kawasaki co.,ltd. koji airexmedia.firabcn.es/content/s109015/presentaciones/kawasaki_koji.pdfcase...
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Overviewof
Lowvolta
geElectron
Beam
sterilizatio
nsystem
andtheBe
nefits
Case
stud
yintheapplicationof
LowVo
ltage
EBsystem
forN
estSyringe
Tubs
Filling
Line
andVialFilling
Line
aswell
KojiKa
wasaki
Airexco.,Ltd.
Pharam
aProcess20
15AirexCo
.,Ltd.
1.Tren
dab
outp
refilledsyrin
geto
beused
2.Evalua
tionof
tubsurfacede
contam
inationto
introd
ucethetubinto
anasep
ticfillin
gisolator
3.Astud
yof
mou
seho
le4.
Overviewof
Electron
Beam
sterilizatio
n5.
Bene
fitof
LowVo
ltage
EB6.
Case
stud
yof
theap
plicationof
LowVo
ltage
EB
7.Lesson
learne
d8.
Summery
Agen
da
Sterilizatio
nforT
ubof
Syrin
geBa
rrels
Sterilizatio
nforV
ialCon
tainers
Pharam
aProcess20
15AirexCo
.,Ltd.
+8.0%
CAGR
+8.0%
CAGR
PFSmarket
willcontinue
togrow
PFSmarketw
illgrow
upto
>5bioun
itsin20
20One
ofthegrow
thdriver
istheBiotechdrugs
Source
;Vision
gan,Prefilled
syrin
geandRe
latedsystem
world
marketo
utlook
2010
2025
Pharam
aProcess20
15AirexCo
.,Ltd.
Drugsa
ndde
vices
forn
ewera
Needs
forP
FScompa
tible
with
biologics
Before
Future
LMW,
synthe
tic
Oral
Injection
Biotech
Pharam
aProcess20
15AirexCo
.,Ltd.
Pharam
aProcess20
15AirexCo
.,Ltd.
Metho
dof
tub
surfacede
contam
ination
tointrod
uceit
into
anasep
ticfillin
gisolator
Metho
d
1Au
toDe
bag
2Alcoho
l3
VHP
4UV
5EB
Isolator
GradeA
CBGradeC/D
GradeAair
mou
seho
le
Evalua
tionof
tab
surfacede
contam
inationto
introd
uceaasep
ticfillin
gisolator
Metho
dcost
Runn
ing
GMP
Valid
ati
onSA
LRe
sidu
alchem
icalsCycle
time
Easy
ordifficult
tocombine
with
isolator
Total
Cost
compa
tibility
point
1Au
toDe
bag
710
11
210
99
6.1
2Alcoho
l7
92
22
77
75.6
3VH
P4
77
67
42
44.6
4UV
59
33
510
69
5.4
5EB
29
109
109
109
7.0
Weightin
g35
515
105
520
510
0To
point
Base
data
isOliver
Vogt
Case
Stud
y:UtilizingElectron
Beam
SurfaceDe
contam
inationto
Tran
sfer
Sterile
Syrin
geBa
rrelsintoan
Isolated
Asep
ticSyrin
geFilling
Line
(Pha
rmaen
gine
ering)
Jan.2010
Pharam
aProcess20
15AirexCo
.,Ltd.
Metho
dsissues
Tren
dim
ages
1Au
toDe
bagging
Isitpo
ssibleto
deba
gwith
No
contam
inationintheprocess?
Isitallowed
topu
titintoan
isolator
throughamou
seho
le?
2Alcoho
lNot
effectivede
contam
ination
canbe
mad
e.Po
tentialtocatch
fireinthene
xtprocess.
3VH
PLonger
cycletim
e.Co
ncernof
VHP’sresidu
e
4UV
Disinfectio
neffectiven
esson
the
shad
owarea
5EB
Xray,Ozone
,pan
iclegene
ratio
n,Higher
cost,Low
erlifetim
e
Evalua
tionof
tub
SurfaceDe
contam
inationto
introd
uceinto
anasep
ticfillin
gisolator
Pharam
aProcess20
15AirexCo
.,Ltd.
Alcoho
l
Auto
Deba
gging
UV
VHP
EB
Prob
lem
ofEB
tabsterilizatio
ntheprob
lem
oftheEB
was
foun
dou
tbylong
timeactual
operation
Alcoho
l
Auto
Deba
gging
UV
VHP
EB
Pharam
aProcess20
15AirexCo
.,Ltd.
Auto
Deba
ggingMetho
d
Isitpo
ssibleto
deba
gwith
No
contam
inationintheprocess?
Isitallowed
topu
titintoan
isolator
throughamou
seho
le?
Pharam
aProcess20
15AirexCo
.,Ltd.
Auto
Deba
ggingMetho
d
Isolator
Grad
eA
Grad
eC
mou
seho
leP=
20~25Pa
Airv
elocity
is6~10m/s
Transfer
corridor
GradeD
Surrou
ndenvironm
ent
GradeC
DeBa
g1Tran
sfer
hatch
Disin
fect–Protect
Filling
satirize
dcontaine
rGrad
eD
Controlledarea
Wareh
ouse
receipt
Controlsup
plychain
Notouch
tran
sfer
zone
Grad
eB
Non
interven
tion
Deba
g2
Removeou
terp
acking
tolim
itparticleµ
transfer
Isolator
Grad
eA
Tubs
areintrod
uced
throughthe
Mou
seho
leinto
the
isolator(Grade
Aasep
ticarea)
Pharam
aProcess20
15AirexCo
.,Ltd.
Astud
yof
mou
seho
le
A M
ouse
hole
is ty
pica
lly u
sed
for
taki
ng o
ut fi
nish
ed s
eale
d pr
oduc
ts
from
the
isol
ator
.
Pharam
aProcess20
15AirexCo
.,Ltd.
Pressurized
Air
Quantity
PositivePressure
Degree
Surrou
nding
cond
ition
Isolator
Volume
Mou
seHo
le
Ope
ratio
n
Additio
nalTun
nel
Prod
ucts
Astud
yof
mou
seho
leInflu
ence
factor
Position
Ope
ratio
nSpeed
Halfsuits
Gloves
Return
AirP
osition
Prod
uctio
nSpeed
Movem
ento
fOpe
rator
Shape
Size
Type
ofcontaine
r
AirF
lowof
AirC
onditio
ning
Breath,Sne
eze
ofPerson
Size Shape
Invasion
ofNon
asep
ticAir
Pharam
aProcess20
15AirexCo
.,Ltd.
Pharam
aProcess20
15AirexCo
.,Ltd.
Astud
yof
mou
seho
leSummaryof
expe
rimen
tDA
IICHI
Pharm.:Ko
jima,Yamuchi
JGC
Watanabe,Sagara,Ono
VTR
Particle
Coun
ter
Anem
ometer
Device
toObserve
aAirF
low
Isolator
Mou
seHo
le
Additio
nal
tunn
el
HSStud
y(Nov.200
2JapanHe
alth
Sciences
Foun
datio
n
Pharam
aProcess20
15Airex
Co.,Ltd.
AStud
yof
Mou
seHo
leTopics
Isolator
Isolator
Isolator
Theremight
bean
invasion
ofairsurroun
ding
isolator
even
ifinstallin
gad
ditio
nalpiece
oftunn
elfora
mou
seho
le.
Alittle
airrateof
positive
pressure
from
isolatorb
ya
smallm
ouse
holehapp
ensto
causeareversalof
curren
tof
airb
yradicalglove
operation.
Aninvasio
nof
pollutio
nairw
asconfirm
edina
mou
seho
leby
expiratio
ninthecase
of40
Paof
internal
pressure.
Possibility
ofan
unexpe
cted
prob
lem
Aplan
such
asshap
eof
isolator,a
size
characteristic,settin
gof
internalpressure
inconsiderationof
usean
dshap
eof
amou
seho
leareim
portan
t.
Astud
yof
mou
seho
leon
Auto
Deba
ggingMetho
d
Isitfeasibleto
introd
uceanyite
ms
asep
ticallythroughtheMou
seho
leinto
theisolator?
Pharam
aProcess20
15AirexCo
.,Ltd.
Atthemou
seho
letheAirv
elocity
~6m/s
Test
pro
cedu
re
Isolator
Grad
eA
Grad
eC
ISO5airCB
Isolator
CB
Sprayrib
oflavin
onaba
gby
using
atw
oflu
idno
zzle.
+20P
a
1.Sprayrib
oflavinon
aba
gby
usingatw
oflu
idno
zzle
2.removingthedo
ubleba
gsheetson
eby
onecarefully
byha
nd3.
verifyto
checkatraces
oftherib
oflavinon
thetub
Pharam
aProcess20
15AirexCo
.,Ltd.
Atthemou
thho
leTh
eAirv
elocity
6m/s
Test
resu
ltW
e fo
und
the
trac
e of
the
ribof
lavi
n on
the
tub
Isolator
GradeA
GradeC
ISO5airCB
Isolator
CB
Apply
riboflavinon
aba
gby
usinga
twoflu
idno
zzle.
+20P
a
Topof
Tab
Side
ofTab
Topof
bag
Pharam
aProcess20
15AirexCo
.,Ltd.
Is it
feas
ible
to in
trod
uce
any
item
s as
eptic
ally
th
roug
h th
e M
ouse
hole
into
the
isol
ator
?
It ha
s a
high
er R
isk
to in
todu
ce a
tub
into
an
isol
ator
thro
ugh
a M
outh
hole
as
eptic
ally
with
rem
ovin
g th
e un
stab
le
shap
e ba
g (d
ebag
ging
).Th
e ris
k go
es m
uch
high
er e
spec
ially
in
case
of a
filli
ng w
ith la
rger
am
ount
and
hi
gher
spe
ed. Ph
aram
aProcess20
15AirexCo
.,Ltd.
Electron
Beam
stria
tionMetho
d
Xray,Ozone
,pan
iclegene
ratio
n,Higher
cost,Low
erlifetim
e
Pharam
aProcess20
15AirexCo
.,Ltd.
Trad
ition
alElectron
Beam
Arou
ndfor>
50years,wellkno
wnsterilizatio
ntechno
logy
Benefitsfor
pharmaceu
ticalandmed
icalde
vice
manufacturer
Large,expe
nsive,high
mainten
ance,profoun
dcover
Severe
man
agem
entisreq
uired
Offlin
eprocess
Ratin
gsEB
Irrad
iatio
nUnit
Inpu
tvoltage
Max.70K
V,Singleph
ase10
0V(50/60
Hz)
Power
consum
ption
less
than
500W
EBCo
ntrolpan
elPo
wer
consum
ption
less
than
800W
Rotary
pump
Power
consum
ption
less
than
250W
New
Electron
Beam
SmartE
B©System
1.Alwaysb
eing
kept
tobe
evacua
tedby
using
vacuum
pump.
2.Lowvolta
gesystem
(Max70
KV,4mA)
3.At
thetim
eof
theelectron
windo
wda
maged
,on
lyne
edto
replacethewindo
w
Hamam
atsu
Photon
ics
Pharam
aProcess20
15AirexCo
.,Ltd.
Overviewof
theLowVo
ltage
Electron
Beam
System
Electron
sare
emitted
asthermions
from
anelectron
gun
Acceleratedinbe
tweenelectrod
esap
pliedhigh
volta
geVa
cuum
pumpalwayss
ucks
theairintothevacuum
cham
ber
Emitelectron
stoou
tsidepa
ssingthroughthewindo
w
Defle
ctioncoil
anod
eAp
pliedhigh
volta
ge(accelerated
electron
s)Electron
gun(filam
ent)
High
volta
gepo
wer
supp
ly
atmosph
ere
Vacuum
pump
coil
(orbit,
focusa
djustm
ent)
High
vacuum
(app
rox10
6 Pa)
Irrad
iated
obstacle
Windo
wto
emittheelectron
s
Pharam
aProcess20
15AirexCo
.,Ltd.
Electron
smakean
entryinto
atmosph
ereand
interactwith
theairm
olecules
then
goingto
becomedispersedwith
losin
gtheire
nergy
Travelinglength
intheairfor
electron
beam
,tobe
depe
ndingon
acceleratin
gvolta
ge.
Lowvolta
geEB
scatterin
g
125
kV15
0 kV
Ordinarysystem
SmartE
B©
80 m
m
240
mm
160
mm
050
kV
80 k
V
Air
image
Distan
cefrom
windo
w
Rangeof
EBWindo
wto
emit
theelectron
s
Pharam
aProcess20
15AirexCo
.,Ltd.
Sour
ce:
Cle
ghor
n, D
unn,
Nab
lo.
“Ste
riliz
atio
n of
pla
stic
con
tain
ers
usin
g el
ectr
on b
eam
irra
diat
ion
dire
cted
thro
ugh
the
open
ing.
” Jo
urna
l of
App
lied
Mic
robi
olog
y, V
olum
e 93
Page
937
-Dec
embe
r 200
2
EBisEffective
onMicroorganism
s
Dos
e(K
gy)
0 -6
Dos
e(K
gy)
0 -6
6D10
=10.2kG
y
Log survival friction (log N/N0)
ControlD
oselevelo
fSurfaceSterilizatio
nEB
Effectiven
esso
nDVa
lue
BacillusP
umilusS
poresA
TCC#27
142(E60
1)
D10
=1.7kG
y6D
10=10.2kG
yMinim
umdo
se=15
~25
kGy>
ItisMagicfig
ure,no
realratio
nal,bu
ttoconsider
safety
marginetc.
Dose
levelata
nypo
into
nthecontaine
r’ssurface
Gy>15~25
kgy
Reference:From
“ElectronBe
amSensitivitie
sintheSpores
ofBa
cillusp
umilusE
601
Strain”J.An
tibact.An
tifun
g.Ag
entsVo
l.17,No.7,19
89by
Y.Watanabe,H.
ItoandI.
Ishigaki,and
“InLine
Electron
sterilizatio
nandIts
Applicationto
Asep
ticPackaging”
March
1985
byP.M.Fletche
r,J.Aa
ronson
andS.V
.Nablo
Bene
fitof
LowVo
ltage
EB
Dryan
dLowtempe
rature
process
Quite
lowOzone
gene
ratio
nQuite
lowim
pactto
objectives
Compa
rativ
elylowen
ergy
consum
ption
Easy
mainten
ance
atsite
Stainlesssteelplatecoverise
noughto
cutx
ray
Unn
ecessary
ofthespeciallicen
seLowop
eratingcost
Inlin
ean
din
houseprocess
Continuo
ustreatm
entw
ithmon
itorin
gan
drecordingforG
MP
parameters
Basically
surfaceor
core
sterilizatio
n
Case
stud
yof
application
ofLowVo
ltage
EB
UtilizingEB
Sterilizatio
nforT
ubof
Syrin
geBa
rrelsIntrodu
cedinto
anIsolated
Asep
ticFilling
Line
Layout
ofsyrin
getab
fillin
gprocessc
ombine
dwith
EBtub
sterilizatio
n
Filling
area
EBIsolator(VHP
Gde
contam
ination)
EBtunn
elisinstalledbefore
thefillingprocess.
Surfaceof
tabs
aresterilizedby
theEbe
amFilledwith
theliquidprod
uct,then
willbe
conveyed
tothe
nextprocess
Tabsupp
ly
Pharam
aProcess20
15AirexCo
.,Ltd.
SmartE
B©Co
ncep
tofn
ewEB
Sterilizatio
nforsurface
decontam
inationof
tubof
syrin
geba
rrels
1.ThreeEB
emitterstobe
used
2.Irradiatio
nshallbedo
newith
movingandturningatub
3.To
keep
alwaysthe
distance
almoste
qualbe
tweenthe
irradiatio
nwindo
wandtheob
stacleto
besterilized
4.To
keep
unidire
ctionalairflo
wdu
ringsterilizin
g
VTR
Pharam
aProcess20
15AirexCo
.,Ltd.
1.Ebe
amdo
semapping
ontubsurfa
ceof
outsideandinsid
e2.
Resid
ualO
zone
gasa
nalysis
insid
etubs
3.Tempe
rature
riseinthetubs
4.Influ
ence
oftheEbe
amto
tabs
andsyrin
ges
5.Airflowanalysisinsid
eof
unit
6.Perfo
rmance
ofthetubs
conveying
Verificationof
Ebe
amVa
lidation
61.7
41.0
60.3 48
.4
62.4
75.4
61.7
47.1
45.7
44.4
53.3
54.0
41.7
71.5 73
.0
52.3
52.6 51
.2
39.7
25.0
25.0
1scan
1scan
1scan
1scan
Dose
map
ping
ontheSide
irrad
iatio
ntest(4
timescan
)
[kGy
]
Ebe
amdo
secanob
tain25
kGy>
ateverywhe
re
VTR
ColdSpot
Pharam
aProcess20
15AirexCo
.,Ltd.
2scan
area
2scan
area
2scan
area
2scan
area
4tim
esscan
area
1scan
area
Dose
imagemap
ping
4tim
esscan
area
4tim
esscan
area
Pharam
aProcess20
15AirexCo
.,Ltd.
Outsid
eSurface58
.9kG
y
0.0
0.0
0.0
0.0
0.0
0.0
0.00.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
Insid
edo
seare0kG
y
Dose
map
ping
inside
tubs
(4tim
esscan
)
Pharam
aProcess20
15AirexCo
.,Ltd.
Ozone
gasa
nalysis
inside
tubs
Ozone
tester’sSpecificatio
nManufacturerThermoFisher
SCIENTIFIC
Mod
el49
iMetho
dUltravioleta
bsorption
spectrom
etry
Gassam
plingvolume2.0L/m
inTransportatio
nspeed:75
mm/sec
Measuremen
tprocedu
reIrrad
iatio
nTaking
thetubou
tMeasuremen
t
Samplingpo
rt
Result
Residu
alOzone
conc.(p
pm)
N1
N2
N3
AVE.
0.00
40.006
0.009
0.006
Pharam
aProcess20
15AirexCo
.,Ltd.
Tempe
rature
chan
ge(
)
P1P2
P3AV
E.
0.1
0.1
0.2
0.1
Thermocoup
le
Tempe
rature
riseinthetubs
Measurementp
rocedu
rePrep
arethermocou
ple
Irradiatio
nMeasurement
Pharam
aProcess20
15AirexCo
.,Ltd.
Before
After
Influ
ence
oftheEbe
amto
tabs
andsyrin
ges
1.Pe
rform
Ebe
amscan
ning
thetubs
2.Co
mpa
rethesurfaceon
thetub
andtheap
pearan
ceof
thesyrin
geforthe
tested
sample
before
&afterthe
irrad
iatio
n,an
dcheckwhe
ther
theEbe
amha
sgiven
anyim
pacton
there.
3.Re
sult
AnyCo
lorcha
nges
orDe
form
ations
Pharam
aProcess20
15AirexCo
.,Ltd.
Isolator
Airflowan
alysisinside
ofun
it
Tokeep
unidire
ctiona
lairflo
wdu
ringsterilizing
Pharam
aProcess20
15AirexCo
.,Ltd.
Actualsite
view
Pharam
aProcess20
15AirexCo
.,Ltd.
Tub
EBem
itters
Inside
ofEB
unit
VTR
Pharam
aProcess20
15AirexCo
.,Ltd.
Summeryof
theresults
surfacede
contam
inationof
tubof
syrin
geba
rrels
1.Sm
artE
BTMsystem
canguaran
teethedo
serate
levelof
“25
kGy”
2.EB
dose
hasn
otpe
netrated
into
theinside
ofthetub
3.Re
sidu
alozon
econcen
trationinthetubs
were
“0.01
ppm
(Max)”
4.Tempe
rature
riseinthetubs
wereconformed
“<0.1
”5.
Anyinflu
ence
oftheEBe
amirrad
iatio
nto
thetabs,and
totheba
rrels
6.To
keep
unidire
ctiona
lairflo
wdu
ringsterilizing
Pharam
aProcess20
15AirexCo
.,Ltd.
Utilizing
EBSterilizatio
nforV
ialCon
tainer
into
anIsolated
Asep
ticFilling
Line
Case
stud
yof
applicationof
LowVo
ltage
EB
Exam
ples
ofthesurfa
ceEB
sterilizatio
nforsyringe
containe
rsare
rare
now
Noresults
sofarh
asbe
enfoun
dinthat
ofthevialcontaine
rs
CompleteIn
Line
process
Qualityassuranceto
beincreased.(M
oreeffectivecomparedwith
OffLine
configurationinthemanagem
enta
spect.)
Easy
tope
rform
thesterility
validation.
ToachievetheKillrate
25kG
yon
who
lesurfaces
Stabilizatio
nof
theconveyingprocess
Establish
ingof
sterility
validation
Deterio
ratio
nof
thecontaine
rs?
Prod
uct’s
change
inthenature
?
EBSterilizatio
nforp
lasticvialcontaine
rs
Effectsinthesolutio
n
Req
uire
d K
ill ra
te
Issu
es
Lyop
Lyop
Layout
ofvialfillin
gprocess
combine
dwith
EBsterilizatio
n
Filling
area
EBAirw
ashing
Containe
rsupp
ly
Isolator(VHP
decontam
ination)
EBtunn
elisinstalledbefore
thefillingprocess.
Vialsc
leaned
byairspray
forb
eing
transferredto
EBVialsa
redirectlysterilizedby
the3u
nitsEbe
ams
Filledwith
theliquidprod
uct,then
willbe
conveyed
tothe
lyop
hilizer
Pharam
aProcess20
15AirexCo
.,Ltd.
Out
view
offillin
gprocess
combine
dwith
vialEB
sterilizatio
n
VTR
Pharam
aProcess20
15AirexCo
.,Ltd.
Summeryof
theresults
UtilizingEB
Sterilizatio
nforV
ialCon
tainers
1.System
canguaran
teethedo
serate
levelo
f“
25kG
y”on
who
lesurfaceof
vialcontaine
rs2.
Anyinflu
ence
oftheEBe
amirrad
iatio
nto
the
vialcontaine
rs3.
Tokeep
Grad
eAdu
ringsterilizing
4.Speedof
vialsterilizatio
nis20
0vials/min
5.FD
Aap
proved
Pharam
aProcess20
15AirexCo
.,Ltd.
1.Th
epa
rameterstocontrolthe
EBdo
seissimply
show
nas
inbe
low
Eelectronacceleratin
gvolta
geEelectrontube
current
Obstacle’sm
ovingspeed
Obstacle’sd
istance
Lesson
sLearned
2.Lowvolta
gean
dlowcurren
tEBha
smany
advantages
asinbe
low
Inlineprocessisd
evelop
edUniform
dose
mapping
LowOzone
gene
ratio
nEasy
keep
unidire
ctionalflowandGradeA
Lead
coverisu
nnecessary
Pharam
aProcess20
15AirexCo
.,Ltd.
Evalua
tionof
tubsurface
decontam
inationto
introd
uceit
into
anasep
ticfillin
gisolator
Pharam
aProcess20
15AirexCo
.,Ltd.
Summary1
1.ThesePFSprod
uctio
nscanbe
expe
cted
togrow
upinthe
future
2.Itisacrucialissue
howto
introd
ucene
stsyrin
getubs
into
aniso
lator
3.Ithasb
eenclearn
owthat
contam
inationriskisinvolved
inifintrod
ucingthetubs
throughmou
seho
leinto
theiso
lator
with
debagging,Then
, you
need
totake
areallycareful
attentioninusingthismetho
d.4.
Ontheothe
rhand,thebe
stsolutio
nforintrodu
cing
tubs
into
aniso
latorw
ouldbe
tousetheLowvolta
geEbe
amsterilizatio
nsystem
that
canpe
rfectlydisin
fecttheou
ter
surfaceof
thetubs.
Summary2
5.Thelowvolta
geEbe
amsterilizatio
nsystem
caneasily
shieldXray,andadditio
nally
that
haslotsof
advantages
such
asthepriceandthelifetim
e.6.
Inthesedays,thisE
beam
system
hasb
eeninitiated
toapplyforthe
sterilizatio
nof
containe
rssuch
asforv
ials,
Inadditio
n,ne
wapplications
ofthissystem
forn
ewtechno
logies
likeRe
gene
rativ
emed
icine,Nan
ofilm
and
Microne
edlesa
restarted,itwou
ldbe
comeakey
techno
logy
forthe
pharmaceu
ticalmanufacturin
ginthe
future.
Para
digm
shi
ft
Ifyouha
vean
yqu
estio
ns,
please
contactm
eby
kawasaki@
airexx.co.jp
Than
kyouvery
much
fory
oura
tten
tion