Ster
ile p
acka
ging
of l
iqui
d ph
arm
aceu
tical
sU
sing
rom
mel
ag b
otte
lpac
kbl
ow-fi
ll-se
al m
achi
nes
Moh
amm
ad S
adeg
hiV.
P. R
&D
Hol
opac
k In
tern
atio
nal C
orp.
1 Te
chno
logy
Circ
leC
olum
bia,
SC
292
03Te
l: (8
03) 8
06-3
300
Con
tent
s
�bo
ttlep
ack
His
tory
�B
low
Fill
Sea
l pro
cess
�M
anuf
actu
ring
�C
onta
iner
Des
ign
botte
lpac
kH
isto
ry
botte
lpac
k®B
FS m
achi
ne h
isto
ry
�196
0s-I
nven
tion
of th
e B
FS p
roce
ss
-Firs
t bot
telp
ack
prot
otyp
e 19
63
-Low
cap
acity
with
one
mol
d
-Rel
ay c
ontr
olle
d
-No
asep
tic s
yste
ms
-Big
ger f
ill v
olum
e
-Cus
tom
ers
in G
erm
any
and
Euro
pe
�197
0s-M
ediu
m-h
igh
capa
city
mac
hine
with
2-1
0 m
olds
-Mac
hine
for s
mal
l fill
vol
umes
(0.2
-50
mL)
-Mac
hine
des
igns
for a
sept
ic fi
lling
(pro
duct
filte
rs,
CIP
, SIP
)-P
isto
n do
sing
/tube
dos
ing
syst
ems
for b
ig/s
mal
l
volu
mes
-rel
ay-c
ontr
olle
d m
achi
nes
-Wor
ldw
ide
mac
hine
exp
ort;
licen
se p
rodu
ctio
n in
U
SA
�198
0s-H
igh
capa
city
mac
hine
for s
mal
l fill
vol
umes
with
15
mol
ds (t
ype
4010
M)
-Aut
omat
ic m
achi
ne p
rogr
am c
hang
es
-Tim
e pr
essu
re d
osin
g as
sta
ndar
d sy
stem
-PLC
con
trol
led
mac
hine
s -A
larm
mes
sage
on
disp
lay
-Pro
duct
ion
docu
men
tatio
n
�19
90s
-New
bot
telp
ack®
mac
hine
gen
erat
ion
(Typ
es 3
21/3
21M
-36
0/36
0M)
-Cle
an/D
irty
conc
ept m
achi
ne d
esig
n-I
ncre
ased
leve
l of a
utom
atio
n us
ing
PLC
s-D
evel
opm
ent o
f Co-
extr
usio
n an
d PE
T pr
oces
sing
tech
niqu
e fo
r BFS
-I
SO 9
001
Cer
tific
ate
botte
lpac
k®B
FS m
achi
ne ty
pes
-tod
ay
�Sin
gle
paris
on ty
pes
for b
ottle
man
ufac
turin
g
(50
-200
0ml).
Mac
hine
Typ
es:
-301
2 (o
ne m
old)
-321
(one
mol
d)
-360
(tw
o m
olds
)
Cap
acity
rang
e: ~
250
-4,
000
bottl
es/h
�Mul
tiple
par
ison
type
s fo
r am
poul
e m
anuf
actu
ring
(0,2
-50
ml).
Mac
hine
Typ
es:
-301
2 M
(one
mol
d)
-321
M (o
ne m
old)
-360
M (t
wo
mol
ds)
-401
0 M
(fift
een
mol
ds)
Cap
acity
rang
e: ~
2,5
00 -
30,0
00 a
mpo
ules
/h
botte
lpac
k®m
odel
301
2/32
1C
apac
ities
up
to 9
,000
via
ls p
er h
our
botte
lpac
k®m
odel
360
Hig
her c
apac
ities
up
to 1
8,00
0 vi
als
per h
our
Blo
w F
ill S
eal P
roce
ss
Con
vent
iona
l vs.
BFS
Supp
ly of
con
tain
ers
Tran
spor
t int
o ste
rile ro
om
Cont
aine
r clea
ning
Cont
aine
r ste
riliza
tion
Tran
spor
t pro
cess
und
erst
erile
cond
itions
Prep
. fillin
g pr
oduc
t for
ste
rile
fillin
g
Asep
tical
ly o
pera
ting
filler
Tran
sp. u
nder
ste
rile c
ondit
ion
Capp
ing
unde
r ste
rile
cond
ition
Clos
ure
part
supp
ly, c
leanin
g,st
eriliz
atio
n
Out
put f
rom
ster
ile ro
om
Supp
ly o
fpl
astic
gran
ulate
Prep
arat
ion
ofpr
oduc
t for
ster
ile fil
ling
Asep
tic m
anuf
actu
ring,
fillin
g an
d clos
ing
in th
ebl
owin
g m
old w
ithou
t cha
ngin
g the
pla
ce
BFS
Pro
cess
Ove
rvie
w
Par
ison
Ex
trut
ion
Mol
din
g by
bl
owin
g an
d va
cuu
m
Filli
ng
Con
tain
er
seal
ing
Pro
duct
�Pl
astic
mel
ting
and
ext
rusi
on (1
70-2
30°C
; up
to 3
50
bar)
�Ex
trus
ion
prov
ides
ste
riliz
atio
n an
d de
pyro
gena
tion
Proc
ess
step
1 Extr
uder
H
ead
Paris
on
Paris
on
head M
old
Mul
tiple
par
ison
ex
trus
ion
Sing
le p
aris
on
extr
usio
n
Sing
le/M
ultip
le p
aris
on e
xtru
sion
Paris
on
�M
ain
mol
d se
als
the
low
er p
aris
on e
nd
�Th
e pa
rison
is s
epar
ated
by
a kn
ife
�St
erile
air
kept
in th
e pa
rison
Proc
ess
step
2 Hol
ding
jaw
Hea
d M
old
Esca
ping
st
erile
air
Ster
ile a
ir sh
ower
bo
x
�R
apid
mol
d m
ovem
ent t
o fil
ling
posi
tion
�St
erile
air
show
er b
ox (1
00) p
rote
cts
fillin
g po
int
�Blo
win
g/fil
ling
unit
at re
st p
ositi
on
Proc
ess
step
3
Air s
uppl
y
Pre-
filte
r
Ster
ile a
ir fil
ter
Ster
ile a
ir sh
ower
bo
x
Filli
ng
poin
t
Ster
ile F
illin
g Sp
ace
Blo
w &
Fill
pip
e
�Low
ered
blo
win
g/fil
ling
unit
is p
lace
d tig
htly
on
top
of m
ain
mol
d
�Blo
w m
oldi
ng b
y st
erile
air
and/
or v
accu
m
Proc
ess
step
4a
Ster
ile P
rodu
ct
�Fill
ing
-Tim
e pr
essu
re d
osin
g
Proc
ess
step
4b
Filli
ng
Asep
tic P
ipin
g an
d St
erile
filtr
atio
n
�Pr
oduc
t Filt
ers
-0.
2 m
icro
n�
Paris
on A
ir Fi
lter
�St
erile
spa
ce A
ir Fi
lters
Prod
uct
supp
ly
Con
stan
t bu
ffer a
ir
Prod
uct
tank
Dos
ing
bloc
k, ti
mer
co
ntro
lled
Con
tain
er
Tim
e Pr
essu
re D
osin
g
Hea
d m
ould
se
aled
�Fill
ing
need
les
with
draw
into
the
ster
ile s
pace
�Hea
d m
old
seal
s co
ntai
ner h
erm
etic
ally
Proc
ess
step
5
Seal
ing
Man
ufac
turin
g
Ove
rvie
w
Man
ufac
turin
g C
ompo
nent
s
�Fi
ll Su
ite�
Mac
hine
Qua
lific
atio
n�
Bul
k So
lutio
n�
Util
ities
Fill
Suite
Fill
Suite
Env
ironm
ent
�Fi
ll su
ites
are
desi
gned
to s
epar
ate
the
BFS
m
achi
ne�s
ase
ptic
par
t fro
m it
s ut
ilitie
s
Bas
ic b
otte
lpac
k® m
achi
ne la
y-ou
t
Plas
tic
gran
ulat
e ho
pper
Mec
hani
cal c
abin
et
Elec
tron
ic
cabi
net
Filli
ng
syst
em
Buf
fer
tank
Mai
n fr
ame
Paris
on
head
Mol
d m
ovem
ent
Fill
Suite
Seg
rega
tion
The
�Dirt
y� S
ide
�Se
para
ting
pote
ntia
l sou
rces
of c
onta
min
ants
fr
om th
e fil
ling
envi
ronm
ent
Stai
nles
s St
eele
Bar
rier W
all
Fill
Suite
Seg
rega
tion
The
�Dirt
y� S
ide
�Se
para
ting
pote
ntia
l sou
rces
of c
onta
min
ants
fr
om th
e fil
ling
envi
ronm
ent.
Fill
Suite
Seg
rega
tion
The
�Cle
an�
Side
�H
ouse
s th
e pa
rison
ext
rusi
on, a
nd s
teril
e fil
ling
spac
e un
der a
ste
rile
lam
inar
air
hood
LUW
A C
urta
in
Ster
ile la
min
ar a
ir ho
od
�R
oom
Cla
ss 1
00,0
00
�LU
WA,
Lam
inar
Ste
rile
Air S
how
er, C
lass
10
,000
�St
erile
Fill
ing
Spac
e,
Cla
ss 1
00
Mac
hine
Qua
lific
atio
n
Mai
n ac
tiviti
es o
f Mac
hine
Qua
lific
atio
n
�In
stal
latio
n Q
ualif
icat
ion
(IQ)
-Che
ck o
f the
mai
n co
mpo
nent
s fo
r cor
rect
ness
acco
rdin
g sp
ecifi
catio
n (m
ater
ial a
nd ty
pe)
�O
pera
tiona
l Qua
lific
atio
n (O
Q)
-Che
ck o
f mai
n fu
nctio
ns o
f the
equ
ipm
ent
�Pe
rfor
man
ce Q
ualif
icat
ion
(PQ
)-C
heck
of p
roce
sses
func
tions
and
effi
cien
cies
, ou
tput
, cap
abili
ties
etc.
�Pro
cess
Qua
lifca
tions
-3 x
Med
ia fi
lls
-3 x
SIP
-Val
idat
ion
(Ste
riliz
atio
n in
Pla
ce) w
ith
biol
ogic
al in
dica
tors
(BI)
-3 x
CIP
-Val
idat
ion
(Cle
anin
g in
Pla
ce)
Bul
k So
lutio
n
Bul
k So
lutio
n
�So
lutio
n is
tran
sfer
red
into
th
e H
oldi
ng ta
nk th
roug
h a
0.2
mic
ron
Pall
Filte
r
�So
lutio
n in
the
Hol
ding
ta
nk is
mai
ntai
ned
unde
r po
sitiv
e pr
essu
re w
ith
ster
ile a
ir
Util
ities
Stab
le s
uppl
y an
d qu
ality
of u
tiliti
es
�Ele
ctric
pow
er:
!C
onne
ctio
n: 3
5-10
0 kW
, dep
endi
ng o
n m
achi
ne
type
!C
onsu
mpt
ion:
25-
60 k
W, d
epen
ding
on
mac
hine
ty
pe
�Com
pres
sed
air:
oil a
nd m
oist
ure
free
qua
lity,
8 b
ar
min
.
�Coo
ling
wat
er:~
1.3
-2.
0 m
3 /h a
t 12°
C a
nd 4
bar
; di
rt fi
ltere
d at
55
mic
ron
�Pur
e st
eam
(SIP
):~
25-4
0 kg
/h p
artic
le fi
ltere
d
Con
tain
er D
esig
n
Poin
ts to
con
side
r for
con
tain
er d
esig
n:
�Res
in ty
pe fo
r BFS
�N
eed
for a
utoc
lavi
ng�O
xyge
n / V
apor
per
mea
tion
�Lig
ht s
ensi
tivity
�Fill
vol
ume
-dos
age
volu
me
�Clo
sure
des
igns
�Lab
elin
g O
ptio
ns
Res
in f
or B
FS te
chno
logy
Low
den
sity
poly
ethy
lene
(LD
PE)
Hig
h de
nsity
poly
ethy
lene
(HD
PE)
Polyp
ropy
lene
(PP)
Den
sity
(g/c
m3 )
0,91
5-0,
930,
94-0
,95
0,89
5-0,
905
Mel
ting
inde
x(g
/10
min
)0,
2-2
~2
~2
Cla
rity
good
poor
good
Gas
per
mea
tion
med
ium
med
ium
med
ium
Vapo
r per
mea
tion
good
exce
llent
exce
llent
Dro
p re
sist
ance
exce
llent
good
satis
fact
ory
Sque
ezab
ility
exce
llent
satis
fact
ory
poor
Reg
ulat
ory
conf
orm
ityEP
III,
Ed 1
997
3.1.
4U
SP, c
lass
VI
FDA,
CFR
177-
1520
(c) 2
.2
EP II
I, Ed
199
7 3.
1.5
USP
cla
ss V
IEP
III,
Ed 1
997
3.1.
6U
SP, c
lass
VI
FDA,
CFR
177-
1520
(c) 3
.2Ap
plic
atio
nex
ampl
esey
e dr
ops
inha
latio
nsoi
ntm
ents
/cre
mes
LVP/
SVP
irrig
atio
n so
lutio
nsor
al s
olut
ions
topi
cal s
olut
ions
irrig
atio
n so
lutio
nsLV
PSV
Pey
e dr
ops
Auto
clav
ing
�PP,
aut
ocla
ving
pos
sibl
e at
121
°C, 1
5 m
in
�PE,
med
ium
den
sity
(0,9
28 -
0,93
), au
tocl
avin
g at
10
6 -1
10°C
, pro
long
ed c
ycle
tim
e
�PE,
low
den
sity
(0,9
15-0
,928
): as
eptic
fill
for h
eat
sens
itive
pro
duct
s
Oxy
gen/
Vap
or p
erm
eatio
n
�PE
, PP
limite
d ba
rrie
r pro
pert
ies
for o
xyge
n an
d C
O2
�M
achi
ne o
pera
tion
with
nitr
ogen
inst
ead
of s
teril
e ai
r�Se
cond
ary
pack
agin
g by
pou
chin
g/ov
er w
rapp
ing
-sup
port
ed b
y ni
trog
en-u
se o
f oxy
gen
abso
rber
Ligh
t sen
sitiv
ity�S
econ
dary
pac
kagi
ng in
to li
ght-p
rote
ctiv
e po
uche
s/ca
rton
s
�Ext
rusi
on o
f col
ored
par
ison
Fill
volu
me
-Mul
ti do
se c
onta
iner
s
�Mul
ti do
se c
onta
iner
-ste
rile
befo
re fi
rst
ap
plic
atio
n-c
ritic
al: p
rese
rvat
ives
-add
ition
al c
ap/in
sert
for
re-c
losu
re fu
nctio
n
Mul
ti-do
se e
ye d
rop
& e
ar d
rop
bottl
es
Rec
losa
ble
bottl
e fo
r con
tact
le
nse
clea
ning
Fill
volu
me
-U
nit d
ose
cont
aine
r
�Uni
t dos
e co
ntai
ner
-no
pres
erva
tives
-no
capp
ing
part
-d
efin
ed d
ose
volu
me
-eas
y to
app
ly
Uni
t-dos
e pa
ckag
es fo
r co
ntac
t len
s ca
reU
nit-d
ose
eye,
ear
&
nose
dro
ps
Oin
tmen
ts &
cre
ams
Bel
ow c
onta
iner
s fo
r rec
tal &
vag
inal
app
licat
ions
Enem
as w
ith c
annu
la o
r thr
eads
Spec
ialty
des
igns
Spec
ialty
Des
igns
Clo
sure
Des
igns
a) S
tand
ard
twis
t-off
b) T
hrea
d fo
r big
ger c
aps/
w
ider
ope
ning
c) T
hrea
d fo
r pin
cap
s
d) M
embr
ane
clos
ure
Inse
rtio
n of
sto
pper
s,
nozz
les,
etc
.
Clo
sure
Des
igns
Labe
ling
Labe
ling
Opt
ions
a)Em
boss
ing
b)Pa
per l
abel
on
tabs
c)D
irect
prin
ting
on ta
bs
d)C
onve
ntio
nal L
abel
s
a) E
mbo
ssin
g-En
grav
ed M
olds
�A
mirr
or im
age
of in
form
atio
n is
en
grav
ed o
n th
e su
rfac
e of
a m
old�
s ca
vity
.
�Sm
all v
acuu
m p
orts
on
the
mol
d su
rfac
e pu
ll in
the
soft
plas
tic
embo
ssin
g th
e co
ntai
ner.
Engr
aved
Mol
d
Embo
ssed
Lab
elin
g
Embo
ssin
g
No
leac
habl
es
Ensu
re e
ach
unit
is
trac
eabl
e
Labe
ls c
an n
ot b
e re
mov
ed
Ensu
res
100%
labe
ling
of c
onta
iner
s
Diff
icul
t to
read
on
clea
r co
ntai
ners
No
mai
nten
ance
of l
abel
in
vent
orie
s
Con
sPr
os
b) P
aper
Lab
els
on T
abs
�Th
e m
old
is d
esig
ned
with
a
tab,
or f
lag
on th
e ta
il or
th
e ca
p.
�Ta
b is
a s
olid
sur
face
pr
ovid
ing
spac
e fo
r pap
er
labe
ls
Pape
r Lab
el o
n Ta
b
Pape
r lab
el o
n Ta
b
Gre
atly
redu
ces
pote
ntia
l lea
chin
g in
to
the
solu
tion
Pote
ntia
l lea
chin
g of
la
bel a
dhes
ive
into
so
lutio
n
Cle
arer
to re
adC
ons
Pros
c) D
irect
Prin
ting
on T
abs
�In
k je
t prin
ting
on ta
bs
with
bar
code
s, a
nd
prod
uct i
nfor
mat
ion
Dire
ct P
rintin
g on
Tab
Dire
ct p
rintin
g on
the
Tab
Allo
ws
for b
arco
de
prin
ting
on li
ne
Gre
atly
redu
ces
pote
ntia
l lea
chin
g in
to
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tial
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ntia
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arer
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Pros
d) C
onve
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abel
ing
Than
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Ster
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acka
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of l
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arm
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sing
rom
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otte
lpac
kbl
ow-fi
ll-se
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achi
nes
Moh
amm
ad S
adeg
hiV.
P. R
&D
Hol
opac
k In
tern
atio
nal C
orp.
1 Te
chno
logy
Circ
leC
olum
bia,
SC
292
03Te
l: (8
03) 8
06-3
300