y )1 2 2 4 32 c o n t a c t s u p p li e rGr a n u lati o n Qu a li t y o f A P Ia ll p a r a m e t e r s h a v e t o b e r e e v a lua t e d3 4 3 36A d a p t inte r n a l s p e c if ic a t ion o f p h y s ic a l p a r a m e t e r s ( e . g . d e n s it y , m e t a b il it y w e t a t il it y )1 2 2 4 32 c o n t a c t s u p p li e rOv e r v iew R i s k be f or e c ot ro l M a x 36 R i s k a f t e r c ont ro l M