prashant equipment validation.pdf

Microbiological validation: equipment and operators Dr Farshid SADEGHIPOUR Head of product ion Central Pharmacy, Ge neva University Hosp itals EAHP Foundation Seminar:

“Patient Safety; More About Compounding" 23-25 May, 2008 Krakow, Poland

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Useful Definitions

” g in d n u o p m o C R ,r tu U a o On i b

d n a l o P , w o

e m S n o ti a d n u o F P H A E

k a r K , 8 0 0 2 y a M 5 2 3 2

IP H G E D A S id h s r a F r D

A e r o M ; ty e f a S t n e ti a P “

s r o t a r e p o d n a t n e m ip u q e : n t io a id l a v l a c i g lo o i b ro ic M

 Process 

validation

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined attributes.

specifications

and

quality

GMP PIC/S - EU

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3

Useful Definitions

R U O IP H G E D A S d i h rs a F r D

r, a n i m e S n ito a d n u o F P H A E

” g n i d n u o p m o C t u o b A re o M ; y t fe a S t n e ti a “P

d n la o P , w o k a r K , 8 0 0 2 y a M 5 2 3 2

s r o t a r e p o d n a t n e m p i u q e : n io t a id l a v l a c i g o l io b o r c i M

 Microbiological 

Monitoring

Microbiological monitoring is the responsibility of the pharmaceutical manufacturer. It may include environmental monitoring where product is manufactured. GMP PIC/S - EU

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Useful Definitions

” g in d n u o p m o C R ,r tu U a o On i b

d n a l o P , w o

e m S n o ti a d n u o F P H A E

k a r K , 8 0 0 2 y a M 5 2 3 2

IP H G E D A S id h s r a F r D

A e r o M ; ty e f a S t n e ti a P “

s r o t a r e p o d n a t n e m ip u q e : n t io a id l a v l a c i g lo o i b ro ic M



Media fill test (MFT) 

Method of evaluating an aseptic process using a microbial growth medium (Media fills are synonymous to simulated product fills, broth trials, broth fills etc.). GMP PIC/S - EU

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Basis

R U O IP H G E D A S d i h rs a F r D

r, a n i m e S n ito a d n u o F P H A E

” g n i d n u o p m o C t u o b A re o M ; y t fe a S t n e ti a “P

d n la o P , w o k a r K , 8 0 0 2 y a M 5 2 3 2

s r o t a r e p o d n a t n e m p i u q e : n io t a id l a v l a c i g o l io b o r c i M







Hot topics in the inspection and GMP compliance of sterile production of drugs either in industrial pharmaceutical or in hospital pharmacy. The microbiological validation of the different sterile and aseptic production equipments are now unavoidable The media fill tests and the microbiological validation of the operators in the hospital pharmacy is becoming also part of the standard operating procedures

Cleanrooms Microbiological Monitoring

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Air Viable-Particles Monitoring

R U O IP H G E D A S d i h rs a F r D

r, a n i m e S n ito a d n u o F P H A E

” g n i d n u o p m o C t u o b A re o M ; y t fe a S t n e ti a “P

d n la o P , w o k a r K , 8 0 0 2 y a M 5 2 3 2

s r o t a r e p o d n a t n e m p i u q e : n io t a id l a v l a c i g o l io b o r c i M



Settle plates : 



Bio-impactor : 



Air hovered and accelerated by a fan on a culture medium plate

Filtration method : 



Culture media agar plates placed open during production process

Air filtered on a porous or agar media retaining microorganisms and setting this sampling support on a culture media plate

Results expressed in CFU/plate

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Surface monitoring

” g in d n u o p m o C R ,r tu U a o On i b

d n a l o P , w o

e m S n o ti a d n u o F P H A E

a k r K , 8 0 0 2 y a M 5 2 3 2

IH P G E D A S id h s r a F r D

A e r o M ; ty e f a S t n e ti a P “

s r o t a r e p o d n a t n e m ip u q e : n t io a id l a v l a c i g lo o i b ro ic M



Count-tact® plates : 



Flat surfaces , without any roughness

Swab sampling :  

Uneven surfaces, corners Transfer on culture media plates

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Operators’ Gloves monitoring

R U O IP H G E D A S d i h rs a F r D

r, a n i m e S n ito a d n u o F P H A E

” g n i d n u o p m o C t u o b A re o M ; y t fe a S t n e ti a “P

d n la o P , w o k a r K , 8 0 0 2 y a M 5 2 3 2

s r o t a r e p o d n a t n e m p i u q e : n io t a id l a v l a c i g o l io b o r c i M



Print of the five fingers laid gently on a blood culture plate

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Two types of Monitoring

” g in d n u o p m o C R ,r tu U a o On i b

d n a l o P , w o

e m S n o ti a d n u o F P H A E

k a r K , 8 0 0 2 y a M 5 2 3 2

IP H G E D A S id h s r a F r D

A e r o M ; ty e f a S t n e ti a P “

s r o t a r e p o d n a t n e m ip u q e : n t io a id l a v l a c i g lo  o i b ro  ic M

In Process Monitoring

« At REST » Monitoring

Define the critical points to monitor Define ALERT (Re-Control) & ALARM (Action) limits To not interfere with the process or add any site contamination S. Fleury, HUG Pharmacy Course, 2008

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In Process Monitoring (PIC/S & BPF)

R U O IP H G E D A S d i h rs a F r D

r, a n i m e S

n o ti a d n u o F P H A E

” g n i d n u o p m o C t u o b A re o M ; y t fe a S t n e ti a “P

d n la o P , w o k a r K , 8 0 0 2 y a M 5 2 3 2

Surfaces

s r o Ai r t a r e p o Non-viable s P. Viable P. d n a 0.5µm 5µm CFU/m3 CFU/4h t n e A < 3500 0 1< 1< m p i B < 350000 < 2000