Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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1~80130
SPECIFICATION
Pharmaceutical filters must meet rigid requirements, and for
this reason most designs of commercial filters are not acceptable. All
portions of the filter assembly that come into contact with the fluid to be ;
5 filtered must be sterile and moreover contamination of the downstream
filtered effluent by ur~iltered material bypassing the filter cannot be
tolerated, because of the dangerous and possibly even fatal conseq!lences
to the patient, to whom the filtered pharmaceutical fluid material may
eventually be administered.
It is common practice in the pharmaceutical industry to sterilize
a filter in situ in the system in which it is used. This means that the
sterilizing fluid, usually steam or ethylene oxide gas, must reach every
part of the filter, even on the outside of any r~ nt seal, due to the pos-
sibilit~ of the seal's pumping contaminants into the system during internal
15 pressure changes. This requirement makes unacceptable for pharmaceuti-
cal use any filter having internal resilient seals that prevent access of
sterilizing gas to any part of the interior of the filter ~lnit.
Moreover, commercial filters normally provide sealing to the
filter housing in a manner to compel fluid flow through the filter, but with
20 leakage paths at the sealing element such that unfiltered $1uid bypassing the
sealing element due to a faulty seal can enter and contaminate the filtered
downstream effluent.
U. S. patent No. 3,696j932 patented October 10, 1972 provides a
filter design which makes impossible bypass OI a filter with contamination
25 of the downstream effluent, by providing a leakage path which extends
to the outside of the housing. This leakage path is delineated between
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specially structured end cap and filter housing parts, and by eliminating
sealing means, but relying instead upon an integrated welding or fusing
of the housing and end cap component parts, where feasible, and a
tapered seal between the parts where not feasible. This design has
5 however proved expensive to manufacture, and the resulting high cost
o~ the filter assemblies has limited their usefulness to areas where
high cost can be tolerated, such as in blood filter transfusions,
e~tracorporeal blood circulation systems, and similar applications
where the life of the patient is at stake,and the cost of a filter as-
10 sembly is minor compared to other aspects of the procedure
A further design difficulty is posed by the necessity that allcomponent parts of the filter assembly that come into contact with
fluid be absolutely sterile. This requires fabrication from materials
that can be made sterile without deterioration, and this precludes the
15 usual materials ~ construction of commercial filter assemblieæ,
particularly filter elements. It also precludes as well as any com-
plication~ in design, such as nooks, crevice~, and crannies, in
which bacteria may lodge, and escape unscathed in the steriliza-
tion procedure.
In some cases, it is perfectly feasible to reuse a filter
assembly after replacement of the filter element and resterilization.
This requires a design which in addition is easy to assemble and
disassemble, and which permits such assembly and disassembly
without contamination of sterile parts, or alternatively, which
25 permits sterilization of the completed filter assembly. This intro-
duces other complications. Joints such as threaded cylindrical
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joints are not acceptable, because they provide locations where
bacteria and other contamination can lodge, with such adequate
protection from the sterilization conditions as to allow their sur-
vival and persistence in the presumably sterilized filter assembly.
Egemplary commercial filter designs which have interesting
features but which overall are unsuitable for pharmaceutical appli-
cation are those disclosed in IJ. S. patents Nos. 2,808,937 to Ol~ear~
dated October 8, 1957, No. 2,931,507 to Kent dated April 5, 1960, and
No 3,856,683 to Parr dated December 24, 1974
O'Meara No. 2,808,937 provides a filter with two housing
parts held together by a ~T-ring metal clamp, with a filter element in
between. This filter has however an insufficient surface area for the
volume it occupies, and is in no way suitable for fine filtration, be-
cause there is no support for the filter element against differential
15 pressure. It i8 clearly intended for use only as a coarse gravity
filter, in which event there i8 only a small proportion of material
removed relative to the volume treated, as in the filtration of milk.
Kent No. 2,931,50q provides a filter for use with gases and
liquids such as gasoline and oil, with a removable filter unit, but
20 assembly and disassembly requires the removal of a number of bolts,
and the device is of a rather heavy and bulky construction, and
unsterilizable .
Parr No. 3,856,683 provides a dual flow fluid filter with
identical filters arranged back to back with a peripheral dam there-
25 between, which compels fluid flow to proceed from the outside of onefilter into the interior, and then into the interior of the other filter and
back to the outside. This design is unsuitable where only one filter
is sufficient
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In accordance wîth the invention, a filter assembly is pro-
vided for filtering pharmaceutical fluid materials which can be
æterilized in situ in a fluid line because ever~T portion of the interior
of the assembly is accessible to sterilizing fluid, and which provides
5 a leakage path at the filter seal to the outside of the assembly, so that
there is no danger of contaminating downstream filtered effluent with
unfiltered fluid material, in the event of leal~age past the filter seal.
The invention in one aspect provides a filter assembly free
from internal seals but having a replaceable filter element, for fil-
10 tering pharmaceutical fluid materials wUhout danger of microor-
ganism contamination of downstream filter effluent, comprising, in
combination, a filter housing comprising first and second housing
parts; the first housing part having a first fluid chamber open at one
side, a fluid port opening into the first fluid chamber, and a peripheral
15 sealing lip; the second housing part having a second fluid chamber
open at one side, a fluid port opening into the second fluid chamber,
and a peripheral sealing lip; sealing means between the peripheral
lips and sealing with at least one of the peripheral lips against
leakage to the exterior of the filter housing; retaining means holding
20 the peripheral lip9 of the housing parts and sealing means in fluid-
tight ~ealing juxtaposition, a filter element disposed in the second
fluid chamber in the second housing part and comprising a tubular
filter confined between and permanently sealed in a fluid-tight seal
to end caps at each end thereof, of which a first end cap is closed
25 and a second end cap has an opening therethrough communicating
the interior of the tubular filter with the first fluid chamber, and
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a peripheral lip integral with the second end cap and extending into
sealing engagement on one side with one side of the sealing means,
and shaped to seal on its other side against one side of one periph-
eral sealing lip of the other housing part, and to fit between the
5 sealing means and the peripheral sealing lip, the periphe~al lip of
the second end cap extending across and closing off the open sides
of the first and second fluid chambers without any internal seal, so
that fluid communication therebetween is restrlcted to the opening
in the second end cap via the filter, and the leakage paths at the .
I0 end cap, integral peripheral lip, and housing part peripheral lip
past the sealing means therebetween do not bypass the filter, but .
run to the exterior of the housing between the housing parts, so that
there are no internal leakage paths.
A preferred embodiment of the invention is illustrated in
15 the drawings, in which: .
Figure 1 represents a longihdinal section through a
filter assembly in accordance with the in~ent~on; and
Figure 2 represents a cross-sectional view taken along
the line 2-2 of Figllre 1, and showing the ribbed portion o~ one
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20 end cap of the filter.
The filter assembly shown in Figures 1 and 2 comprises
a first, normally the bottom, housing part 1, a second, normally
the top, housing part 2, and a filter element 3 disposed in the second
housing part 2 The first housing part 1 has a.fluid port 4, leading
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into a first fluid chamber 5. The second housing part 2 has a
fluid port 6, leading into a second fluid chamber 7.
In the arrangement shown, the fluid port 6 would normally
be the un~iltered fluid inlet into the housing, and the fluid chamber 7
5 the upstream unfiltered fluid chamber. The fluid chamber 5 would
receive filtered fluid from the filter, and the fluid port 4 would serve
as the filtered fluid outlet port from the houæing. However, the
reverse is also possible, with flow in the reverse direction. Also,
the housing part 1 can be at the top, and part 2 at the bottom; the
10 assembly can also be arranged horizontally, or at any desired angle
to the horizontal or vertical.
The filter element 3 comprises a tubular filter 8 confined
between end caps 9,10, each sealed to the ends of the filter tube 8
by a potting compound 11. The filter 8, in this case a bacteria proof
15 filter, pore size absolute less than 0.3 micron, such as a membrane
or porous plastic sheet, is supported on an internal core 12, in this
case a tube made of polypropylene or other plastic, with a number of
ports 13 therethrough, for flow of fluid passing through the filter 8,
into or out from the interior chamber 14 of the filter 8. The exterior
20 of the filter is confined within a wrap 30 of extruded polypropylene or
other plastic netting such as Vexar*.
It will now be seen that the chamber 5 is in fluid communica-
tion with the interior chamber 14 of the tubular fllter by way of the
aperture 15 in the end cap 10. Since the end cap 9 closes off the
25 other end of the tubular filter, fluid flow between the chambers 5
and 7 and the filter 8 is only via the interior chamber 14 of the
filter 8.
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The end cap 10 has a peripheral lip 16 that extends all the
way across ~ d amber 7, closing off that side of the chamber. The
peripheral lips 17,18 of the housing parts 1, 2 are each indented so
as to embrace a sealing ring 19, such as a conventional O-ring o~
G rubber or other resilient material, and it will be noted that the
terminal end portion 16a of the lip 16 of the end cap 10 is also
curved so as to fit against the interior wall of the flange 17, between
it and the ring 19, thus sealing off the chamber 7 at the ring 19.
It will now be apparent that because of the lip 16 of the
10 fluid chambers 5, q are effectively separated against fluid flow
therebetween, except through the filter 8 and the open interior 14
of the filter. The extension 16a of the lip 16 into sealing juxta-
position to the sealing ring 19 ensures that any leakage that may
arise at the seal cannot bypass the end cap 10 and its lip 16, but
15 instead passes to the exterior of the filter housing between the
two housing parts 1, 2, at their lips 17, 18, through the opening 21
therebetween.
The two housing parts 1, 2, at their lips 17,18, are held in
sealing relation against the O-ring 19 and the lip 16 of the end cap
20 lO by the V-ring clamp 22. The legs of the V-ring are spread
apart, forming a tapered clamp at the junction of the two housing
parts. The clamp 22 is provided with a lever-actuated toggle 23,
and extends about the circumference of the joint. Closure is
completed by snapping the lever 20 back, and released by snapping
25 the lever open. Adjustment of the clamping action can be provided
by shortening or 1en~eni~the clamp by the adjustment screw 24.
The toggle action clamp is of conventional typea and forms no part
of the invention9 but it does provide a certain secure seal at the
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joint between the two housing parts.
Each of the ports 4, 6 is provided with a standardized
connection 25, for attachnlent to a fluid line.
The housing part 2 is also provided with a port 26, serving
5 as a vent, drain or inlet feed port, and a port 27 serving as a vent,
drain or inlet feed port, but these are not essential, and either or
both can be omitted. For convenience, the ports 26,27 can be provided
with Luer* fittings or Pharmaseal* fittings, for reception of con-
tainers or delivery means with standardized mating Luer* or
10 Pharmaseal~k fittings. ! The ports 26, 27 are also provided with caps
29, so that they can be kept normally closed, but opened when
desired, such as to vent air via port 26 from within the chamber 7
at the time the filter is filled (possibly via port 27) preparatory to
being put on-stream.
Instead of a cap, the port 27 can be fitted with a valve option-
alb provided with a Luer* fitting, for sampling of fluid within the
chambers 7 and 5 while it is onstream, or so as to ascertain when con-
taminatio~ build-up requires removal of the filter from service.
Assembly and disassembly of the filter is quite simple. The
20 clamp 22 is removed, whereupon the housing part 2 can simply be lifted
off, exposing the filter element 3. This can be removed after removing
the O-ring seal 19, and replaced, after which the housing part 2 can
again be put in position, and the clamp 22 reimposed.
The end cap 10 is provided with a plurality of external
25 ribs la, which project outwardly into chamber 5 (as seen in Figure 2),
and come into juxtaposition to or even into contact with the surface
of the housing part 1. These help to retain the end cap 10 and with
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it the filter element 3 in position under high differential fluid pres-
sure applied from the upstream ur~iltered side of the filter element,
and relieve strain on the lips 16,16a of the end cap that might lead
to distortion and rupture of the seal. Further support for the
5 filter 8 against such differential fluid pressure is provided by the
internal core 12 and outer wrap 30, preventing distortion or blow
out of the filter under high differential pressure, such as might
develop with heavy contaminant loading, in either direction of
flow through the filter.
In normal use, fluid flow would be as indicated by the
arrow, via port 6 as inlet, to port 4 as outlet, since the ex~erior
surface of the filter 8 has a larger available volume than the
interior, for collection of contaminants removed by the filter.
However, if the volume of contaminants to be removed is not
15 unduly great, fluid flow can equally well proceed via port 4 as
inlet to port 6 as outlet, with the contaminants being collected on
the inside surface of the filter. Under such reverse flow, since
the differential fluid pressure is applied against the inside of the
filter, the external supporting sheath 30 about the exterior of the
20 filter 8, assumes the function of the internal core 12.
The filter assembly of the invention is not position-
sensitive, and can be oriented as desired, horizontally, vertically9
or at any selected angle to the horizontal or vertical. Normally9
however, the filter assembly will be oriented as shown in the
25 drawings, with the housing part 2 uppermost.
The housing parts can be formed of any desired material.
For use as a pharmaceutical filter, all parts must be sterilizable.
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Inert metals not susceptible to corrosion or attack by the pharma-
ceutical fluid being filtered can be used, of which stainless steel
is preferable, and aluminum and nickel-chromium alloys also
acceptable. Plastic materials which are sufficiently rigid to be
5 capable of retaining their dimensions under pressure, and inert
enough to withstand the sterilization procedures, can also be used,
and will be found preferable in many instances because of their ease
of fabrication by molding to any desired co~Eiguration. Suitable
plastic materials înclude polyesters, polycarbanates, polyoxy-
10 methylene resins, polyamides, phenylformaldehyde resins, poly-
tetrafluoroethylene, polychlorotrifluoroethylene, polypropylene
polyethylene, polybutylene and polysulfones.
The filter will be of a material selected to withstand
attack by the pharmaceutical fluid being filtered, and also withstand
15 the internal pressures of the system, while at the same time being
sufficiently inert to withstand sterilization procedures. Metal an~
plastic can be used. Metallir wire mesh, such as stainless steel
mesh, aluminum wire mesh, and similar inert metallic wire mate-
rials can be used. Plastic monoiLament mesh is also suitable,
20 such as, for example, nylon mesh, polypropylene mesh, and poly-
ester mesh(particularly the polyester mesh described and claimed
inU.S. patentsNos.3,701,433, 3,765,537, and3,765,536,patented,
respectively, October 21, 1972, October 16, 1973, andOctober 16,1973).
The pore size of the filter can be as large or as small as
25 required, ranging from as low as about 0.01 micron up to about
1,000 microns and more. It is frequently desirable to use a plu-
rality of filter layers of differing porosity, usually with the porosity
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decreasing in the direction of flow, as in the filter cascades of
patents Nos. 3,765,537 and 3,765,536.
For pharmaceutical uses, the filter should be capable
of removing bacteria. This requires an absolute pore size below
5 0.3 micron. For this purpose, porous membranes and sheets of
plastic are preferred.
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Suitable materials are described in U. S patents Nos.
3,238, 056, 3,246,767, 3,353, 682, 3, 573,158 and 3, 696, 932,
patented, respectively, March 1, 1966, April 19, 1966,
10November 21, 1967, March 30, 1971, and October 10, 1972.
- ~t is quite advantageous to form the housing, end caps,
and filter of the same plastic material, such as polypropylene,
polyamide, or polytetrafluoroethylene.
It will be apparent that the filter assembly of the inven-
15 tion possesses numerous advantages, particularly adapting it for
use as a pharmaceutical filter. The filter element end cap with
an integrally molded sealing lip eliminates the necessity for
internal seals, and provides an acceptable sanitary sterile
closure. In the event of a damaged or faulty seal, it is impos~
20 sible for downstream filtered effluent to be contaminated by
upstream unfiltered influent, since there is no internal leakage
path. The lips of the two housing parts are formed to mate
precisely with the sealing means and the sealing lip of the end
cap, thus providing positive sealing with a minimum of clamping
25 force, since there are no internal fittings or glands. The
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interior surfaces of all the filter assembly parts are com-
pletely and easily accessible, for positive sterilization and
sanitary cleaning. The sealing means and the ribbed configura-
tion of the element end cap downstream of the filter are
5 precisely mated, so as to guarantee the integrity of the filter
element under the most rigorous operating conditions. The
applicability of Luer-lok* and/or Pharmaseal Iittings to
the line vent and drain connections make the assembly
adaptable ~or connection to any kind of standardized receptacle
10 or delivèxy means. If the housing parts and filter element end
caps are prepared in polished dies, precisely finished and
polished, a housing of superior appearance and cleanability
is obtained.
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