Patent Description:
In some forms, a syringe may be provided with separate components that may be assembled as needed for particular tasks. One such syringe includes a barrel having an open distal tip. A mount or adaptor may be secured to the tip of the barrel and provide a structure for removably attaching a cap or needle. Further, the cap can include an elastomeric insert that sealingly engages the tip to create a sterile barrier. <CIT> discloses an example of a syringe having a tip cap.

Syringes such as these can be subjected to a sterilization process with the cap secured to the barrel. <CIT> discloses a method for producing a sterilized packaged medical article. <CIT> discloses aseptic vial piercing and sterilization systems. <CIT> discloses a sterility indicator. In certain instances, it is necessary to confirm that the interface between the cap and barrel tip is sterile after a sterilization process. Accordingly, one or more of the syringes from a batch may be subjected to a sterilization verification or validation process to ensure that the sterilization process was successful. One such verification process involves positioning a long, flat, rectangular biological indicator (BI) strip between the barrel tip and the elastomeric insert prior to the sterilization process. After the sterilization process is complete, the BI strip can be tested to ensure that the strip has been fully sterilized or otherwise sterilized to sufficient degree by the process. The geometry or configuration of conventional BI strips is such that it may create an open channel between the elastomeric insert and the barrel tip, which tends to skew sterilization verification results.

The present disclosure sets forth sterilization verification methods and assemblies embodying advantageous alternatives to existing sterilization verification methods and assemblies, and that may address one or more of the challenges or needs mentioned above, as well as provide other benefits and advantages.

An aspect of the disclosure includes a syringe sterilization verification assembly including a syringe, a tip cap assembly, and a biological indicator (BI) member. The syringe includes a barrel having a tip. The tip cap assembly includes an insert having a skirt configured to receive the tip. The biological indicator (BI) member has an annular portion disposed around at least a portion of the tip and disposed radially between the tip and the skirt of the insert.

In some versions, the annular portion of the BI member comprises a wire member wound in a spiral configuration.

In some versions, the annular portion of the BI member has an elongated sleeve-like shape with a frusto-conical configuration complementary to a configuration of the tapered tip of the barrel.

In some versions, the tip of the barrel defines a channel receiving the BI member.

In some versions, a proximal end of the BI member extends to a location external to a connection between the skirt and the tapered tip of the barrel such that the proximal end of the BI member is not disposed radially between the tapered tip and the skirt of the insert.

In some versions, the BI member extends <NUM> degrees around the tip of the barrel.

In some versions, the BI member comprises an axial dimension that is less than an axial dimension of the tip.

In some versions, the BI member comprises filter paper carrying bacteria spores.

In some versions, the bacteria spores are generally uniformly dispersed across the entire surface of the BI member.

In some versions, the bacteria spores comprise Bacillus atrophaeus (BA) bacterial spores and/or Geobacillus stearothermophilus (GST) bacterial spores.

Another aspect of the disclosure provides a method for verifying sterilization. The method includes providing a syringe including a barrel and a tip. The method further includes mounting a tip cap assembly on the tip. The method further includes disposing an annular portion of a biological indicator (BI) member around the tapered tip. The method also includes mounting a tip cap assembly having an insert with a skirt on at least a portion of the tip, the skirt having a cavity sized to receive the tip therein, wherein mounting the tip cap assembly on the tip causes the annular portion of the BI member to be disposed radially between the skirt of the insert and the tip. And the method also includes subjecting the syringe, the tip cap assembly, and the BI member to a sterilization process. Finally, the method can include testing the BI member for sterilization.

In some versions, disposing the annular portion of the BI member around at least a portion of the tip comprises wrapping a wire around the tip in a spiral configuration.

In some versions, disposing the annular portion of the BI member around at least a portion of the tip comprises disposing a BI member having an elongated sleeve-like shape with a frusto-conical configuration on the tip.

In some versions, the method also includes disposing the BI member into a channel on the tip.

In some versions, the method also includes disassembling the tip cap assembly and the syringe to access the BI member prior to testing the BI member for sterilization.

In some versions, testing the BI member for sterilization comprises exposing the BI member to media to check for bacterial growth.

Yet another aspect of the disclosure includes a method for verifying sterilization that includes providing a syringe including a barrel and a tip. The method also includes mounting a tip cap assembly on the tip, the tip cap assembly having an insert with a skirt having a cavity to receive the tip therein. The method also includes inoculating an interface between the insert and the tip. The method also includes subjecting the syringe and tip cap assembly to a sterilization process. The method also includes testing the syringe and tip cap assembly for sterilization.

In some versions, inoculating the interface between the insert and the tip comprises penetrating through the insert with a needle and dispensing an inoculation medium between the insert and the tip.

In some versions, the method also includes aseptically disassembling the tip cap assembly and the syringe.

In some versions, testing the syringe and tip cap assembly for sterilization comprises exposing the syringe and tip cap assembly to media to check for bacterial growth.

In accordance with a further aspect, a syringe sterilization verification assembly is disclosed that includes a syringe having a barrel with a tapered tip and a tip cap assembly including an insert with a skirt configured to receive and sealingly engage the tapered tip. The assembly further includes a biological indicator (BI) member that has an annular portion disposed around the tapered tip radially between the tapered tip and the skirt of the insert.

According to some forms, the assembly can include one or more of the following aspects: the annular portion of the BI member is a wire member having a spiral configuration; the annular portion of the BI member has a planar disk-like shape in at least an initial configuration prior to being disposed radially between the tapered tip and the skirt of the insert; the annular portion of the BI member has an elongated sleeve-like shape with a frusto-conical configuration complementary to a configuration of the tapered tip of the barrel; or a proximal end of the BI member can extend to a location external to a connection between the skirt and the tapered tip of the barrel such that the proximal end of the BI member is not disposed radially between the tapered tip and the skirt of the insert.

In accordance with another aspect, a method for verifying sterilization is disclosed that includes providing a syringe including a barrel, a tapered tip, and a Luer collar with a threaded surface, mounting a tip cap assembly on the tapered tip; disposing an annular portion of a biological indicator (BI) member around the tapered tip, and mounting a tip cap assembly having an insert with a skirt on the tapered tip by engaging a threaded surface of the tip cap assembly with the threaded surface of the Luer collar. The skirt has a cavity sized to sealingly receive the tapered tip therein and mounting the tip cap assembly on the tapered tip causes the annular portion of the BI member to be disposed radially between the skirt of the insert and the tapered tip. The method further includes subjecting the syringe, the tip cap assembly, and the BI member to a sterilization technique and testing the BI member for sterilization.

According to some forms, the method can include one or more of the following aspects: disposing the annular portion of the BI member around the tapered tip can include wrapping a wire around the tapered tip in a spiral configuration; the annular portion of the BI member has a planar disk-like shape at least prior to being disposed around the tip of the barrel; or the method can include disassembling the tip cap assembly and the syringe to access the BI member.

In accordance with another aspect, a syringe sterilization verification assembly is disclosed that includes a syringe having a barrel with a tapered tip , wherein a channel is formed in an exterior surface of the tapered tip, a tip cap assembly including an insert having a skirt configured to receive and sealingly engage the tapered tip, and a biological indicator (BI) member disposed in the channel between the tapered tip and the skirt of the insert.

According to some forms, the BI member can be an elongate strip and/or the channel can have an annular configuration extending around the tapered tip.

In accordance with another aspect, a method for verifying sterilization is disclosed that includes providing a syringe including a barrel, a tapered tip, and a Luer collar with a threaded surface, disposing a biological indicator (BI) member in a channel formed in an exterior surface of the tapered tip, and mounting a tip cap assembly having an insert with a skirt on the tapered tip by engaging a threaded surface of the tip cap assembly with the threaded surface of the Luer collar. The skirt has a cavity sized to sealingly receive the tapered tip therein and mounting the tip cap assembly on the tapered tip causes the annular portion of the BI member to be disposed radially between the skirt of the insert and the tapered tip. The method further includes subjecting the syringe, the tip cap assembly, and the BI member to a sterilization technique and testing the BI member for sterilization.

According to some forms, the method can include one or more of the following aspects: disposing the BI member in the channel can include disposing the BI member within an annular channel extending around the tapered tip; the method can include forming the channel in the tapered tip by laser etching; or the method can include disassembling the tip cap assembly and the syringe to access the BI member.

In accordance with another aspect, a method for verifying sterilization is disclosed that includes providing a syringe including a barrel, a tapered tip, and a Luer collar with a threaded surface, mounting a tip cap assembly on the tapered tip, where the tip cap assembly has a threaded surface mating with the threaded surface of the Luer collar and has an insert with a skirt having a cavity to sealingly receive the tapered tip therein. The method further includes inoculating an interface between the insert and the tapered tip, subjecting the syringe and tip cap assembly to a sterilization technique, and testing the syringe and tip cap assembly for sterilization.

According to some forms, the method can include one or more of the following aspects: inoculating the interface between the insert and the tapered tip can include penetrating through the insert with a needle and dispensing an inoculation medium between the insert and the tapered tip; the method can include aseptically disassembling the tapered tip cap assembly and the syringe; or testing the syringe and tip cap assembly for sterilization can include exposing the syringe and tip cap assembly to media to check for growth.

Syringe sterilization verification assemblies and methods are described herein that provide consistently reliable results. In some forms, the assemblies and methods utilize biological indicator (BI) members having an annular portion to extend around a tip of a syringe barrel. In alternative or additional forms, the tip of the syringe barrel can include a channel sized to receive the BI member therein. Other forms can utilize a direct inoculation of an interface between a tip cap assembly insert and the tip of the syringe barrel. The BI members disclosed herein may include any conventional or novel materials/compositions and may include, for example, filter paper carrying bacteria spores. In some cases the bacteria spores can include Bacillus atrophaeus (BA) spores and/or in some versions Geobacillus stearothermophilus (GST) bacterial spores. Other spores may be possible. Such BI members can assist with sterility assurance programs by being placed in exposure to the sterilization process, subsequent to which the BI members can be removed, incubated, and tested to determine if any of the bacteria spores survived. In some versions, the bacteria spores are uniformly dispersed across the entire exposed surfaces of the BI members disclosed herein. in other versions, the bacteria spores may be disperse across less than the entire exposed surfaces.

Turning now to <FIG> and <FIG>, a hypodermic syringe <NUM>, which in certain embodiments may be configured as a Luer lock syringe, is shown that includes a barrel <NUM> formed from any suitable material, such as a glass or a polymer. The barrel <NUM> includes a proximal end <NUM>, a distal end <NUM> having a tip <NUM> (shown in <FIG>), and a cylindrical sidewall <NUM> extending between the proximal and distal ends <NUM>, <NUM>. The tip <NUM> and sidewall <NUM> define a reservoir <NUM> to receive a therapeutic product <NUM>. The tip <NUM> further defines a passageway <NUM> (shown in <FIG>) fluidly connected to the reservoir <NUM>. With continued reference to <FIG>, the distal end <NUM> of the barrel <NUM> includes a rear portion <NUM> that has a frusto-conical configuration transitioning to the tip <NUM>. The tip <NUM> has a frusto-conical sidewall <NUM> having a predetermined taper. A plunger-stopper <NUM> is disposed within the reservoir <NUM> in a sliding, fluid-tight engagement with the sidewall <NUM>. As shown in <FIG>, the syringe <NUM> can further include a plunger rod <NUM> configured to engage the plunger-stopper <NUM> and drive the plunger-stopper <NUM> through the barrel <NUM> to thereby dispense the therapeutic product <NUM> through the tip <NUM>. The plunger rod <NUM> can be integrally formed with the plunger-stopper <NUM> or can have a distal end <NUM> sized to engage the barrel sidewall <NUM> and retain the plunger rod <NUM> within the barrel <NUM>. The plunger rod <NUM> can include a proximal platform <NUM> so that a user can conveniently push the plunger rod <NUM> through the barrel <NUM>. Alternatively, the syringe <NUM> can be configured for an automatic drug delivery device having a plunger rod and associated drive mechanism such as an on-body injector or autoinjector.

As shown in the embodiments of <FIG>, the syringe <NUM> further includes a Luer collar <NUM> to provide a mount for components of the syringe <NUM>. In a first embodiment, the Luer collar <NUM> can be integral with the barrel <NUM> and extend forward from the rear portion <NUM> of the distal end <NUM> thereof. The Luer collar <NUM> has a tubular configuration sized to extend around the tip <NUM> of the syringe barrel <NUM>. The Luer collar <NUM> has proximal and distal ends <NUM>, <NUM> and a sidewall <NUM> extending therebetween. The proximal end <NUM> of the collar <NUM> can include an inwardly projecting portion <NUM> that extends to the tip <NUM> of the barrel <NUM>. In a second embodiment, the Luer collar <NUM> can be attached to the barrel <NUM>. Pursuant to this, the inwardly projecting portion <NUM> can be an array of inwardly projecting radial protrusions that are sized to fictionally engage the tip <NUM> of the barrel <NUM>. In an alternative form, the inwardly projecting portion <NUM> can have an annular configuration. So configured, the collar <NUM> can be press fit onto the tip <NUM> by moving the collar <NUM> in a proximal direction over the tip <NUM>. The inwardly projecting portion <NUM> can be configured to deflect as the collar <NUM> is press fit onto the tip <NUM> so that the collar <NUM> is frictionally retained on the tip <NUM>. The sidewall <NUM> has an internally threaded surface <NUM> to threadingly receive other components of the syringe <NUM> and mount the other components to the barrel <NUM>.

The syringe <NUM> further includes a tip cap assembly <NUM> that secures to the collar <NUM> to seal to the barrel tip <NUM>. The tip cap assembly <NUM> includes an insert <NUM> and a cap <NUM>. The insert <NUM> includes a head <NUM> at a distal end <NUM> thereof and a skirt <NUM> extending outwardly from the head <NUM> at a proximal end <NUM>. The skirt <NUM> defines an interior cavity <NUM> sized to sealingly engage the barrel tip <NUM> and the cap <NUM> includes a sidewall <NUM> having an exteriorly threaded surface <NUM> that are configured to engage the threaded surface <NUM> of the collar <NUM> to thereby secure the tip cap assembly <NUM> to the collar <NUM> and to the barrel <NUM>. The insert <NUM> is made of an elastomeric material such that the skirt <NUM> can resiliently expand over and sealingly engage the tip <NUM>. It will be understood that in addition to the tip cap assembly <NUM>, the Luer collar <NUM> can be utilized to attach a needle assembly for an injection operation.

A first example syringe sterilization verification assembly <NUM> is shown in <FIG>. The assembly <NUM> includes a BI member <NUM>. The BI member <NUM> has a body <NUM> with at least a portion <NUM> having an annular configuration sized and configured to be disposed around the tip <NUM> of the barrel <NUM>. In one example, the body <NUM> has a planar disk-like shape. In some versions, the body <NUM> has an annular sleeve shape with a continuous, unbroken exterior surface <NUM>. In one form, the body <NUM> can be formed from a material that is at least partially deformable so that the body <NUM> can be disposed over and tightly engaging the taper of the barrel tip <NUM> without damage. In another form, the body <NUM> can have a frusto-conical configuration, as shown in <FIG>, with a taper generally complementary to the taper of the barrel tip <NUM> so that the body <NUM> can be disposed thereon to tightly engage the barrel tip <NUM>.

As shown in <FIG>, to verify that the syringe barrel <NUM> and tip cap assembly <NUM> mounted thereto has been sterilized, at least a portion of the BI member <NUM> is disposed in an interface <NUM> between the skirt <NUM> and the barrel tip <NUM>. In the disclosed version, the BI member <NUM> extends <NUM> degrees in an annular configuration within the interface <NUM>, while having an axial dimension that is less than the axial dimension of the interface <NUM>. In some versions, the BI member <NUM> can have the same axial dimension of the interface <NUM>. This <NUM> degree annular configuration advantageously ensures that based on subsequent testing that the sterilization process was effective around the entirety of the interface <NUM>, barrel tip <NUM>, and skirt <NUM>. This is in contrast to merely along one linear side of the barrel tip <NUM> as was previously attainable through the use of conventional BI strips. In one approach, the BI member <NUM> can be disposed radially between the skirt <NUM> and the barrel tip <NUM>. This can be achieved by placing the BI member <NUM> onto the barrel tip <NUM> and, if the Luer collar <NUM> is a separate component, subsequently mounting the Luer collar <NUM> and tip cap assembly <NUM> to the barrel tip <NUM> so that at least a portion of the BI member <NUM> is disposed within the tip/skirt interface <NUM> radially therebetween. In one example, the skirt <NUM> can deflect portions of the BI member <NUM> that project radially outward from the barrel tip <NUM> as the tip cap assembly <NUM> is mounted on the barrel tip <NUM>. In another example, in the embodiment of the body <NUM> having a planar disk-like shape, the BI member <NUM> can be disposed in a generally planar configuration extending around an end of the skirt <NUM> between the skirt <NUM> and the radially inward extending portion <NUM> of the Luer collar <NUM>. The Luer collar <NUM> and tip cap assembly <NUM> can be threadingly engaged together when mounted to the barrel tip <NUM>, the Luer collar <NUM> can be mounted to the barrel tip <NUM> and the tip cap assembly <NUM> can be subsequently coupled to the Luer collar <NUM> by threading the cap <NUM> to the Luer collar <NUM>, or the tip cap assembly <NUM> can be coupled to the integral Luer collar <NUM>. Alternatively, the Luer collar <NUM> can be mounted to the barrel tip <NUM> first, followed by the BI member <NUM> being disposed on the barrel tip <NUM>, and finally the tip cap assembly <NUM> can be secured to the Luer collar <NUM> by engaging the threaded surfaces <NUM>, <NUM> of the Luer collar <NUM> and cap <NUM>.

If desired, a proximal end <NUM> of the body <NUM> can extend out of the tip/skirt interface <NUM> to extend along the barrel tip <NUM> toward the rear portion <NUM> of the distal end <NUM>. The continuous, unbroken exterior surface <NUM> of the BI member <NUM> provides a uniform layered structure with the skirt <NUM> and barrel tip <NUM> that better ensures a reliable sterilization verification process.

A second example syringe sterilization verification assembly <NUM> is shown in <FIG>. The assembly <NUM> includes a BI member <NUM> having a body <NUM> with at least a portion <NUM> having an annular configuration sized and configured to be disposed around the tip <NUM> of the barrel <NUM>. In this example, the body <NUM> is a wire member that can be wrapped around the barrel tip <NUM> to create the annular portion <NUM>. Specifically, the wire member <NUM> can be wrapped along a length of the barrel tip <NUM> so that the annular portion <NUM> of the body <NUM> has a spiral configuration that sequentially increases in diameter to be complementary to the taper of the barrel tip <NUM>. In one form, the BI member <NUM> can be made of a shape-retentive material so that the body <NUM> will hold its shape after being wrapped around the barrel tip <NUM>. As with the version described with reference to <FIG>, the BI member <NUM> of the version in <FIG> extends <NUM> degrees around the tip <NUM> of the barrel <NUM>, even if possessing an axial dimension less than an axial dimension of the tip <NUM>. In some versions, the BI member <NUM> can be coiled additional times around the tip <NUM> such that the two have the same axial dimension. Regardless, this winding <NUM> degree configuration advantageously ensures that based on subsequent testing that the sterilization process was effective around the entirety of the tip <NUM>.

As shown in <FIG>, to verify that the syringe barrel <NUM> and tip cap assembly <NUM> mounted thereto has been sterilized, at least a portion of the BI member <NUM> is disposed in an interface <NUM> between the skirt <NUM> and barrel tip <NUM>. This can be achieved by wrapping the BI member <NUM> around the barrel tip <NUM> and subsequently mounting the Luer collar <NUM> and tip cap assembly <NUM> to the barrel tip <NUM> so that at least a portion of the BI member <NUM> is disposed within the tip/skirt interface <NUM> radially between the skirt <NUM> and the barrel tip <NUM>. The Luer collar <NUM> and tip cap assembly <NUM> can be threadingly engaged together when mounted to the barrel tip <NUM> or the Luer collar <NUM> can be mounted to the barrel tip <NUM> and the tip cap assembly <NUM> can be subsequently coupled to the Luer collar <NUM> by threading the cap <NUM> to the Luer collar <NUM>. Alternatively, the Luer collar <NUM> can be mounted to the barrel tip <NUM> first, followed by the BI member <NUM> being wrapped around the barrel tip <NUM>, and finally the tip cap assembly <NUM> can be secured to the Luer collar <NUM> by engaging the threaded surfaces <NUM>, <NUM> of the Luer collar <NUM> and cap <NUM>.

If desired, a proximal end <NUM> of the body <NUM> can extend out of the tip/skirt interface <NUM> to extend along the barrel tip <NUM> toward the rear portion <NUM> of the distal end <NUM>. The minimal cross-sectional area of the BI member <NUM> provides a reliable sealing engagement with the skirt <NUM> and the barrel tip to better ensure a reliable sterilization verification process.

After the syringe <NUM>, tip cap assembly <NUM>, and BI member <NUM>, <NUM> have been assembled into the sterilization verification assembly <NUM>, <NUM>, the assembly <NUM>, <NUM> can be subjected to a suitable sterilization process, such as irradiation, chemicals, e.g., ethylene oxide, peracetic acid, ozone, or nitrogen dioxide, heat, pressure, etc. After the assembly <NUM>, <NUM> has been sterilized, the BI member <NUM>, <NUM> can be tested to ensure that the sterilization process fully sterilized the skirt/tip interface <NUM>, <NUM>. To test the BI member <NUM>, <NUM>, a user can grip the proximal end <NUM>, <NUM> and pull the BI member <NUM>, <NUM> out from the interface <NUM>, <NUM>, particularly with the wire member embodiment. Alternatively, a user can disassemble the tip cap assembly <NUM> from the Luer collar <NUM> to expose the BI member <NUM>, <NUM> for testing. Testing the BI member <NUM>, <NUM> for sterilization can include exposing the BI member <NUM>, <NUM> to media to check for growth.

A third example syringe sterilization verification assembly <NUM> is shown in <FIG>. The assembly <NUM> includes a BI member <NUM> having a body <NUM> configured to be disposed <NUM> degrees around the tip <NUM> of the barrel <NUM> in a manner similar to the BI member <NUM> described with reference to <FIG> above. Further, the barrel tip <NUM> can define a recess or channel <NUM> along a portion thereof reducing the sidewall thickness of the tip <NUM>. The channel <NUM> can have a depth corresponding to a thickness of the BI member <NUM> so that with the BI member <NUM> disposed within the channel <NUM>, the outer surface of the BI member <NUM> is generally co-planar with the adjacent portions of the barrel tip <NUM>. Further, the BI member <NUM> and the channel <NUM> can have complementary dimensions so that the BI member <NUM> is tightly received therein providing a sealing engagement between the BI member <NUM> and the bottom and side surfaces of the channel <NUM>. In the illustrated form, the channel <NUM> has an annular configuration extending around a circumference of the barrel tip <NUM>. Other configurations, such as a spiral configuration, a longitudinal channel extending along a longitudinal length of the barrel tip <NUM>. The BI member <NUM> can be a strip of suitable material or a ring-shaped member suitable for the particular channel <NUM> configuration. With the strip and annular channel <NUM> embodiment, the strip can have a length corresponding to a circumference of the channel <NUM> so that ends of the strip engage one another when the strip is disposed within the channel <NUM>. The channel <NUM> can be formed by any suitable method, including, for example, glass forming or etching using any process, such as laser, acid, abrasive blasting, etc. Regardless, as with the previously described embodiments, the BI member <NUM> of the version in <FIG> extends <NUM> degrees around the tip <NUM> of the barrel <NUM>, even if possessing an axial dimension less than an axial dimension of the tip <NUM>. This <NUM> degree configuration advantageously ensures that based on subsequent testing that the sterilization process was effective around the entirety of the tip <NUM>.

As shown, to verify that the syringe barrel <NUM> and tip cap assembly <NUM> mounted thereto has been sterilized, at least a portion of the BI member <NUM> is disposed in an interface <NUM> between the skirt <NUM> and barrel tip <NUM>. This can be achieved by disposing and/or wrapping the BI member <NUM> within the channel <NUM> of the barrel tip <NUM> and subsequently mounting the Luer collar <NUM> and tip cap assembly <NUM> to the barrel tip <NUM> so that at least a portion of the BI member <NUM> is disposed within the tip/skirt interface <NUM>. The Luer collar <NUM> and tip cap assembly <NUM> can be threadingly engaged together when mounted to the barrel tip <NUM> or the Luer collar <NUM> can be mounted to the barrel tip <NUM> and the tip cap assembly <NUM> can be subsequently coupled to the Luer collar <NUM> by threading the cap <NUM> to the Luer collar <NUM>. Alternatively, the Luer collar <NUM> can be mounted to the barrel tip <NUM> first, followed by the BI member <NUM> being disposed within the channel <NUM> of the barrel tip <NUM>, and finally the tip cap assembly <NUM> can be secured to the Luer collar <NUM> by engaging the threaded surfaces <NUM>, <NUM> of the Luer collar <NUM> and cap <NUM>.

After the syringe <NUM>, tip cap assembly <NUM>, and BI member <NUM> have been assembled into the sterilization verification assembly <NUM>, the assembly <NUM> can be subjected to a suitable sterilization process, such as irradiation, chemicals, e.g., ethylene oxide, peracetic acid, ozone, or nitrogen dioxide, heat, pressure, etc. After the assembly <NUM> has been sterilized, the BI member <NUM> can be tested to ensure that the sterilization process fully sterilized the skirt/tip interface <NUM>. To test the BI member <NUM>, a user can disassemble the tip cap assembly <NUM> from the Luer collar <NUM> to expose the BI member <NUM> for testing. Testing the BI member <NUM> for sterilization can include exposing the BI member <NUM> to media to check for growth.

A fourth example syringe sterilization verification assembly <NUM> is shown in <FIG>. In this form, the assembly <NUM> includes an inoculation device <NUM> that can be utilized to inoculate an interface and/or cavity <NUM> between the skirt <NUM> and barrel tip <NUM>. The inoculation device <NUM> can be a syringe <NUM> with a needle <NUM>, for example. The needle <NUM> has a gauge to be inserted through the insert <NUM> of the tip cap assembly <NUM> to dispense the inoculation medium and the elastomer of the insert <NUM> can fully seal the insert opening created by the needle <NUM>. The Luer collar <NUM> and tip cap assembly <NUM> can be mounted to the barrel tip <NUM> in any of the ways described herein. Thereafter, the assembly <NUM> can be subjected to a suitable sterilization process, such as irradiation, chemicals, e.g., ethylene oxide, peracetic acid, ozone, or nitrogen dioxide, heat, pressure, etc. After the assembly <NUM> has been sterilized, a user can disassemble the tip cap assembly <NUM> from the Luer collar <NUM> and the insert <NUM> and barrel tip <NUM> can be tested to ensure that the sterilization process fully sterilized the skirt/tip interface <NUM>. Testing the insert <NUM> and barrel tip <NUM> for sterilization can include exposing the insert <NUM> and/or barrel tip <NUM> to media to check for growth.

The above description describes various assemblies, devices, and methods for use with a drug delivery device. It should be clear that the assemblies, drug delivery devices, or methods can further comprise use of a drug or medicament listed below with the caveat that the following list should neither be considered to be all inclusive nor limiting. The drug or medicament will be contained in a reservoir. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the drug or medicament. The primary container can be a cartridge or a pre-filled syringe. As used herein, the term drug can be used interchangeably with other similar types of phrases and can be used to mean any type of medicament, therapeutic or non-therapeutic injectable such as traditional and non-traditional pharmaceuticals, nutraceuticals, nutritional supplements, prodrugs (e.g., a compound or molecule which is administered in an inactive or less active state but is cleaved/processed to form the active drug inside the recipient), biologics, biologically active compounds, biologically active molecules, biologically active agents, etc..

For example, the drug delivery device or more specifically the reservoir of the device may be filled with colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceutical products, such as an erythropoiesis stimulating agent (ESA), which may be in a liquid or a lyophilized form. An ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-<NUM>, INS-<NUM>, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well as the molecules or variants or analogs thereof as disclosed in the following patents or patent applications: <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>.

An ESA can be an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate erythropoietin receptor; antibodies that bind to erythropoietin receptor and activate the receptor; or peptides that bind to and activate erythropoietin receptor. Erythropoiesis stimulating proteins include, but are not limited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, pegylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1/hematide), and mimetic antibodies. Exemplary erythropoiesis stimulating proteins include erythropoietin, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind and activate erythropoietin receptor (and include compounds reported in <CIT> and <CIT>) as well as erythropoietin molecules or variants or analogs thereof as disclosed in the following patents or patent applications: <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>.

Examples of other pharmaceutical products for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); other biological agents such as Enbrel® (etanercept, TNF-receptor /Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim , G-CSF, hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device may also be used with a therapeutic antibody, a polypeptide, a protein or other chemical, such as an iron, for example, ferumoxytol, iron dextrans, ferric glyconate, and iron sucrose. The pharmaceutical product may be in liquid form, or reconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof:.

Also among non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each and all of those described in:.

Also included can be a sclerostin antibody, such as but not limited to romosozumab, blosozumab, or BPS <NUM> (Novartis). Further included can be therapeutics such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally, included in the device can be a monoclonal antibody (IgG) that binds human Proprotein Convertase Subtilisin/Kexin Type <NUM> (PCSK9). Such PCSK9 specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab), as well as molecules, variants, analogs or derivatives thereof as disclosed in the following patents or patent applications: <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

Also included can be talimogene laherparepvec or another oncolytic HSV for the treatment of melanoma or other cancers. Examples of oncolytic HSV include, but are not limited to talimogene laherparepvec (<CIT> and <CIT>); OncoVEXGALV/CD (<CIT>); OrienX010 (<NPL>); G207, <NUM>; NV1020; NV12023; NV1034 and NV1042 (<NPL>).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-<NUM> is expressed by various cells or and is present in the extracellular matrix; it inhibits all the major cartilage-degrading metalloproteases, and may play a role in role in many degradative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as in cancer and cardiovascular conditions. The amino acid sequence of TIMP-<NUM>, and the nucleic acid sequence of a DNA that encodes TIMP-<NUM>, are disclosed in <CIT>. Description of TIMP mutations can be found in <CIT> and <CIT>.

Also included are antagonistic antibodies for human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecule that target the CGRP receptor and other headache targets. Further information concerning these molecules can be found in <CIT>.

Additionally, bispecific T cell engager (BiTE®) antibodies, e.g. BLINCYTO® (blinatumomab), can be used in the device. Alternatively, included can be an APJ large molecule agonist e.g., apelin or analogues thereof in the device. Information relating to such molecules can be found in <CIT>.

In certain embodiments, the medicament comprises a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in <CIT>, and <CIT>, and <CIT>. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in <CIT>. In particularly preferred embodiments, the medicament comprises a therapeutically effective amount of the anti-TSLP antibody designated as A5 within <CIT>.

Although the drug delivery devices, methods, and components thereof, have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the invention because describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention. For example, components described herein with reference to certain kinds of drug delivery devices, such as on-body injector drug delivery devices or other kinds of drug delivery devices, can also be utilized in other kinds of drug delivery devices, such as autoinjector drug delivery devices.

Claim 1:
A syringe sterilization verification assembly comprising:
a syringe (<NUM>) including a barrel (<NUM>) having a tip (<NUM>);
a tip cap assembly (<NUM>) including an insert (<NUM>) having a skirt (<NUM>) configured to receive the tip (<NUM>); and
a biological indicator, BI, member (<NUM>, <NUM>, <NUM>), characterized in that the biological indicator member (<NUM>, <NUM>, <NUM>) having an annular portion (<NUM>, <NUM>) disposed around at least a portion of the tip (<NUM>) and disposed radially between the tip (<NUM>) and the skirt (<NUM>) of the insert (<NUM>).