Aseptic filter vent valve and port for integrity testing

The present disclosure relates to a filter capsule that supports direct integrity testing of an internal filter element. The filter capsule includes a filter housing having an inlet port, an outlet port, a passage running longitudinally between the inlet port and outlet port and holding a filter element, and an aseptic vent assembly. The filter housing also includes an integrity test assembly that can be used as a direct connection for integrity testing hardware, as opposed to upstream of the filter capsule. In one embodiment, the integrity test assembly comprises a body having a bore formed through its interior and a movable plunger within the bore. The plunger includes a handle to move the plunger between a closed position and an open position. Various seals between the plunger and the bore form a fluid tight seal between various portions of the plunger and the bore.

FIELD OF THE DISCLOSURE

The present disclosure generally relates to filtration of gas and liquid media. In particular, the present disclosure relates to a filtration device comprising an integrated aseptic valve and port for integrity testing.

BACKGROUND

High purity filtration of aqueous media, such as in the fields of biotechnology, chemistry, electronics, pharmaceuticals, and the food and beverage industries requires the use of sophisticated filter modules that are not only capable of a high degree of separation, but that will tend to prevent contamination of the environment, of the medium to be filtered, and of the resulting filtrate. This is designed to prevent unwanted, often dangerous organisms, such as bacteria or viruses, as well as environmental contaminants, such as dust, dirt, and the like from entering into the process stream and end product. Similarly, filter capsules help to prevent contamination of a highly validated clean room due to exposure from the contents of the process stream. To ensure sterility, it would be desirable to have a completely sealed system. However this is not always possible with the processes that take place in production.

To ensure sterility of the filtrate, filter modules must maintain their integrity throughout the filtration process. Accordingly, integrity testing of sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. General guidelines require integrity testing of filter modules after filtration, and recommend integrity testing of filter modules prior to use. Typically this testing is initially performed after sterilization to ensure that the filter is not damaged; accordingly, care must be taken to ensure that sterility of the filter, and thus the filtrate, is not compromised. Post-processing, the filter integrity test may be performed again either in situ or separated from the assembly and tested in a separate room to determine whether the filter was compromised during use. This information can be used to alert operators to a potential problem immediately after processing, and to quickly take corrective action. Further, FDA guidelines require that integrity testing documentation be included with batch product records.

There are a variety of methods of integrity testing, including the diffusion test and the pressure hold test. The diffusion test measures the rate of gas transfer through a filter to be tested. At differential gas pressures below the bubble point, gas molecules migrate through water-filled pores of a wetted membrane following Fick's Law of Diffusion. The gas diffusional flow rate for a filter is proportional to the differential pressure and the total surface area of the filter. At a pressure approximately 80% of the minimum bubble point, the gas which diffuses through the filter membrane can be measured to determine a filter's integrity. A diffusional flow reading exceeding a value stated by the manufacturer indicates a variety of problems, including an incorrect temperature, wrong pore size, incompletely wetted membrane, non-integral membrane or seal, or inadequate stabilization time. The pressure hold test, also known as the pressure decay or pressure drop test, is a variation of the diffusion test. In this test, a highly accurate gauge is used to monitor upstream pressure changes due to gas diffusion through the filter. Because there is no need to measure gas flow downstream of the filter, any risk to downstream sterility is eliminated.

Typically, integrity testing is performed with specialized integrity testing hardware. Examples include the Integritest® 4 Series Automated Filter Integrity Test Instrument (commercially available from EMD Millipore Corporation) and the Sartocheck® line of filter integrity testing systems (commercially available from Sartorius Corporation). To perform integrity testing of a filter module installed in an assembly, an end user would attach the integrity testing hardware to a secondary aseptic connection located upstream of the filter capsule. To ensure that no contaminants are introduced, the secondary aseptic connection may comprise a Lynx ST Valve (commercially available from EMD Millipore Corporation) and an aseptic phobic filter between the capsule filter and the integrity testing equipment. Using clamps or other means, the end user isolates the desired integrity testing flow path from other components of the assembly and activates the integrity testing equipment, which performs the integrity test and provides the result.

However, integrity testing is sensitive to a variety of factors related to the composition and complexity of an assembly. A typical flow path for integrity testing on an assembly may include various tubing, flex points, T-connections, gaskets, and other components between the integrity test hardware and a filter capsule. Integrity testing may stress these components, leading to false integrity test failures that are a result of loose connections or compression. Thus, it may not be clear whether the integrity test is testing the filter or the isolated flow path. Further, including new connections to support integrity testing hardware presents new failure points and increases the complexity of the system. Moreover, attaching integrity testing hardware to components downstream of the filter increases the likelihood of contamination.

In light of the above, a need exists for an improved device, system, and method for performing integrity testing of filter assemblies.

SUMMARY

The problems of the prior art are addressed by a novel design for a filter capsule containing a filter element. The filter capsule includes an integrity test assembly comprising an aseptic port and valve on the upstream side of the capsule that can be used to perform an integrity test of an internal filter element. In this way, integrity testing is performed as close as possible to the filter element, and problems associated with performing integrity testing farther upstream or downstream of the filter are minimized or eliminated. Further, the integrity test assembly is an aseptic connection that can withstand multiple actuations without compromising sterility.

In one embodiment, a filter capsule that supports direct integrity testing of an internal filter element includes a filter housing having an inlet port, an outlet port spaced from the inlet port, a passage or housing volume between the inlet port and the outlet port and containing a filter element. The filter capsule further includes a vent assembly and an integrity test assembly. In some embodiments, the vent assembly and integrity test assembly present an aseptic connection. In certain embodiments, the integrity test assembly further comprises a body having a bore formed through at least a portion of its interior and having a cam slot. A movable plunger contained with the bore includes a cam contained with the cam slot and an actuator such as a handle to move the plunger between a closed position and an open position. One or more seals are located between the plunger and the bore to form a fluid tight seal. In certain embodiments, there are multiple seals, including a shut-off seal, an outside seal, and a sterility seal.

In certain embodiments, a disposable or single use filtration assembly includes an integrity testing device, a source of fluid to be processed, a holding container, and a filtration device. The filtration device includes an inlet port in fluid communication with said source of fluid and an outlet port in fluid communication with said holding container. The filtration device further includes a filter element, an aseptic vent port, and an aseptic integrity test assembly. In some embodiments, the integrity test assembly includes a body having a bore formed through a portion of its interior, a plunger within the bore, an actuator such as a handle to move the plunger between a closed position and an open position. The integrity test assembly further includes a shut-off seal, an outside seal, and a sterility seal. Integrity testing of the filtration device and filter element may be performed by attaching the integrity testing hardware to the integrity test assembly and then actuating the integrity test assembly.

In yet another embodiment, a method for performing an integrity test of a filter element via a port of a filter capsule includes attaching a gas line to an integrity test assembly on a filter capsule, pressuring the filter capsule, measuring a resulting pressure change, and determining whether the pressure change indicates that a filter contained within the filter capsule has been compromised. In one embodiment, the pressure change is measured downstream of the filter element; in certain embodiments, the pressure change is measured upstream.

DETAILED DESCRIPTION

FIG. 1illustrates an example of a filtration assembly10for aseptically processing a fluid solution. The filtration assembly10may either be disposable (i.e., single use) or reusable. The filtration assembly10includes a secure sterile connection12for attachment to a container holding a solution to be processed. Once the sterile connection12is actuated, solution flows through tubing14or the like to a filter capsule16. In this example, the filter capsule16contains a sterilizing filter that effectively removes viruses, bacteria, and any other contaminants from the solution. For example, the filter capsule16may be an Opticap disposable capsule sterilizing filter, commercially available from EMD Millipore Corporation. Excess gas and liquid may be vented or sampled through vent valves18on the filter capsule, and stored in a venting container such as bag20. Filtrate then proceeds to a sterile holding container such as bag22. The filtrate may also be sampled by a sampling container such as bag24. Finally, filtrate proceeds to a dosing loop26for a pump (not shown), such as a peristaltic pump, and to a final connection28. The final connection28may be surrounded by a protective bag29, which helps to ensure that the final connection28does not become contaminated prior to being transferred to a sterile filling area for further processing.

As noted above, to ensure sterility of the final filtered product, sterilizing filters must be integrity tested after processing. In one example, to perform an integrity test of the filter capsule16, a gas line30is positioned in fluid communication with the tubing14upstream of the filter capsule16through a secondary aseptic connection32. To ensure sterility, the secondary aseptic connection32may include an aseptic phobic filter and a Lynx ST valve (commercially available from EMD Millipore Corporation) or the like. A measurement device is then positioned upstream of the gas line30, a bag34is placed downstream of the filter to capture excess air, gas, and liquid, and a desired flow path starting from gas line30, to the filter capsule16, and ending at the bag34is isolated using clamps or other means. The gas line30is activated and deactivated after a period of time, and a decay in pressure over time is measured by the measurement device. The resulting data is compared to known acceptable values for the filer element contained within the filter capsule16. If the integrity test indicates that the filter element has not been compromised, then it can be safely assumed that the filtrate to be dispensed by the final connection28is sterile.

Conventional filter capsules, and in particular the vent ports, are prone to issues.FIG. 2provides a cross-sectional view of the filter capsule16ofFIG. 1. The filter capsule16comprises a housing36having an inlet port42and an outlet port44spaced from the inlet port42. Within the housing36is a housing volume comprising a passage running longitudinally between the inlet port42and outlet port44. A filter element40is housed within the housing volume and is sealed to the outlet port44, such that a fluid entering the inlet port42must pass through the filter element40before exiting the outlet port44, thus filtering and sterilizing the fluid downstream of the filter capsule16. Excess gas and fluid may be vented or sampled through either of vent valves18, each of which includes two seals, an exterior seal48and an interior seal49, to prevent external contamination. However, the vent valves18are not intended for multiple actuations, and may break after repeated use. The vent valves18are also prone to accidental contact with exterior surfaces, and may thus become contaminated. For example, contact with exterior surfaces may lead to contamination of the exterior seal48. As the vent valve18is actuated, the exterior seal48rides within the body of the vent valve18and contaminates the interior surface, potentially leading to contamination of the interior seal49. Contamination of the interior seal49leads to contamination of the filter environment and process stream. Contact with exterior surfaces may also cause the vent valve18to break if sufficient force is encountered.

FIG. 3illustrates a filter capsule50according to one embodiment of the present disclosure. The filter capsule50comprises a housing52, inlet housing54with an inlet port56, outlet end cap58with an outlet port60, and a vent assembly62. In certain embodiments, the housing52is generally cylindrical to prevent an uneven distribution of pressure within. In use, the inlet port56and outlet port60are connected to a filtration assembly (such as that shown inFIG. 1) and used to filter the product from a fluid container to remove viruses, bacteria, or other contaminants, for example. The vent assembly62may be used to vent the filter capsule or sample the fluid therein. In some embodiments, the vent assembly62is aseptic. Further, in certain embodiments, the housing52is formed from molded plastic. However, in other embodiments, stainless steel may be used.

In this embodiment, the outlet end cap58is thermally sealed to the housing52. However, in certain embodiments, the outlet end cap58and housing52may comprise a single component. Similarly, in this embodiment, the inlet housing54is molded together with the housing52; however, in certain embodiments, the inlet housing54and housing52may be separately formed and then bonded together. Various combinations are possible within the scope of the disclosure. Further, while the filter element40of this embodiment is heat sealed to the outlet end cap58, in certain embodiments the filter element40may be a removable and replaceable element. Still other embodiments include housings52comprising steel or other materials that allow for a reusable, as opposed to a single-use, filter capsule50.

In comparison to the filter capsule16ofFIGS. 1-2, the filter capsule50may include several additional components. In certain embodiments, the housing52includes feet64connected to the housing near the inlet housing54and outlet end cap58. Each foot64can function as a resting point for the filter capsule50when it is placed horizontally on a surface, thus stabilizing the filter capsule50and preventing accidental or unwanted movement. In this embodiment, the feet64comprise a looped member and therefore may also be used to fasten or otherwise secure the filter capsule50within an assembly. The filter capsule50may also include a handle66at each end of the housing52, which can be used for manipulating and transporting the filter capsule50but also protects the filter capsule and ports from accidental contact with exterior surfaces, thus helping to prevent contamination.

Additionally, in certain embodiments, the filter capsule50includes an integrity test assembly100formed in the inlet housing54near the inlet port56. Like the vent assembly62, the integrity test assembly100can be used for venting and sampling the contents of the filter capsule50prior to filtration. Further, the integrity test assembly100may be used as a direct aseptic connection that facilitates a variety of integrity test methods, such as air/water diffusion, bubble point, and/or water intrusion tests. When actuated to an open position, the integrity test assembly100may be connected to integrity testing hardware, such as a gas line. When the integrity test is complete, the integrity test assembly100may then be closed and the hardware removed, without impacting sterility of the product within. Thus, the integrity test assembly100provides a direct aseptic connection to a filter capsule that can be leveraged for integrity testing, venting, or sampling. Further, the integrity test assembly100reduces the integrity testing flow path to nearly zero by providing an aseptic connection directly to the filter element40itself.

In this embodiment, the integrity test assembly100is formed as a part of the inlet housing54. Thus, the integrity test assembly100is an integral component of the filter capsule50. Attempting to remove the integrity test assembly100from the filter capsule50will irreversibly damage or contaminate the filter capsule50, thus rendering the filter capsule50unsuitable for use within a filtration assembly. However, in certain embodiments, the integrity test assembly100may be removable.

FIGS. 4A-Billustrate an embodiment of an inlet housing54of the filter capsule50in further detail. In these views, only the inlet housing54containing the inlet port56, integrity test assembly100, foot64, and handle66is shown. While this view shows the inlet housing54separate from the housing52, in this embodiment the inlet housing54and housing52are comprised of a single component. However, in certain embodiments, the inlet housing54may be a separately formed and removable component.

As shown inFIG. 4A, the handle66is connected to each side of the filter capsule50. The handle66serves several purposes. For example, the handle66can be used to manipulate or install the filter capsule50in a filtration assembly (such as the assembly ofFIG. 1) without accidental contact with the integrity test assembly100, thus helping to maintain sterility. The handle66also protects the integrity test assembly100from accidental contact with outside components, or if the filter capsule50is inadvertently dropped. Further, the handle66can also be used as a foot to support the filter capsule50when the filter capsule50is placed horizontally. For example, if the filter capsule50is placed on its side or is knocked over when initially standing on its feet64, the filter capsule50will come to rest on the handle66, rather than on the integrity test assembly100.

However, in some situations, the handle66may interfere with closely situated components within an assembly, and thus be an unwanted component. Accordingly, in certain embodiments, the handle66may be omitted from the filter capsule50. However, in certain embodiments, as shown inFIG. 4B, the handle66may be a separately formed and removable element. In this case, the handle66may releasably snap onto the inlet housing54via a handle notch68and between guiding ridges70. The handle notch68and guiding ridges70retain the handle66in a desired position. In the embodiment shown, the guiding ridge70tapers inwardly near the receiving notch so as not to interfere with the graspable portion of the handle66. In some embodiments, the handle66may then be removed by urging the edges of the handle66away from the handle notch68. Accordingly, the handle66may be repeatedly removed and reattached to the inlet housing54.

However, in certain embodiments, the handle66may not be removable. Rather, in these embodiments, the handle66is provided separately from the filter capsule50and may only be snapped in place and secured to the filter capsule50if so desired by the end user. In the non-removable embodiment, attempted removal of the handle66will result in breakage of either the handle66or the inlet housing54or both. For example, one means of permanently attaching or securing the handle66to the inlet housing54is by a heat stake rivet.

Similarly,FIGS. 5A-Billustrate an embodiment of an outlet end cap58shown separated from the housing52. The outlet end cap58has two feet64in comparison to the single foot64of inlet housing54; however, any number of feet64may be used for either component. The outlet end cap58also features a handle66that may be removable or otherwise attachable and reattachable via a handle notch68and guiding ridges70. The guiding ridge70tapers inwardly near the handle notch68so as not to interfere with the graspable portion of the handle66. In this embodiment, as shown, the handle66protects the vent assembly62.

FIG. 6illustrates a cross-sectional view of an embodiment of a filter capsule50. Similar to the filter capsule16ofFIGS. 1-2, within the filter capsule50is a filter element40. In certain embodiments, the filter element40is sealed to the outlet port60of the outlet end cap58, such that a fluid entering the inlet port56from upstream must pass through the filter element40before exiting through the outlet port60, thus filtering the fluid. The filter element40may comprise any kind of filter, including pleated filters, hydrophobic filters, hydrophilic filters, or sterilizing filters. The vent assembly62and integrity test assembly100may have a similar design, and each includes a connection72,102; a connector actuator such as a handle74,104; and one or more seals76,106. In certain embodiments, the connection72on the vent assembly62is a barb connection, which may be attached to plastic tubing connected to a venting or sampling container such as a bag. To vent or sample the contents of the filter capsule50, the vent assembly62is actuated such as by rotating the connector actuator or handle74, thus opening the vent assembly62. The integrity test assembly100has a larger diameter than the vent assembly62, so as to provide sufficient flow characteristics necessary for integrity testing. In this embodiment, the connection102on the integrity test assembly100is a TC connection, which may be attached to a gas line, integrity testing hardware, or a venting or sampling bag. Similar to the vent assembly62, the integrity test assembly100may be actuated by rotating the handle104. The one or more seals76,106on each port ensure sterility of the contents of the filter capsule50despite multiple actuations, making each port aseptic. Further, while in this embodiment the vent assembly62uses a barb connection and the integrity test assembly100uses a TC connection, various connections are within the scope of the disclosure. For example, in certain embodiments, Luer connections or other forms of connections may be used in either the vent assembly62or integrity test assembly100.

In certain embodiments, an integrity test assembly100is provided on both the inlet housing54and outlet end cap58. Alternately, the outlet end cap58may have an integrity test assembly100, and the inlet housing has only a vent assembly62. Either the integrity test assembly100or vent assembly62may also be present elsewhere on the housing52or on an assembly. For example, an integrity test assembly100and/or vent assembly62may be located downstream of the filter capsule50. As noted previously, the integrity test assembly100is an integral component of the filter capsule50and may not be removed. However, in certain embodiments, the integrity test assembly100may be removable. Various embodiments, locations, and numbers of the integrity test assembly100and vent assembly62are within the scope of the disclosure.

FIGS. 7-8illustrate cross-sectional views of certain embodiments of an integrity test assembly100in the closed and open positions, respectively. As noted above, the integrity test assembly100may be of similar construction as the vent assembly62; however, the integrity test assembly100has a greater diameter to provide sufficient flow characters to facilitate integrity testing. Of course, the integrity test assembly100may also be used for aseptic venting or sampling, just like the vent assembly62. In the embodiment shown, the integrity test assembly100comprises an opening or port on the filter capsule50having a body108extending from the inlet housing54. The body108defines a bore110and comprises three sections. A first section112of the body108closest to the filter capsule50has a first inner diameter that is smaller than the inner diameter of a second section116. A transition section114between the first section112and second section116has an inner diameter that increases linearly from the first section112to the second section116. While in this embodiment the inner diameter of the transition portion increases linearly, in other embodiments the inner diameter may increase non-linearly, such as exponentially or via a step function. The body108further comprises a receiving notch118in communication with a cam slot120. In this embodiment, the receiving notch118is a raised portion of the body108that is formed over the cam slot120. As will be explained further below, the receiving notch118is configured to receive a cam, such that the cam may enter the cam slot120.

The integrity test assembly100further comprises a valve that can be actuated to an open position and a closed position, thus facilitating fluid or gas transfer either into or out of the filter capsule50. The valve comprises a plunger128positioned within the bore110, creating a fluid tight seal between the body108and plunger128via one or more seals132,134,136such as O-rings. The plunger128has a shape corresponding to the bore110. The plunger comprises a cam125(as shown inFIG. 9), which in the embodiment shown, extends radially from the plunger body and is configured to fit and track within the cam slot120. In this embodiment, the cam125and cam slot120define the linear extent of movement of the plunger128within the bore110. Rotating a connector actuator or handle104causes the cam125to traverse the cam slot120. In this embodiment, the integrity test assembly100is in the closed position when the cam125is in a portion of the cam slot120closest to the inlet housing54; similarly, the integrity test assembly100is in the open position when the cam125is in a portion of the cam slot120farthest from the inlet housing54.

The plunger128has a diameter configured to match the configuration of the body108. In this embodiment, the plunger128comprises three portions corresponding to the three sections112,114,116of the body108. Similar to the sections of the body108, a first portion122has an outer diameter that is smaller than the outer diameter of a second portion126. A transition portion between the first portion122and second portion126has an outer diameter that is configured to match the configuration of the transition section114of the bore110. For example, in this embodiment, the diameter of the transition section increases linearly from the outer diameter of the first portion122to the outer diameter of the second portion126. As will be explained in further detail below, the plunger128acts as a valve and cooperates with the body108to actuate the integrity test assembly100. During actuation of the integrity test assembly100to an open position, the plunger128traverses the bore110such that the first portion122of the plunger128aligns with the transition section114of the body108, creating a fluidic channel in communication with the interior of the filter capsule50. When the integrity test assembly100is actuated to a closed position, the plunger128traverses the bore110such that the first portion122of the plunger128aligns with the first section112of the body108, thus closing the fluid channel.

Further, in this embodiment, the plunger128comprises one or more cavities142. The cavities142help to reduce friction during translation of the plunger128within the bore110. In certain embodiments, the cavities142may be larger, smaller, have different shapes, or not be present.

Various seals are arranged along the length of the plunger128to form a fluid tight seal between various portions of the plunger128and the body108. In this embodiment, the integrity test assembly100includes three seals: a shut-off seal132, an outside seal134, and a sterility seal136. As shown, the seals are contained in annular grooves138formed in the plunger128. In various embodiments, the seals132,134,136may be 0-rings, either pre-formed and retained within the annular grooves138, or formed in place in the annular grooves138. However, if desired, different configurations of seals and their placements can be used. For example, seals may be held in grooves in the inner surface of the bore110.

Within the plunger128is an axial channel130, which is in communication with the connection102. The axial channel130is further in communication with a radial channel144located between the shut-off seal132and outside seal134. In this embodiment, the axial channel130and radial channel144together form a T-shaped fluidic channel that may be used to transfer fluid, gas, or other substances into or out of the filter capsule50when the integrity test assembly100is actuated to an open position.

In the closed position (as shown inFIG. 7), the radial channel144is not in communication with the interior of the filter capsule50due to the shut-off seal132being in contact with the first section112of the body108, and fluid within the filter capsule50is contained. In this position, the sections112,114,116of the body108are respectively aligned with the corresponding portions122,124,126of the plunger128. Rotating the connector actuator or handle104urges the cam125along the cam slot120, causing the plunger128to move towards an open position (as shown inFIG. 8). In the open position, the plunger128has moved laterally away from the filter capsule50such that the first portion122of the plunger128is aligned with the transition section114of the body108. This creates an open space between the shut-off seal132and transition section114, thus forming a fluidic connection between the contents of the filter capsule50and the radial channel144. Thus, fluid within the filter capsule50may exit through the created open space, into the radial channel144, into the axial channel130, and out through the connection102. Similarly, a gas or fluid may be provided to the filter capsule50along the same path. To enter the closed position and re-establish a seal between the shut-off seal132and first inner section112, the connector actuator or handle104is rotated in the opposite direction.

To use the integrity test assembly100for venting or sampling, tubing and a venting or sampling container such as a bag are aseptically connected to the connection102. The integrity test assembly100is then actuated to the open position by rotating the connector actuator or handle104. The contents of the filter capsule50may then traverse the radial channel144and axial channel130, exiting via the connection102. Once venting or sampling is complete, the integrity test assembly100is actuated to the closed position, and the tubing and venting or sampling container is removed. The vent assembly62may be used in a similar manner. Once venting or sampling is complete, the integrity test assembly100may then enter the closed position by appropriately actuating the connector actuator or handle104. This may be accomplished by rotating the connector actuator or handle104in the opposite direction, thus placing the shut-off seal132back into contact with the surface of the bore110at the first section112and reestablishing the liquid-tight seal between the plunger128and bore110(as shown inFIG. 7).

The integrity testing assembly100provides numerous advantages for testing the integrity of the filter element40when compared to previous approaches. If pre-filtration integrity testing is desired, a gas line or other integrity testing hardware is aseptically attached to the connection102. The integrity test assembly100is then actuated to an open position, creating an aseptic fluid connection between the integrity testing hardware and contents of the filter capsule50. The gas line or integrity testing hardware is then activated, thus pressurizing the contents of the filter capsule50. To perform a diffusion test, the resulting increase in pressure downstream is measured and compared to known values for the filter element. To perform a pressure drop test, the decrease in pressure over time upstream of the filter element is similarly measured and compared to known values. If the filter meets the known values, it can be safely assumed that the filter element is not compromised.

The integrity test assembly100may then be actuated to a closed position, and the gas line or integrity testing hardware may be removed without compromising the process stream. Once the filtration process is complete, this process may be repeated to determine whether the filter was compromised during filtration, and thus whether the resulting filtrate is sterile. Despite multiple actuations and multiple rounds of integrity testing, the integrity test assembly100remains aseptic and prevents contamination of the process stream. Further in contrast to the prior art, the use of a filter capsule50with an integrated integrity test assembly100results in the advantage that no additional components for integrity testing are required upstream of the filter capsule50. Each of these additional components represented an additional failure or contamination point. Further, these additional components did not ensure sterility through multiple actuations or rounds of integrity testing. In contrast, the present disclosure features an integral integrity test connection that maintains sterility despite multiple actuations, and is located directly at the filter capsule itself, the desired point of interest.

FIGS. 9A-Care side views of an embodiment of an integrity test assembly100, illustrating the cam slot120in further detail.FIG. 9Aillustrates the integrity test assembly100in an open position. As previously described, in the open position, the transition portion124of the plunger128is aligned with the first section112of the body108. In this embodiment, the cam slot120comprises five segments: an open segment146, first transition segment148, receiving segment150, second transition segment152, and closed segment154. In the open position, the cam125is located in the open segment146of the cam slot120. The open segment146is sized to accommodate the cam125, and has a slope perpendicular to the longitudinal axis of the plunger128. Thus, as the cam125traverses the open segment146, its position along the longitudinal axis of the body108does not change. This feature is useful because it enables the integrity test assembly100to enter the open position prior to the cam125reaching the end of the cam slot120, thus ensuring that the integrity test assembly100is fully opened, but allowing for additional rotation of the handle104after entering the open position. Further, the open segment146may comprise a detent156slowing movement of the cam125within the open segment146, providing tactile feedback to an end user that the integrity test assembly100has entered the open position.

To begin closing the valve, the connector actuator or handle104is rotated, causing the cam125to enter the first transition segment148. The first transition segment148has a path that is sloped towards the filter capsule50. As the cam125traverses the first transition segment148, the plunger128begins to enter the closed position, such that the transition portion124of the plunger128begins to align with the first section112of the body108. As shown inFIG. 9B, continuing to rotate the handle104causes the cam125to then enter the receiving segment150. Halfway between the open and closed positions, the receiving segment150is in communication with the receiving notch118. Thus, when the plunger128is first positioned within the bore110(e.g., during manufacture of the filter capsule50), the cam125is in the receiving segment150. Like the open segment146, the receiving segment150has a slope perpendicular to the longitudinal axis of the plunger128such that the plunger128does not move towards or away from the filter capsule50as the cam125traverses the receiving segment150. Thus, an end user may slightly rotate the handle104without causing the plunger128to move towards the open or closed positions, providing a finer degree of control.

Continuing to rotate the connector actuator or handle104causes the cam125to enter the second transition segment152. Like the first transition segment148, the second transition segment152has a path that is sloped towards the filter capsule50. As shown inFIG. 9C, the second transition segment152is connected to the closed segment154. Like the open segment146and receiving segment150, the closed segment154has a slope perpendicular to the longitudinal axis of the plunger128such that the plunger128does not move towards or away from the filter capsule50as the cam125traverses the closed segment154. Similarly, this feature is useful because it enables the integrity test assembly100to enter the closed position prior to the cam125reaching the end of the cam slot120, thus ensuring that the integrity test assembly100is fully closed and allowing additional rotation of the handle104after entering the closed position. Further, the closed segment154may also comprise a detent156slowing movement of the cam125within the closed segment154, providing tactile feedback to an end user that the integrity test assembly100has entered the closed position. The combination of detent156and additional rotation without exiting the closed position is particularly useful because it minimizes inadvertent opening (and the potential for contamination) of the integrity test assembly100.

In certain embodiments, additional cams and cam slots may be used. For example, in certain embodiments, an integrity test assembly100comprises a pair of cams within cam slots disposed 180 degrees from one another along the body of an integrity test assembly. In certain embodiments, cam slots may be longer or shorter depending on the level of actuation desired per rotation of a connector actuator or handle. In certain embodiments, a plunger may enter the closed or open positions only on reaching a respective end of a cam slot. Various embodiments are considered to be within the scope of the disclosure.

FIG. 10is a perspective view illustrating the integrity test assembly100with the plunger128separated from the bore110. In this embodiment, the plunger128is a molded plastic component formed of polyethersulfone, a relatively strong material that helps make the integrity test assembly100robust and less susceptible to bending, breaking, melting, or other modes of failure. The plunger128contains annular grooves138in which the seals132,134,136are placed. The shut-off seal132is located in the first portion122, whereas the outside seal134and sterility seal136are located in the second portion126. As previously noted, the transition portion124has a diameter that transitions linearly between that of the first portion122and second portion126. However, in other embodiments, the transition portion124may transition in a different manner or be absent from the plunger128. Further, the plunger128includes a cam125and an indicator strip140.

To build the integrity test assembly100, the plunger128is inserted into the bore110such that the cam125enters the receiving notch118. Rotating the handle104about the longitudinal axis of the integrity test assembly100causes the cam125to follow the path of the cam slot120, thus limiting the length of travel of the plunger128within the bore110. As described above, in this embodiment the cam slot120comprises a single cam slot120having multiple segments extending about the diameter of the body108. However, in certain embodiments, the cam slot120may comprises two cam slots on each side of the body108. Additionally, the use of the receiving notch118is beneficial because it allows for an elongated cam125that may extend through and protrude from the cam slot120, preventing accidental slippage of the cam125out of the cam slot120and into the bore110.

An indicator strip140is another useful feature that readily indicates to an end user whether the plunger128is in either the open or closed positions. In this embodiment, the indicator strip140is placed on the plunger128such that it is visible only when the integrity test assembly100is in the open position, placing the portion of the plunger128having the indicator strip140outside of the bore110. Thus, an end user may view the indicator strip140and understand that the integrity test assembly100is in the open position. Similarly, an end user may understand that an inability to view the indicator strip140means that the integrity test assembly100is closed.

FIG. 11is a cross-sectional view of an integrity test assembly100in the open position and highlights the benefits of the use of the outside seal134and sterility seal136. In the open position, sterile liquid within the filter capsule50may flow past the shut-off seal132, into the radial channel144, through the axial channel130, and out of the integrity test assembly100via the connection102. Typically, outside air and external contaminants are prevented from coming into contact with the sterile liquid by the outside seal134. However, after multiple actuations, some contamination may pass the outside seal134as the plunger128rides within the bore110. The provision of the sterility seal136as an additional seal upstream of the outside seal134prevents this form of contamination by defining a “safe area” between the outside seal134and sterility seal136in which the sterility seal136may ride, but the outside seal134never comes into contact. Thus, the outside seal134never comes into contact with a surface touched by the sterility seal136, and therefore is less likely to experience contamination. This features helps ensure that the integrity test assembly100(and if desired, vent assembly62) provide an aseptic connection to the contents of the filter capsule50. Further, compared to the vent valves18of previous filter capsules16, this feature provides the integrity test assembly100and vent assembly62to remain aseptic despite repeated actuations.

As noted above, this aseptic property allows the integrity test assembly100to be used for a variety of purposes. For example, the integrity test assembly100may be used for venting of built-up gas within the filter capsule50. Alternately, the integrity test assembly100may be used for sampling of media within the filter capsule50. For both of these purposes, the integrity test assembly100ensures that despite multiple actuations, the contents of the filter capsule remain sterile and not exposed to the outside environment. Further, the integrity test assembly100may function as a valve, allowing for an integrity test connection that can be removed from the filter capsule50without compromising product sterility. Providing an integrity test assembly100directly on the filter capsule50greatly simplifies the design of an assembly, as the need to set up a connection upstream for integrity testing hardware is eliminated. Further, the use of a sterility seal136in both the vent assembly62and integrity test assembly100helps to ensure an aseptic connection, thus reducing the risk of product and environmental contamination.

In certain embodiments, the integrity test assembly100may be a removable, replaceable, or single-use component. For example, rather than being molded directly to the inlet housing54, the integrity test assembly100may include a sanitary flange that may be mated to a corresponding port on the filter capsule50.

In certain embodiments, the axial channel130and/or radial channel144may be formed in a separate element, as opposed to within the plunger128. For example, as shown in the embodiment ofFIG. 12, the bore110may include an auxiliary port158located between the shut-off seal132and outside seal134. Tubing160or the like is then connected to the auxiliary port158. Actuating the integrity test assembly100then allows fluid to flow past the shut-off seal132and out the auxiliary port to a downstream component or other device, or alternately to be used as a connection for integrity testing. In certain embodiments, the radial channel144and axial channel130may comprise a single fluid channel. In certain embodiments, multiple channels may be used to create a fluidic connection between the interior of the filter capsule50and the connection102.

As described above, seals may be mounted on the plunger128. However, if desired, different configurations of seals and their placements can be used. For example, at least some seals may be held in grooves of the bore110as opposed to the plunger128. In another embodiment, the outside seal134and sterility seal136may be replaced with a single linear or gland seal that covers a similar distance between the outside seal134and sterility seal136, such that one end of the seal never comes into contact with a surface of the bore110in contact with the other end of the seal.

In the disclosed embodiments above, the integrity test assembly100is formed of a plastic material including polyethersulfone. The integrity test assembly100may be formed by machining the body108and plunger128and then applying the necessary seals and the like, or preferably by molding the body108and the plunger128separately and assembling them together with the necessary seals and other components. The integrity test assembly100may be made of a variety of plastic materials. For example, in the embodiment disclosed, the inlet housing54and body108are formed from polypropylene. However, the plunger128is formed from polyethersulfone, which results in a plunger128that is stronger and having better dimensional stability. However, a variety of materials may be used for any of these components. Similarly, other components of the filter capsule50may comprise a variety of materials.