p didier meyer-bolum 1.pdf · isolators containment aseptic increasing reliability of operation...

© La Calhène 1997P #####

VALIDATION OF BARRIER VALIDATION OF BARRIER VALIDATION OF BARRIER VALIDATION OF BARRIER ISOLATION TECHNOLOGYISOLATION TECHNOLOGYISOLATION TECHNOLOGYISOLATION TECHNOLOGYVALIDATION OF BARRIER VALIDATION OF BARRIER VALIDATION OF BARRIER VALIDATION OF BARRIER ISOLATION TECHNOLOGYISOLATION TECHNOLOGYISOLATION TECHNOLOGYISOLATION TECHNOLOGY

Didier A. Meyer ; www.lacalhene.frIKEV ; ISTANBUL May the 3rd , 2002.Didier A. Meyer ; www.lacalhene.fr

IKEV ; ISTANBUL May the 3rd , 2002.

Michel Chabert


The Isolation ContinuumThe Isolation Continuum

Asep

tic C

y tot

oxic

Clo

sed

Asep

tic O

pen

Cyt

otox

ic C

los e

d

Barri

er S

yste

m

Barri

er S

yste

m

Bios

afet

y C

abin

et

Lam

inar

Flo

w H

ood

Cla

ssifi

e d R

oom

Cla

ssifi

ed R

oom

Un-

clas

sifie

d R

oom

Un-

clas

sifie

d R

oom

Isolators

ContainmentAseptic

Incr

easi

ng R

elia

bilit

y of

Ope

ratio

n

Positive Pressure Negative Pressure

Increased sterility assurance Increased worker protection

Asep

tic C

lose

d


EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)REGULATIONS FOR THE ISOLATORS (1)

� GMP 1985 & 1992� European Pharmacopea 1998 Edition� US Pharmacopea <1116> «Microbiological

evaluation of clean rooms and otherenvironments »

� USP <1208> « Sterility testing - Validation of isolator systems »

� UK « Isolators for the aseptic preparation of Pharmaceuticals » (yellow book)

� GMP 1985 & 1992� European Pharmacopea 1998 Edition� US Pharmacopea <1116> «Microbiological

evaluation of clean rooms and otherenvironments »

� USP <1208> « Sterility testing - Validation of isolator systems »

� UK « Isolators for the aseptic preparation of Pharmaceuticals » (yellow book)


EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND EXISTING RECOMMENDATIONS AND REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)REGULATIONS FOR THE ISOLATORS (2)

� PICS recommendations to the inspectors for «Isolators used for aseptic processing andsterility testing »

� ISO 10648-2 on the classification of leakrates of separative enclosures

� PDA TR 34 on « Design and Validation of Isolator Systems for the manufacturing andtesting of Health care Products »

� A3P « Guide Pratique d ’Utilisation des Isolateurs »

� PICS recommendations to the inspectors for «Isolators used for aseptic processing andsterility testing »

� ISO 10648-2 on the classification of leakrates of separative enclosures

� PDA TR 34 on « Design and Validation of Isolator Systems for the manufacturing andtesting of Health care Products »

� A3P « Guide Pratique d ’Utilisation des Isolateurs »


Texts to come …Texts to come …Texts to come …Texts to come …Texts to come …Texts to come …Texts to come …Texts to come …

�ISO 209 working group 7, in 2002 where isolators are one of the (separative enclosures)

�PIC/PICS on gassed isolators�ASPEC “ Guide Isolateurs -

Qualifications “

�ISO 209 working group 7, in 2002 where isolators are one of the (separative enclosures)

�PIC/PICS on gassed isolators�ASPEC “ Guide Isolateurs -

Qualifications “


REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648----2...2...2...2...REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648REQUESTS FROM ISO 10648----2...2...2...2...

� Classification of enclosures according to theirleaktightness

� Intended for « sensitive products requiring a special atmosphere and/or a sterile medium » i.e. applicable for the isolators

� When to be done:� Factory Acceptance Test�Site Acceptance Test�Operational Qualification Test�Monitoring Test

� Classification of enclosures according to theirleaktightness

� Intended for « sensitive products requiring a special atmosphere and/or a sterile medium » i.e. applicable for the isolators

� When to be done:� Factory Acceptance Test�Site Acceptance Test�Operational Qualification Test�Monitoring Test


Isolator,The Panacea for Sterile Process?Isolator,The Panacea for Sterile Process?

� Not replacing terminal sterilization processes

� Not avoiding the aseptic techniques

� Not allowing parametric release

� Not replacing terminal sterilization processes

� Not avoiding the aseptic techniques

� Not allowing parametric release


ManipulationManipulationManipulationManipulationManipulationManipulationManipulationManipulation


Gloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User GuidelinesGloves: Choice and User Guidelines


THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE ISOLATORSISOLATORSISOLATORSISOLATORS

THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE THE GLOVE : THE WEAKEST POINT OF THE ISOLATORSISOLATORSISOLATORSISOLATORS

� Material must transmit the sensitivity� Important mechanical constraint : hole, cutting, tear� Difficult to see its integrity� Fragile barrier between the hand of the operator and

the contaminated and/or sterile environment� Degradation of the materials with the sterilising

agents (H2O2, PAA)

� Material must transmit the sensitivity� Important mechanical constraint : hole, cutting, tear� Difficult to see its integrity� Fragile barrier between the hand of the operator and

the contaminated and/or sterile environment� Degradation of the materials with the sterilising

agents (H2O2, PAA)

p didier meyer-bolum 1.pdf · isolators containment aseptic increasing reliability of operation...

Documents