Patent Description:
Additionally, the following related and co-owned U. applications are <CIT>, having Attorney Docket No.: <NUM>/52018P (entitled STERILE PRODUCT BAG WITH FILTERED PORT); <CIT>, having Attorney Docket No.: <NUM>/52019P (entitled DUAL CONTAINER SYSTEM FOR PRODUCT RECONSTITUTION); <CIT>, having Attorney Docket No.: <NUM>/52032P (entitled MEDICAL PRODUCT INCLUDING PRE-FILLED PRODUCT BAG WITH FILTERED FLUID PORT); and <CIT>, having Attorney Docket No.: <NUM>/52050P (entitled FILTERED PRODUCT BAG WITH COMPACT FORM FACTOR), each filed on July <NUM>, <NUM>.

This disclosure relates to a medical syringe and, in particular, a medical syringe system for reconstituting and administering a sterile medicament or nutritional product to a patient.

Often, drugs and nutrients are mixed with a diluent before being delivered to a patient. The diluent may be, for example, a dextrose solution, a saline solution or even water. Many such drugs or nutrients are supplied in a concentrated form such as powder, liquid, gel, foam, etc., and packaged in glass or plastic vials.

In order for the concentrate to be administered to a patient, it must first undergo reconstitution. As used herein, the term reconstitution includes not only liquidization of non-liquid concentrates but also dilution of liquid concentrates.

One way of reconstituting a concentrate is first to inject a diluent into the vial holding the concentrate. This may typically be performed by a pre-filled syringe having a liquid diluent contained in the syringe barrel. After the rubber stopper of the vial is pierced by the syringe needle, the liquid is injected into the vial. The vial is shaken to reconstitute and dilute the concentrate with the liquid. The liquid is then withdrawn back into the syringe. These steps may be repeated several times to ensure complete reconstitution of the concentrate. After the final mixing, the syringe is withdrawn and the reconstituted medication may then be injected into an administration set for bolus intravenous administration to a patient or into the medication port of a parenteral solution container (e.g., an IV bag) containing a medical solution or diluent such as dextrose or saline solution. The drug, now further diluted with the medical solution in the parenteral solution container, is delivered through an administration set for intravenous administration to the patient. Other methods of administration to the patient may also include attaching a needle to the syringe and proceeding with a venous, intramuscular or subcutaneous injection.

In other embodiments, the concentrate may already be present in the syringe in a lyophilized or other concentrated form. Diluent is then added to the syringe and the reconstitution may take place within the syringe barrel. The syringe assembly may be construted where it contains a single chamber or there may be dual chambers where the diluent is added to one of the chambers with the concentrate contained in the other and the assembly provides for mixing of the components of the chamber.

If the syringe is pre-filled with the container, the sterility is provided by steam or heat sterilizing the syringe after filling with the diluent. The high temperatures present in the sterilization cycle will limit the materials that may be used for the barrel and stopper and may impact the frictional forces between the barrel and stopper. The pre-filled syringe may also cause the syringe to have a shelf life that must be monitored to insure the syringe is used before the expiration of the shelf life. If diluent is added to the syringe, the addition will likely be made by a health care provider using aseptic technique such as connecting the syringe to a container of diluent under a hood. Failure to practice such technique may cause the diluent to contain contaminants and impact sterility.

<CIT>Yis a prior art document and describes a disposable intravenous push-type injection of aseptic filtration which is formed by gumming and connecting a needle pipe, a needle handle, a capillary, an upper shell, a filter membrane, a needle pedestal and a syringe in series. It does not disclose connecting an outlet of a filtration device to a delivery opening of a syringe barrel.

<CIT> is a prior art document that describes an air block for industrial, medical, and non-medical uses, wherein the air block is either removably connected to the proximalend of the catheter or it is integral to the proximal end of the catheter. It does not disclose disclose introducing a pharmaceutical fluid into a syringe barrel through a filter membrane and gas permeable membrane (<NUM>) would prevent the passing and filtration of a liquid, such as a pharmaceutical solution, into the syringe barrel.

<CIT> is a prior art document that describes a needle filter apparatus including a filter housing having a first end and a second end and having portions defining a filter chamber, and a filter media secured in the filter chamber. it does not disclose connecting an outlet of a filtration device to a delivery opening of a syringe barrel.

None of above mentioned prior art documents disclose a product concentrate disposed in a bore of a syringe between a stopper and a distal end and introducing a pharmaceutical fluid into the bore of the syringe barrel through the filter membrane such that a sterilized pharmaceutical fluid can be mixed with the product concentrate in the bore.

While the specification concludes with claims particularly pointing out and distinctly claiming the subject matter that is regarded as the present disclosure, it is believed that the disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may have been simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omissions of elements in some figures are not necessarily indicative of the presence or absence of particular elements in any of the exemplary embodiments, except as may be explicitly delineated in the corresponding written description. None of the drawings are necessarily to scale.

The present disclosure is directed to a novel device and method related to reconstituting a product concentrate directly in a syringe barrel. Generally, the syringe barrel includes at least one chamber and is provided to a hospital or pharmacist, for example, with a product concentrate pre-filled therein. On demand, a pharmacist can introduce a pharmaceutical fluid such as a diluent into the empty chamber through a sterilization filter such that the sterilized pharmaceutical fluid can be used to reconstitute the product concentrate into a sterile, patient deliverable product. Subsequent to reconstitution, but prior to patient administration, the sterilizing filter can be removed from the syringe and tested to ensure proper filtration was achieved.

To meet the foregoing, the present disclosure provides various embodiments of syringe systems. A first embodiment described primarily with reference to <FIG> includes a conventional single chamber syringe with a sterilizing filter attached to its administration end for receiving a pharmaceutical fluid during the reconstitution process. A second embodiment described primarily with reference to <FIG> includes a system similar to <FIG> but the syringe is a dual chamber syringe with a sterilizing filter attached to its administration end for receiving a pharmaceutical fluid during the reconstitution process. The dual-chamber syringe may allow for the provision of product concentrate in one chamber and diluent in the other, while maintaining separation between the two until mixing is desired. This may allow some flexibility in the process of introducing diluent on-demand. A third embodiment described primarily with reference to <FIG> includes a system similar to <FIG> and <FIG> but the sterilization filter is connected to the syringe via a valving mechanism and includes an additional administration port separate the filtration device. This arrangement may allow some flexibility in the types of administration connections that can be achieved. Fourth and fifth embodiments are described with reference to <FIG> and <FIG>, respectively, each including a system with two separate syringes in selective communication with one another via a valving arrangement. A first syringe is empty and initially fluidly coupled to a sterilization filter, while the second syringe can be pre-filled with a product concentrate. Similar to the dual-chamber system, this dual-syringe system may allow for the provision of product concentrate in one syringe and diluent in the other, while maintaining separation between the two until mixing is desired. This may allow some flexibility in the process of introducing diluent on-demand. Each of these embodiments will now be described in more detail.

<FIG> illustrates a first embodiment of a syringe system <NUM> constructed in accordance with the principles of the present disclosure including a syringe <NUM> and a filtration device <NUM> attached to the syringe <NUM>. <FIG> illustrates the syringe <NUM> coupled to the filtration device <NUM> and the syringe <NUM> with the filtration device <NUM> removed. The syringe <NUM> can include a relatively conventional syringe in that it includes a syringe barrel <NUM> and a plunger assembly <NUM> slidably disposed in the syringe barrel <NUM>. More specifically, the syringe barrel <NUM> includes a proximal end <NUM> carrying a finger flange <NUM> and defining a barrel opening <NUM>, a distal end <NUM> defining a delivery opening <NUM> and carrying a connection fitting (not shown) such as a Luer connector, and a hollow bore <NUM> extending between the proximal and distal ends <NUM>, <NUM>. The plunger assembly <NUM> includes a stopper <NUM> and a plunger rod <NUM>, the stopper <NUM> being slidably disposed in the bore <NUM>. So configured, when the bore <NUM> of the barrel <NUM> contains a fluid such as a medicament or nutrient solution for patient administration, a user can depress the plunger rod <NUM> in a known manner to express the fluid out of the delivery opening <NUM> at the distal end <NUM> of the barrel <NUM>.

In some embodiments, the syringe <NUM> of <FIG> can be pre-filled with a product concentrate <NUM> that requires reconstitution prior to patient administration. In some versions, the concentrate <NUM> can be introduced into the bore <NUM> either before or after the syringe <NUM> is attached to the filtration device <NUM>. That is, in some versions, either before or after the filtration device <NUM> is attached to the syringe <NUM>, the product concentrate <NUM> can be introduced into the bore <NUM> through the barrel opening <NUM> and then the plunger assembly <NUM> can be inserted into the bore <NUM> to seal the barrel opening <NUM>. In other versions, the product solution can be introduced into the bore <NUM> of the barrel <NUM> and subsequently lyophilized in the barrel <NUM>. This lyophilization could occur in the absence of the plunger assembly <NUM> such that water vapor exhausts out of the barrel opening <NUM>, or with the plunger assembly <NUM> sealing the barrel opening <NUM>, in which case water vapor can exhaust through the filtration device <NUM>.

The filtration device <NUM>, as mentioned, is attached to the distal end <NUM> of the syringe barrel <NUM> and, in the version depicted in <FIG>, includes a stem <NUM>, a filter membrane <NUM> disposed in-line with the stem <NUM>, and a sterile closure cap <NUM>. In the depicted version, the filter membrane <NUM> can include a hollow tubular filter membrane disposed inside of the stem <NUM>, examples of which will be described below. In other versions, however, other filter membrane arrangements can be used. The stem <NUM> is a hollow narrow tube having an inlet <NUM> and an outlet <NUM> fluidly connected to the delivery opening <NUM> of the syringe barrel <NUM>. The sterile closure cap <NUM> sealably covers the inlet <NUM> of the stem <NUM> to maintain sterility until necessary to remove the cap <NUM> during use. In other versions, the system does not include a cap <NUM>, but rather, can include a split septum or membrane disposed in the stem <NUM> adjacent the inlet <NUM>, and which can be pierced by a filling tube or nozzle being inserted into the inlet <NUM>.

So configured, a pharmaceutical fluid such as a water, saline, a solution, a diluent, etc., may be introduced into the inlet <NUM> of the stem <NUM>, and passed through the filter membrane <NUM>, out of the outlet <NUM>, which leads to the delivery opening <NUM> and bore <NUM> of the syringe barrel <NUM>. In those embodiments where the bore <NUM> of the syringe <NUM> is pre-filled with a product concentrate <NUM>, the introduction of the pharmaceutical fluid through the filtration device <NUM> can be followed by a mixing of the pharmaceutical fluid with the concentrate <NUM> to reconstitute to the concentrate <NUM> into a patient deliverable product. Mixing may occur without manual manipulation of the syringe <NUM>, or may be influenced by tipping, shaking, or otherwise imparting forces onto the syringe <NUM> to ensure mixing.

With continued reference to <FIG>, a portion of the stem <NUM> disposed between the outlet <NUM> and the distal end <NUM> of the syringe barrel <NUM> can include a port tube <NUM>. This port tube <NUM> can be identified as a "seal and cut area. " The phrase "seal and cut area" <NUM> pertains to the manner in which the syringe bore <NUM> is sealed and the filtration device <NUM> cut off after introducing fluid to the syringe <NUM> through the filtration device <NUM>. That is, the disclosed arrangement is designed such that after the bore <NUM> receives fluid from the filtration device <NUM>, a sealing mechanism can be employed to seal the stem <NUM> closed in the "seal and cut area," which is between the filter membrane <NUM> and the distal end <NUM> of the syringe <NUM>. Thus, the "seal and cut area" <NUM> in this version is a portion of the stem <NUM> where the filter membrane <NUM> does not reside. Sealing of the "seal and cut area" <NUM> can be achieved with a heat sealer or any other device, including for example clamping a clamp onto the "seal and cut area" <NUM>. Once the stem <NUM> is sealed, the stem <NUM> is cut at a location above the seal but below the filter membrane <NUM> to seal off the bore <NUM> of the syringe <NUM>. Cutting may be achieved with a knife or any other device.

To ensure that the filter membrane <NUM> performed properly, a filter integrity test can be performed on the filter membrane <NUM>. A filter integrity test is facilitated by the arrangement of the "seal and cut area" (second part <NUM>) of the stem <NUM>, which allows for the filtration device <NUM> and, more specifically, the filter membrane <NUM> of the filtration device <NUM> to be separated intact from the remainder of the now-sealed syringe <NUM>. For example, after the stem <NUM> and filter membrane <NUM> are separated from the syringe <NUM>, a filter testing device (not shown) may be pre-programmed or controlled to perform a filter integrity test on the filter membrane <NUM>. Examples of filter integrity tests might include a bubble point test, a pressure degradation test, a water intrusion test, a water flow test, or any suitable test known in the art. A pressure degradation test is a method for testing the quality of a filter either before or after the filter has been used. In the preferred embodiment, the filter membrane <NUM> is tested after the solution passes through the filter membrane <NUM> and into the bore <NUM> of the syringe <NUM>. To perform the filter integrity test using a pressure degradation test procedure, a test head (not shown) engages the stem <NUM> and applies an air pressure of a predetermined value to the inlet <NUM> and filter membrane <NUM>. In one embodiment, the pre-determined value is the pressure where gas cannot permeate the filter membrane <NUM> of an acceptable filter membrane <NUM>. A pressure sensor, or other method of measuring the integrity of the filter membrane <NUM>, is located within the test head and measures the pressure decay or diffusion rate through the filter membrane <NUM>. The results from the integrity test are assessed to determine the quality of the filter membrane <NUM>, and therefore the quality of the solution that previously passed through the filter membrane <NUM> and into the syringe <NUM>. If the pressure sensor measures a decay or a unexpected rate of decay, then the filter membrane <NUM> fails the test and it can be determined that the solution in the syringe <NUM> is unsatisfactory. Alternatively in a bubble point test, the test head gradually increases the pressure applied to the filter membrane <NUM>, and the increase in pressure is measured in parallel with the diffusion rate of the gas through the filter membrane <NUM>. Any disproportionate increase in diffusion rate in relation to the applied pressure may indicate a hole or other structural flaw in the filter membrane <NUM>, and the filter membrane <NUM> would fail the integrity test.

Thus, it can be appreciated that the disclosed arrangement of the "seal and cut area" <NUM> of the syringe system <NUM> of <FIG> advantageously facilitates the filter integrity test, and a determination that the fluid in the syringe <NUM> is either sterile or has the potential of being compromised may be made with a high degree of certainty.

As mentioned above, the stem <NUM> provides an isolated fluid connection between the inlet <NUM> of the filtration device <NUM> and the bore <NUM> of the syringe <NUM>, such that once the fluid is filtered through the filter membrane <NUM>, the filtered fluid passes directly into the sterilized environment of the bore <NUM> of the syringe <NUM>. Hence, after the bore <NUM> of the syringe <NUM> receives the sterilized fluid and the stem <NUM> is sealed and cut, this results in a sealed syringe <NUM>, as illustrated on the right-hand side of <FIG>. Specifically, a tip <NUM> of the port tube <NUM> is heat sealed closed such that the fluid in the bore <NUM> of the syringe <NUM> remains sterile until the syringe <NUM> is opened, punctured, or otherwise compromised. This sealed tip <NUM> of the port tube <NUM> serves as a tip protector for the syringe <NUM>, particularly protecting the distal end <NUM>, until it is removed from the syringe <NUM> by a nurse or other technician to connect to a needle or Luer Activated Device (LAD), for example. That is, to subsequently administer the contents of the syringe <NUM> to a patient, the port tube <NUM> can be removed from the distal end <NUM> of the syringe <NUM> and the syringe <NUM> can be attached to a conventional delivery needle with a standard connection or perhaps directly to a LAD as is known in the art.

As mentioned above, the syringe <NUM> of the syringe system <NUM> of the present disclosure may be pre-filled with a product concentrate <NUM> that requires reconstitution prior to patient administration. The syringe <NUM> of <FIG> can be used to contain product concentrate <NUM> directly in the bore <NUM> of the barrel <NUM>. <FIG> depicts an alternative embodiment of the system <NUM>, however, where the syringe <NUM> includes a dual chamber syringe. Specifically, the system <NUM> includes a syringe <NUM> and a filtration device <NUM> attached to the syringe <NUM>. The system of <FIG> is substantially similar to that of <FIG> so only the differences will be described in any detail. Specifically, the syringe <NUM> includes a syringe barrel <NUM> including a bore <NUM> divided into a first chamber 105a and a second chamber 105b separated by a dual-chamber stopper <NUM>. The first chamber 105a is disposed between the dual-chamber stopper <NUM> and the proximal end <NUM> of the syringe barrel <NUM>. The second chamber 105b is disposed between the dual-chamber stopper <NUM> and the distal end <NUM> of the syringe barrel <NUM>. That is, the dual-chamber stopper <NUM> provides a fluid tight seal with the syringe barrel <NUM> to prevent all fluid communication between the first and second chambers 105a, 105b, until desired. So configured, the first chamber 105a can be pre-filled with a product concentrate <NUM> stored in a sterile environment. When it is desired to reconstitute the concentrate <NUM> and deliver the reconstituted product to a patient, a pharmaceutical fluid can be introduced into the second chamber 105b through the filtration device <NUM> in a manner same as that described above with reference to <FIG>. The stem <NUM> of the filtration device <NUM> can be sealed and cut, the integrity of the filtration device <NUM> can be tested. Then, the dual-chamber stopper <NUM> can be moved to open a flow path between the first and second chambers 105a, 105b, which allows the pharmaceutical fluid in the second chamber 105b to mix with the concentrate <NUM> in the first chamber 105a to reconstitute the final product. Subsequent steps for patient administration can be identical to those suggested above with respect to the system <NUM> of <FIG>.

While the systems <NUM> in <FIG> and <FIG> have included the seal and cut area <NUM> of the stem <NUM> immediately adjacent to the distal end <NUM> of the syringe <NUM> for sealing the syringe <NUM> and removing the filtration device <NUM> for integrity testing, other embodiments can be configured differently. For example, <FIG> depicts an alternative embodiment of a syringe system <NUM> constructed in accordance with the principles of the present disclosure including a syringe <NUM>, a filtration device <NUM> attached to the syringe <NUM>, and a valving arrangement <NUM> disposed between the filtration device <NUM> and the syringe <NUM>. The valving arrangement includes a three-way valve <NUM>, a port tube <NUM>, a fill tube <NUM>, and an administration tube <NUM>. The three-way valve <NUM> includes a first port 141a, a second port 141b, and a third port 141c. The fill tube <NUM> is connected between the first port 141a of the three-way valve <NUM> and the outlet <NUM> of the filtration device <NUM>. The port tube <NUM> is connected between the second port 141b of the three-way valve <NUM> and the delivery opening <NUM> at the distal end <NUM> of the syringe <NUM>. The administration tube <NUM> is connected to the third port 141c of the three-way valve <NUM> and is adapted to be connected to an administration set, for example, during patient administration.

With the configuration illustrated in <FIG>, the bore <NUM> of the syringe <NUM> can again be provided empty or pre-filled with a product concentrate <NUM> as described above. Moreover, the bore <NUM> of the syringe <NUM> may include a single chamber as described with reference to <FIG> or can be a dual-chamber syringe as described with reference to <FIG>. Furthermore, the filtration device <NUM> can be identical to the filtration devices described above. Accordingly, the detail and operation of these components need not be repeated.

When the syringe <NUM> is pre-filled with a product concentrate <NUM> and a pharmacist or other handler is prepared to reconstitute the product for patient delivery, a pharmaceutical fluid can be introduced into the syringe barrel <NUM> via the filtration device <NUM>. First, the three-way valve <NUM> is manipulated to a first configuration which opens fluid communication between the first and second ports 141a, 141b, but closes fluid communication between the second and third ports 141b, 141c. This can be achieved by a manual manipulation of a knob or lever provided on the three-way valve <NUM>, for example. In this first configuration of the three-way valve <NUM>, the filtration device <NUM> is freely open to communicate with the syringe <NUM>. Accordingly, a pharmaceutical fluid can be introduced into the inlet <NUM> of the stem <NUM> of the filtration device <NUM>. This fluid is then sterilized by passing through the filter membrane <NUM>. The sterilized fluid then travels out of the outlet <NUM> of the stem <NUM> and into the fill tube <NUM>, through the first port 141a and out of the second port 141b of the three-way valve <NUM>. Finally, the sterilized fluid passes through the port tube <NUM> and into the bore <NUM> of the syringe <NUM> via the delivery opening <NUM>.

With a desired amount of sterilized pharmaceutical fluid introduced into the syringe <NUM> via the filtration device <NUM>, the stem <NUM> can be sealed and cut at the "seal and cut" area <NUM> located adjacent to the outlet <NUM> of the stem <NUM>. In some versions, because the system <NUM> includes the three-way valve <NUM>, the stem <NUM> may not necessarily need to be sealed before cutting. Sealing the stem <NUM> therefore seals access to the syringe <NUM>, and cutting allows for the filtration device <NUM> to undergo integrity testing as described above. With the stem <NUM> sealed, the pharmaceutical fluid in the syringe <NUM> can be mixed with the product concentrate <NUM> to reach a desired product mixture for patient administration. When ready for administration, the administration tube <NUM> can be connected to an administration set such as a LAD or needle. Then, the three-way valve <NUM> can be manipulated to a second configuration where the second port 141b is fluidly connected to the third port 141c, but not fluidly connected to the first port 141a. Thus, the syringe <NUM> is in fluid communication with the administration tube <NUM> for patient delivery. While the foregoing version of the system in <FIG> has been described as including the step of sealing the stem <NUM> prior to cutting, in alternative versions, the three-way valve <NUM> could be equipped with a third configuration wherein each of the first, second, and third ports 141a, 141b, 141c is closed off from the other ports 141a, 141b, 141c. Thus, when the three-way valve <NUM> occupies this third configuration, the sterility of the product concentrate and pharmaceutical fluid in the bore <NUM> of the syringe <NUM> would be maintained.

While each of the foregoing embodiments of the syringe system <NUM> of the present disclosure have included a single syringe <NUM>, other embodiments can be arranged otherwise. For example, <FIG> depicts one alternative embodiment of a syringe system <NUM> constructed in accordance with the principles of the present disclosure and including a first syringe 102a, a filtration device <NUM>, a second syringe 102b, and a valving arrangement <NUM> providing selective fluid flow communication between the filtration device <NUM> and the first syringe 102a, and between the first syringe 102a and the second syringe 102b. The construct of the filtration device <NUM> and each of the first and second syringes 102a, 102b can be identical to the same components described above such that the details will not be repeated.

The valving arrangement <NUM> includes a first three-way valve 133a, a first port tube 135a, a diverter tube <NUM>, a second three-way valve 133b, a second port tube 135b, and an administration tube <NUM>. In <FIG>, the first and second port tubes 135a, 135b and the diverter tube <NUM> are illustrated schematically with broken lines, but it should be appreciated that these would include conventional tubular fluid lines or something equivalent.

The first three-way valve 133a is disposed between the filtration device <NUM> and the first syringe 102a for selectively controlling fluid communication between the filtration device <NUM> and the first syringe 102a, and also between the first syringe 102a and the second syringe 102b. More specifically, the first three-way valve 133a includes a first port 141a, a second port 141b, and a third port 141c. The first port 141a is connected to the outlet <NUM> of the stem <NUM> of the filtration device <NUM>. The second port 141b is connected to the delivery opening <NUM> at the distal end <NUM> of the first syringe 102a via the first port tube 135a. The third port 141c is connected to the diverter tube <NUM>.

The second three-way valve 133b is disposed between the second syringe 102b and the administration tube <NUM> for selectively controlling fluid communication between the first syringe 102a and the second syringe 102b, and between the second syringe 102b and the administration tube <NUM>. More specifically, the second three-way valve 133b includes a first port 145a, a second port 145b, and a third port 145c. The first port 145a is connected to the diverter tube <NUM>. The second port 145b is connected to the delivery opening <NUM> at the distal end <NUM> of the second syringe 102a via the second port tube 135b. The third port 145c is connected to the administration tube <NUM>.

With the configuration illustrated in <FIG>, the second syringe 102b is configured to contain a product concentrate (not shown in <FIG>), while the first syringe 102a is adapted to receive a sterilized pharmaceutical fluid via the filtration device <NUM> and subsequently mix that pharmaceutical fluid into the second syringe 102b to reconstitute the product concentrate <NUM>.

Accordingly, when a pharmacist or other handler is prepared to reconstitute the product for patient delivery, a pharmaceutical fluid can be introduced into the first syringe 102a via the filtration device <NUM>. First, the first three-way valve 133a is manipulated into a first configuration which opens fluid communication between the first and second ports 141a, 141b, but closes fluid communication between the second and third ports 141b, 141c. This can be achieved by a manual manipulation of a knob or lever <NUM> provided on the first three-way valve 133a, for example. In this first configuration of the first three-way valve 133a, the filtration device <NUM> is freely open to communicate with the first syringe 102a. Accordingly, a pharmaceutical fluid can be introduced into the inlet <NUM> of the stem <NUM> of the filtration device <NUM>. This fluid is then sterilized by passing through the filter membrane <NUM>. The sterilized fluid then travels out of the outlet <NUM> of the stem <NUM>, through the first port 141a and out of the second port 141b of the first three-way valve 133a. Finally, the sterilized fluid passes through the first port tube 135a and into the bore <NUM> of the first syringe 102a.

With a desired amount of sterilized pharmaceutical fluid introduced into the first syringe 102a via the filtration device <NUM>, the stem <NUM> can be sealed and cut at the "seal and cut" area <NUM> located adjacent to the outlet <NUM> of the stem <NUM>. Sealing the stem <NUM> therefore seals access to the first syringe 102a, and cutting allows for the filtration device <NUM> to undergo integrity testing as described above.

Next, it is necessary to move the sterilized pharmaceutical fluid from the first syringe 102a to the second syringe 102b to reconstitute the product concentrate container therein. To achieve this, the first three-way valve 133a can be manipulated to a second configuration where the second port 141b is fluidly connected to the third port 141c, but not fluidly connected to the first port 141a. Additionally, the second three-way valve 133b can be manipulated into a first configuration where its first port 145a is in fluid communication with its second port 145b, but not with the third port 145c. Thus, with the first three-way valve 133a in its second configuration and the second three-way valve 133b in its first configuration, the first syringe 102a is in fluid communication with the diverter tube <NUM>, which is in fluid communication with the second syringe 102b. So configured, a user can force the sterilized pharmaceutical fluid from the first syringe 102a using the plunger assembly <NUM> in a known manner, through the first three-way valve 133a, through the diverter tube <NUM>, through the second three-way valve 133b, and into the second syringe 102b to mix with the product concentrate. To the extent necessary, a user may further desire to force the mixture back and forth between the first and second syringes 102a, 102b to ensure complete and thorough reconstitution of the product.

Once the product is sufficiently reconstituted it can be stored in the second syringe 102b and the second three-way valve 133b can be manipulated into a second configuration where the second port 145b is in fluid communication with the third port 145c, but not the first port 145a. So configured, the second syringe 102b is in fluid communication with the administration tube <NUM>, which again can be connected to an administration set, a LAD, or a needle for example, for patient administration. Manual depression of the plunger assembly <NUM> on the second syringe 102b can thus force the mixed product out of the second syringe 102b to the patient.

As with the embodiment in <FIG>, the first three-way valve 133a of the system of <FIG> could be equipped with a third configuration wherein each of the first, second, and third ports 141a, 141b, 141c is closed off from the other ports 141a, 141b, 141c. Thus, when the first three-way valve 133a occupies this third configuration, the sterility of the product concentrate and pharmaceutical fluid in the bore <NUM> of the first syringe 102a would be maintained. This could be an alternative to sealing the stem <NUM> prior to cutting the filtration device <NUM> off of the system <NUM> for testing.

<FIG> depict another embodiment of a syringe system <NUM> constructed in accordance with the principles of the present disclosure and including a first syringe 1102a, a filtration device <NUM>, a second syringe 1102b, and a valving arrangement <NUM> providing selective fluid flow communication between the filtration device <NUM> and the first syringe 1102a, and between the first syringe 1102a and the second syringe 1102b. The construct of the first and second syringes 1102a, 1102b can be identical to any of the same components described above such that the details will not be repeated.

The valving arrangement <NUM> includes a three-way valve <NUM> with a single body defining a first port 1135a, a second port 1135b, and a third port 1135c. Internally, the three-way valve <NUM> can define a Y-shaped passageway <NUM> including a first path 1139a, a second path 1139b, and a third path 1139c. The first port 1135a is coupled to and in fluid communication with the filtration device <NUM>, the second port 135b is coupled to and in fluid communication with the first syringe 1102a, and the third port is coupled to and in fluid communication with the second syringe 1102b. As also depicted, the three-way valve <NUM> includes a switch <NUM> operably coupled to a valve member (not shown) disposed inside of the body of the three-way valve <NUM>. The switch <NUM> can be manually manipulated between a first position depicted in <FIG>, wherein the three-way valve <NUM> occupies a first configuration, and a second position depicted in <FIG>, wherein the three-way valve <NUM> occupies a second configuration. In the first position of the switch and <NUM> and first configuration of the valve <NUM>, the first syringe 1102a is in fluid communication with the filtration device <NUM> via the first and second paths 1135a, 1135b, and not in fluid communication with the second syringe 1102b. In the second position of the switch <NUM> and the second configuration of the valve <NUM>, the first syringe 1102a is in fluid communication with the second syringe 1102b via the second and third paths 1135b, 1135c, and not in communication with the filtration device <NUM>.

With the configuration illustrated in <FIG>, the second syringe 1102b is initially configured to contain a product concentrate (not shown), while the first syringe 1102a is adapted to receive a sterilized pharmaceutical fluid via the filtration device <NUM> and subsequently mix that pharmaceutical fluid into the second syringe 1102b to reconstitute the product concentrate in a manner similar to that described above in reference to <FIG>, for example.

Accordingly, when a pharmacist or other handler is prepared to reconstitute the product for patient delivery, a pharmaceutical fluid can be introduced into the first syringe 1102a via the filtration device <NUM>. First, the first three-way valve <NUM> is manipulated into the first position (<FIG>) which opens fluid communication between the first syringe 1102a and the filtration device <NUM>. This can be achieved by a manual manipulation of the switch, as mentioned above. Accordingly, a pharmaceutical fluid can be introduced into an inlet <NUM> of the filtration device <NUM>. This fluid is then sterilized by passing through a filter membrane of the filtration device <NUM>. The sterilized fluid then travels out of an outlet <NUM> of the filtyration device <NUM>, through the first port 1135a and out of the second port 1135b of the three-way valve <NUM>. Finally, the sterilized fluid passes directly into the first syringe 1102a. As the first syringe 1102a is filled, a user may slowly withdraw the plunger from the syringe 1102a to accommodate receipt of the fluid.

With a desired amount of sterilized pharmaceutical fluid introduced into the first syringe 1102a, the filtration device <NUM> can be sealed and cut in a manner identical to that described above with other embodiments, and finally integrity tested to ensure the sterility of the fluid in the first syringe 1102a. The device with the filtration device <NUM> removed is illustrated in <FIG>.

Next, it is necessary to move the sterilized pharmaceutical fluid from the first syringe 1102a to the second syringe 1102b to reconstitute the product concentrate contained therein. To achieve this, the switch <NUM> on the three-way valve <NUM> can be manipulated to the second position, which is shown in <FIG>. Here, the first syringe 1102a is in fluid communication with the second syringe 1102b via the third port 1135c, but not with the first port 1135a. In fact in some versions, the first port 1135a is sealed off because in order to remove the filtration device <NUM> for integrity testing, the filtration device <NUM> is sealed and cut a at a location adjacent to the first port 1135a. As such, in some versions, with the switch <NUM> in the second position, the first syringe 1102a may continue to be in fluid communication with the first port 1135a, but the first port 1135a is sealed closed so no fluid can pass therethrough. Instead, all fluid leaving the first syringe 1102a will flow to the second syringe 1102b.

So configured, a user can force the sterilized pharmaceutical fluid from the first syringe 1102a using the plunger in a known manner, through the three-way valve <NUM>, and into the second syringe 1102b to mix with the product concentrate. This can be seen with the arrows presented on <FIG>, where the plunger on the first syringe 1102a is depressed and the plunger on the second syringe 1102b is withdrawn. To the extent necessary, a user may further desire to force the mixture back and forth between the first and second syringes 1102a, 1102b, as illustrated in <FIG>, to ensure complete and thorough reconstitution of the product. During this mixing between the first and second syringes 1102a, 1102b, the switch <NUM> remains in the second position.

Once the product is sufficiently reconstituted it can be stored in the second syringe 1102b, as illustrated in <FIG>. Then, for patient administration, the second syringe 1102b can be removed from the three-way valve <NUM> and a delivery needle <NUM> can be attached, as illustrated in <FIG>.

As mentioned, the filtration device <NUM> of the various systems <NUM> of the present disclosure are capable of sterilizing fluid as it passes through the filter membrane <NUM>. The filtration device <NUM> and filter membrane <NUM> can take various forms and the present disclosure is not necessarily limited to any one form.

For example, <FIG> illustrates one embodiment of a filtration device <NUM> for use with any of the syringe systems <NUM> describe above in <FIG> and <FIG>. The filtration device <NUM> can include a hollow fiber membrane <NUM> with one sealed end <NUM> and one open inlet end <NUM>. The sealed end <NUM> can be capped or it may be sealed with a heat seal, an adhesive, or some other means. A plurality of pores <NUM> along the surface <NUM> of the filter membrane <NUM> allow a pharmaceutical fluid that entered the filter membrane <NUM> at the open inlet end <NUM> to exit the filter membrane <NUM>. In one version, the stem <NUM> surrounds the filter membrane <NUM> in a generally concentric configuration so filtered pharmaceutical fluid exiting the filter membrane <NUM> is contained within the stem <NUM> and ultimately passed out of the outlet <NUM> of the filtration device <NUM>.

As depicted in <FIG>, a hollow connector <NUM> can be used to secure the stem <NUM> and the filter membrane <NUM> together. The open inlet end <NUM> of the filter membrane <NUM> is sealingly connected to an open outlet end <NUM> of the hollow connector <NUM>. The connection may be achieved by gluing the open inlet end <NUM> of the filter membrane <NUM> to the open outlet end <NUM> of the connector <NUM> with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector <NUM> such as cyclohexanone. In the version depicted, the open outlet end <NUM> of the connector <NUM> comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet end <NUM> of the filter membrane <NUM>. As such, an outer diameter of the open outlet end <NUM> of the connector <NUM> is substantially similar to or slightly smaller than an inner diameter of the open inlet end <NUM> of the filter membrane <NUM>. In some versions, the open inlet end <NUM> of the filter membrane <NUM> may be welded to the open outlet end <NUM> of the connector <NUM> by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet end <NUM> of the filter membrane <NUM> to partially melt it), laser welding if the hollow connector <NUM> is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filter membrane <NUM> may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector <NUM>. Other designs and configurations for connecting the filter membrane <NUM> to the connector <NUM> are intended to be within the scope of the present disclosure.

The hollow connector <NUM> further includes a fluid inlet <NUM>. A pharmaceutical fluid can be fed via a connected fluid supply line, for example, into the fluid inlet <NUM> of the hollow connector <NUM>. In some versions, the fluid inlet <NUM> can include a Luer type fitting or other standard medical fitting. The pharmaceutical fluid can then travel through the hollow connector <NUM> and exit into the filter membrane <NUM> through the open outlet end <NUM> of the hollow connector <NUM>. The hollow connector <NUM> also includes a sealing surface <NUM> to which the stem <NUM> is attached. The sealing surface <NUM> in this version is cylindrical and has a diameter larger than a diameter of the open outlet end <NUM>, and is disposed generally concentric with the open outlet end <NUM>. In fact, in this version, the outer diameter of the sealing surface <NUM> is generally identical to or slightly smaller than an inner diameter of the stem <NUM>. So configured, the stem <NUM> receives the sealing surface <NUM> and extends therefrom to surround and protect the filter membrane <NUM> without contacting the surface <NUM> of the filter membrane <NUM>. The stem <NUM> can be fixed to the sealing surface <NUM> with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem <NUM> receives the pharmaceutical solution after it passes through the pores <NUM> in the filter membrane <NUM>. From there, the now filtered solution passes out of the outlet <NUM> of the stem <NUM>.

<FIG> illustrate an alternative hollow connector <NUM>, similar to connector <NUM>, for securing the stem <NUM> and the hollow fiber filter membrane <NUM> of <FIG> together. The connector <NUM> includes an open outlet end <NUM> carried by a stem structure that extends in a first direction from a bearing plate <NUM> and is adapted to be sealingly connected to the open inlet end <NUM> of the filter membrane <NUM>. The connection may be achieved by gluing the open inlet end <NUM> of the filter membrane <NUM> to the open outlet end <NUM> of the connector <NUM> with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector <NUM> such as cyclohexanone. In the version depicted, the stem structure of the open outlet end <NUM> of the connector <NUM> comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet end <NUM> of the filter membrane <NUM>. As such, an outer diameter of the open outlet end <NUM> of the connector <NUM> is substantially similar to or slightly smaller than an inner diameter of the open inlet end <NUM> of the filter membrane <NUM>. In some versions, the open inlet end <NUM> of the filter membrane <NUM> may be welded to the open outlet end <NUM> of the connector <NUM> by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet end <NUM> of the filter membrane <NUM> to partially melt it), laser welding if the hollow connector <NUM> is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filter membrane <NUM> may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector <NUM>. Other designs and configurations for connecting the filter membrane <NUM> to the connector <NUM> are intended to be within the scope of the present disclosure.

The hollow connector <NUM> further includes a fluid inlet <NUM>, which is also a stem structure, extending in a second direction (opposite the first direction) from the bearing plate <NUM>. A pharmaceutical fluid can be fed via a connected fluid supply line, for example, into the fluid inlet <NUM> of the hollow connector <NUM>. In some versions, the fluid inlet <NUM> can include a Luer type fitting or other standard medical fitting. The pharmaceutical fluid can then travel through the hollow connector <NUM> and exit into the filter membrane <NUM> through the open outlet end <NUM> of the hollow connector <NUM>.

The hollow connector <NUM> also includes a sealing surface <NUM> to which the stem <NUM> is attached. The sealing surface <NUM> in this version is a cylindrical shroud extending from the bearing plate <NUM> in the first direction and has a diameter larger than a diameter of the open outlet end <NUM>. The sealing surface <NUM> is disposed generally concentric with the open outlet end <NUM>. As such, in this embodiment, the shroud of the sealing surface <NUM> surrounds the stem structure of the open outlet end <NUM> such that an annular gap <NUM> resides between the two. In fact, in this version, the outer diameter of the sealing surface <NUM> is generally identical to or slightly smaller than an inner diameter of the stem <NUM>. So configured, the sealing surface <NUM> of the connector <NUM> can be received by the stem <NUM> such that the stem <NUM> extends therefrom to surround and protect the filter membrane <NUM> without contacting the surface <NUM> of the filter membrane <NUM>. The stem <NUM> can be fixed to the sealing surface <NUM> with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem <NUM> receives the pharmaceutical fluid after it passes through the pores <NUM> in the filter membrane <NUM>. From there, the now filtered fluid passes out of the outlet <NUM> of the stem <NUM> and to the syringe <NUM>.

While the foregoing version of the filter membrane <NUM> has been described as including a single filter membrane <NUM>, in other embodiments within the scope of the present disclosure, the filter membrane <NUM> may include multiple filter membranes <NUM>. A few nonlimiting examples of multiple membrane filters will be discussed below.

In one version of the foregoing assembly of <FIG>, and as mentioned, the stem <NUM> includes an inner diameter that is larger than an outer diameter of the filter membrane <NUM>, and the stem <NUM> includes a longitudinal dimension that is larger than a longitudinal dimension of the filter membrane <NUM>. As such, when the stem <NUM> and filter membrane <NUM> are assembled onto the connector <NUM>, the filter membrane <NUM> resides entirely within (i.e., entirely inside of) the stem <NUM> and a gap exists between the inner sidewall of the stem <NUM> and the outer sidewall of the filter membrane <NUM>. As such, fluid passing into the filter membrane <NUM> passes out of the plurality of pores <NUM> and flows without obstruction through the gap and along the inside of the stem <NUM>. In some versions, the stem <NUM> can be a flexible tube, a rigid tube, or can include a tube with portions that are flexible and other portions that are rigid. Specifically, in some versions, a stem <NUM> with at least a rigid portion adjacent to the filter membrane <NUM> can serve to further protect the filter membrane <NUM> and/or prevent the filter membrane <NUM> from becoming pinched or kinked in a flexible tube. In other versions, such protection may not be needed or desirable. In one embodiment, the stem <NUM> has an internal diameter in the range of approximately <NUM> to approximately <NUM>, and a longitudinal dimension in the range of approximately <NUM> to approximately <NUM>. In one embodiment, the internal diameter of the stem <NUM> is about <NUM> to about <NUM> larger than the outer diameter of the filter membrane <NUM>. And, the filter membrane <NUM> has an outer diameter in the range of approximately <NUM> to approximately <NUM>, a longitudinal dimension in the range of approximately <NUM> to approximately <NUM>, and a wall thickness in the range of approximately <NUM> to approximately <NUM>. Furthermore, in one version each of the plurality of pores <NUM> in the filter membrane <NUM> have a diameter less than or equal to approximately <NUM> microns. In some versions, each pore has a diameter less than or equal to a value in a range of approximately <NUM> microns to approximately <NUM> microns, for instance, approximately <NUM> to approximately <NUM> microns. In some versions, each pore has a diameter that is less than or equal to approximately <NUM> microns. In some versions, each pore has a diameter that is less than or equal to a value in a range of approximately <NUM> microns to approximately <NUM> microns. In some versions, each pore has a diameter that is less than or equal to a value in a range of approximately <NUM> microns to approximately <NUM> microns. These pore sizes coupled with the disclosed geometrical dimension of the stem <NUM> and filter membrane <NUM> ensure acceptable flow rates through the filter membrane <NUM> for filling syringes with patient injectable solutions such as sterile water, sterile saline, etc. In other versions, any or all of the dimensions could vary depending on the specific application.

Suitable materials for the filter membrane <NUM> can include polyolefins (e.g., PE, PP), polyvinylidene fluoride, polymethylmethacrylate, polyacrylonitrile, polysulfone, and polyethersulfone. In some embodiments within the scope of the present disclosure, the filter membrane <NUM> may be comprised of a blend of polysulfone or polyethersulfone and polyvinylpyrrolidone. In other embodiments within the scope of the present disclosure, the filter membrane <NUM> can include a polymer containing cationic charges, e.g. polymers bearing functional groups like quaternary ammonium groups. A suitable example for such polymers is polyethyleneimine. The filter membrane <NUM> may be manufactured by known techniques including, e.g., extrusion, phase inversion, spinning, chemical vapor deposition, 3D printing, etc. Suitable materials for the stem <NUM> include PVC, polyesters like PET, poly(meth)acrylates like PMMA, polycarbonates (PC), polyolefins like PE, PP, or cycloolefin copolymers (COC), polystyrene (PS), silicone polymers, etc..

Additional details regarding some possible versions of the filter and the specific construction of the membrane, for example, can be found in European Patent Application No. <CIT>, and additionally in <CIT>.

Thus far, the hollow fiber membrane <NUM> in <FIG>, for example, has been described as being located within the stem <NUM>. In other embodiments, the filter membrane <NUM> may include its own housing or other support structure, which is coupled to the stem <NUM> either in place of the connector <NUM> in <FIG> or connector <NUM> in <FIG>, or at a location between two portions of the stem <NUM>.

For example, <FIG> is a front view of a filter assembly <NUM> for a syinge (not pictured) having a single U-shaped hollow fiber filter membrane <NUM> contained within a filter body <NUM>. The filter membrane <NUM> is secured to a filter membrane housing <NUM> in the U-shaped configuration with an adhesive (i.e., a UV curing acrylic adhesive), an epoxy, welding, bonding, or other means. The filter membrane housing <NUM> is connected to the filter body <NUM> at an outlet portion <NUM> of the filter body <NUM>. An inlet portion <NUM> is sealably connected to the outlet portion <NUM> of the filter body <NUM> at a joint or other seam. The inlet portion <NUM> of the filter body <NUM> has an inlet <NUM> by which a pharmaceutical fluid may enter the filter assembly <NUM>. The pharmaceutical fluid then enters the filter membrane <NUM> through a plurality of pores <NUM>, travels through the filter membrane <NUM>, exits the filter membrane <NUM> at filter membrane outlets <NUM>, and exits the filter body <NUM> at filter outlet <NUM>. The filter outlet <NUM> may then be connected to the syringe (not pictured) via the stem <NUM> of a syringe (not pictured). In <FIG>, the flow of fluid through the assembly <NUM> has been described as moving from the inlet <NUM> of the inlet portion <NUM> to the outlet <NUM> of the outlet portion <NUM>. However, the same assembly <NUM> could be used in the opposite direction such that fluid enters the outlet1018 of the outlet portion <NUM> and exits the inlet <NUM> of the inlet portion <NUM>. In this alternative configuration, fluid would first enter the inlet <NUM>, pass into the filter membrane <NUM> at the filter membrane outlets <NUM>, and exit through the pores <NUM> and finally the inlet <NUM>.

<FIG> is an alternate embodiment of the filter assembly <NUM> depicted in <FIG>. In <FIG>, the filter <NUM> includes two U-shaped hollow fiber filter membranes <NUM> are secured to a filter membrane housing <NUM> in the U-shaped configuration with an adhesive (i.e., a UV curing acrylic adhesive), an epoxy, welding, bonding, or some other means. The filter membranes <NUM> and filter membrane housing <NUM> are contained within a filter body <NUM> having an inlet portion <NUM> with inlet <NUM> sealably connected to an outlet portion <NUM> having filter outlet <NUM>. In other embodiments, a filter may include more than two U-shaped hollow fiber filter membranes arranged as depicted in <FIG>. In <FIG>, like in <FIG>, the flow of fluid through the assembly <NUM> has been described as moving from the inlet portion <NUM> to the outlet portion <NUM>. However, the same assembly <NUM> could be used in the opposite direction such that fluid enters the outlet portion <NUM> and exits the inlet portion <NUM> as described above relative to <FIG>.

<FIG> is a further alternative filter assembly. Specifically, in <FIG>, a plurality of linear membrane filters <NUM> are secured directly together in a parallel side-by-side configuration for what can be referred to as a fiber bundle. The filters <NUM> in <FIG> can be secured together with adhesive (i.e., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. In other versions, the plurality of filters <NUM> can be manufactured together as one piece by way of any of the manufacturing techniques described above.

<FIG> provides another alternative in which a securement device <NUM> includes a number of blocks defining a plurality of grooves <NUM> identical to the number of hollow fiber membrane filters <NUM>. The blocks of the securement device <NUM> may be sandwiched together and used to hold the plurality of hollow fiber membrane filters <NUM> in the side-by-side configuration. The securement device <NUM> depicted in <FIG> allows for two sets of the hollow fiber membrane filters <NUM> of <FIG> to be stacked relative to each other. The fiber bundle including the membrane filters <NUM> and the securement device <NUM> may be placed in a filter body, such as that discussed with respect to <FIG>.

<FIG> is an isometric view of another version of a fiber bundle <NUM> for a syringe (not pictured) having a plurality of parallel hollow fiber membrane filters <NUM> similar to <FIG>, but wherein the parallel filters <NUM> are arranged in a circular pattern by a circular holder <NUM>. The fiber bundle <NUM> may be placed in a filter body, such as that discussed with respect to <FIG>.

<FIG> and <FIG> illustrate two additional devices for coupling fiber bundles to a stem in accordance with the present disclosure. <FIG> discloses a connector <NUM> for connecting a three-fiber bundle to a stem. Specifically, the connector <NUM> includes a first hollow body 866a and a second hollow body 866b. The first body 866a includes a solution inlet <NUM>, which is a stem structure, extending from a bearing plate <NUM>. A pharmaceutical fluid can be fed via a connected fluid supply line, for example, into the fluid inlet <NUM> of the first hollow body 866a of the connector <NUM>. In some versions, the fluid inlet <NUM> can include a Luer type fitting or other standard medical fitting.

The hollow connector <NUM> also includes a sealing surface <NUM> to which the stem <NUM> is attached. The sealing surface <NUM> in this version is a cylindrical shroud extending from the bearing plate <NUM> in a direction opposite to a direction of extension of the fluid inlet <NUM>. The sealing surface <NUM> is disposed generally concentric with the fluid inlet <NUM>. As such, in this embodiment, the shroud of the sealing surface <NUM> defines a cylindrical cavity (not shown in the drawings) for receiving a portion of the second hollow body 866b of the connector <NUM>.

The second hollow body 866b, as depicted, includes a support plate <NUM> and three open outlet ends <NUM> extending from the support plate <NUM>. Additionally, the support plate <NUM> includes an outer diameter that is essentially the same as or slightly smaller than an inner diameter of the cavity of the shroud of the sealing surface <NUM> such that when assembled, the support plate <NUM> is positioned into the cavity. In one version, the support plate <NUM> includes a seal member <NUM> around its periphery to form a fluid tight seal with the inner surface of the shroud of the sealing surface <NUM> when inserted into the cavity. Friction, adhesive, or some other means may retain the support plate <NUM> in connection with the shroud of the sealing surface <NUM>.

As mentioned, the second body 866b includes three open outlet ends <NUM> extending from the support plate <NUM>. Each open outlet end <NUM> is adapted to be sealingly connected to an open inlet end <NUM> of one of three filters <NUM>. The connection may be achieved by gluing open inlet ends <NUM> of the filters <NUM> to the open outlet ends <NUM> with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector <NUM> such as cyclohexanone. In the version depicted, the stem structure of the open outlet ends <NUM> of the connector <NUM> comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet ends <NUM> of the filters <NUM>. As such, an outer diameter of the open outlet ends <NUM> is substantially similar to or slightly smaller than an inner diameter of the open inlet ends <NUM> of the filters <NUM>. In some versions, the filters <NUM> may be welded to the open outlet ends <NUM> of the connector <NUM> by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet ends <NUM> of the filters <NUM> to partially melt it), laser welding if the hollow connector <NUM> is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filters <NUM> may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector <NUM>. Other designs and configurations for connecting the filters <NUM> to the open outlet ends <NUM> are intended to be within the scope of the present disclosure.

Finally, as with previously described embodiments, the sealing surface <NUM> of the connector <NUM> can be received by the stem <NUM> such that the stem <NUM> extends therefrom to surround and protect the filters <NUM> without contacting the surfaces <NUM> of the filters <NUM>. The stem <NUM> can be fixed to the sealing surface <NUM> with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem <NUM> receives the pharmaceutical solution after it passes through the pores <NUM> in the filter membrane <NUM>. From there, the now filtered solution passes out of the outlet <NUM> of the stem <NUM>.

<FIG> discloses a connector <NUM> for connecting a seven-fiber bundle to a stem. Specifically, the connector <NUM> includes a first hollow body 966a and a second hollow body 966b that can be connected to the first hollow body 966a with an adhesive or via other means. The first body 966a includes a solution inlet <NUM>, which is a stem structure, extending from a bearing plate <NUM>. A pharmaceutical fluid can be fed via a connected fluid supply line, for example, into the fluid inlet <NUM> of the first hollow body 966a of the connector <NUM>. In some versions, the fluid inlet <NUM> can include a Luer type fitting or other standard medical fitting.

The second hollow body 966b, as depicted, includes a hollow cylindrical support collar <NUM> in which seven hollow fiber membrane filters <NUM> can be disposed parallel to each other, as shown in <FIG>. In one version, the support collar <NUM> can include a support plate <NUM> carrying seven open outlet ends <NUM> extending into the collar <NUM> for connecting to the filters <NUM> in a manner similar to that described above regarding <FIG>. The connection may be achieved by gluing the filters <NUM> to the open outlet ends <NUM> with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector <NUM> such as cyclohexanone. In the version depicted, the stem structure of the open outlet ends <NUM> of the connector <NUM> comprises a hollow cylindrical member that fits inside of and is fixed to the filters <NUM>. As such, a diameter of the open outlet ends <NUM> is substantially similar to or slightly smaller than an inner diameter of the filters <NUM>. In some versions, the filters <NUM> may be welded to the open outlet ends <NUM> of the connector <NUM> by, for example, heat welding (e.g., introducing a hot conical metal tip into the filters <NUM> to partially melt it), laser welding if the hollow connector <NUM> is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filters <NUM> may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector <NUM>. Other designs and configurations for connecting the filters <NUM> to the open outlet ends <NUM> are intended to be within the scope of the present disclosure.

Finally, the collar <NUM> of this embodiment includes a sealing surface <NUM> that can be received by the stem <NUM> such that the stem <NUM> extends therefrom. The stem <NUM> can be fixed to the sealing surface <NUM> with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem <NUM> receives the pharmaceutical fluid after it passes through the pores <NUM> in the filters <NUM>. From there, the now filtered fluid passes out of the outlet <NUM> of the stem <NUM>.

From the foregoing, it can be seen that various filtering arrangements can serve the principles of the present disclosure including introducing fluid to the syringe system <NUM> in a sterilized manner. This fluid is then often mixed with a concentrate (e.g., medicament, drug, nutrient, etc.).

While the filtration device <NUM> throughout the disclosure has been described as including a hollow fiber filter or a plurality of hollow fiber filters, in other versions of the disclosure the filtration device <NUM> can include other forms of filter assemblies including, for example, a flat filter carried within a housing. The flat filter could have any of the same characteristics as the hollow fiber filter described herein, only its geometrical shape and configuration would be different.

Claim 1:
A method of reconstituting a medicinal or nutritional product, the method comprising:
providing a syringe (<NUM>) comprising a syringe barrel (<NUM>) having a proximal end (<NUM>) defining a barrel opening (<NUM>), a distal end (<NUM>) defining a delivery opening (<NUM>), a bore (<NUM>) extending between the proximal end and the distal end, a stopper (<NUM>) disposed in the bore of the syringe barrel, and a product concentrate (<NUM>) disposed in the bore between the stopper and the distal end;
connecting an outlet (<NUM>) of a filtration device (<NUM>) to the delivery opening of the syringe barrel, the filtration device comprising a stem (<NUM>) and a filter membrane (<NUM>) disposed in line with the stem, the filter membrane optionally having a plurality of pores (<NUM>) each with a nominal pore size in a range of approximately <NUM> to approximately <NUM>; and
fluidly coupling a source of a pharmaceutical fluid to an inlet (<NUM>) of the filtration device and introducing the pharmaceutical fluid into the filtration device to pass through the filter membrane and into the bore of the syringe barrel such that a sterilized pharmaceutical fluid can be mixed with the product concentrate in the bore.