Prefilled syringe with embedded filter

Abstract

Apparatus and method for filtering syringe fluid contents through a filter embedded in a syringe. The filter can be sealed inside a housing located proximal to the syringe distal outlet, distal to the unfiltered fluid contents, and the housing exterior can be fluid-tightly sealed against the syringe interior wall. Prior to filtering, the housing can block unfiltered fluid access to the filter. The unfiltered fluid can be sealed between the syringe plunger, the interior wall, and the housing. Propulsion of the unfiltered fluid distally can unblock the housing from flowing unfiltered fluid to the filter. The fluid-tight seal inside the housing can restrict fluid passage to the distal outlet to a path through the filter. The unfiltered fluid can be pushed through the unblocked housing and filter. The filtered fluid, relatively free of particulate matter larger than the filter average pore size, can flow to the distal outlet for delivery to a target site.

Description

[Background technology]

[0001] background Prefilled syringes (PFS) are frequently used to deliver medications to target sites. PFS offer users several advantages over traditional syringes. Beyond eliminating the user step of loading the syringe with medication, these advantages typically also include improved accuracy and consistency of administration, reduced pre-delivery exposure of the delivery needle to a non-sterile environment, and reduced likelihood of inadvertent needlestick injuries.

[0002] However, there are some drawbacks to using a PFS. A PFS is typically intended for use after a period of storage, possibly for an extended period of time. During storage, contact adhesion can form between the PFS syringe plunger and the inner wall of the PFS syringe barrel. The adhesion can require a high break-loose force to overcome such "stiction" to initiate plunger movement within the barrel. Over the storage period, molecular deposits can form along the inner wall. The adhesion and deposits can require a high glide force to maintain plunger movement within the barrel during drug delivery. High break-loose and / or high glide forces can be difficult for users to achieve, maintain, or adjust. The application of such high forces by users can cause discomfort to patients receiving PFS injections.

[0003] To minimize complications associated with adhesion / deposition, PFS manufacturing typically involves lubrication of the inner barrel wall and / or the exterior of the plunger. While lubrication generally improves break-loose and glide force requirements, it frequently introduces other complications. Over time, the material used for lubrication, typically a silicone oil-based material, can migrate from the lubricated surface and form free-floating particles within the PFS's liquid contents. Such particles can further grow through self-aggregation and / or drug molecule attachment.

[0004] Independent of lubricant-related complications, prolonged exposure to the drug and drug molecules on surfaces within the PFS can result in particle-forming self-aggregation of the drug molecules.

[0005] Most of the aforementioned particles are considered non-therapeutic and, in some cases, may be harmful to the patient.

[0006] Particles can be removed immediately prior to delivery by passing the PFS contents through a filter of appropriate pore size. A standard approach to filtering syringe contents involves securing a filter between the delivery needle and the distal delivery outlet of the syringe barrel immediately prior to drug delivery to the target site. However, implementing such an approach likely negates many of the PFS's advantages of safety and ease of use.

[0007] It would therefore be desirable to provide a device and method for filtering the contents of a PFS that is closed in time prior to drug delivery in a manner that maintains the benefits of PFS use.

[0008] Manufacturing a PFS with an integrally attached filter can result in fouling of the filter with drug and / or particles, deposits, and aggregates during storage. Such fouling can reduce the usability and functionality of the filter during drug delivery.

[0009] Therefore, it would also be desirable to provide devices and methods for filtering PFS contents that are closed at the time prior to drug delivery in a manner that isolates the PFS contents from the filter during PFS storage prior to delivery and allows the PFS contents to access the filter surface during delivery. Summary of the Invention

[0010] Brief Description of Disclosure A device and method for filtering the contents of a PFS is provided that is closed at the time prior to drug delivery in a manner that maintains the benefits of PFS use.

[0011] Provided are devices and methods for filtering the contents of a closed PFS at a time prior to drug delivery in a manner that isolates the drug from the filter during storage of the PFS prior to delivery and allows the drug to easily flow through the filter during delivery, thereby allowing access to the surface.

[0012] The devices and methods directed to the above are provided as disclosures of a filter embedded within a PFS near the distal delivery outlet of the PFS, the filter being closed from proximally stored drug prior to drug delivery and open to drug flow during drug delivery.

[0013] Apparatus and methods directed to the above are provided as disclosures of a filter housing housed within a PFS near a distal delivery outlet of the PFS, the filter housing preventing drug access to a filter housed within the filter housing prior to drug delivery, and the filter housing allowing drug access to the filter during drug delivery.

[0014] The method may include a method of manufacturing a filter housing.The method may include a method of manufacturing a pre-filled syringe. [Brief explanation of the drawings]

[0015] Objects and advantages of the present invention will become apparent from the following detailed description considered in conjunction with the accompanying drawings, in which like reference characters refer to like parts throughout.

[0016] [Figure 1] 1 is a schematic diagram of an apparatus according to the principles of the present invention;

[0017] [Figure 2] 1 is an isometric view of an apparatus according to the principles of the present invention, with selected exterior features shown in partial cross-section to provide an unobstructed view of interior features;

[0018] [Figure 3] 1 is an exploded isometric view of an apparatus in accordance with the principles of the present invention;

[0019] [Figure 4] 1 is an isometric view of an apparatus according to the principles of the present invention with selected features shown in partial cross-section;

[0020] [Figure 5] 1 is a partial cross-sectional view of an apparatus according to the principles of the present invention;

[0021] [Figure 6] 6 is a cross-sectional view of the device shown in FIG. 5, taken along line 6-6 (shown in FIG. 5).

[0022] [Figure 7] 7 is an isometric view of an apparatus according to the principles of the present invention, with selected features shown in partial cross-section, illustrating a stage of use subsequent to the view shown in FIG. 6;

[0023] [Figure 8] 8 is a partial cross-sectional view of the device shown in FIG. 7, taken along line 8-8 (shown in FIG. 7).

[0024] [Figure 9] 1 is an isometric view of an apparatus according to the principles of the present invention, with selected exterior features shown in partial cross-section to provide an unobstructed view of interior features;

[0025] [Figure 10] 1 is an exploded isometric view of an apparatus in accordance with the principles of the present invention;

[0026] [Figure 11] 1 is a partial cross-sectional view of an apparatus according to the principles of the present invention;

[0027] [Figure 12] 12 is a partial cross-sectional view of the device shown in FIG. 11 taken along line 12-12 (shown in FIG. 11).

[0028] [Figure 13]13 is a partial cross-sectional view of an apparatus according to the principles of the present invention, taken from the same perspective as FIG. 12, showing a stage of use subsequent to the view shown in FIG. 12;

[0029] [Figure 14] 14 is an isometric view of an apparatus according to the principles of the present invention, with selected features shown in partial cross-section, illustrating a stage of use subsequent to the view shown in FIG. 13; DETAILED DESCRIPTION OF THE INVENTION

[0030] Detailed Description Devices and methods are provided for a filter embedded in a syringe. The device may include a syringe with a filter embedded in the syringe. The device may include a filter housing with a filter secured within the housing. The housing may be housed in the syringe. The syringe may be a PFS.

[0031] The method may include a method for manufacturing a device.

[0032] The apparatus may include a fluid delivery device. The device may deliver a filtered fluid. The device may be configured to deliver the filtered fluid. The filtered fluid may be delivered from a distal outlet of the device. The device may define a longitudinal axis.

[0033] The device can include a fluid reservoir. The reservoir can be coaxially disposed about the longitudinal axis. The reservoir can contain a fluid. The fluid can include a medication. The fluid can be filtered through a filter to deliver the filtered fluid.

[0034] The filter may have an average pore size. The average pore size may be from about 0.01 microns to about 10 microns. The average pore size may be from about 0.01 microns to about 1 micron. The average pore size may be from about 1 micron to about 10 microns. The filter may have any suitable average pore size. Any suitable average pore size may include an average pore size of 0.1 microns to about 0.3 microns. Any suitable average pore size may include an average pore size of about 4 microns to about 6 microns.

[0035] Any suitable average filter pore size may include an average pore size selected to be smaller than the average effective diameter of particulate matter to be filtered from the unfiltered fluid. The average effective diameter of particulate matter to be filtered from the unfiltered fluid may be about 0.4 microns. The average effective diameter of particulate matter to be filtered from the unfiltered fluid may be about 7 microns.

[0036] Also contemplated for use in the invention are specialized filters configured to retain substances based on the substance's charge. Also contemplated for use in the invention are specialized filters configured to retain substances through binding of the substance to specific molecular species immobilized on and / or in the specialized filter. Such species may include polypeptides. Polypeptides may include portions of antibodies. Such species may include polynucleotide chains. Polynucleotide chains may include portions of DNA. Polynucleotide chains may include portions of RNA. Specialized filters may be used to remove substances from the contents of the PFS fluid that are smaller than the pore size of the specialized filter (at least in the direction of fluid flow through the specialized filter). Specialized filters may also retain substances based on size.

[0037] The container may include a syringe barrel. The syringe barrel may define a barrel axis. The barrel axis may be coaxially disposed with the longitudinal axis.

[0038] The syringe barrel may include a wall. The wall may include a polymer. The polymer may include a plastic polymer. The wall may include glass. The glass may include borosilicate glass.

[0039] The wall may include an inner wall. The inner wall may be coaxially disposed about the longitudinal axis. The inner wall may be a boundary for the fluid. The inner wall may radially constrain the fluid.

[0040] The device may include a filter. The filter may be embedded within the container. The filter may be disposed proximal to the distal outlet. The filter may be disposed across the longitudinal axis. The filter may be disposed between the fluid and the distal outlet.

[0041] The device may include a filter housing. The filter may be secured within the filter housing. The filter housing may be disposed within the container. The filter housing may be disposed proximal to the distal outlet. The filter housing may be disposed between the fluid and the distal outlet. The filter housing may be housed within the container. The filter housing may be configured to maintain the filter oriented transverse to the longitudinal axis.

[0042] The filter housing may include a recessed element that seals against the inner wall. The recessed element may include an exterior rib. The exterior rib may be located along the exterior of the filter housing. The exterior of the filter housing may include a contour that is complementary to a contour of the inner wall. The exterior of the filter housing may have a convex contour that is complementary to a concave contour of the inner wall. The recessed element may be configured to seal against the inner wall. The recessed element may be configured to prevent fluid from passing between the filter housing and the inner wall.

[0043] The filter housing may include a proximal filter cap. The filter housing may include a distal filter base. The filter may be maintained in place between the filter base and the filter cap. The filter may be maintained in place across the longitudinal axis by engagement of the filter base and the filter cap. The filter may be secured to the filter base. The filter may be secured to the filter cap.

[0044] The filter base may be configured to provide distal support to the filter. The distal support may be provided in a central region of the filter. The distal support may be provided by a proximal central protrusion of the filter base. A proximal surface of the central protrusion may be disposed distally in close proximity to the filter. A distal side of the central region of the filter may be disposed proximally in close proximity to the central protrusion. A distal side of the central region of the filter may contact the central protrusion. The filter may be secured to the central protrusion. The filter may not be secured to the central protrusion.

[0045] The filter base may include a proximal rim. The proximal rim may support a proximal surface of the filter base. The filter may be attached to the proximal surface. The periphery of the filter may be attached to the proximal surface.

[0046] The region of the filter circumferentially tangent to the filter periphery can be bonded to the proximal surface of the proximal rim, the region can be located on the distal surface of the filter, or the region can be located inside the filter periphery.

[0047] The region may be joined to the proximal surface of the proximal rim of the filter base with a fluid-tight seal. The region may be joined to the proximal surface by welding. The weld may be created by a laser welding process. The weld may be created by a chemical welding process. The seal may extend circumferentially around the filter periphery. The seal may extend circumferentially around all of the filter periphery. The seal may be configured to prevent fluid passage between the interior of the filter base and any of the filter periphery.

[0048] Additionally or alternatively, the filter base and filter cap may cooperate within the filter housing to provide a fluid-tight seal around the filter. The filter cap may include an internal filter cap circumferential seal rib. The filter cap circumferential seal rib may include a plurality of filter cap circumferential seal ribs. The one or more filter cap circumferential seal ribs may be configured to extend distally within the filter housing. The filter base may include an internal filter base circumferential seal rib. The filter base circumferential seal rib may include a plurality of filter base circumferential seal ribs. The one or more filter base circumferential seal ribs may be configured to extend proximally within the filter housing. A region of the filter inside the filter periphery may be sealed by compression of the one or more filter cap circumferential seal ribs against the filter. A region of the filter may be sealed by compression of the one or more filter base circumferential seal ribs against the filter. A region of the filter may be sealed by compression of the filter between the one or more filter cap circumferential seal ribs and the one or more filter base circumferential seal ribs.

[0049] The filter base may be secured to the filter cap. Interference between the filter cap protrusion and the filter base recess may be configured to secure the filter cap to the filter base.

[0050] The opposing surfaces of the filter cap protrusion and the filter base recess may be contoured to complement one another. The opposing surfaces may feature complementary contours. The complementary contours may be approximate. The interference between the filter cap protrusion and the filter base recess may provide a fluid-tight seal. The fluid-tight seal may prevent fluid from passing between the opposing surfaces.

[0051] The interference between the filter cap recess and the filter base protrusion can be configured to secure the filter cap to the filter base. The opposing surfaces of the filter cap recess and the filter base protrusion can be contoured to complement one another. The opposing surfaces can feature complementary contours. The complementary contours can be approximate. The interference between the filter cap recess and the filter base protrusion can provide a fluid-tight seal. The fluid-tight seal can prevent fluid from passing between the opposing surfaces.

[0052] The filter cap protrusion can be disposed along a portion of the inner surface of the filter cap. The filter cap recess can be disposed along a portion of the inner surface of the filter cap. The inner surface of the filter cap can be a circumferential inner surface of the filter cap.

[0053] The filter base recess may be disposed along a portion of the outer surface of the filter base. The filter base protrusion may be disposed along a portion of the outer surface of the filter base. The outer surface of the filter base may be a circumferential outer surface of the filter base.

[0054] The filter cap protrusion may be disposed along a portion of the outer surface of the filter cap. The filter cap recess may be disposed along a portion of the outer surface of the filter cap. The filter base recess may be disposed along a portion of the inner surface of the filter base. The filter base protrusion may be disposed along a portion of the inner surface of the filter base.

[0055] The fluid-tight seal provided by the interference of the opposing surfaces of the filter cap and the filter base may be a circumferential seal. The circumferential seal may prevent fluid passage between the opposing surfaces all around the circumference of the filter housing. The circumferential seal may prevent fluid passage between the interior of the filter housing and the exterior of the filter housing.

[0056] The filter housing wall can be configured to seal against the interior wall of the vessel. The filter housing wall can be a perimeter wall. The filter housing wall that seals against the interior vessel wall can prevent fluid passage between the exterior of the filter housing and the interior wall.

[0057] The wall may include a filter cap sealing flange. The filter cap sealing flange may be disposed along an outer periphery of the filter cap. The filter cap sealing flange may include a plurality of filter cap sealing flanges.

[0058] The circumferential wall may include a filter base sealing flange. The filter base sealing flange may be disposed along an outer periphery of the filter base. The filter base sealing flange may include a plurality of filter base sealing flanges.

[0059] The wall may include a filter base sealing surface. The sealing surface may be supported by a section of the body of the filter base. The section of the body of the filter base supporting the sealing surface may be a distal section of the body. The sealing surface may be disposed along a distal outer region of a cone of the filter base. The sealing surface may be disposed along a distal outer region of a truncated cone of the filter base.

[0060] The exterior of the filter base may feature a contour at least generally complementary to the distal internal taper of the syringe barrel. The sealing surface may be arranged to seat against the distal internal taper. The distal internal taper may seat along a portion of the inner wall. The sealing surface may be configured to compress against the distal internal taper. The sealing surface may be configured to seal against the distal internal taper. The sealing surface sealing against the distal internal taper may prevent fluid passage between the distal exterior of the filter base and the distal internal taper. The sealing surface sealing against the distal internal taper may prevent fluid passage between the housing and the inner wall.

[0061] The container may enclose a quantity of fluid. The quantity may be a quantity of prefilled medication in the PFS. The quantity of prefilled medication may include a dose of medication. The quantity of prefilled medication may include an amount expected to be lost in syringe preparation prior to delivery. The amount expected to be lost in syringe preparation prior to delivery may include an amount expected to be lost due to syringe priming. The amount expected to be lost in syringe preparation prior to delivery may include an amount expected to be lost due to a filtering process. The filtering process may include a filter. The filtering process may include a filter housing.

[0062] The amount of prefilled medication in the PFS can be sealed within the container by a syringe plunger positioned proximal to the fluid. The plunger can be configured to slidingly seal against the interior wall. The plunger can be configured to prevent proximal flow of fluid between the interior wall and the exterior of the plunger.

[0063] The plunger can be configured to propel the fluid toward the distal outlet. Longitudinal movement of the plunger toward the distal outlet can cause propulsion of the fluid toward the distal outlet. To effect drug delivery, a user can move the plunger longitudinally toward the distal outlet.

[0064] The device can include a plunger rod configured to move the plunger distally toward the distal outlet. To effect drug delivery, a user can move the plunger rod longitudinally toward the distal outlet.

[0065] The plunger rod may be configured to move the plunger proximally away from the distal outlet.

[0066] Prior to delivery of the filtered fluid, a quantity of pre-filled medication can be placed between the plunger and the filter, and prior to delivery, the quantity can be placed between the distal face of the plunger and the proximal side of the filter.

[0067] Prior to delivery of the filtered fluid, a quantity of prefilled medication can be disposed between the plunger and the filter housing. Prior to delivery, the quantity can be disposed between a distal face of the plunger and a proximal exterior of the filter housing. Prior to delivery, the quantity can be proximally bounded by the distal face of the plunger. Prior to delivery, the quantity can be distally bounded by the proximal exterior of the filter housing.

[0068] A filter cap may comprise a proximal exterior of the filter housing and may be configured to block fluid access to the filter prior to delivery, and fluid may be configured to unblock the filter cap from flow of distally propelled fluid when propelled distally by the plunger.

[0069] The filter housing can be configured to prevent fluid from contacting the filter before the fluid is propelled toward the distal outlet. The filter housing can be configured to prevent fluid from flowing to the filter before propulsion. The filter housing can be configured to prevent fluid from accessing the filter before propulsion.

[0070] Prior to propulsion of fluid toward the distal outlet, the proximal exterior of the filter housing can be configured to prevent fluid from contacting the filter. The proximal exterior of the filter housing can be configured to prevent fluid from flowing to the filter prior to propulsion. The proximal exterior of the filter housing can be configured to prevent fluid from accessing the filter prior to propulsion.

[0071] Initiating a push of the fluid toward the distal outlet can increase fluid pressure on the filter housing. The increase in fluid pressure on the filter housing can change the configuration of the filter housing. Initiating a push in the distal direction can increase fluid pressure on the proximal outside of the filter housing. The increase in fluid pressure on the proximal outside of the filter housing can change the configuration of the proximal outside of the filter housing. The increase in fluid pressure on the proximal outside of the filter housing can change the configuration of the proximal side of the filter housing.

[0072] The filter housing may be configured to allow fluid access to the filter after propulsion begins. The filter housing may be configured to allow fluid flow to the filter after propulsion begins. The filter housing may be configured to allow fluid to contact the filter after propulsion begins.

[0073] The proximal side of the filter housing can be configured to allow fluid access to the filter after thrusting begins. The proximal side of the filter housing can be configured to allow fluid flow to the filter after thrusting begins. The proximal side of the filter housing can be configured to allow fluid to contact the filter after thrusting begins.

[0074] The filter cap may include a cylindrical body. The cylindrical body may be arranged coaxially with the longitudinal axis. Such a coaxial arrangement may be approximated. The cylindrical body may have an interior that includes the interior of the distal cap. The cylindrical body may have an inner wall. The inner wall may be a cylindrical wall.

[0075] In embodiments of the filter cap, the cylindrical body may include a collar disposed at the proximal end of the body. The collar may include a collar rim along an inner surface of the collar. The rim may extend radially inward.

[0076] The proximal side of the filter housing may include a proximal plug of the filter cap. The proximal plug may include a circumferential plug groove disposed along the exterior of the plug. The circumferential groove may extend radially inward into the body of the plug. The groove may have a concave contour complementary to a radially inward convex contour of the collar rim. The plug and rim may be configured to compress relative to one another. The concave contour of the groove and the convex contour of the rim may be configured to compress relative to one another. When the groove and rim are compressed relative to one another, interference may occur between the plug and the collar. The interference between the plug and the collar may provide a force to maintain the plug within the collar.

[0077] The interference between the plug and the collar may provide a seal against fluid flow between the plug and the collar. Prior to initiating the propulsion of fluid toward the distal outlet, the seal between the plug and the collar may prevent fluid from entering the interior of the cylinder. Prior to initiating the propulsion, the seal between the plug and the collar may prevent fluid from entering the interior of the filter cap. Prior to initiation, the seal may prevent fluid from entering the interior of the filter housing.

[0078] The seal between the proximal plug and collar can be configured to be overcome by thrusting. The seal between the plug and collar can be configured to be overcome by initiation of thrusting. The seal can be configured to be overcome by increasing fluid pressure on the proximal outside of the filter housing as thrusting begins.

[0079] An increase in fluid pressure proximally outside the filter housing can exert a distal force on the proximal plug. The distal force on the plug can be greater than the force maintaining the plug within the collar. The distal force on the plug can move the plug distally relative to the collar and into the interior of the filter cap.

[0080] As fluid pressure increases proximally outside the filter housing, the proximal plug can undergo distal movement relative to the collar into the interior of the filter housing. Distal movement of the plug into the interior of the filter housing can open the unplugged collar to fluid flow through it, with flow continuing into the interior of the filter housing and filter.

[0081] The proximal plug may define a cylinder axis. Prior to delivery, the cylinder axis may be coaxially disposed with the longitudinal axis. Prior to initiating fluid propulsion toward the distal outlet, the cylinder axis may be coaxially disposed with the longitudinal axis when the plug and collar are sealed together. Such coaxial arrangement may be generally coaxial.

[0082] The proximal plug may include one or more tabs extending radially outward perpendicular to the cylinder axis. The tabs may be located distal to the plug groove. The tabs may be located at the distal end of the plug. The effective cross-sectional diameter of the plug in the plane of the tabs may be about 50% to about 95% of the inner diameter of the inner wall of the filter cap cylinder.

[0083] The tab may be configured to maintain the orientation of the cylinder axis coaxial with the longitudinal axis during distal movement of the plug relative to the collar. The tab may be configured to maintain the orientation of the cylinder axis coaxial with the longitudinal axis after distal movement. The tab may maintain the orientation of the cylinder axis coaxial with the longitudinal axis by interference between the tab and an inner wall of the filter cap cylinder. The tab may maintain the orientation of the cylinder axis coaxial with the longitudinal axis by interference between the inner wall and an extreme radial edge of the tab. Such a coaxial orientation may be generally coaxial.

[0084] The plug may include one or more inter-tab gaps. The inter-tab gaps may be disposed along the outer surface of the plug. The inter-tab gaps may be disposed between circumferentially adjacent, opposing side edges of the tabs. In embodiments featuring two or more tabs, the inter-tab gaps may be disposed between circumferentially adjacent, opposing side edges of circumferentially adjacent tabs. The inter-tab gaps may be configured to allow fluid flow between the proximal exterior of the filter housing and the interior of the barrel during distal movement of the plug relative to the collar into the interior of the barrel. The inter-tab gaps may be configured to allow fluid flow between the proximal exterior of the filter housing and the interior of the barrel after distal movement of the plug. During and after distal movement, the inter-tab gaps may provide a passageway for fluid to flow from the proximal exterior of the fluid housing into the interior of the barrel to the filter.

[0085] In another embodiment of the filter cap, the cylindrical body may include a diaphragm ring support disposed at the proximal end of the body. The ring support may be disposed perpendicular to the longitudinal axis. Such perpendicular orientation may be approximate. The ring support may have a circumference concentric with the cylindrical body. The ring support may support a diaphragm disposed within the circumference of the ring support. The ring support may support a diaphragm concentric with the circumference of the ring support. The diaphragm may occupy an area concentric with the circumference of the ring support. The diaphragm may completely occupy the area concentric with the circumference. The area may have an area spanning from about 30% to about 95% of the proximal exterior of the filter housing. The area may be located proximal to the ring support. The area may be located at least generally flush with the ring support. The area may be located distal to the ring support.

[0086] The filter cap may include a diaphragm. The diaphragm may seal the proximal side of the filter housing against fluid flow from outside the proximal exterior of the fluid housing to the interior of the filter cap before actuation. Before actuation, the diaphragm may close the proximal side of the filter housing to prevent fluid flow into the interior of the filter cap. In response to actuation, the diaphragm may open the proximal side of the filter housing to flow into the interior of the filter cap.

[0087] The diaphragm can include an initially closed diaphragm. The initially closed diaphragm can prevent fluid flow to the filter. The diaphragm can be configured to be opened by fluid urged distally. The diaphragm can be configured to provide a passageway for fluid flow to the filter when opened.

[0088] The diaphragm may include a slit diaphragm. The slit diaphragm may include one or more slits. The slit diaphragm may include multiple slits. Prior to the initiation of distal thrust and the associated increase in fluid pressure on the proximal side of the distal cap, the slit may not fully penetrate the thickness of the diaphragm. The increase in fluid pressure may fully open the slit across the thickness of the diaphragm. Prior to the initiation of distal thrust and the associated increase in fluid pressure on the proximal side of the distal cap, the slit may not fully penetrate the thickness of the diaphragm along the entire length of the slit. The increase in fluid pressure may more nearly fully open the slit along the entire length of the slit.

[0089] The slit may penetrate completely through the thickness of the diaphragm before the onset of distal thrust and the associated increase in fluid pressure on the proximal side of the distal cap. The parallel-facing edges of the slit may compress together before thrust begins to provide a seal against fluid flow from the proximal exterior of the filter cap to the interior of the filter cap.

[0090] The diaphragm may include one or more diaphragm flaps. The diaphragm flaps may close along opposing edges of the slit. When closed, the diaphragm flaps may present an area coextensive with the diaphragm. When opened by an increase in fluid pressure proximal to the closed filter housing, the diaphragm flaps may extend distally into the filter cap. A portion of the diaphragm flaps may be positioned within the cylindrical body when the diaphragm flaps are opened. A portion of the open diaphragm flaps may be positioned within the cylindrical body at an acute angle from the closed position of the diaphragm flaps. A portion of the open diaphragm flaps may be positioned generally parallel to the inner wall of the cylindrical body. A portion of the open diaphragm flaps may be positioned within the cylindrical body at an obtuse angle from the closed position of the diaphragm flaps.

[0091] When opened, the diaphragm flap can be folded distally into the filter cap. The diaphragm flap can be folded at a hinge element supported by the diaphragm ring support. The hinge element can include a region along the distal surface of the diaphragm. The region along the distal surface can include a groove extending into the diaphragm material. The groove can extend proximally from the distal surface into the diaphragm material and / or distally from the proximal surface into the material. The groove extending into the diaphragm material can be arranged along a line segment encompassed by the ring support. The groove extending into the diaphragm material can be arranged along a circular arc concentric with the cylinder. The diaphragm material along the groove tends to fold more easily than the diaphragm material located away from the groove. The diaphragm material along the groove tends to fold more easily distally than the diaphragm material located away from the groove.

[0092] The diaphragm can be configured to reclose after being opened. The diaphragm can be configured to reclose after cessation of fluid flow. The diaphragm can be configured to reclose after cessation of distal propulsion of fluid.

[0093] The apparatus may include a filter housing for embedding within a drug container of a device for delivering a filtered drug. The device may define a longitudinal axis. The device may deliver the filtered drug from a distal outlet of the device. The filter housing may be configured to be embedded within the container proximal to the distal outlet.

[0094] The filter housing may include a filter base. The filter base may be configured to support the filter. The filter may be disposed in the filter base.

[0095] The filter may include an acrylic polymer. The filter may include polyethersulfone. The filter may include any suitable material. The suitable material may include polyvinylidene fluoride.

[0096] The filter may be configured to prevent particles larger than the maximum pore size of the filter from passing through the filter. The filter may be configured to retain particles larger than the maximum pore size of the filter. The filter may be configured to delay particles larger than the average pore size of the filter from passing through the filter. The filter may be configured to retain particles larger than the average pore size of the filter.

[0097] The average pore size of the filter can be about 5 microns. The average pore size of the filter can be any suitable average pore size. Any suitable average pore size can be about 0.2 microns.

[0098] The filter housing can be configured to provide a seal around the perimeter of the filter, which, when sealed, can be configured to prevent passage of medication around the perimeter.

[0099] The exterior of the filter housing can be configured to provide a seal against an interior wall of the container, and the seal can be configured to prevent distal flow of the agent between the interior wall and the filter housing.

[0100] The agent may be disposed within the container. The agent may be disposed within the container proximal to the filter. The agent may be disposed within the container distal to the longitudinally slidable plunger. The plunger may be configured to seal against the interior wall. The plunger may be configured to slidably seal against the interior wall. The plunger may be configured to propel the agent toward the distal outlet.

[0101] The filter housing may include a filter cap, which may be configured to mate with the base.

[0102] The agent may contact a proximal exterior aspect of the filter cap. Prior to delivery of the agent, the filter cap may be configured to block access to the filter by the agent. Prior to delivery of the agent, the proximal exterior aspect of the filter cap may be configured to block access to the filter by the agent.

[0103] The filter cap can be configured to be unblocked by distal thrust of a drug at a proximal exterior aspect of the filter cap. An unblocked filter cap can allow drug flow through the filter.

[0104] The proximal exterior aspect of the filter cap may include a proximal plug disposed on a collar of the filter cap. The proximal plug may seal the collar. The proximal plug may seal the collar against the flow of a drug. The proximal plug may seal the collar against the flow of a drug into the interior of the proximal cap. The proximal plug may seal the collar toward the filter against the flow of a drug into the interior of the filter housing. The proximal plug may be configured to move distally relative to the collar by a drug driven distally. Moving the proximal plug relative to the collar may open the collar to the flow of a drug through the collar.

[0105] The proximal exterior aspect of the filter cap can include a diaphragm. The diaphragm can be a slit diaphragm. The diaphragm can be initially closed. The diaphragm can be closed prior to delivery of the drug. Prior to delivery of the drug, the diaphragm can be closed against drug flow. The diaphragm can be configured to be opened by drug being driven distally. The open diaphragm can provide passage for drug flow.

[0106] A method of manufacturing an apparatus can include a method of manufacturing a drug device for delivering a filtered drug from a distal outlet of a delivery device.The device can define a longitudinal axis.

[0107] A method of manufacturing a device can include providing a drug container coaxially disposed on an axis, the container can have a distal outlet, and the container can have a proximal opening.

[0108] The method may include assembling a filter housing. Assembling the filter housing may include providing a filter base. The filter base may be configured to support the filter. Assembling the filter housing may include disposing the filter on a surface of the base. The surface may be an exterior aspect of the base. The surface may be a top surface of the base.

[0109] Assembling the filter housing may include sealing the periphery of the filter against fluid flow. The filter housing may include an inner surface configured to seal the periphery of the filter against fluid flow. The inner surface may be a surface of the base. The inner surface may be a circumferential surface of the base. The inner surface may be a surface of the base. The filter may be sealed to the inner surface via a laser welding process. The filter may be sealed to the inner surface via any suitable process. Any suitable process may include depolymerization and subsequent repolymerization of materials of the inner surface and / or filter relative to each other.

[0110] Assembling the filter housing may include providing a filter cap. Assembling the filter housing may include joining the base to the filter cap. The cap may include ribs. The ribs may be disposed on an exterior of the cap. The ribs may be disposed on an outer periphery of the cap. The ribs may surround an outer periphery of the cap. The ribs may be configured to seal against an interior wall of the container.

[0111] The cap can include an exterior aspect. The exterior aspect can include a structural component of the cap. The exterior aspect can be configured to block fluid access to the filter prior to delivery. The exterior aspect can be configured to be unblocked to provide fluid access to the filter during delivery.

[0112] The method can include introducing a filter housing into the vessel. The filter housing can be introduced into the vessel through the proximal opening. The filter housing can be introduced into the vessel with the base disposed distally. The filter housing can be introduced into the vessel with the base disposed distally relative to the axis.

[0113] The method may include embedding a filter housing within the container. The filter housing may be embedded within the container proximal to the distal outlet.

[0114] The method may include sealing the ribs to the inner wall. Sealing the ribs to the inner wall may provide a fluid-tight seal against flow of the medicament between an exterior of the cap and the inner wall. Sealing the ribs to the inner wall may provide a fluid-tight seal against flow of the medicament between an exterior of the filter housing and the inner wall.

[0115] The method can include transferring the agent to the container through the proximal opening.

[0116] The method may include providing a longitudinally slidable plunger. The method may include inserting the plunger into the container through the proximal opening. The plunger may be configured to seal the medicament inside the container. The plunger may be configured to slidingly seal against the interior wall. The plunger may be configured to propel the medicament toward the distal outlet. The inserting may be performed without propelling the medicament distally enough to unblock the external aspect.

[0117] The method may include providing a plunger rod. The method may include introducing the plunger rod into the container through the proximal opening. The plunger rod may be configured to urge the plunger distally within the container. The plunger rod may be configured to abut a proximal surface of the plunger. The plunger rod may be configured to attach to the proximal surface of the plunger.

[0118] The filter housing can be introduced into the container with the exterior aspect disposed proximally relative to the axis. The exterior aspect can include an initially closed diaphragm configured to be opened by a distally driven agent, thereby providing passage for agent flow. The exterior aspect can include a proximal plug disposed in and sealing a proximal collar of the filter cap. The plug can be configured to be moved distally relative to the collar by a distally driven agent, thereby opening the collar for agent flow.

[0119] A pharmaceutical agent may comprise a combination of one or more compounds. A compound may comprise a naturally occurring substance. A compound may comprise a substance derived from a naturally occurring substance. A compound may comprise a synthetically produced substance. A compound may comprise a chimeric substance. A compound may comprise an engineered substance. A compound may comprise a humanized substance. A compound may comprise a substance produced by recombinant technology. A compound may comprise a substance modified by recombinant technology.

[0120] The compounds may include drugs that are acceptable for patient therapeutic treatment. The compounds may include substances used in therapeutic protocols. The compounds may include substances used in diagnostic protocols. The compounds may include substances used in experimental protocols. The compounds may include substances that are compatible with use with the devices and methods of the present invention.

[0121] The pharmaceutical agents may include any of the pharmaceutical agents listed herein, alone or in combination with one or more other listed pharmaceutical agents, or in combination with one or more other unlisted pharmaceutical agents. Pharmaceutical agents may include anti-glaucoma agents, other ophthalmic agents, neuroprotective agents, antibacterial agents, anti-inflammatory agents (including steroidal and non-steroidal compounds), and biological agents including hormones, enzymes or enzyme-related components, antibodies or antibody-related components, oligonucleotides (including DNA, RNA, short interfering RNA, and other suitable oligonucleotides such as antisense oligonucleotides), DNA / RNA vectors, viruses or viral vectors, peptides, and proteins. The pharmaceuticals may include ophthalmic medications, including glaucoma medications, such as angiostatin, anecortaveacetate, thrombospondin, vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors, and anti-VEGF drugs such as ranibizumab (LUCENTIS®), bevacizumab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib, and sorafenib, as well as antiangiogenic agents, including any of a variety of known small molecules and transcription inhibitors with anti-angiogenic effects, and adrenergic antagonists, including beta-blockers such as atenolol, propranolol, metipranol, betaxolol, carteolol, levobetaxol, levobunol, and timolol. The pharmaceuticals may include platelet-derived growth factor (PDGF) inhibitors and anti-PDGF drugs. The pharmaceuticals may include transforming growth factor (TGF) inhibitors and anti-TGF drugs.Medications may include anti-inflammatory agents, including glucocorticoids and corticosteroids, such as betamethasone, cortisone, dexamethasone, dexamethasone 21-phosphate, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, prednisolone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, beclomethasone, budesonide, flunisolide, fluorometholone, fluticasone, hydrocortisone, hydrocortisone acetate, and rimexolone; and nonsteroidal anti-inflammatory agents, including diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, ketorolac, salicylate, indomethacin, naxoprene, naproxen, piroxicam, and nabumetone. The pharmaceutical agent may include an anti-cytokine agent, the pharmaceutical agent being tocilizumab (ACTEMRA). 登録商標 )). The pharmaceutical agent may include an anti-interleukin-6 agent, such as fluticasone. The pharmaceutical agent may include an anti-complement agent, including those that target complement factor D (e.g., an anti-complement factor D antibody or antigen-binding fragment thereof), such as lampalizumab, and those that target complement factor H (e.g., an anti-complement factor H antibody or antigen-binding fragment thereof). The pharmaceutical agent may include an angiopoietin-specific agent, such as an angiopoietin-2 antibody or antigen-binding fragment thereof. The pharmaceutical agent may include human growth hormone. The pharmaceutical agent may include any suitable pharmaceutical agent, whether or not listed above.

[0122] The drug may include one or more derivatives of any of the above drugs. The drug may include advanced forms of any of the above drugs. The drug may include mutant forms of any of the above drugs. The drug may include combinations of any of the above drugs. The combinations may be incorporated into multiple specific molecules. Multiple specific molecules may exhibit properties of their constituent parts. Multiple specific molecules may exhibit properties different from their constituent parts.

[0123] The volume of drug enclosed in the device can be substantially determined during manufacturing. The volume can be set in anticipation of drug loss that may result from manipulation of the device prior to executing the drug delivery stroke via the final distal movement of the plunger within the syringe barrel to the filter. Such manipulation can include syringe priming. The volume can depend on the scenario for which the device is intended. Exemplary ranges of volume values ​​include about 0.025 milliliters to about 0.05 milliliters, about 0.05 milliliters to about 0.1 milliliters, about 0.1 milliliters to about 0.25 milliliters, about 0.25 milliliters to about 0.5 milliliters, about 0.5 milliliters to about 1 milliliter, about 1 milliliter to about 2 milliliters, about 2 milliliters to about 3 milliliters, about 3 milliliters to about 4 milliliters, about 4 milliliters to about 5 milliliters, about 5 milliliters to about 6 milliliters, about 6 milliliters to about 7 milliliters, about 7 milliliters to about 8 milliliters, about 8 milliliters to about 9 milliliters, about 9 milliliters to about 10 milliliters, or any other suitable range of volumes. Any other suitable range of volumes may be enclosed within the device.

[0124] Providing the filter base may include manufacturing the filter base. Providing the filter cap may include manufacturing the filter cap. Manufacturing the filter base and / or the filter cap may be achieved through a molding process. Manufacturing the filter base and / or the filter may be achieved by an injection molding process. The injection molding process may include a bi-injection molding process.

[0125] Providing the plunger may include manufacturing the plunger. Providing the plunger rod may include manufacturing the plunger rod. Manufacturing the plunger and / or plunger rod may be achieved through a molding process. Manufacturing the plunger and / or plunger rod may be achieved by an injection molding process. The injection molding process may include a dual injection molding process.

[0126] The method can include selecting a material for manufacturing the delivery component. The material can be selected for its material properties. The material properties from which the material can be selected can facilitate operation of the device. The material properties from which the material can be selected can facilitate operation of the delivery device. The properties can include chemical inertness, elasticity, transparency, and other suitable properties. Other suitable properties can include hardness.

[0127] For example, in the case of a filter, the properties may include average pore size, resilience to impact stress, and other relevant properties. Other relevant properties may include chemical inertness. Other relevant properties may include sealing ability to the material of the filter housing.

[0128] The filter may include a filter material. The filter material may include a polymer material. The filter material may include an acrylic polymer. The filter material may include polyethersulfone. The filter material may include any suitable filter material. The suitable filter material may include polyvinylidene fluoride.

[0129] The plunger may include a plunger material. The plunger material may include a polymer material. The plunger material may include an elastomeric material. The plunger material may include a thermoplastic elastomer (TPE). The plunger material may include a natural rubber. The plunger material may include a compound made from natural rubber. The plunger material may include a synthetic rubber. The plunger material may include a compound made from synthetic rubber. The plunger material may include a silicone rubber. The plunger material may include a compound made from silicone rubber. The plunger material may include a butyl rubber. The plunger material may include a compound made from butyl rubber. The plunger material may include a material selected to reduce interaction between the plunger and the medicament. The plunger material may include an elastic material. The plunger material may include a material having a hardness of less than about 80 Shore A (ASTM D2240 Type A hardness scale). The plunger material may facilitate movement of the plunger within the barrel. The plunger material may facilitate engagement of the plunger with the inner wall of the barrel.The plunger material may facilitate sealing of the plunger against the inner wall of the barrel.

[0130] The plunger material may include a plunger lubricity material. The plunger lubricity material may coat the plunger material. The plunger material may support the plunger lubricity material. The plunger lubricity material may include polytetrafluoroethylene (PTFE). The plunger lubricity material may include ethylene tetrafluoroethylene (ETFE). The plunger lubricity material may include silicone oil. The silicone oil may be cross-linked silicone oil. The plunger lubricity coating may include a material selected to reduce interaction between the plunger and the medicament. The plunger lubricity material may facilitate movement of the plunger within the barrel. The plunger lubricity material may facilitate engagement of the plunger with the inner wall of the barrel. The plunger lubricity material may facilitate sealing of the plunger against the inner wall of the barrel.

[0131] The plunger rod may include a rod material. The rod material may include a polymer material. The rod material may include a thermoplastic polymer. The rod material may include polyoxymethylene. The rod material may include polypropylene. The rod material may include nylon. The rod material may include PTFE. The rod material may include ABS. The rod material may include polycarbonate. The rod material may include polysulfone. The rod material may include an acrylic polymer. The rod material may include poly(methyl methacrylate) (PMMA). The rod material may include a hard material. The rod material may include a material having a hardness greater than about 80 Shore A. The rod material may include a material having a low coefficient of friction. The rod material may include a material having a coefficient of friction of about 0.01 to about 0.5.

[0132] The rod material may include a rod lubricity material. The rod lubricity material may coat the rod material. The rod material may support the rod lubricity material. The rod lubricity material may include one or more of the plunger lubricity materials. For example, the rod lubricity material may include silicone oil. The silicone oil may be cross-linked silicone oil. The rod lubricity material may facilitate movement of the plunger rod within the proximal opening of the container.

[0133] The container may include a barrel material. The barrel material may include a polymeric material. The barrel material may include an amorphous material. The barrel material may include a polymer. The barrel material may include a thermoplastic polymer. The barrel material may include a cyclic olefin polymer (COP). The barrel material may include a cyclic olefin copolymer (COC). The barrel material may include polypropylene. The barrel material may include PMMA. The barrel material may include polycarbonate. The barrel material may include glass. The barrel material may include Type 1 borosilicate glass. The barrel material may include a translucent material. The barrel material may include a transparent material.

[0134] The barrel material may include a barrel lubricant material. The barrel lubricant material may coat the barrel material. The barrel lubricant material may coat the inner wall of the container. The barrel material may support the barrel lubricant material. The barrel lubricant material may include one or more of the plunger lubricants. For example, the barrel lubricant material may include a silicone oil. The silicone oil may be a cross-linked silicone oil. The barrel lubricant material may facilitate movement of the plunger within the barrel.

[0135] The filter base may include a filter base material. The base material may include a polymer material. The base material may include a thermoplastic elastomer (TPE). The base material may include one or more of the plunger materials. The base material may include a material that is harder than the plunger material.

[0136] The filter cap may include a filter cap material. The cap material may include a polymer material. The cap material may include a thermoplastic elastomer (TPE). The cap material may include one or more of the plunger materials. The cap material may include a material that is harder than the plunger material. The cap material may include a material that is less hard than the plunger material.

[0137] The cap material may include a diaphragm material. The cap material may include a plug material. The plug material and / or the diaphragm material may include a material that is harder than the plunger material. The plug material and / or the diaphragm material may include a material that is less hard than the plunger material.

[0138] The apparatus and methods described herein are exemplary. Apparatus and methods according to the present invention will now be described with reference to the figures, which show exemplary features of apparatus according to the principles of the present invention.

[0139] Some devices may omit features shown and / or described in connection with the exemplary devices. Some embodiments may include features not shown or described in connection with the exemplary methods. Features of the exemplary devices may be combined. For example, one exemplary embodiment may include features shown in connection with another exemplary embodiment.

[0140] An apparatus may include some or all of the features of the exemplary apparatus and / or some or all of the steps of the exemplary method.

[0141] The apparatus and methods of the present invention are described in connection with exemplary device embodiments and features. The device will now be described with reference to the accompanying drawings, which form a part of this specification. It will be understood that other embodiments may be utilized and structural, functional, and procedural changes may be made without departing from the spirit and scope of the present invention.

[0142] The figures use like part numbers in the tens and units digits to refer to like features.

[0143] FIG. 1 illustrates, in simplified form, an exemplary fluid delivery device 100. The delivery device 100 may define a longitudinal device axis L (it is understood that the longitudinal axis L is defined in all subsequent figures, even if not shown). The delivery device 100 may include a container 102. The container 102 may be disposed coaxially with the axis L. The container 102 may include a syringe barrel. The container 102 may include an inner barrel wall 106. The container 102 may contain a fluid 165. The container 102 may be pre-filled with the fluid 165. The fluid 165 may include a medication.

[0144] Filter housing 120 may be housed within container 102. Filter housing 120 may be housed within container 102 proximal to distal outlet 104. Filter housing 120 may be disposed perpendicular to axis L. Filter housing 120 may include an embedding element 122. Embedding element 122 may facilitate housing of filter housing 120 within container 102.

[0145] The containment of filter housing 120 within vessel 102 can be fluid-tight. Potting element 122 can be compressed against inner wall 106. Compression of potting element 122 against inner wall 106 can prevent passage of fluid 165 between inner wall 106 and the longitudinal exterior of filter housing 120.

[0146] Filter housing 120 may include a distal filter base 130. Filter housing 120 may include a proximal filter cap 140. Filter base 130 and filter cap 140 may be secured to one another. Filter base 130 and filter cap 140 may be sealed to one another.

[0147] The filter housing 120 may contain the filter 110. The filter housing 120 may support the filter 110. The filter 110 may be secured within the filter housing 120. The filter 110 may be sealed to the filter housing 120. The filter housing 120 may maintain the filter 110 across the axis L.

[0148] 2 shows an exemplary fluid delivery device 200. Delivery device 200 may include device features having the same relationships, properties, and functions as the features of device 100 described above (shown in FIG. 1), as indicated by like reference characters. These device features may include an axis L, a reservoir 202, a distal outlet 204, an inner wall 206, a filter 210, a filter housing 220, a filter base 230, a filter cap 240, and a fluid 265 (illustratively shown as spots).

[0149] The device 200 may include a syringe plunger rod 268. The plunger rod 268 may abut against a syringe plunger 266. The plunger rod 268 may be connected to the plunger 266.

[0150] As shown, fluid 265 may be bounded by plunger 266, inner wall 206, and filter housing 220. More specifically, fluid 265 may be bounded by a distal face of plunger 266, inner wall 206, and a proximal exterior aspect of filter cap 240.

[0151] Plunger rod 268 can be configured to move plunger 266 distally within container 202. Plunger 266 can be configured to propel fluid 265 toward distal outlet 204. Distally propelled fluid 265 can be configured to apply a distal force to a proximal exterior aspect of filter cap 240.

[0152] Filter 210 is shown just proximal to filter base 230. The region distal to the proximal exterior aspect of filter cap 240 that is adjacent filter 210 and in contact with fluid 265 is shown as devoid of fluid 265. Similarly, outlet 204 is shown as devoid of fluid. Generally, hollow device regions located distal to the proximal exterior aspect of filter cap 240 are shown as devoid of fluid in views showing the invention in an operational configuration prior to commencing to propel fluid 265 toward distal outlet 204. Such an operational configuration may be considered a pre-filtering configuration, including a PFS storage configuration.

[0153] 3 shows details of device features that may have the same relationships, properties, and functions as features of one or both of the above-described delivery devices 100 and 200 (shown in FIGS. 1 and 2, respectively), as indicated by like reference characters. These device features may include a filter 310, a filter housing 320, embedding elements 322a and 322b (collectively, embedding elements 322), a filter base 330, and a filter cap 340.

[0154] The exploded view of Figure 3 shows filter base 330 and filter cap 340 separated from one another and spaced apart from filter 310. Figure 3 also shows filter cap proximal plug 341 and filter cap proximal collar 342 separated from one another. Figure 3 may provide an unobstructed view of features of filter housing 320 that may be more difficult to identify in a view of assembled filter housing 320 (such as filter housing 220 shown in Figure 2).

[0155] The filter 310 may include a central filter region 312. The filter 310 may include a peripheral filter region 314. The peripheral region 314 may be a distal periphery. The peripheral region 314 may extend radially inward from the periphery of the filter 310.

[0156] Filter base 330 may include a proximal central protrusion 332. Central protrusion 332 may be configured to provide support to filter 310. Central protrusion 332 may be configured to provide support to central region 312.

[0157] Filter base 330 may include a proximal rim 335. Proximal rim 335 may support a proximal rim surface 334. Proximal rim 335 may be configured to provide support to filter 310. Proximal rim 335 may be configured to provide support to perimeter 314. Perimeter 314 may be disposed on surface 334. Perimeter 314 may be sealed to surface 334. All of perimeter 314 may be sealed to surface 334. Perimeter 314 may be sealed to surface 334 along all of surface 334. Sealing perimeter 314 along surface 334 may provide a fluid-tight seal configured to prevent fluid from passing between the interior of filter base 330 and any of the perimeter of filter 310.

[0158] Filter base 330 may include a circumferential protrusion 336. Filter base 330 may include a circumferential recess 338. Protrusion 336 and / or recess 338 may be configured to mechanically interfere with distal internal features (not shown) of filter cap 340. The interference of protrusion 336 and / or recess 338 with the internal features of filter cap 340 may cause filter base 330 and filter cap 340 to fit together. The interference of protrusion 336 and / or recess 338 with the internal features of filter cap 340 may secure filter base 330 and filter cap 340 together.

[0159] The protrusions 336 and / or recesses 338 can be configured to compress against internal features of the filter cap 340. Compression of the protrusions 336 and / or recesses 338 against the internal features of the filter cap 340 can provide a fluid-tight seal between the filter base 330 and the filter cap 340. The internal features of the filter cap 340 can be configured to compress against the protrusions 336 and / or recesses 338. Compression of the internal features of the filter cap 340 against the protrusions 336 and / or recesses 338 can provide a fluid-tight seal between the filter base 330 and the filter cap 340.

[0160] Filter cap 340 may include a hollow cylindrical body 324. Cylindrical body 324 may include a distal rim 326. Distal rim 326 may be configured to receive at least a portion of filter base 330. Distal rim 326 may be configured to longitudinally receive filter 310 and proximal rim 335.

[0161] The cylindrical body 324 can include a distal embedding element 322a. The embedding element 322a can be located along the distal rim 326. The embedding element 322a can be located along the circumferential exterior of the cylindrical body 324. The cylindrical body 324 can include a proximal embedding element 322b. The embedding element 322b can be located along the circumferential exterior of the cylindrical body 324.

[0162] Each of the embedding elements 322 can be configured to compress against an inner barrel wall of the delivery device (such as against the inner wall 106 of the delivery device 100, as shown in FIG. 1 ). Compression of the embedding elements 322 against the inner barrel wall can provide a fluid-tight seal between the inner barrel wall and each of the embedding elements 322.

[0163] The proximal plug 341 may include a plug groove 343a. The groove 343a may extend radially inward into the body of the plug 341. The groove 343a may extend circumferentially around the body. The proximal plug 341 may include a proximal groove riser 343b. The groove 343a may include a groove riser 343b. The groove riser 343b may extend circumferentially around the body. The groove riser 343b may comprise a proximal side of the groove 343a. The groove riser 343b may extend shallower into the body than the full depth of the groove 343a.

[0164] The proximal collar 342 may include an inwardly protruding proximal rim 344. The rim 344 may be configured to mechanically interfere with the groove 343a. The interference of the groove 343a and the rim 344 may fit the plug 341 and the collar 342 together. The interference of the groove 343a and the rim 344 may secure the plug 341 and the collar 342 together. The groove riser 343b may be configured to maintain the plug 341 within the collar 342, providing a contact / friction force by interfering with the rim 344 to oppose distal forces that may act on the proximal exterior of the plug 341.

[0165] Rim 344 can be configured to compress against groove 343 a. Compression of rim 344 against groove 343 a can provide a fluid-tight seal between plug 341 and collar 342, thereby sealing assembled filter cap 340 against fluid in the device's pre-filtering configuration.

[0166] Figure 4 shows details of device features that may have the same relationships, properties, and functions as features of one or both of delivery devices 100 and 200 (shown in Figures 1 and 2, respectively), as indicated by like reference characters, and / or may be shown in Figure 3. These device features may include a reservoir 402, a distal outlet 404, an inner wall 406, a filter 410, an embedding element 422, a cylinder 424, a rim 426, a filter base 430, a rim 435, a protrusion 436, a recess 438, a filter cap 440, a plug 441, a collar 442, a groove 443a, a groove riser 443b, an inwardly protruding rim 444, and a fluid 465.

[0167] 4 shows a cylindrical body 424 housed within a container 402 having embedded elements 422a and 422b compressed against an inner wall 406. The compression of embedded elements 422a and 422b against the inner wall 406 can provide a fluid-tight seal against the passage of fluid 465 between the inner wall 406 and the longitudinal exterior of the cylindrical body 424.

[0168] An inwardly projecting proximal rim 444 is shown interfering with plug groove 443a and plug groove riser 443b. Interference of rim 444 with groove 443a and groove riser 443b may fit plug 441 and collar 442 together. Interference of rim 444 with groove 443a and groove riser 443b may secure plug 441 and collar 442 together.

[0169] Interference of rim 444 with groove 443a and / or groove riser 443b can provide a contact / friction force that can maintain plug 441 within collar 442. The contact / friction force can be configured to oppose a distal force that can be exerted on the proximal exterior of plug 441 by distally propelled fluid 465.

[0170] An increase in pressure applied to fluid 465 can result in an increase in the magnitude of the distal force exerted by distally propelled fluid 465 on the proximal exterior of plug 441. The increase in the magnitude of the distal force exerted by distally propelled fluid 465 on the proximal exterior of plug 441 can overcome the contact / friction forces that maintain plug 441 within collar 442.

[0171] The rim 444 can be configured to compress against the groove 443 a. The rim 444 can be configured to compress against the groove riser 443 b. Compression of the rim 444 against the groove 443 a and / or the groove riser 443 b can provide a fluid-tight seal between the plug 441 and the collar 442. The seal between the plug 441 and the collar 442 can prevent the passage of fluid 465 between the plug 441 and the collar 442. The seal between the plug 441 and the collar 442 can prevent the passage of fluid 465 into the interior 428 of the cylinder 424.

[0172] The materials and / or geometry of collar 442 (particularly rim 444) and / or plug 441 (particularly groove 443a and groove riser 443b) may be preselected (as shown) to keep plug 441 sealed within collar 444 under the pre-filtering pressure of fluid 465, and may also be preselected (as shown) to move plug 441 distally relative to rim 444 into interior 428 under a higher pressure that is easily achievable by the user at the start of propelling fluid 465 toward distal outlet 404, causing collar 442 to open and allowing fluid 465 to flow through rim 444.

[0173] The filter cap proximal plug 441 can include a distal plug face 445. The plug face 445 can be supported by a distal section of the body of the plug 441. The distal section of the body of the plug 441 can extend radially outward as a tab 447. The tab 447 can extend perpendicular to a cylinder axis (not shown) defined by the plug 441. The cylinder axis can intersect the center of the face 445. The cylinder axis can intersect the center of the proximal outer surface of the plug 441.

[0174] The plug 441 may be maintained within the collar 444 (shown) with a cylinder axis orientation at least generally coaxial with the longitudinal axis L (not shown). As the plug 441 moves into the interior 428 to begin propelling the fluid 465 toward the distal outlet 404, the tab 447 may maintain the cylinder axis orientation generally coaxial with the longitudinal axis. During and after distal movement of the plug 441, the extreme radial edges of the tab 447 may interfere with the inner wall 429 of the cylindrical body 424, with the cylinder axis remaining generally coaxial with the longitudinal axis L. The interference between the extreme radial edges of the tab 447 and the inner wall 429 may occur intermittently as the plug 441 wobble during its longitudinal passage toward the filter 410 and thereafter as the fluid 465 continues to flow distally through the plug 441 toward the filter 410. Such intermittent interference may prevent plug 441 from being angled against the sides of inner wall 429 and possibly wedged between the sides of inner wall 429 .

[0175] The filter cap proximal plug 441 may include an inter-tab gap 449 disposed perpendicular to the cylinder axis between circumferentially adjacent opposing side edges of the tabs 447. During and after distal movement of the plug 441, the inter-tab gap 449 may provide a passage for distal flow of fluid 465 through the plug 441 toward the filter 410.

[0176] During and after distal movement of plug 441, distal flow of fluid 465 through plug 441 through inter-tab gap 449 (as well as distal flow of fluid 465 between inner wall 429 and the extreme radial edges of tabs 447) may provide a cushion between plug 441 and inner wall 429. During distal movement of plug 441, as surface 445 approaches filter 410, flow of fluid 465 across surface 445 may provide a cushion between plug 431 and filter 410. After distal movement of plug 441, as surface 445 resides closely proximal to filter 410, flow of fluid 465 across surface 445 may provide a cushion between plug 431 and filter 410.

[0177] The filter cap distal rim 426 may extend radially outward as an embedding element 422a. The rim 426 may extend radially inward as a filter cap protrusion 446. The filter cap protrusion 446 may be located along the rim 426. The filter cap protrusion 446 may be located along the circumferential interior of the cylindrical body 424. The filter cap recess 448 may be disposed parallel to the filter cap protrusion 446. The filter cap recess 448 may be located along the circumferential interior of the cylindrical body 424.

[0178] The filter cap protrusions 446 may mechanically interfere with the filter base recesses 438. The interference of the filter cap protrusions 446 and the filter base recesses 438 may fit the filter cap 440 and the filter base 430 together. The interference of the filter cap protrusions 446 and the filter base recesses 438 may secure the filter cap 440 and the filter base 430 together. The filter cap protrusions 446 may be configured to compress against the filter base recesses 438. The compression of the filter cap protrusions 446 against the filter base recesses 438 may provide a fluid-tight seal between the filter cap 440 and the filter base 430. The seal between the filter cap 440 and the filter base 430 may prevent the passage of fluid 465 between the filter cap protrusions 446 and the filter base recesses 438.

[0179] The filter base protrusions 436 may mechanically interfere with the filter cap recesses 448. The interference of the filter base protrusions 436 and the filter cap recesses 448 may fit the filter cap 440 and the filter base 430 together. The interference of the filter base protrusions 436 and the filter cap recesses 448 may secure the filter cap 440 and the filter base 430 together. The filter base protrusions 436 may be configured to compress against the filter cap recesses 448. The compression of the filter base protrusions 436 against the filter cap recesses 448 may provide a fluid-tight seal between the filter cap 440 and the filter base 430. The seal between the filter cap 440 and the filter base 430 may prevent the passage of fluid 465 between the filter base protrusions 436 and the filter cap recesses 448.

[0180] Distal to the seal between the filter base 430 and the filter cap 440, the filter base 430 may include a conical surface 431. The surface 431 may be contoured complementarily to a distal internal taper of the container 402 leading to the distal outlet 404. The surface 431 may be compressed against the distal internal taper. The compression of the surface 431 against the distal internal taper may provide a fluid-tight seal between the surface 431 and the distal internal taper. The seal between the surface 431 and the distal internal taper may prevent passage of filtered fluid exiting the passageway 433 into the distal outlet 404 between the surface 431 and the distal internal taper while propelling the fluid 465 toward the distal outlet 404.

[0181] Surface 431 may terminate distally as filter base end protrusion 437. End protrusion 437 may comprise the distal-most aspect of filter base 430.

[0182] FIG. 5 provides a partial cross-sectional view of the device of FIG. 4 taken in the plane of the page and distal to plug face 445 of FIG.

[0183] Figure 5 shows details of device features that may have the same relationships, properties, and functions as features of one or both of delivery devices 100 and 200 (shown in Figures 1 and 2, respectively), as indicated by like reference characters, and / or may be shown in Figures 3 and / or 4. These device features may include a reservoir 502, a distal outlet 504, an inner wall 506, a filter 510, a central region 512, a peripheral portion 514, an embedding element 522a, a cylindrical body 524, a distal rim 526, an interior portion 528, a filter base 530, a (frusto-)conical surface 531, a central protrusion 532, a passageway 533, a rim surface 534, a rim 535, a filter base protrusion 536, an end protrusion 537, a filter base recess 538, and a filter cap protrusion 546 and a filter cap recess 548.

[0184] 5 shows central region 512 of filter 510 positioned in close proximity to central protrusion 532. Central protrusion 532 may support central region 512. The support of central region 512 may oppose distal forces acting on filter 510 during distal propulsion of fluid within interior 528, at and after the initiation of propelling the fluid contents of the device (not shown) toward distal outlet 504.

[0185] Periphery 514 of filter 510 is shown disposed closely proximal to rim surface 534. Filter 510 can be sealed to rim surface 534 along periphery 514 to provide a fluid-tight seal against the passage of fluid between rim surface 534 and periphery 514. Interior 528 is shown devoid of fluid 565, and during distal propulsion of the fluid contents of the device, interior 528 contains distally directed fluid. The fluid-tight seal between rim surface 534 and peripheral portion 514, together with the fluid-tight seals between convex portion 546 and concave portion 538, and between convex portion 536 and concave portion 548, together with the fluid-tight seals between inner wall 506 and both (frusto-)conical surface 531 and embedded element 522a, restrict distal fluid reaching filter 510 to flow (and be filtered) through filter 510, through passage 533, end protrusion 537, and onto distal outlet 504 for delivery (and any preceding pre-delivery syringe preparation steps).

[0186] FIG. 6 provides a view of the device of FIG. 5 taken distally along line 6-6, with the line shown parallel and distal to filter 510.

[0187] Figure 6 shows details of device features that may have the same relationships, properties, and functions as features of one or both of delivery devices 100 and 200 (shown in Figures 1 and 2, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, and / or 5. These device features may include a container 602, an inner wall 606, a cylindrical body 624, an inner wall 629, and a filter base 630, a central protrusion 632, a passageway 633, a rim surface 634, and a rim 635.

[0188] 6 shows a circumferential embodiment of rim 635 closely positioned along inner wall 629. Rim 635 can be configured to compress against inner wall 629 and provide a fluid-tight seal against the passage of fluid between filter base 630 and inner wall 629. The fluid-tight seal between filter base 630 and inner wall 629 can help restrict the path of distal migration of fluid propelled distally into passageway 633 (as discussed above in the description of FIG. 5).

[0189] Figure 7 shows an exemplary medication delivery device 700. Delivery device 700 may have one or more device features having the same relationships, properties, and functions as features of one or both of delivery devices 100 and 200 (shown in Figures 1 and 2, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, and / or 6. These device features may include a reservoir 702, a distal outlet 704, an inner wall 706, a filter 710, a central region 712, a cylinder 724, an interior 728, an inner wall 729, a filter base 730, a central projection 732, a passageway 733, an end projection 737, a filter cap 740, a plug 741, a collar 742, a groove 743a, a groove riser 743b, an inwardly protruding rim 744, a distal face 745, and a fluid 765 and a plunger 766.

[0190] FIG. 7 shows device 700 in an operating configuration following the movement of plug 741 from collar 742. This configuration may be considered a filtering configuration. To achieve the depicted configuration, a user has already begun to urge plunger 766 within container 702 distally toward outlet 704, resulting in an increase in pressure within fluid 765. The increase in fluid pressure exerts a distal force on the proximal exterior of plug 741, which is still maintained within collar 742 (as shown in FIG. 4) by the interference contact / friction force of inwardly protruding rim 744 and groove 743a (and its groove elevated portion 743b). (See FIG. 4 for details of the interference mechanism.) A further increase in fluid pressure applied by the user via plunger 766 then results in a distal force sufficient to overcome the interference contact / friction force, thus displacing plug 741 distally from collar 742.

[0191] To achieve the filtering configuration shown in FIG. 7 , following distal movement of plug 741 from collar 742, plug 741 passed through interior 728 toward filter 710. Plug 741 was driven toward filter 710 by distal fluid 765 propelled by the user's distal movement of plunger 766 against interior wall 706. Distal face 745 of plug 741 was moved distally to be positioned closely proximal to central region 712 of filter 710. As distal movement of plunger 766 continued, fluid continued to flow distally away along face 745 through unplugged collar 742 into interior 728, between interior wall 729 and the longitudinal exterior of plug 741, from where it was forced through filter 710.

[0192] FIG. 7 shows filtered fluid 767 (illustratively shown as spots) emerging from filter 710 and disposed distally of filter 710. Filtered fluid 767 may be the filtrate of fluid 765. Filtered fluid 767 may differ in content from fluid 765. Fluid 765 may contain particulate matter of a size that filter 710 can retain while fluid 765 is propelled distally onto and into filter 710. Fluid 767 may be free of particulate matter from fluid 765 that was retained by filter 710. The size of particulate matter from fluid 765 that can be retained by filter 710 may depend on the pore size of filter 710. The pore size of filter 710 may be the average effective pore size. (As explained above, the use of specialty filters in the present invention may extend the range of distinction between the contents of the filtrate and the pre-filtered PFS fluid beyond the size of dissolved / suspended particles, broadening the range of charge profiles and / or molecular identities.)

[0193] As shown, filtered fluid 767 may fill passageway 733 and extend past end protrusion 737 to fill distal outlet 704, from which it may be directed for delivery of filtered fluid 767 (and for any preceding pre-delivery syringe preparation steps). As more fluid 765 is propelled onto and into filter 710 by the user's further distal movement of plunger 766 from its depicted position, freshly filtered fluid 767 may continue to flow distally from filter 710, through passageway 733 to distal outlet 704, and then toward delivery.

[0194] FIG. 8 provides a view of the device of FIG. 7 taken proximally along line 8-8, which is shown parallel and proximal to filter 710.

[0195] Figure 8 shows details of device features that may have the same relationships, properties, and functions as one or more features of delivery devices 100, 200, and 700 (shown in Figures 1, 2, and 7, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, and / or 6. These device features may include a reservoir 802, an inner wall 806, a cylindrical body 824, an interior 828, an inner wall 829, a plug 841, a distal surface 845, tabs 847, inter-tab gaps 849, and fluid 865.

[0196] 8 shows plug 841 at least generally centrally disposed within inner wall 829 of cylindrical body 824. The centering of plug 841 within inner wall 829 may result from a generally equal amount of distally propelled fluid 865 passing along the longitudinal sides of plug 841. The region of interior 828 disposed between inner wall 829 and inter-tab gap 849 may provide for the passage of a greater amount of fluid 865 than the region disposed between inner wall 829 and tab 847. The shapes of plug 841, tab 847, inter-tab gap 849, and inner wall 829 may be preselected to achieve a desired flow rate of fluid 865.

[0197] FIG. 8 shows fluid 865 disposed across distal surface 845. Passage of fluid 865 along and distally away from distal surface 845 (out of the page of FIG. 8, toward the viewer) can intermittently shift plug 841 relative to the filter (not shown). The intermittent shifting of plug 841 relative to the filter can contribute to dynamically changing the thickness of fluid 865 between the filter and distal surface 845. Dynamically changing the thickness of fluid 865 between the filter and distal surface 845 can reduce particle accumulation on the proximal side of the filter. Reducing particle accumulation on the proximal side of the filter can contribute to maintaining the filtering efficiency of the filter. The thickness of fluid 865 between the filter and distal surface 845 can help mitigate direct contact of the filter with distal surface 845.

[0198] Passage of fluid 865 along and distally away from distal surface 845 can intermittently shift plug 841 relative to inner wall 829. The intermittent shifting of plug 841 relative to wall 829 can lead tab 847 into intermittent interference with wall 829. The intermittent interference of tab 847 with wall 829 can help maintain a cylindrical axis (not shown) of plug 841 wobbling approximately collinear with longitudinal axis L. Maintaining the collinearity of the cylindrical axis of plug 841 with axis L can prevent plug 841 from distorting against and / or possibly becoming wedged between the sides of inner wall 829.

[0199] As explained in the description of FIG. 4 , preventing plug 841 from distorting against and / or possibly becoming wedged between the sides of inner wall 829 was also considered as plug 841 moves distally within interior 828 after moving distally from within a collar (not shown) of cylindrical body 824. The functional role of tab 847 may begin immediately upon release of plug 841 from the collar, at the start of distal passage of plug 841 into interior 828, prior to substantial flow of fluid 865 along the longitudinal exterior of plug 841. Interference of tab 847 against inner wall 829 may serve to brake distally propelled plug 841 at its initial moment of distally propelled movement into interior 828.

[0200] 9 shows an exemplary medication delivery device 900. Delivery device 900 may have one or more device features having the same relationships, properties, and functions as one or more features of delivery devices 100, 200, and 700 (shown in FIGS. 1, 2, and 7, respectively), as indicated by like reference characters, and / or may be shown in FIGS. 3, 4, 5, 6, and / or 8. These device features may include a reservoir 902, a distal outlet 904, an inner wall 906, a filter housing 920, a filter base 930, and a fluid 965, a plunger 966, and a plunger rod 968.

[0201] The device 900 is shown in a pre-filtering operational configuration, showing the distal hollow portion of the filter base 930 and the distal outlet 904 devoid of fluid.

[0202] Filter housing 920 may include a filter base 930 and a filter cap 940. Filter cap 940, similar to the filter caps previously shown and described, may be configured to block fluid access to a filter (not shown) in a pre-filtering operating configuration of device 900 and to allow fluid access to the filter in a filtering operating configuration of device 900. Filter cap 940 may differ in structure and mode of operation from the filter caps previously shown and / or described with reference to FIGS.

[0203] The filter caps previously illustrated and / or described with reference to Figures 2-8 may be considered removable plug filter caps. Filter cap 940 need not be a removable plug filter cap. Filter cap 940 may be considered an openable diaphragm filter cap. Openable diaphragm filter caps may include rupturable diaphragm filter caps as a category. The differences in structure and mode of operation of openable diaphragm filter caps from removable plug filter caps are illustrated and / or described with reference to Figures 10-14.

[0204] Figure 10 shows details of device features that may have the same relationship, properties, and function as one or more features of delivery devices 100, 200, 700, and 900 (shown in Figures 1, 2, 7, and 9, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, 6, and / or 8. These device features may include a filter 1010, a central region 1012, a peripheral portion 1014, a filter housing 1020, embedding elements 1022a and 1022b (collectively, embedding elements 1022), a hollow cylindrical body 1024, a distal rim 1026, a filter base 1030, a proximal central projection 1032, a proximal rim surface 1034, a proximal rim 1035, a circumferential protrusion 1036 and a circumferential recess 1038, and a filter cap 1040.

[0205] The exploded view of Figure 10 shows the filter base 1030 and filter cap 1040 separated from one another and spaced apart from the filter 1010. Figure 10 may provide an unobstructed view of features of the filter housing 1020 that may be more difficult to identify in a view of the assembled filter housing 1020 (such as the filter housing 920 shown in Figure 9).

[0206] Protrusions 1036 and / or recesses 1038 may be configured to mechanically interfere with distal internal features (not shown) of filter cap 1040. The distal internal features of cap 1040 may have the same relationship, properties, and function as distal internal features of one or more of delivery devices 200 and 700 (shown in FIGS. 1 and 2, respectively) and / or may be shown in FIGS. 4, 5, 6, 7, and / or 8 described above.

[0207] Interference of the protrusions 1036 and / or recesses 1038 with distal internal features of the filter cap 1040 may cause the filter base 1030 and the filter cap 1040 to fit together. Interference of the protrusions 1036 and / or recesses 1038 with distal internal features of the filter cap 1040 may cause the filter base 1030 and the filter cap 1040 to lock together.

[0208] The protrusions 1036 and / or recesses 1038 can be configured to compress against distal internal features of the filter cap 1040. Compression of the protrusions 1036 and / or recesses 1038 against the distal internal features of the filter cap 1040 can provide a fluid-tight seal between the filter base 1030 and the filter cap 1040. The distal internal features of the filter cap 1040 can be configured to compress against the protrusions 1036 and / or recesses 1038. Compression of the distal internal features of the filter cap 1040 against the protrusions 1036 and / or recesses 1038 can provide a fluid-tight seal between the filter base 1030 and the filter cap 1040.

[0209] Distal rim 1026 can be configured to receive at least a portion of filter base 1030. Distal rim 1026 can be configured to longitudinally receive filter 1010 and proximal rim 1035.

[0210] As shown, the embedded element 1022b may be located along the circumferential exterior of the cylindrical body 1024. The embedded element 1022b may extend completely around the circumferential exterior of the cylindrical body 1024. The embedded element 1022b may not extend completely around the circumferential exterior of the cylindrical body 1024.

[0211] The embedding element 1022 can be compressed against a wall (not shown) of the inner container of the device. Compression of the embedding element 1022 against the wall of the inner container can provide a fluid-tight seal against the passage of fluid between the embedding element 1022 and the wall of the inner container.

[0212] The filter cap 1040 may define a cylinder axis (not shown). The cylinder axis may be centered relative to the circumference of the circumferential exterior of the cylindrical body 1024. The cylinder axis may be parallel to the longitudinal exterior of the cylindrical body 1024. The cylinder axis may be parallel to and centered relative to the inner cylindrical wall (not shown) of the cylindrical body 1024. The cylinder axis may be centered relative to the circumference of the distal rim 1026. The cylinder axis may intersect the circumferential center of the diaphragm 1054. The cylinder axis may be at least generally coaxial with the device longitudinal axis (not shown).

[0213] A structural difference of the filter cap 1040 from a removable plug filter cap may be located in the proximal portion of the filter cap 1040. The proximal portion of the filter cap 1040 may include a diaphragm ring support 1052. The ring support 1052 may be located along the proximal outer rim of the filter cap 1040. The ring support 1052 may be located along the entire proximal outer rim. The ring support 1052 may be located within the proximal outer rim. The ring support 1052 may be located on the inner circumference of the proximal outer rim. The ring support 1052 may span the entire inner circumference of the proximal outer rim. The ring support 1052 may be integral to the proximal outer rim. The proximal outer rim may support the ring support 1052.

[0214] The ring support 1052 may support a diaphragm 1054. The diaphragm 1054 may be integral to the inner periphery of the ring support 1052. The diaphragm 1054 may span the entire inner periphery of the ring support 1052. The diaphragm 1054 may completely occupy an area concentric with the inner periphery of the ring support 1052.

[0215] The diaphragm 1054 may include a diaphragm slit 1055. The cylinder axis of the cylinder 1024 may intersect the slit 1055. The cylinder axis may extend through a midpoint of the length of the slit 1055. The system 1055 may include multiple slits.

[0216] The slits 1055 may traverse an area of ​​the diaphragm 1054 along a gap in the diaphragm 1054. The slits 1055 may traverse an area of ​​the diaphragm 1054 along a diameter of the diaphragm 1054. The slits 1055 may be disposed along a diameter of the diaphragm 1054. The slits 1055 may be disposed along the entire diameter of the diaphragm 1054. The slits 1055 may be disposed along a portion of the diameter of the diaphragm 1054.

[0217] The slit 1055 may traverse the entire depth of the entire thickness of the diaphragm 1054. The slit 1055 may traverse a portion of the depth of the entire thickness of the diaphragm 1054. The slit 1055 may extend from a proximal surface of the diaphragm 1054 into the diaphragm 1054 and traverse a portion of the depth of the entire thickness of the diaphragm 1054 distally. The slit 1055 may extend from a distal surface (not shown) of the diaphragm 1054 into the diaphragm 1054 and traverse a portion of the depth of the entire thickness of the diaphragm 1054 proximally.

[0218] The diaphragm 1054 can be configured in a pre-filtering configuration to prevent passage of PFS fluid to the filter 1010. The diaphragm 1054 can be configured to be opened in transition from the pre-filtering configuration to the filtering configuration by distal urging of the PFS fluid against a proximal face of the diaphragm 1054. The diaphragm 1054 can be configured in the filtering configuration to allow passage of the contents of the PFS fluid through the filter 1010 from the open diaphragm 1054.

[0219] FIG. 11 provides a partial cross-sectional view of the distal portion of the device of FIG.

[0220] Figure 11 shows details of features of the device that may have the same relationships, properties and functions as one or more features of delivery devices 100, 200, 700 and 900 (shown in Figures 1, 2, 7 and 9, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, 6, 8 and / or 10. Features of these devices may include a container 1102, a distal outlet 1104, an inner wall 1106, a filter 1110, a central region 1112, a peripheral portion 1114, a filter housing 1120, an embedding element 1122 (embedding element 1122a and embedding element 1122b), a cylindrical body 1124, a distal rim 1126, an interior portion 1128, a filter base 1130, a (frusto-conical) conical surface 1131, a central protrusion 1132, a passageway 1133, a rim surface 1134, a rim 1135, a filter base protrusion 1136, an end protrusion 1137, a filter base recess 1138, a filter cap 1140, a filter cap protrusion 1146, a filter cap recess 1148, a diaphragm ring support 1152, a diaphragm 1154, a diaphragm slit 1155, and a fluid 1165.

[0221] 11, the interior 1128 of the cylindrical body 1124, the passageway 1133, and the distal outlet 1104 are shown devoid of fluid 1165. The slit 1155 may be closed to the flow of fluid 1165 through the diaphragm 1154, preventing distal flow of fluid 1165 into the interior 1128 and distally towards the filter 1110.

[0222] The diaphragm 1154 may include diaphragm flaps. The diaphragm flaps may include diaphragm flap 1158a. The diaphragm flaps may include diaphragm flap 1158b. The diaphragm flaps may be closed to each other at the slit 1155. The diaphragm flaps may be sealed to each other at the slit 1155.

[0223] The diaphragm flaps, closed and / or sealed relative to each other, can provide a fluid-tight seal against distal movement of fluid 1165 into interior 1128. An increase in fluid pressure applied by a user in initiating a transition of the delivery device to a filtering operating configuration can achieve sufficient pressure within fluid 1165 to overcome the force closing and / or sealing slit 1155 against distal fluid movement through diaphragm 1154. User-applied pressure can cause diaphragm 1154 to open at slit 1155. User-applied pressure can cause diaphragm 1154 to rupture at slit 1155.

[0224] In a filtering configuration (not shown), achieved by opening / bursting the slits 1155 due to an increase in user-applied pressure within the fluid 1165, the distally propelled fluid can flow into the interior 1158. The distally propelled fluid can drive the flaps 1158a and / or 1158b to fold into the cylinder body 1124. The folded flaps 1158a and / or 1158b can extend into the interior 1128. The folded flaps 1158a and / or 1158b can extend into the interior 1128 at an acute angle from the depicted position of the flaps. The folded flaps 1158a and / or 1158b can extend into the interior 1128 at least approximately perpendicular from the depicted position of the flaps. Folded flap 1158a and / or flap 1158b can extend into interior 1128 at an obtuse angle from the depicted position of the flap.

[0225] The flaps 1158a and / or flaps 1158b may fold at hinge elements 1156. The hinge elements 1156 may be supported by the ring support 1152. The hinge elements 1156 may include a region encompassed by and along the circumference of the distal surface of the diaphragm 1154. The region encompassed by the circumference of the distal surface of the diaphragm 1154 may include a groove extending proximally into the material of the diaphragm 1154. A corresponding region seated along the proximal surface of the diaphragm 1154 may include a groove (not shown) extending distally into the material of the diaphragm 1154. The groove extending into the material of the diaphragm may be disposed along a line segment encompassed by the support ring 1152. The groove extending into the material of the diaphragm may be disposed along an arc concentric with the cylindrical body 1124. The material of the diaphragm 1154 positioned along the groove may be more collapsible than the material of the diaphragm 1154 positioned away from the groove.

[0226] FIG. 12 provides a view of the device of FIG. 11 taken proximally along line 12-12, with the line shown running through interior 1128 and the line positioned parallel to and proximal to filter 1110.

[0227] Figure 12 shows details of device features that may have the same relationships, properties, and functions as one or more features of delivery devices 100, 200, 700, and 900 (shown in Figures 1, 2, 7, and 9, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, 6, 8, 10, and / or 11. These device features may include container 1202, inner wall 1206, embedding element 1222b, cylindrical body 1224, filter cap 1240, and diaphragm ring support 1252, diaphragm 1254, diaphragm slit 1255, diaphragm hinge element 1256, and diaphragm flaps 1258a and 1258b.

[0228] The embedding element 1222b can compress against the inner wall 1206. When the embedding element 1222b is compressed against the inner wall 1206, it can help store the filter cap 1240 within the container 1202. When the embedding element 1222b is compressed against the inner wall 1206, it helps store the filter cap 1240 in the cylinder axis of the cylinder, at least generally coaxial with the device axis (neither axis shown).

[0229] Compression of the embedding element 1222b against the inner wall 1206 may contribute to sealing the embedding element 1222b against the inner wall 1206. The sealing of the embedding element 1222b against the inner wall 1206 may provide a fluid-tight seal against distal (i.e., from the page towards the viewer in FIG. 12 ) passage of the contents of the PFS fluid (not shown) between the embedding element 1222b and the inner wall 1206.

[0230] 12 shows the distal face of diaphragm 1254. The distal face of diaphragm 1254 may be the face of diaphragm 1254 that is inside of barrel 1224 (as shown in FIG. 11). Opposite ends of flaps 1258a and 1258b may be closed and / or sealed to one another along slit 1255, providing diaphragm 1254 with a fluid-tight seal against distal passage of PFS fluid contents through diaphragm 1254 into barrel 1224.

[0231] FIG. 13 provides the same view as that taken in FIG. 12, but of the device of FIG. 12 at the beginning of the filtering operation configuration where the distally propelled PFS fluid contents have opened / ruptured the diaphragm.

[0232] Figure 13 shows details of device features that may have the same relationships, properties, and functions as one or more features of delivery devices 100, 200, 700, and 900 (shown in Figures 1, 2, 7, and 9, respectively), and / or may be shown in Figures 3, 4, 5, 6, 8, 10, 11, and / or 12, as indicated by like reference characters. These device features may include a container 1302, an inner wall 1306, and embedding element 1322b, a cylindrical body 1324, a filter cap 1340, a diaphragm ring support 1352, a diaphragm 1354, a diaphragm slit 1355, a diaphragm hinge element 1356, and diaphragm flaps 1358a and 1358b, and a fluid 1365.

[0233] 13 illustrates an early stage of a filtering operation configuration in which fluid 1365 propelled distally within container 1302 against the outer surface (not shown) of diaphragm 1354 may achieve sufficient pressure to open / rupture diaphragm slit 1355. As diaphragm slit 1355 opens / ruptures in response to the pressure, fluid 1365 is shown beginning to enter the space between the opposing edges of flaps 1358a and 1358b. Flaps 1358a and 1358b may bend away from each other. Flaps 1358a and 1358b may begin to fold distally into cylinder 1324. Flaps 1358a and 1358b may begin to fold along hinge element 1356. Hinge element 1356 may be supported by ring support 1352.

[0234] Diaphragm 1354 may be configured to reseal when distal propulsion of fluid 1365 falls below the pressure required to generate sufficient pressure to open / rupture slit 1355 by causing the opposing ends of flaps 1358a and 1358b to approach each other and reclose, sealing the slit. Diaphragm 1354 may be configured to remain open / ruptured even after the slit opens / ruptures, even if the force of distal propulsion of fluid 1365 falls below the force required to generate sufficient pressure to open / rupture slit 1355. Diaphragm 1354 may be configured such that a drop in fluid pressure causes diaphragm 1354 to reclose prior to a particular preselected stage of opening of slit 1355 and distal folding of flaps 1358a and 1358b into cylinder 1324. Diaphragm 1354 may be configured such that after a particular preselected stage of opening of slit 1355 and distal folding of flaps 1358a and 1358b into cylinder 1324, diaphragm 1354 does not reclose even when fluid pressure is reduced.

[0235] Figure 14 shows an exemplary drug delivery device 1400. Delivery device 1400 may have one or more apparatus features having the same relationships, properties, and functions as one or more features of delivery devices 100, 200, 700, and 900 (shown in Figures 1, 2, 7, and 9, respectively), as indicated by like reference characters, and / or may be shown in Figures 3, 4, 5, 6, 8, 10, 11, 12, and / or 13. These device features may include a container 1402, a distal outlet 1404, an inner wall 1406, a filter 1410, a central region 1412, a filter housing 1420, a cylindrical body 1424, an interior 1428, a filter base 1430, a central projection 1432, a passageway 1433, end projections 1437, a filter cap 1440, a diaphragm ring support 1452, a diaphragm 1454, a diaphragm hinge element 1456, a diaphragm flap 1458a, a diaphragm flap 1458b, and a fluid 1465, a plunger 1466, and a fluid 1467.

[0236] 14 shows device 1400 in an operational filtering configuration following the opening / rupture of the diaphragm slit (shown in FIG. 13) by a user who has already propelled plunger 1466 in container 1402 distally toward outlet 1404, creating enough pressure in fluid 1465 to open / rupture diaphragm 1454. (Compare FIGS. 12 and 13 for the shift from the pre-filtering configuration to the beginning of the filtering configuration.)

[0237] 14 , after opening / rupturing the diaphragm 1454, the user continues distal movement of the plunger 1466, forcing the fluid 1465 through the open / ruptured diaphragm 1454, into the interior 1428, between the distally folded diaphragm flaps 1458a and 1458b, and out the proximal face of the filter 1410. The proximal projections 1432 provide support to the central region 1412, supporting the filter 1410 against sudden forces applied to the filter 1410 by the distally forced fluid 1465 first encountering the proximal face of the filter 1410. As the distally forced fluid 1465 continues to encounter the proximal face of the filter 1410, the fluid 1465 is forced through and filtered by the filter 1410.

[0238] 14 shows filtered fluid 1467 emerging from and positioned distal to filter 1410. Filtered fluid 1467 may be the filtrate of fluid 1465. Filtered fluid 1467 may differ in content from fluid 1465. Fluid 1465 may contain particulate matter of a size that filter 1410 can retain while fluid 1465 is propelled distally onto and into filter 1410. Fluid 1467 may be free of particulate matter from fluid 1465 that was retained by filter 1410. The size of particulate matter from fluid 1465 that can be retained by filter 1410 may depend on the pore size of filter 1410. The pore size of filter 1410 may be the average effective pore size. (As explained above, the present use of specialized filters can extend the range of distinction between the contents of the filtrate and pre-filtered PFS fluid beyond the size of dissolved / suspended particles, and can extend the range of charge profiles and / or molecular identities.)

[0239] Diaphragm flaps 1458a and 1458b are shown folded into interior 1428 with their distal ends (which were the flap edges that faced each other and closed / sealed the diaphragm slit prior to the opening / rupture of diaphragm 1410) facing and proximal to the proximal face of filter 1410. The folding of diaphragm flaps 1458a and 1458b occurs at diaphragm hinge element 1456, which is supported by diaphragm ring support 1452. Filtering of fluid 1465 to produce fluid 1467 may be achieved with less extreme folding of diaphragm flaps 1458a and 1458b into interior 1428 than depicted.

[0240] As shown, filtered fluid 1467 may fill passageway 1433 and extend past end protrusion 1437 to fill distal outlet 1404, from which it may be directed for delivery (and for any preceding pre-delivery syringe preparation steps) of filtered fluid 1467. As more fluid 1465 is propelled onto and into filter 1410 by the user's further distal movement of plunger 1466 from its depicted position, freshly filtered fluid 1467 may continue to flow distally from filter 1410, through passageway 1433 to distal outlet 1404, and then toward delivery.

[0241] After the flow of distally forced fluid 1465 through interior 1428 to filter 1410 ceases, diaphragm flaps 1458a and 1458b may deploy rearward toward the position occupied in a pre-filtering configuration (as shown in FIGS. 11 and 12). The extent of such deployment may be set by prior selection of the materials, structure, and shape of diaphragm 1454, diaphragm flaps 1458a and 1458b, diaphragm ring support 1452, and diaphragm hinge element 1456. Such deployment may re-close diaphragm 1454.

[0242] Thus, provided are devices and methods, including methods of manufacture, for filtering the contents of a PFS fluid prior to drug delivery, which are closed at the time prior to drug delivery in a manner that isolates the filter from the fluid until delivery begins, while maintaining the benefits of using a PFS. Those skilled in the art will appreciate that the present invention can be practiced in embodiments other than those described, which are presented for purposes of illustration and not limitation. The present invention is limited only by the scope of the following claims.

Claims

1. 1. A device for delivering filtered fluid from a distal outlet of a fluid delivery device, the device defining a longitudinal axis; a fluid in a fluid container, the container being disposed coaxially with the longitudinal axis; and a filter embedded within the container, the filter comprising: between the distal outlet and the fluid; and a filter disposed across the longitudinal axis.

2. The delivery device of claim 1 , further comprising a filter housing including a proximal filter cap and a distal filter base.

3. The filter is fixed within the filter housing; The delivery device of claim 2 , wherein the filter housing is housed within the container.

4. The delivery device of claim 2 , wherein the filter base is configured to provide distal support for the filter.

5. The delivery device of claim 4 , wherein the distal support is provided at a central region of the filter by a proximal central protrusion of the filter base.

6. The delivery device of claim 5 , wherein the filter is not secured to the proximal central projection.

7. The delivery device of claim 2 , wherein a periphery of the filter is attached to a proximal surface of the filter base.

8. 3. The delivery device of claim 2, wherein an area of ​​the filter circumferentially bordering a filter periphery is joined to a proximal face of the filter base with a fluid-tight seal, the seal configured to prevent passage of the fluid between the interior of the filter base and any of the filter periphery.

9. The delivery device of claim 2 , wherein the filter base is secured to the filter cap.

10. The delivery device of claim 2 , wherein interference between at least one filter cap protrusion and at least one filter base recess is configured to secure the filter cap to the filter base.

11. The delivery device of claim 10 , wherein the at least one filter base recess and the at least one filter cap protrusion are contoured to be at least generally complementary to one another.

12. the at least one filter cap protrusion is disposed along a portion of the inner surface of the filter cap; The delivery device of claim 10 , wherein the at least one filter base recess is disposed along a portion of an outer surface of the filter base.

13. The delivery device of claim 2 , wherein interference between the at least one filter cap surface protrusion and the at least one filter base surface recess is configured to provide a fluid-tight seal.

14. The delivery device of claim 2 , wherein interference between the at least one filter cap surface recess and the at least one filter base surface protrusion is configured to provide a fluid-tight seal.

15. 3. The device of claim 2, wherein the wall of the filter housing is configured to seal against an interior wall of the vessel, thereby preventing passage of the fluid between an exterior of the filter housing and the interior wall.

16. The delivery device of claim 15 , wherein the wall includes a filter cap sealing flange disposed along an outer periphery of the filter cap.

17. The delivery device of claim 16 , wherein the filter cap sealing flange comprises a plurality of filter cap sealing flanges.

18. The delivery device of claim 15 , wherein the wall includes a filter base sealing surface supported by a distal section of a body of the filter base.

19. 10. The delivery device of claim 1, wherein the filter has an average pore size of about 1 micron to about 10 microns.

20. 20. The delivery device of claim 19, wherein the average pore size is from about 4 microns to about 6 microns.

21. 10. The delivery device of claim 1, wherein the filter has an average pore size of about 0.01 microns to about 1 micron.

22. 22. The delivery device of claim 21, wherein the average pore size is from about 0.1 microns to about 0.3 microns.

23. preventing the fluid from contacting the filter before propelling the fluid toward the distal outlet; The delivery device of claim 1 , further comprising a filter housing configured to allow the fluid to contact the filter after the propulsion begins.

24. a plunger slidable proximally of the fluid, the plunger comprising: sealing the fluid within the vessel; a plunger configured to propel the fluid toward the distal outlet; and a filter cap configured to block fluid access to the filter prior to the delivery; The delivery device of claim 1 , wherein the fluid, when propelled by the plunger, unblocks the cap to the flow of the fluid toward the distal outlet.

25. The filter cap includes a proximal plug disposed on a collar and sealing the collar against the flow of fluid to the filter, the plug comprising: Distal movement by distally propelled fluid relative to said collar, thereby The delivery device of claim 2 , configured to open the collar to the flow of the fluid therethrough.

26. 26. The delivery device of claim 25, wherein the plug includes a plug groove extending radially inward along an exterior of the plug.

27. 27. The delivery device of claim 26, wherein the collar includes a collar rim extending radially inward along an inner surface of the collar.

28. 28. The delivery device of claim 27, wherein prior to the delivery, the plug seals the collar against the flow by interference between the plug groove and the collar rim.

29. The plug is defining a cylinder axis that is at least generally coaxially disposed with said longitudinal axis prior to delivery; 30. The delivery device of claim 28, comprising at least one tab distal to the plug groove extending radially outward perpendicular to the cylinder axis with a tab-to-tab gap disposed circumferentially along the exterior of the plug.

30. the at least one tab is a plurality of tabs; 30. The delivery device of claim 29, wherein the inter-tab gap is disposed between circumferentially adjacent, opposing side edges of circumferentially adjacent tabs.

31. the at least one tab is one tab; 30. The delivery device of claim 29, wherein the inter-tab gap is disposed between circumferentially adjacent opposing side edges of the one tab.

32. 30. The delivery device of claim 29, wherein the at least one tab is configured to maintain an orientation of the cylinder axis at least generally coaxial with the longitudinal axis after distal movement of the plug relative to the collar.

33. 30. The delivery device of claim 29, wherein the filter cap comprises a cylindrical body including the collar disposed at a proximal end of the cylindrical body.

34. 34. The delivery device of claim 33, wherein the inter-tab gap is configured to allow the flow of the fluid between the exterior of the plug and the interior of the barrel after distal movement of the plug relative to the collar into the interior of the barrel.

35. The filter cap includes an initially closed diaphragm that prevents the flow of the fluid to the filter, the diaphragm comprising: opened by distally propelled fluid, thereby The delivery device of claim 2 , configured to provide a passage for the flow of the fluid.

36. 36. The delivery device of claim 35, wherein the diaphragm is a slit diaphragm.

37. 37. The delivery device of claim 36, wherein the slit diaphragm comprises a single slit.

38. 37. The delivery device of claim 36, wherein the slit diaphragm includes a plurality of slits.

39. 36. The delivery device of claim 35, wherein the diaphragm is configured to reclose after opening.

40. 36. The delivery device of claim 35, wherein the diaphragm is configured to reclose after the flow of the fluid has stopped.

41. 36. The delivery device of claim 35, wherein the diaphragm is configured to reclose after distal propulsion of the fluid has ceased.

42. The delivery device of claim 1 , wherein the fluid comprises a drug.

43. The delivery device of claim 1 , wherein the container comprises a syringe barrel.

44. The delivery device of claim 1 , wherein the container wall comprises a plastic polymer.

45. 1. A filter housing for embedding within a drug container of a device, the device defining a longitudinal axis, the device for delivering filtered drug from a distal outlet of the device, the filter housing comprising: A filter base configured to support a filter, the filter comprising: disposed on the base, a filter base configured to prevent passage of particles larger than a maximum pore size of the filter; a filter cap configured to mate with the base; The filter housing is configured to be embedded in the vessel proximal to the distal outlet.

46. 46. ​​The filter housing of claim 45, wherein the filter housing is further configured to provide a seal around the periphery of the filter, the periphery being configured to prevent passage of the agent when sealed.

47. 46. ​​The filter housing of claim 45, wherein an exterior of the filter housing is configured to provide a seal against an interior wall of the container, the seal configured to prevent distal flow of the agent between the interior wall and the filter housing.

48. The filter cap is blocking access to the filter by the agent prior to the delivery of the agent, the agent comprising: Within the container, proximal to the filter, and a longitudinally slidable plunger disposed distally of the plunger, the plunger comprising: sealing against the interior wall of the container; configured to propel the agent toward the distal outlet; The drug is positioned to contact a proximal exterior aspect of the cap; The filter cap is 46. ​​The filter housing of claim 45, further configured to be unblocked by urging the agent distally to the side, thereby creating an unblocked cap, the unblocked cap allowing flow of the agent to the filter.

49. 46. ​​The filter housing of claim 45, wherein the filter comprises an acrylic polymer.

50. 46. ​​The filter housing of claim 45, wherein the filter comprises polyethersulfone.

51. 46. ​​The filter housing of claim 45, wherein the filter comprises polyvinylidene fluoride.

52. 46. ​​The filter housing of claim 45, wherein the filter has an average pore size of about 5 microns.

53. 46. ​​The filter housing of claim 45, wherein the filter has an average pore size of about 0.2 microns.

54. The embodiment includes a proximal plug disposed and sealing to a collar of the filter cap, the plug comprising: a distally driven agent moving distally relative to the collar, thereby 49. The filter housing of claim 48, configured to be open to the flow of the agent through the collar.

55. The above aspect is opened by a distally propelled agent, thereby 49. The filter housing of claim 48, comprising an initially closed diaphragm configured to provide passage for the flow of the agent.

56. 1. A method of manufacturing a drug delivery device for delivering a filtered drug, the device defining a longitudinal axis, the method comprising: providing a drug container coaxially disposed on said axis, said container having a distal outlet and a proximal opening; Assembling a filter housing, providing a filter base configured to support a filter; disposing the filter on a surface of the base; sealing the periphery of said filter against fluid flow; joining the base with a filter cap, the cap comprising: a rib configured to seal against an interior wall of the container; An external aspect, blocking fluid access to the filter prior to said delivering; an exterior aspect configured to be unblocked to provide fluid access to the filter during the delivery; introducing the filter housing into the container through the proximal opening with the base disposed distally and the exterior aspect disposed proximally relative to the axis; embedding the filter housing within the container proximal to the distal outlet; sealing the rib against the interior wall; and via the proximal opening, transferring the agent to the container; and Inserting a longitudinally slidable plunger, said plunger comprising: sealing the medicament within the container; inserting configured to propel the agent toward the distal exit.

57. 57. The method of claim 56, wherein said inserting is performed without propelling said agent distally enough to unblock said external aspect.

58. 57. The method of claim 56, wherein the housing includes an inner surface configured to seal around the filter.

59. The exterior aspect includes a proximal plug disposed on a collar of the filter cap and sealing the collar of the filter cap, the plug comprising: a distally driven agent moving distally relative to the collar, thereby 57. The method of claim 56, configured to open to the flow of the agent through the collar.

60. The external aspect is opened by a distally propelled agent, thereby 57. The method of claim 56, comprising an initially closed slit diaphragm configured to provide passage for the flow of the agent.

Images