System for final filtration of cellular products suitable for injection

Abstract

Embodiments of the disclosure are related to transparent systems and filters for filtering a therapeutic cellular product. Systems and filters disclosed herein include transparent filters having a transparent filter housing resistant to polar organic solvents, and a woven filter membrane resistant to polar organic solvents and having an average pore size of at least about 18 micrometers. Systems disclosed herein include a receptacle configured to receive a filtered therapeutic cellular product from a filter. Such receptacles include a transparent outer layer resistant to polar organic solvents, and an inner layer resistant to polar organic solvents superimposed onto an inner surface of the outer layer, where the inner layer forms a predetermined pattern of protuberances defining a plurality of channels for evacuation of air therebetween.

Description

SYSTEM FOR FINAL FILTRATION OF CELLULAR PRODUCTS SUITABLE FOR INJECTIONCROSS-REFRENCE TO RELATED APPLICATIONS

[0001] The present application claims the priority benefit of U.S. Provisional Application No.63 / 745,953, filed January 16, 2025, which is hereby incorporated by reference in its entireties.TECHNICAL FIELD

[0002] The present disclosure relates to the field of transparent systems and filters for filtering a therapeutic cellular product.BACKGROUND

[0003] Cell therapy involves sterile sealed containers to grow customized biological cells. Sterilization of added fluids is done by passing fluid through a so called ‘sterilizing filter’ which filters cells greater than 0.2 microns (um), and thus removes all bacteria and viruses. However, existing cells and viruses collected from the patient are not sterilized. During a final cell processing step, engineered therapeutic cells for transfer into a final patient are stored in bags which contain added buffers and a cyroprotectant.

[0004] U.S. Pharmacopeial Convention standards state that fluids to be introduced into a patient must not contain visible particles. Unfortunately, plastic disposables commonly used in the cell therapy space are made under medical device specifications, which allow for a small percentage of visible particles. More specifically, current cell therapy products are placed into ethylene vinyl acetate (EVA) pouches which have a frosted film surface. This makes visual inspection of small particles unnecessarily difficult. What is needed is a system for making the visual inspection of cell therapy products easier with regards to the final filtering steps and placement of the cellular therapy solutions into a final bag for patient delivery. More specifically, what is needed is a transparent system for facilitated viewing of any foreign visible particles of greater than 50 microns.SUMMARY

[0005] Briefly, and in general terms, the present disclosure is directed to transparent systems and filters for filtering a therapeutic cellular product. Systems and filters disclosed herein includetransparent filters having a transparent filter housing resistant to polar organic solvents, and a woven filter membrane resistant to polar organic solvents and having an average pore size of at least about 18 micrometers. Systems disclosed herein include a receptacle configured to receive a filtered therapeutic cellular product from a filter. Such receptacles include a transparent outer layer resistant to polar organic solvents, and an inner layer resistant to polar organic solvents superimposed onto an inner surface of the outer layer, where the inner layer forms a predetermined pattern of protuberances defining a plurality of channels for evacuation of air therebetween.

[0006] An embodiment of the disclosure is related to a filter for therapeutic cellular products, the filter including a transparent filter housing and a woven filter membrane. In such an embodiment, the transparent filter housing includes a non-polar polymer resistant to a polar organic solvent and an internal channel formed by the transparent filter housing. The internal channel spans from a first opening disposed at a first end of the transparent filter housing to a second opening disposed at a second end of the transparent filter housing. The woven filter membrane is disposed within the internal channel and is resistant to the polar organic solvent. The woven filter has an average pore size of at least about 18 micrometers.

[0007] An embodiment of the disclosure is related to a system for filtering a therapeutic cellular product. The system includes a filter for the therapeutic cellular product, a woven filter membrane, an input structure, an output structure, and a receptacle. In such an embodiment, the filter includes a transparent filter housing, the transparent filter housing including: a non-polar polymer resistant to a polar organic solvent; an internal channel formed by the transparent filter housing, where the internal channel spans from a first opening disposed at a first end of the transparent filter housing to a second opening disposed at a second end of the transparent filter housing, and a woven filter membrane disposed within the internal channel, where the woven filter membrane is resistant to the polar organic solvent and has an average pore size of at least about 18 micrometers. The input structure is formed by the transparent filter housing and is configured to allow access to the first opening. The output structure is formed by the transparent filter housing and is configured to allow passage of a filtered cellular product from the internal channel of the transparent filter housing through the second opening of the transparent filter housing. The receptacle is fluidly connected to the output structure and is configured to receive the filtered therapeutic cellular product from the filter. The receptacle includes: a transparent outer layer resistant to the polar organic solvent; and an inner layer resistant to the polar organic solvent superimposed onto an inner surface of the outer layer, where the inner layer forms a predetermined pattern of protuberances. In such an embodiment, the transparent outer layer and the inner layer form a cavity configured to containthe filtered therapeutic cellular product, and the predetermined pattern of protuberances defines a plurality of channels for evacuation of air therebetween.

[0008] Embodiments of the disclosure also relate to methods for using the abovementioned filter and system for filtering a therapeutic cellular product by flowing the therapeutic cellular product through the filter or system described above.

[0009] Other aspects and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, illustrating the principles of the invention by way of example only.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The teachings claimed and / or described herein are further described in terms of exemplary embodiments. These exemplary embodiments are described in detail with reference to the drawings. These embodiments are non- limiting exemplary embodiments, in which like reference numerals represent similar structures throughout the several views of the drawings, and wherein:

[0011] FIG. 1 is a schematic of a system for filtering a therapeutic cellular product according to an embodiment of the disclosure.

[0012] FIGs 2A - 2C are views of a filter for filtering a therapeutic cellular product according to an embodiment of the disclosure.

[0013] FIG. 3 is a cross-sectional view of a receptacle for receiving a filtered therapeutic cellular product from a filter according to an embodiment of the disclosure.DETAILED DESCRIPTION

[0014] The present disclosure addresses the need for a transparent filter and filter system for facilitated viewing of any foreign visible particles of greater than 50 microns in a final cell therapy product that is to be administered to a patient.

[0015] It will be understood that descriptions herein are exemplary and explanatory only and are not restrictive of the invention as claimed. In this application, the use of the singular includes the plural unless specifically stated otherwise.

[0016] All documents, or portions of documents, cited in this application, including but not limited to patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purpose. As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0017] As used in this Specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0018] Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive and covers both “or” and “and”.

[0019] The term “and / or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and / or” as used in a phrase such as “A and / or B” herein is intended to include A and B; A or B; A (alone); and B (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0020] The terms “e.g.,” and “i.e.” as used herein, are used merely by way of example, without limitation intended, and should not be construed as referring only those items explicitly enumerated in the specification.

[0021] The terms “or more”, “at least”, “more than”, and the like, e.g., “at least one” are understood to include but not be limited to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 1920, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54. 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83. 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111 , 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149 or 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000 or more than the stated value. Also included is any greater number or fraction in between.

[0022] Conversely, the term “no more than” includes each value less than the stated value. Also included is any lesser number or fraction in between.

[0023] The terms “plurality”, “at least two”, “two or more”, “at least second”, and the like, are understood to include but not limited to at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 1920, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56. 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85. 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149 or 150, 200, 300, 400,500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000 or more. Also included is any greater number or fraction in between.

[0024] Unless specifically stated or evident from context, as used herein, the term “about” refers to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, “about” or “approximately” may mean within one or more than one standard deviation per the practice in the art. “About” or “approximately” may mean a range of up to 10% (i.e., ±10%). Thus, “about” may be understood to be within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, 0.01%, or 0.001% greater or less than the stated value. When particular values or compositions are provided in the instant disclosure, unless otherwise stated, the meaning of “about” or “approximately” should be assumed to be within an acceptable error range for that particular value or composition.

[0025] Units, prefixes, and symbols used herein are provided using their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range.

[0026] As used throughout, the term “cryoresistant” refers to a material or object resistant to damage from freezing or from low temperatures. In some embodiments, cryoresistant refers to a material or object that maintains structural integrity at low temperatures (e.g., less than 150degrees C). Maintaining structural integrity means the material or object stays fit for its purpose and / or maintains safety standards as environmental conditions change (e.g., increasing and / or decreasing temperatures).

[0027] As used throughout, the term “reversibly engage” refers to a connection that is not fixed and as such, the two or more objects joined by such a connection can be attached to each other when in use, and removed from each other when not in use, for example. In some embodiments, reversible engagement may be facilitated by a third object or material (e.g., a first tube being connected to a second tube using a clamp, weld, or adhesive material).

[0028] As used throughout, the term “fluidly connected” refers to a connection between two or more objects or structures that allows for a fluid-tight connection for passing a fluid between the objects or structures. In some embodiments, the two or more objects or structures that are fluidly connected may also be aseptically connected.

[0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related.

[0030] An embodiment of the disclosure is related to a filter for therapeutic cellular products, including a transparent filter housing. In such an embodiment, the transparent filter housing includes: a non-polar polymer resistant to a polar organic solvent: and an internal channel formed by the transparent filter housing, the internal channel spanning from a first opening disposed at a first end of the transparent filter housing to a second opening disposed at a second end of the transparent filter housing. In such an embodiment, the filter also includes a woven filter membrane disposed within the internal channel the woven filter membrane resistant to the polar organic solvent and including an average pore size of at least about 18 micrometers.

[0031] An embodiment of the disclosure is related to the filter above, where the woven filter membrane includes stainless steel. In other embodiments, the woven filter membrane is made from one or more of a titanium (Ti 6A14V) wire preferred for strength, ductility, solvent and short to long term body fluid corrosion resisting. The woven filter membrane is made of a woven continuous wire of a preferred pore sizing method over other manufacturing methods which create small particles which are not desired. Some such membranes can also be made of polymeric membranes. For such polymeric membranes, non-polar DMSO solvent resisting woven extruded filaments are then optionally heat sealed in their final shape. High molecular weight polyolefin polymers polypropylene, and TPX are also contemplated.

[0032] An embodiment of the disclosure is related to the filter above, where the woven filter membrane includes an average pore size of at least 40 micrometers in size.

[0033] An embodiment of the disclosure is related to the filter above, where the woven filter membrane includes a residual hold capacity of less than 1 milliliter. In such an embodiment, the filter housing and membrane will freely drain via gravity when filled with a fluid in any position to a residual hold up volume of less than 1 milliliter.

[0034] An embodiment of the disclosure is related to the filter above, where the non-polar polymer includes one or more of a styrene-butadiene copolymer, a polymethylpentene polymer, a transparent styrene butadiene copolymer, a transparent polymethylpentene polymer preferably or alternatively a specially clarified polyethylene or a polypropylene resin using melt blended materials.

[0035] An embodiment of the disclosure is related to the filter above, where the polar organic solvent includes dimethyl sulfoxide (DMSO), or may be in the form of a DMSO-water solution.

[0036] An embodiment of the disclosure is related to the filter above, where the transparent filter housing further includes: an input structure formed by the transparent filter housing and configured to allow access to the first opening; and an output structure formed by the transparent filter housing and configured to allow passage of a filtered cellular product from the internalchannel of the transparent filter housing through the second opening of the transparent filter housing.

[0037] An embodiment of the disclosure is related to the filter above, where the input structure forms a plurality of input tube fittings, and where each of the plurality of input tube fittings is configured to allow access to the internal channel of the transparent filter housing through the first opening of the transparent filter housing.

[0038] An embodiment of the disclosure is related to the filter above, where the input structure forms three input tube fittings, and where each of the three input tube fittings is configured to allow access to the internal channel of the transparent filter housing through the first opening of the transparent filter housing.

[0039] An embodiment of the disclosure is related to the filter above, where the output structure includes an output tube fitting, and where the output tube fitting is configured to allow passage of the filtered cellular product from the internal channel of the transparent filter housing through the second opening of the transparent filter housing, and through the output tube fitting.

[0040] An embodiment of the disclosure is related to the filter above, where the output structure further includes a second output tube fitting, and where the second output tube fitting is configured to reversibly engage with a vacuum source. In some such embodiments, a Y connector with 2 pinch clamps and using a syringe as a vacuum source can be fastened to the filter.

[0041] An embodiment of the disclosure is related to a system for filtering a therapeutic cellular product, including: a filter for the therapeutic cellular product and a receptacle. In such an embodiment, the filter for the therapeutic cellular product includes: a transparent filter housing, the transparent filter housing including: a non-polar polymer resistant to a polar organic solvent; an internal channel formed by the transparent filter housing, the internal channel spanning from a first opening disposed at a first end of the transparent filter housing to a second opening disposed at a second end of the transparent filter housing; a woven filter membrane disposed within the internal channel, the woven filter membrane resistant to the polar organic solvent and including an average pore size of at least about 18 micrometers; an input structure formed by the transparent filter housing and configured to allow access to the first opening; and an output structure formed by the transparent filter housing and configured to allow passage of a filtered cellular product from the internal channel of the transparent filter housing through the second opening of the transparent filter housing. In such an embodiment, the receptacle is fluidly connected to the output structure. The receptacle is configured to receive the filtered therapeutic cellular product from the filter, and the receptacle includes: a transparent outer layer resistant to the polar organic solvent; and an inner layer resistant to the polar organic solvent superimposed onto an inner surface of the outer layer,the inner layer forming a predetermined pattern of protuberances. In such an embodiment, the transparent outer layer and the inner layer form a cavity configured to contain the filtered therapeutic cellular product, and the predetermined pattern of protuberances defines a plurality of channels for evacuation of air therebetween.

[0042] An embodiment of the disclosure is related to the system above, where the receptacle is cryoresistant. Also, the receptacle is configured to contain patient injectables (when in use), which can be suitably protected by an external cassette. The receptacle may be stored and transported at temperatures as low as -196 Celsius.

[0043] An embodiment of the disclosure is related to the system above, where the receptacle is a tubular receptacle manufactured including a blown tubular film extrusion process.

[0044] An embodiment of the disclosure is related to the system above, where the transparent outer layer of the receptacle includes ethylene- vinyl acetate. In other embodiments, the transparent outer layer is made of any suitable transparent and DMSO-resistant polymers.

[0045] An embodiment of the disclosure is related to the system above, where the transparent outer layer of the receptacle includes between 5% - 30% ethylene vinyl acetate. In some embodiments, the receptacle includes between 18% - 30% vinyl acetate.

[0046] An embodiment of the disclosure is related to the system above, where the polar organic solvent includes dimethyl sulfoxide (DMSO), or may be in the form of a DMSO-water solution.

[0047] An embodiment of the disclosure is related to the system above, where the predetermined pattern of protuberances forms a plurality of parallel ridges.

[0048] An embodiment of the disclosure is related to the system above, where each of the plurality of parallel ridges is between about 0.05 - 0.1 millimeters in height and between about 2.0 - 5.0 millimeters in width.

[0049] An embodiment of the disclosure is related to the system above, where the predetermined pattern of protuberances includes an anti-stick coating.

[0050] An embodiment of the disclosure is related to the system above, where the receptacle is reversibly connected to the output structure including a tube.

[0051] An embodiment of the disclosure is related to the system above, where the woven filter membrane includes stainless steel.

[0052] An embodiment of the disclosure is related to the system above, where the woven filter membrane includes an average pore size of at least about 40 micrometers.

[0053] An embodiment of the disclosure is related to the system above, where the woven filter membrane includes a residual hold capacity of less than 1 milliliter.

[0054] An embodiment of the disclosure is related to the system above, where the non-polar polymer includes one or more of a styrene-butadiene copolymer, a polymethylpentene polymer, a transparent styrene butadiene copolymer, a transparent polymethylpentene polymer preferably or alternatively a specially clarified polyethylene or a polypropylene resin using melt blended materials.

[0055] An embodiment of the disclosure is related to the system above, where the input structure forms a plurality of input tube fittings, and where each of the plurality of input tube feedings is configured to allow access to the internal channel of the transparent filter housing through the first opening of the transparent filter housing.

[0056] An embodiment of the disclosure is related to the system above, where the input structure forms three input tube fittings, and where each of the three input tube feedings is configured to allow access to the internal channel of the transparent filter housing through the first opening of the transparent filter housing.

[0057] An embodiment of the disclosure is related to the system above, where, when in use, a first input tube fitting is fluidly connected to a buffer- solution source, a second input tube fitting is fluidly connected to a sample source including the therapeutic cellular product, and a third input tube fitting is fluidly connected to a cryoprotectant-solution source.

[0058] An embodiment of the disclosure is related to the system above, where the output structure includes an output tube fitting, and where the output tube fitting is configured to allow passage of the filtered therapeutic cellular product from the internal channel of the transparent filter housing through the second opening of the transparent filter housing, and through the output tube fitting.

[0059] An embodiment of the disclosure is related to the system above, where the output structure further includes a second output tube fitting, and where the second output tube fitting is configured to reversibly engage with an external vacuum source.

[0060] An embodiment of the disclosure is related to the system above, where no sterile welding is used to connect the buffer-solution source, therapeutic cell product, and / or cryoprotectant source to the filter, and no sterile welding is used to connect the filter to the receptacle and / or to the vacuum source. In some embodiments, the filter includes a triple tubing fitting on the entrance that can be singly connected to individual input lines to the buffer- solution source, the therapeutic cell product, and / or the cryoprotectant source. Such a configuration allows for more efficient processing before any actual fluid transfer occurs. In such embodiments, to regulate which fluid transfer occurs in what order, pinch clamps on each of the input lines can be used. In such embodiments, the filter contains an output configured to accept two output lines, where each of these output lines are regulated with pinch clamps. In such an embodiment, one output line fillsthe receptacle with one or more of a buffer solution, a cellular products solution, and / or with a water-diluted cryoprotectant (e.g., DMSO). The other output line connects the filter to a vacuum source to drain the line of residual fluid before the next fluid is added to the receptacle. In some embodiments, receptacles are filled by sensitive weighing methods during each filling step.

[0061] An embodiment of the disclosure relates to a method of filtering a therapeutic cellular product including flowing the therapeutic cellular product through any of the filters above.

[0062] An embodiment of the disclosure relates to a method of filtering a therapeutic cellular product including flowing the therapeutic cellular product through any of the systems above.

[0063] As discussed above, an embodiment of the disclosure is related to a system having a tubular receptacle manufactured including a blown tubular film extrusion process. Such an extrusion process is well known. By way of non-limiting example, blown tubular film extrusion uses fine particle filtration filters which prevent most dust particles inside the tubular film as the film is extruded. This allows for a cleaner environment inside the tubular film than is standard for a typical ISO 8 cleanroom where medical device assembly typically takes place. To create an embossed surface on flat die soft medical EVA film the hot film is cast on embossed rollers where it is compressed against the rollers as it cools enabling the film to pick up the surface finish of the rollers. If the film is cooled before being squeezed between the embossing rollers, it would not retain the embossing effect. Blown film collapsing to a lay flat film if embossed while hot would pick up the embossed roller shape but would allow the inside of the tubular film to become stuck together. In view of this added challenge, most medical EVA bags are normally made from lay flat embossed film. In some embodiments, the tubular film made contains internal spaced apart and raised ridges to allow air to be completely removed from the bag when used in a vacuum sealer. In some embodiments, the multilayer tubular film may contain a thin 1-2 mil non tacky low 1-5% EVA film layer so that the lay flat film does not stick together during normal commercial elevated storage temperatures. IN some embodiments, the tubular film uses raised ridges in a softer thicker 12 mil film to enable the simultaneous use of a clear tubular film allowing visual inspection of the interior along with the benefit of raised ridges to prevent large areas inside the tubular film and subsequent produced bag from sticking together preventing normal filling operations from occurring.

[0064] In some embodiments, the interior of the tubular film and receptacle is also free from dust particles due to the cleaner manufacturing technique. In some embodiments, interior raised ridges prevent large smooth flat sections from sticking together for a tubular film made with 18-30 % EVA film that is typically used for cell therapy bags. Receptacles having insides containing large areas that are stuck together do not allow for proper fluid filling to occur. A tubular blown filmmachine that contains polished die lips along with raised interior lines of plastic when combined with a 18-30% EVA plastic produces a clear bag allowing visible inspection to more easily occur without the concerns of film sticking during film production and bag storage over existing frosted Cell therapy EVA bags.

[0065] Various embodiments are described in further detail in the following description.

[0066] As shown in Figures 1, 2A, 2B, 2C, and 3, an embodiment of the disclosure relates to a system 101 for filtering a therapeutic cellular product.

[0067] In such an embodiment, the system 101 includes a filter 201 for the therapeutic cellular product. The filter 201 includes a transparent filter housing 203, where the transparent filter housing 203 includes: a non-polar polymer resistant to a polar organic solvent; an internal channel 205 formed by the transparent filter housing 203, where the internal channel spans from a first opening 207 disposed at a first end of the transparent filter housing 203 to a second opening 209 disposed at a second end of the transparent filter housing 203. The filter 201 also includes a woven filter membrane 211 disposed within the internal channel, where the woven filter membrane is resistant to the polar organic solvent, and where the filter has an average pore size of at least about 18 micrometers. In some embodiments, the filter 201 also includes an input structure (not shown) formed by the transparent filter housing 203 and configured to allow access to the first opening 207. In some such embodiments, the filter 201 also includes an output structure (not shown) formed by the transparent filter housing 203 and configured to allow passage of a filtered cellular product from the internal channel 205 of the transparent filter housing 203 through the second opening 209. The woven filter membrane 211 is made of stainless steel and comprises an average pore size of at least about 40 micrometers. The woven filter membrane has a residual hold capacity of less than 1 milliliter. The filter housing 203 is made of a non-polar polymer selected from one or more of a styrene- butadiene copolymer, a polymethylpentene polymer, a transparent styrene butadiene copolymer, a transparent polymethylpentene polymer preferably or alternatively a specially clarified polyethylene or a polypropylene resin using melt blended materials.

[0068] The system 101 also includes a receptacle 301 fluidly connected to the output structure. In such an embodiment, the receptacle 301 is configured to receive the filtered therapeutic cellular product from the filter 201. In such an embodiment, the receptacle 301 includes: a transparent outer layer 303 resistant to the polar organic solvent, and an inner layer (not shown) resistant to the polar organic solvent superimposed onto an inner surface of the outer layer. The inner layer forms a predetermined pattern of protuberances 305. The transparent outer layer 303 and the inner layer form a cavity configured to contain the filtered therapeutic cellular product. The predetermined pattern of protuberances 305 defines a plurality of channels for evacuation of airtherebetween. In such embodiments, the receptacle 301 is cryorcsistant. The receptacle 301 is a tubular receptacle manufactured comprising a blown tubular film extrusion process. The transparent outer layer 303 of the receptacle 301 is made of between 18%-30% ethylene-vinyl acetate, and is resistant to a polar organic solvent such as dimethyl sulfoxide (DMSO). The predetermined pattern of protuberances 305 forms a plurality of parallel ridges. Each of the plurality of parallel ridges is between about 0.05 - 0.1 millimeters in height and between about 2.0 - 5.0 millimeters in width. In some embodiments, the predetermined pattern of protuberances comprises an anti-stick coating. The receptacle 301 is reversibly connected to the output structure of the filter 201 via a tube (not shown).

[0069] In some embodiments, the input structure of the filter 201 forms a plurality of input tube fittings (not shown). In such an embodiment, each of the plurality of input tube feedings is configured to allow access to the internal channel 205 of the transparent filter housing 203 through the first opening 207 of the transparent filter housing 203. In some such embodiments, the input structure forms three input tube fittings (not shown), where each of the three input tube feedings is configured to allow access to the internal channel 205 of the transparent filter housing 203 through the first opening 207 of the transparent filter housing 203. When the system 101 is in use, a first input tube fitting is fluidly connected to a buffer-solution source 401, a second input tube fitting is fluidly connected to a sample source 403 containing the therapeutic cellular product, and a third input tube fitting is fluidly connected to a cryoprotectant- solution source 405.

[0070] In some embodiments, the output structure 209 includes an output tube fitting (not shown). The output tube fitting is configured to allow passage of the filtered therapeutic cellular product from the internal channel 205 of the transparent filter housing 203 through the second opening 209 of the transparent filter housing 203, and through the output tube fitting. In such an embodiment, the output structure further includes a second output tube fitting (not shown), where the second output tube fitting is configured to reversibly engage with an external vacuum source 407.

[0071] One skilled in the art will realize the subject matter may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting of the subject matter described herein.

Claims

CLAIMSWe Claim:

1. A filter for therapeutic cellular products, comprising :a transparent filter housing, said transparent filter housing comprising:a non-polar polymer resistant to a polar organic solvent; andan internal channel formed by said transparent filter housing, said internal channel spanning from a first opening disposed at a first end of said transparent filter housing to a second opening disposed at a second end of said transparent filter housing; anda woven filter membrane disposed within said internal channel said woven filter membrane resistant to said polar organic solvent and comprising an average pore size of at least about 18 micrometers.

2. The filter of claim 1, wherein said woven filter membrane comprises stainless steel.

3. The filter of claim 1, wherein said woven filter membrane comprises an average pore size of at least 40 micrometers in size.

4. The filter of claim 1, wherein said woven filter membrane comprises a residual hold capacity of less than 1 milliliter.

5. The filter of claim 1, wherein said non-polar polymer comprises one or more of a styrene-butadiene copolymer, a polymethylpentene polymer, a transparent styrene butadiene copolymer, a transparent polymethylpentene polymer preferably or alternatively a specially clarified polyethylene or a polypropylene resin using melt blended materials.

6. The filter of claim 1, wherein said polar organic solvent comprises dimethyl sulfoxide (DMSO), or may be in the form of a DMSO-water solution.

7. The filter of claim 1, wherein said transparent filter housing further comprises:an input structure formed by said transparent filter housing and configured to allow access to said first opening; andan output structure formed by said transparent filter housing and configured to allow passage of a filtered cellular product from said internal channel of saidtransparent filter housing through said second opening of said transparent filter housing.

8. The filter of claim 7, wherein said input structure forms a plurality of input tube fittings, and wherein each of said plurality of input tube fittings is configured to allow access to said internal channel of said transparent filter housing through said first opening of said transparent filter housing.

9. The filter of claim 7, wherein said input structure forms three input tube fittings, and wherein each of said three input tube fittings is configured to allow access to said internal channel of said transparent filter housing through said first opening of said transparent filter housing.

10. The filter of claim 7, wherein said output structure comprises an output tube fitting, and wherein said output tube fitting is configured to allow passage of said filtered cellular product from said internal channel of said transparent filter housing through said second opening of said transparent filter housing, and through said output tube fitting.

11. The filter of claim 10, wherein said output structure further comprises a second output tube fitting, and wherein said second output tube fitting is configured to reversibly engage with a vacuum source.

12. A system for filtering a therapeutic cellular product, comprising:a filter for said therapeutic cellular product, comprising:a transparent filter housing, said transparent filter housing comprising:a non-polar polymer resistant to a polar organic solvent;an internal channel formed by said transparent filter housing, said internal channel spanning from a first opening disposed at a first end of said transparent filter housing to a second opening disposed at a second end of said transparent filter housing;a woven filter membrane disposed within said internal channel, said woven filter membrane resistant to said polar organic solvent and comprising an average pore size of at least about 18 micrometers;an input structure formed by said transparent filter housing and configured to allow access to said first opening; andan output structure formed by said transparent filter housing and configured to allow passage of a filtered cellular product from said internal channel of said transparent filter housing through said second opening of said transparent filter housing; anda receptacle fluidly connected to said output structure, said receptacle configured to receive said filtered therapeutic cellular product from said filter, and said receptacle comprising:a transparent outer layer resistant to said polar organic solvent; and an inner layer resistant to said polar organic solvent superimposed onto an inner surface of said outer layer, said inner layer forming a predetermined pattern of protuberances,wherein said transparent outer layer and said inner layer form a cavity configured to contain said filtered therapeutic cellular product, andwherein said predetermined pattern of protuberances defines a plurality of channels for evacuation of air therebetween.

13. The system of claim 12, wherein said receptacle is cryoresistant.

14. The system of claim 12, wherein said receptacle is a tubular receptacle manufactured comprising a blown tubular film extrusion process.

15. The system of claim 12, wherein said transparent outer layer of said receptacle comprises ethylene-vinyl acetate.

16. The system of claim 15, where said transparent outer layer of said receptacle comprises between 5% - 30% ethylene vinyl acetate.

17. The system of claim 12, wherein said wherein said polar organic solvent comprises dimethyl sulfoxide (DMSO), or may be in the form of a DMSO-water solution.

18. The system of claim 12, wherein said predetermined pattern of protuberances forms a plurality of parallel ridges.

19. The system of claim 18, wherein each of said plurality of parallel ridges is between about 0.05 - 0.1 millimeters in height and between about 2.0 - 5.0 millimeters in width.

20. The system of claim 12, wherein said predetermined pattern of protuberances comprises an anti-stick coating.

21. The system of claim 12, wherein said receptacle is reversibly connected to said output structure comprising a tube.

22. The system of claim 12, wherein said woven filter membrane comprises stainless steel.

23. The system of claim 12, wherein said woven filter membrane comprises an average pore size of at least about 40 micrometers.

24. The system of claim 12, wherein said woven filter membrane comprises a residual hold capacity of less than 1 milliliter.

25. The system of claim 12, wherein said non-polar polymer comprises one or more of a styrene-butadiene copolymer, a polymethylpentene polymer, a transparent styrene butadiene copolymer, a transparent polymethylpentene polymer preferably or alternatively a specially clarified polyethylene or a polypropylene resin using melt blended materials.

26. The system of claim 12, wherein said input structure forms a plurality of input tube fittings, and wherein each of said plurality of input tube feedings is configured to allow access to said internal channel of said transparent filter housing through said first opening of said transparent filter housing.

27. The system of claim 12, wherein said input structure forms three input tube fittings, and wherein each of said three input tube feedings is configured to allow access to said internal channel of said transparent filter housing through said first opening of said transparent filter housing.

28. The system of claim 27, wherein, when in use, a first input tube fitting is fluidly connected to a buffer- solution source, a second input tube fitting is fluidly connected to a sample source comprising said therapeutic cellular product, and a third input tube fitting is fluidly connected to a cryoprotectant-solution source.

29. The system of claim 12, wherein said output structure comprises an output tube fitting, and wherein said output tube fitting is configured to allow passage of said filtered therapeutic cellular product from said internal channel of said transparent filter housing through said second opening of said transparent filter housing, and through said output tube fitting.

30. The system of claim 29, wherein said output structure further comprises a second output tube fitting, and wherein said second output tube fitting is configured to reversibly engage with an external vacuum source.

31. A method of filtering a therapeutic cellular product comprising flowing said therapeutic cellular product through the filter of any of claims 1-11.

32. A method of filtering a therapeutic cellular product comprising flowing said therapeutic cellular product through the system of any of claims 12-30.

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