Processing apparatus

Abstract

A treatment device (10) for a therapeutic product or a biological sample is provided with a proximal end (12b) and a distal end (12a). The device comprises first and second compartments (40, 42) and a first substantially tubular portion (20). The first compartment (40) is in fluid communication with the second compartment (42) via a filter opening (28) arranged in or along the first substantially tubular portion (20). The treatment device (10) may be provided in the form of a kit. A method of using the treatment device (10) or kit is also disclosed.

Description

Technical Field

[0001] The present invention relates to a processing device for use with a therapeutic product or biological sample. In particular, although not exclusively, the present invention relates to a processing device intended for use in a centrifuge. One particular application of the processing device is the rehydration of thawed cell therapy products at the point of care. Although the present invention is described as having particular application to the rehydration of thawed cell therapy products, the processing device of the present invention also has applications outside the therapeutic field. The processing device may be applied to other fields where centrifugal separation is required. Background Art

[0002] Typically, in the prior art process of rehydrating frozen cell therapy products, the product undergoes thawing, cryopreservative removal, washing, and final concentration to a therapeutic dose before being handed over to the surgical team.

[0003] Figure 1 shows the workflow for rehydration of frozen cell therapy products. As shown in Figure 1A, frozen cells are transported in the cryopreservative DSMO in a cryocontainer 1. The cells are thawed in the cryocontainer 1, as shown in Figure 1B.

[0004] As shown in Fig. 1C, the contents in the freezing container 1 are sucked by a pipette 2 and transported to a spin tube 3. Such spin tubes (otherwise known as PCR tubes) are well known in the art. Typically, a spin tube comprises a closed-end container with a hinged lid. During centrifugation, the top of the spin tube 3 lies radially inward, while the bottom of the spin tube lies radially outward. For convenience, radially inward is referred to as the "proximal side", while radially outward is referred to as the "distal side".

[0005] As shown in FIG. 1D , the spin tube 3 is then placed in a centrifuge 4. The effect of centrifugation is that the cells will move distally (i.e. radially outward) in the spin tube 3. When the spin tube is returned to an upright position, the cryopreservative will be located above the cells, as shown. As shown in FIG. 1E , the cryopreservative can then be removed by using a pipette 2.

[0006] As shown in FIG1F , a pipette 2 delivers a fresh suspension of a therapeutic product, such as Ringers solution. As shown in FIG1G , the liquid is stirred to disperse the cells in the fresh suspension. The spin tube 3 is then placed in a centrifuge, as shown in FIG1H . The supernatant is then removed from the spin tube 3 using a pipette, as shown in FIG1I . This washing cycle is repeated multiple times.

[0007] As shown in Figure 1J, the excess suspension is then removed from the spinning tube 3 via the pipette 2. The amount of suspension removed depends on the desired concentration of the therapeutic product. The therapeutic product is then ready to be handed over to the surgical team.

[0008] There are multiple problems with current methods. First, the use of pipettes requires a skilled laboratory technician to perform the process. This is manually intensive and therefore creates a bottleneck. In turn, the need for a skilled laboratory staff creates a bottleneck for scalability. Second, from a biosafety perspective, the use of openable rotating tubes (which need to be opened each time a pipette is used) is risky. This imposes high environmental control requirements, increasing cost and complexity. Third, the use of pipettes runs the risk of extracting therapeutic cells or leaving precious cells instead.

[0009] Therefore, the current approach is not scalable beyond early research use, which limits its utility.

[0010] It is therefore an object of the present invention to overcome or mitigate at least one of the above disadvantages.An alternative object of the present invention is to provide the public with a useful choice over known attachment treatment devices.

[0011] The reference to any prior art in this specification is not an acknowledgement or representation that the prior art forms part of the common general knowledge in any jurisdiction, nor is it a reasonable expectation that the prior art could be understood, considered relevant and / or combined with other prior art by a person skilled in the art. Summary of the invention

[0012] According to a first aspect of the present invention, there is provided a processing device for a therapeutic product or a biological sample, the processing device being provided with a proximal end and a distal end and comprising a first compartment and a second compartment, the processing device comprising a first basic tubular portion, wherein the first compartment is in fluid communication with the second compartment via a filter opening arranged in or along the first basic tubular portion.

[0013] The treatment device can be configured for use in a centrifuge. Accordingly, the treatment device can be combined with features that help it to be used in a centrifuge (such as any commercial desktop centrifuge). For example, the treatment device can be inserted into a conventional 15ml centrifuge tube with or without an insert for fixing. Like this, the treatment device is provided with a proximal end and a distal end, wherein the proximal end is arranged radially inwardly from the distal end during centrifugation.

[0014] The first substantially tubular portion may define a side wall of the first compartment. Accordingly, the filter opening may be disposed on the side wall. The filter opening is preferably elongated. The elongated extent of the filter opening is preferably oriented to be generally or substantially aligned with the longitudinal direction of the first substantially tubular portion. The elongated extent of the filter opening may be oriented along the longitudinal direction of the side wall.

[0015] The sidewall may be a cylindrical sidewall. Alternatively, the sidewall may be tapered. Preferably, the sidewall is tapered in the distal direction. The first substantially tubular portion may have a reduced cross-sectional area along at least a portion of its length. This may include a gradual or stepped reduction, or a combination of a gradual and stepped reduction. Preferably, the cross-sectional area decreases along its length in the distal direction. The sidewall may be conical, or the first substantially tubular portion may include a frustoconical portion or a quasi-frustoconical portion.

[0016] The first substantially tubular portion may have a complex shape. In the most preferred form of the invention, the decreasing cross-sectional area along its length causes the centre line of the cross-sectional area to gradually deviate from the central longitudinal axis of the treatment device. In other words, the first substantially tubular portion has cross sections and the centroids of these cross sections deviate from the central longitudinal axis of the treatment device along at least a portion of the length of the first substantially tubular portion. Accordingly, the first substantially tubular portion is preferably skewed towards one side of the treatment device in the distal direction along its length.

[0017] In case the first substantially tubular portion is skewed towards one side of the treatment device, the filter opening preferably faces the other side of the treatment device. Accordingly, the filter opening faces a void in the treatment device, the void defining a portion of the second compartment.

[0018] The filter opening suitably comprises a filter for filtering the therapeutic product or biological sample. The filter can include any commercially available filter material, one or more media suitable for centrifugal filtration. For example, the filter material, one or more media can include tightly woven textiles, paper, nonwoven fabrics, metal screens or porous media. Preferably, the filter can be operated as a liquid filter to screen cells and maintain them in the first compartment. For example, the filter material can have a pore size of up to 20 μm or in the range of 10 μm to 20 μm. Any smaller filter material is also available, including protein filter sizes as low as kilodalton levels.

[0019] The filter and / or filter opening may be arranged across a shaped, e.g. curved or flat, wide portion of the side wall of the first basic tubular portion. The filter and / or filter opening may extend to the distal end of the first basic tubular portion. Preferably, the filter and / or filter opening is elongated and preferably, its length is narrower than its width. Preferably, the filter and / or filter opening extends a majority of the length of the first basic tubular portion. Preferably, the length of the filter and / or filter opening is approximately half the length of the first basic tubular portion. In an alternative version, the first basic tubular portion may comprise greater than two-thirds of the length of the first basic tubular portion, optionally greater than three-quarters of the length of the first basic tubular portion.

[0020] The first compartment may have a working volume capacity of about 5 mL to a maximum fill level. Preferably, the volume capacity of the first substantially tubular portion of the first compartment is about 1 mL. The filter and / or filter opening may extend from the base of the first compartment to a position corresponding to greater than 100 μL. The first compartment may include markings for indicating a liquid level.

[0021] The preferred surface area of ​​the filter and / or filter opening is preferably at least 30% of the surface area of ​​the first part of the first compartment.

[0022] The filter may be replaceable to allow for repeated use of the treatment device. Alternatively, preferably, the treatment device is disposable.

[0023] Preferably, the first compartment and the second compartment comprise an inner compartment and an outer compartment, respectively, wherein the inner compartment is at least partially disposed within the outer compartment. In this configuration, the second compartment surrounds the first compartment. In the event that the first substantially tubular portion is skewed, the void within the second compartment will define a convenient location for suctioning the filtrate.

[0024] In a preferred form of the device, a needle guide and / or an outlet port may be provided at or near the gap for selectively removing filtrate from the second compartment. Preferably, the processing device includes a second closure for the second compartment. Preferably, the second closure is a sealable closure member. Preferably, the second sealable closure allows the filtrate to be sucked through the sealable closure. For example, the second sealable closure may include a pierceable closure member, which is made of, for example, an elastically deformable material that allows the needle to pass through while allowing the passage to be closed by the elastic properties of the material when the needle is withdrawn. For example, the elastically deformable material may be a plastic material, such as a synthetic rubber, alternatively, a natural rubber.

[0025] A needle guide may be provided to ensure that the needle is properly and at least substantially aligned when inserted into the second compartment.The needle guide may be used in conjunction with the second closure member.

[0026] The first compartment may also include a second substantially tubular portion, which is arranged proximally relative to the first substantially tubular portion. The second substantially tubular portion may constitute the remainder of the working volume of the first compartment, i.e., approximately 4 mL. The first substantially tubular portion and the second substantially tubular portion preferably define an integral vessel, such as an integrally formed vessel.

[0027] The second substantially tubular portion may have a substantially circular sidewall, the center of which is concentric with the central longitudinal axis of the treatment device. The second substantially tubular portion is preferably a continuation of the first substantially tubular portion. In other words, the sidewall of the first substantially tubular portion continues to form the sidewall of the second substantially tubular portion, but the shape changes along the total length of the first compartment.

[0028] In a preferred form of the invention, the substantially tubular inner portion of the processing device comprises at least the first substantially tubular portion and the second substantially tubular portion. The tubular inner portion can be at least partially received in the substantially tubular outer portion. The second compartment is preferably defined between the substantially tubular inner portion and the substantially tubular outer portion. Preferably, the volume of the first compartment can be greater than the volume of the second compartment. This prevents all liquid from entering the second compartment from the first compartment during centrifugation, thereby retaining a residual amount of liquid in the first compartment to retain cells / proteins / biological samples immersed in the liquid. For this reason, the substantially tubular inner portion can protrude proximally beyond the substantially tubular outer portion.

[0029] The substantially tubular inner part and the substantially tubular outer part can be permanently connected or integrally formed. For example, the substantially tubular inner part and the substantially tubular outer part can be interconnected at its proximal region. For example, the substantially tubular inner part can be melted to the substantially tubular outer part. For example, the inner part and the outer part can be melted and melted together. This makes the treatment device become a closed system together with the first closure member and the second closure member as mentioned above and below, wherein it is not easy to enter the first compartment and the second compartment. The substantially tubular inner part and the substantially tubular outer part are preferably commensurate in shape at its proximal region.

[0030] In an alternative form of the invention, the substantially tubular inner portion and the substantially tubular outer portion may be integrally formed, for example 3D printed.

[0031] Alternatively, the inner and outer parts may be threadedly engaged or some other type of assembly, such as a snap fit.

[0032] The substantially tubular inner portion and the substantially tubular outer portion may be formed from a pyrogen-free plastic material. Preferably, the substantially tubular inner portion and the substantially tubular outer portion are formed from a transparent plastic material. Suitably, the treatment device is sterilized before use.

[0033] The proximal end of the device may be closed by a first closure. Preferably, the treatment device comprises a first sealable closure for the first compartment. Preferably, the sealable closure allows injection of a therapeutic product or a biological sample through the sealable closure. For example, the sealable closure may comprise a pierceable closure member, the pierceable closure member being made, for example, of an elastically deformable material capable of allowing a needle to pass through while allowing the passage to be closed by the elastic properties of the material when the needle is withdrawn.

[0034] Preferably, a delivery / retrieval port is provided at the proximal region of the treatment device. In the most preferred form, the delivery / retrieval port is provided by a pierceable closure member. A needle guide may be associated with the closure member to ensure proper and at least substantial alignment of the needle when inserted through the first closure member. More than one needle guide may be present to separate delivery from retrieval to avoid needle contamination.

[0035] In the most preferred form of the invention, the needle guide is at least substantially aligned with the skewed first substantially tubular portion. In this way, the needle injected into the first compartment is less likely to interfere with the tapered sidewall of the first substantially tubular portion.

[0036] Although the foregoing description refers to first and second substantially tubular portions having "side walls", it will be appreciated that there may be more than one side wall, for example where the tubular portions have a square or rectangular cross-section. The substantially tubular inner portion preferably has a distal end wall. The proximal end is preferably completely or at least partially closed by the first closure member.

[0037] The substantially tubular outer portion is sized to receive the substantially tubular inner portion. A proximal seat may be provided to seat the substantially tubular inner portion therein. The substantially tubular outer portion is preferably closed at the distal end by the second closure member. The substantially tubular outer portion may be circular in cross-section, with the cross-sectional area gradually decreasing from the proximal end to the distal end. Accordingly, the substantially tubular outer portion may be frusto-conical.

[0038] The processing device may further be provided with a vent. A vent is required for an otherwise hermetically sealed processing device to allow air to escape when injecting a therapeutic product or biological sample and / or to allow air to be introduced when aspirating a therapeutic product or biological sample.

[0039] The vent is preferably in the form of a peripheral vent. Preferably, the vent is provided on a protruding portion of the substantially tubular inner portion, the protruding portion protruding beyond the substantially tubular outer portion. The vent may include a filter to allow gas exchange but prevent pathogens and / or contaminants from passing through. For example, the vent may incorporate a hydrophobic membrane. The hydrophobic membrane most preferably has a pore size of 0.2 μm to allow gas exchange but block pathogens from passing through.

[0040] In an alternative form of the invention, the first compartment may be adjacent to the second compartment.

[0041] Therapeutic products may include any treatment, therapy, or drug, including biologics, except small molecules.

[0042] Cell processing can include cell rehydration, including cell washing, cell filtration, and cell concentration.

[0043] Any features described below in conjunction with other aspects of the invention may be applied to this aspect of the invention.

[0044] According to another aspect of the invention, there is provided a kit comprising assemblable components for defining a treatment device as set out above or below in conjunction with other aspects.

[0045] According to a related aspect of the first aspect of the present invention, a kit of a processing device for processing a therapeutic product or a biological sample is provided, the kit comprising assemblable components for defining a first compartment and a second compartment, such that in the assembled processing device, the first compartment is in fluid communication with the second compartment via a filter opening, wherein the filter opening is arranged in or along a first basic tubular portion of the device.

[0046] According to a related aspect of the first aspect of the present invention, there is provided a method for processing a therapeutic product or a biological sample using centrifugation, wherein the method comprises:

[0047] delivering the product or sample to the first compartment,

[0048] removing filtrate from the second compartment; and

[0049] The processed product is recovered from the first compartment.

[0050] According to a second aspect of the present invention, there is provided a processing device for a therapeutic product or a biological sample, the processing device comprising a first compartment and a second compartment, wherein the first compartment is in fluid communication with the second compartment via a filter opening, wherein the first compartment and the second compartment are defined by a container portion that is permanently connected or integrally formed.

[0051] For example, the treatment device may be formed by a substantially tubular inner portion and a substantially tubular outer portion. The substantially tubular inner portion may at least partially define the first compartment. The second compartment may be at least partially defined between the substantially tubular inner portion and the substantially tubular outer portion.

[0052] The substantially tubular inner portion and the substantially tubular outer portion may be formed separately and permanently connected in a subsequent processing step.The substantially tubular inner portion and the substantially tubular outer portion may be permanently connected at their proximal end regions.

[0053] In addition, the opposite end of the processing device can be closed by an elastically deformable closing member. A first closing member can be provided to close the first compartment. A second closing member can be provided to close the second compartment.

[0054] The container portion may be formed by an additive manufacturing process, such as 3D printing.

[0055] According to a related aspect of the second aspect of the invention, there is provided a method for processing a therapeutic product or a biological sample using centrifugation, wherein the method comprises:

[0056] delivering the product or sample to the first compartment,

[0057] removing filtrate from the second compartment; and

[0058] The processed product is recovered from the first compartment.

[0059] Any features described above in connection with the first aspect of the invention and below in connection with the other aspects may be applied to this aspect of the invention.

[0060] According to a third aspect of the present invention, there is provided a processing device for a therapeutic product or a biological sample, the processing device comprising a substantially tubular inner portion and a substantially tubular outer portion, the inner portion being at least partially received or receivable within the outer portion such that at least a portion of the inner portion is offset from a central longitudinal axis or centerline of the substantially tubular outer portion.

[0061] Preferably, the processing device is adapted for centrifugal separation.

[0062] In addition, the substantially tubular inner portion and the substantially tubular outer portion may be closed by a closure member. In a preferred form of the invention, the substantially tubular inner portion and the substantially tubular outer portion are closed by respective closure members. These closure members may be arranged at opposite ends of the treatment device. These closure members may be elastically deformable closure members.

[0063] Preferably, the substantially tubular inner portion and the substantially tubular outer portion define an inner compartment and an outer compartment. Preferably, the inner compartment is in fluid communication with the outer compartment via the filter opening. A first closure member may be provided to close the first compartment. A second closure member may be provided to close the second compartment.

[0064] Preferably, the offset of the substantially tubular inner portion is at least substantially aligned with a needle guide for sample delivery and / or retrieval. Additionally or alternatively, positioning a marker on one of the closure members may indicate a preferred needle entry point.

[0065] Preferably, the gap is created by the offset of the substantially tubular inner portion within the substantially tubular outer portion. Preferably, a needle guide for fluid aspiration is at least substantially aligned with the gap. Additionally or alternatively, positioning a marker on the elastically deformable closure member may be at least substantially aligned with the gap.

[0066] The processing device may be provided in the form of a kit.

[0067] Any features described above in conjunction with other aspects of the invention may be applied to this aspect of the invention.

[0068] As used herein, unless the context requires otherwise, the word "comprise" and variations such as "comprising", "including" and "comprising" are not intended to exclude other additives, components, integers or steps.

[0069] Further aspects of the invention and other embodiments described in the preceding paragraphs will become apparent from the following description, given by way of example only and with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] In order to more fully understand the present invention, one embodiment will now be described by way of example with reference to the accompanying drawings, in which:

[0071] FIG1 is a schematic diagram of a prior art method for rehydrating small volume cell therapy;

[0072] Figure 2A is a side elevation view of a processing device according to a preferred embodiment of the present invention;

[0073] Figure 2B yes Figure 2A A side elevation view of the processing device is shown, with additional features cited;

[0074] Figure 2C yes Figure 2A A detailed view of a portion of

[0075] Figure 3A yes Figure 2A A side elevation view of the processing device is shown, with some additional features cited;

[0076] Figure 3B is with Figure 2A A side elevation view of a processing device similar to the processing device shown in FIG. Figure 3C Section AA of

[0077] Figure 3C It passes through Figure 3B A cross-sectional view obtained from AA; and

[0078] Figure 3D yes Figure 3B A side elevation view of the processing device is shown, with some additional features cited;

[0079] Figure 3E It passes through Figure 3D The cross-sectional view obtained by BB;

[0080] Figure 3F It passes through Figure 3C The cross-sectional view obtained by CC;

[0081] Figure 4 is used Figure 2A Schematic diagram of the process of rehydrating a small volume of cells for therapy; DETAILED DESCRIPTION

[0082] like Figure 2A As shown, the processing device 10 according to the preferred embodiment of the present invention is generally in the form of a closed container 12. The closed container 12 is intended for centrifugation. Accordingly, the closed container 12 has a distal end 12a and a proximal end 12b. During centrifugation, the proximal end 12b is intended to be positioned radially inward from the distal end 12b.

[0083] The closed container is composed of a substantially tubular inner portion 14 (hereinafter "inner tube 14") and a substantially tubular outer portion 16 (hereinafter "outer tube 16"). The inner tube 14 is mostly received in the outer tube 16. The inner tube 14 and the outer tube 16 can be made separately from suitable plastic materials and then fused together. The outer tube 16 is substantially frustoconical and has an opening at the proximal end 12b. The outer tube 16 can have an opening at the distal end 12a (but as will be explained, it is closed by an elastically deformable closure member 34). The outer tube 16 may include (as will be combined with Figure 3A and Figure 3F ) needle guide 52.

[0084] The proximal region 18 of the inner tube 14 has an outer shape that is commensurate with the inner shape of the outer tube 16. Accordingly, the inner tube 14 will be placed inside the outer tube 16 by virtue of a gradual reduction in cross-sectional area extending in the distal direction of both the inner tube 14 and the outer tube 16. Thus, the two parts have a tapered fit. The inner tube 14 is thus nested inside the outer tube 16. The inner tube 14 and the outer tube 16 can be fused together in this configuration by heat fusion or a similar process.

[0085] The inner tube 14 includes a first substantially tubular portion 20 and a second substantially tubular portion 22. The first tubular portion 20 is disposed distally of the second tubular portion 22. The first tubular portion 20 and the second tubular portion 22 are both defined by a sidewall extending from the proximal end 12b to the distal end 12a, wherein the cross-sectional area decreases from the proximal end 12b to the distal end 12a. Along some portions of the length, the decrease in cross-sectional area is gradual, while in other portions along the length, there may be a step-like change in cross-sectional area, as shown in the figure.

[0086] The first tubular portion 20 has a proximal portion 24 whose cross-sectional area gradually decreases in the distal direction. However, the reduction in cross-sectional area causes the center of each cross section to move toward one side (eg, Figure 2A left as shown).

[0087] The first tubular portion 20 also has a distal portion 26 that extends distally from the proximal portion 24 toward the distal end of the first tubular portion 20. The cross-sectional area of ​​the distal portion decreases along at least a portion of its length. The distal portion 26 continues distally on the offset trajectory established by the skewed proximal portion 24 so that the first tubular portion 20 extends downwardly along one side of the container 12. Figure 2A Thus, the longitudinal centerline of the first tubular portion 20 is offset from the central longitudinal axis of the outer tube 16, and for that matter, also from the central longitudinal axis of the container 12.

[0088] like Figure 3E As shown, the distal portion 26 is shaped in the form of a housing 21 having a C-shaped cross section. The filter material 28 extends across the outer edge of the C-shaped housing 21. The side of the C-shaped housing 21 adjacent to the inner tube 14' (the left side in the figure) approximates the cylindrical inner circumference of the outer tube 16'.

[0089] like Figure 2A As shown, the distal end of the distal portion 26 is closed by the end wall 15. Figure 3D and Figure 3F As shown in the variation of , the distal end of the distal portion 26 has an internal slope 23. This ensures that the cells 68 are guided toward the filter 28 to avoid dead zones where the cells 68 cannot receive washing.

[0090] Filters and compartments

[0091] On the other side of the distal portion 26 ( Figure 2A2 ), a filter opening 28 is provided. The filter opening 28 is elongated and extends the entire length of the distal portion 26. Having a larger filter opening minimizes clogging of the filter material 28. The filter is preferably a filter with a<=20 μm, which is molded into the side wall of the first tubular portion 20. For example, the inner tube 14 can be formed in a process of overmolding onto an existing filter.

[0092] like Figure 2A As shown, the filter opening 28 faces a void 30 created within the container 12 by the offset first tubular portion 20 .

[0093] The proximal end 12b of the inner tube 14 is closed by an elastically deformable closing member 32. The distal end 12a of the outer tube 16 may be closed by an elastically deformable closing member 34.

[0094] The inner tube 14 and the outer tube 16 together with the closure members 32, 34 define the closed container 12. Within the closed container 12, the inner tube 14, the end wall 15 and the closure member 32 define an inner compartment 40. An outer compartment 42 is defined between the inner tube 14 and the outer tube 16, the end wall 15 and the closure member 34. The outer compartment 42 at least partially surrounds the inner compartment 40.

[0095] The distal wall 15 of the inner tube 14 ends at a point not far from the distal end of the outer tube 16. On the other hand, the proximal end of the inner tube 14 protrudes beyond the proximal end of the outer tube 16 by a relatively short protrusion 36. In this case, the relatively short protrusion 36 ensures that the volume of the inner compartment 40 exceeds that of the outer compartment 42.

[0096] Vent

[0097] Figure 2B and Figure 2C A peripheral vent 46 is shown disposed in the container 12. The peripheral vent 46 is disposed in the protrusion 36 in the proximal region 18. However, the vent 46 may also be disposed in the closure member 32. The vent 46 allows air to escape when a sample or therapeutic product is injected into the container 12, and also allows air to be drawn into the container when the filtrate and / or residue is aspirated from the container 12. This allows pressure equalization during the transfer of the sample / product to an otherwise hermetically sealed container and the aspiration of the filtrate / residue / recovered product out of the otherwise hermetically sealed container. The vent is preferably a filter in the form of a hydrophobic membrane having a pore size of 0.2 μm, which allows gas exchange but prevents pathogens from leaving the container 12 and / or prevents contaminants from entering the container 12. The injected therapeutic product should be sterile, so the function of the vent is to allow pressure equalization during injection / aspiration, but prevent pathogens from entering from the outside.

[0098] In addition, if Figure 2BAs shown, the vent 46 is arranged above a "max fill" line 47 indicating the maximum working volume capacity of the inner tube 14 (5 mL in this example). Between the vent and the maximum fill line 47, a vent protector 48 is arranged. The vent protector 48 is in the form of a peripheral channel formed together with the side wall 49 of the inner tube 14. The channel may extend adjacent to the vent 46. The extent of the channel may correspond substantially only to the extent of the vent 46. Alternatively, the channel may be circumferential.

[0099] In addition, the inner tube 14 is marked with markings to indicate the fill level. Of the (as marked) 5 mL maximum working volume capacity of the inner tube 14, 1 mL is allocated to the first tubular portion 20, and the remaining 4 mL is allocated to the second tubular portion 22. Overall, the inner tube 14 has a capacity greater than 5 mL, but the maximum marked fill capacity is 5 mL to ensure that the maximum fill level is below the vent 46.

[0100] capacity

[0101] The working capacity of the inner compartment 40 of the inner tube 14 (5 mL in this case) is greater than the capacity of the outer compartment 42 (4.5-4.9 mL in this case). This ensures that after centrifugation, the residual amount of liquid must remain in the inner compartment 40. Therefore, in the case where the liquid undergoing centrifugation contains biological cells, these cells will still be in the liquid at the end of centrifugation. By changing the volume difference between the inner compartment and the outer compartment, the processing device can be adjusted to keep different volumes of residual liquid in the inner compartment. This is very convenient in function because some applications may require a final volume of, for example, 0.1-0.5 ml. Other overall sizes are envisioned for other applications. Different versions of the processing device can be obtained to provide different volumes of residual liquid in the inner compartment according to the version. There can be small, medium and large versions.

[0102] Closures

[0103] Figure 3A The form of the closure members 32, 34 is shown. The closure members 32, 34 are in the form of a compressed synthetic material, generally referred to as a "stopper". These closure members 32, 34 are formed of a resiliently compressible material to allow needle penetration to allow for delivery and aspiration of the product / sample, as will be explained subsequently. The closure members 32, 34 are additionally provided with needle guides 50, 52. The closure member 32 incorporating the needle guides 50, 52 may be any of several known brands, typically used as a needle port for an IV bag. For example, a suitable proprietary needle inlet 32' is provided by Medidose ( https: / / www.medidose.com / injection- port4.aspx ). For example, see Figure 3A on the right side.

[0104] Thus, the closure members 32, 34 serve multiple purposes, firstly as closure members for the container 12, secondly as delivery and aspiration ports for syringe delivery and aspiration from the container, and thirdly as needle guides for syringe needles.

[0105] Needle Guide

[0106] like Figure 2A and Figure 3A , the needle guide 50 is aligned with the offset axis of the first tubular portion 20. When delivering a sample / therapeutic product, as will be explained later, the delivery needle will be able to enter the inner compartment 40 without hitting the side wall of the first tubular portion 20 when the first tubular portion 20 is tilted to the left as shown. In addition, during the retrieval process, the inserted needle will be directly in line with the distal portion 26 to recover cells and / or other residual fluids that have not passed through the filter 28.

[0107] In contrast, the distal needle guide 52 is disposed within or facing the void 30. This provides space for the entry of the syringe needle to remove the filtrate from the void 30.

[0108] Suitably, the inner and outer tubes 14, 16 are transparent to enable a laboratory technician / doctor to view the contents of the container 12 and to observe the passage of the delivery and retrieval needles. (However, this process may also be automated).

[0109] Figure 3B and Figure 3C An alternative form of the treatment device 10' is shown in which the needle guide 50 is incorporated into the container 12, in particular into the inner tube 14'. In this form of the invention, the needle guide 50' is not incorporated into the closure member 32. Instead, the needle guide 50' is grafted onto the inner tube 14'. In particular, the side wall of the inner tube 14' has a radially inwardly extending protrusion 55, wherein the needle guide 50' is supported by the protrusion 55. The side wall of the inner tube 14', the protrusion 55 and the needle guide 50' can be formed integrally, for example molded from a plastic material.

[0110] Figure 3B and Figure 3C Also shown is the form of a peripheral vent 46 in the shape of an arc of a circle.

[0111] Similarly, Figure 3E and Figure 3F Shown through Figure 3DThe needle guide 52' is incorporated into the container 12, specifically into the outer tube 16'. The needle guide 52' is grafted onto the outer tube 16'. The side wall of the outer tube 16' has a protrusion 56 extending radially inward, wherein the needle guide 52' is supported by the protrusion 56. The side wall of the outer tube 16', the protrusion 56 and the needle guide 52' can be formed integrally.

[0112] It will be appreciated that like reference numerals will be used to show like parts. However, the addition of a symbol (') will show the location of parts that have been modified for the variant or second embodiment.

[0113] Workflow

[0114] In order to more fully understand the present invention, reference will be made to Figure 4 The workflow using the processing devices 10 and 10' will be described. Figure 4 An end-to-end workflow is shown for rehydration of a frozen cell therapy product that is thawed, washed to remove cryopreservatives, and concentrated to a therapeutic dose for handover to the surgical team. This is a specific and preferred embodiment. However, the invention extends beyond this specific embodiment and may have many other uses in workflows requiring centrifugation.

[0115] like Figure 4 As shown in Figure A, the frozen cells are transported in a cryopreservative (such as DSMO) in a freezing container 58 (shown is one of many commercially available small volume cryovials). The cells are thawed in the freezing container 58, such as Figure 4 As shown in B.

[0116] like Figure 4 C, a syringe 60 is used to draw the contents of the frozen container 58 and transport them to the processing device 10. The syringe 60 can be part of an automatic sample injector. The needle of the syringe 60 pierces the closure member 32 and enters the inner compartment 40 in the inner tube 14. Therefore, the contents of the syringe 60 are deposited in the inner compartment 40. The needle is typically a 20-gauge needle.

[0117] like Figure 4 As shown in FIG. 6D , the processing device 10 is then placed in a centrifuge 62 . As a result of the centrifugation, some of the cryopreservative will pass through the filter openings 28 into the outer compartment 42 .

[0118] like Figure 4E, the cryopreservative can then be removed by using a syringe 64, the needle of which is inserted through the distal closure member 34 into the void 30. In addition, excess cryopreservative can be removed by a syringe 66, the needle of which is inserted into the inner compartment 40, because the cells of the therapeutic product 68 will move to the distal region of the inner compartment 40, and thus the excess cryopreservative can be removed from the inner compartment 40 without disturbing the cells 68. As shown in the figure, Figure 4 The outer compartment 42 is already free of cryopreservative prior to the introduction of the fresh suspension in F. Complete removal is not possible, but this step and the additional washes have the intended functional effect of diluting the DMSO to an acceptable very low concentration (this is often mandated by regulators / pharmacopoeias depending on the target tissue or organ).

[0119] like Figure 4 As shown in F, syringe 70 delivers a fresh suspension for a therapeutic product, such as Ringers solution. Syringe 70 delivers the fresh suspension via a needle inserted through proximal closure 32, proximal needle guide 50 and into inner compartment 40.

[0120] like Figure 4 G, the processing device 10 is then placed in a centrifuge. After centrifugation, some of the suspension will pass through the filter opening 28 and enter the outer compartment 42. The cells 68 of the therapeutic product remain in the inner compartment 40. The distal syringe 74 is then inserted through the distal closure 34 and the distal needle guide 52 to expel the waste suspension from the void 30. Figure 4 As shown, this wash cycle is repeated a number of times depending on the therapeutic product, the level of residual removal desired, the specific cryopreservative concentration to be achieved, etc., as determined by one skilled in the art.

[0121] like Figure 4 J, then the excess suspension is removed from the inner compartment 40 via the proximal syringe 76. The amount of suspension removed depends on the desired concentration of the therapeutic product. The therapeutic product is then ready to be handed over to the surgical team. Handing it over to the surgical team using the same processing device 10 avoids another container, minimizes additional steps, avoids container waste and reduces the possibility of contamination. Further, the fusion of the inner tube 14 and the outer tube 16 means that they cannot be separated, which also reduces the risk of contamination or tampering.

[0122] The syringes 60, 64, 66, etc. may be separate sterile syringes, or alternatively may be the same syringe that is sterilized between processing steps as is known in the art.A syringe may be dedicated to delivering / removing a respective liquid.

[0123] The advantages of the preferred embodiment are as follows:

[0124] 1. Closed cell storage

[0125] The valuable cells never come into contact with the external environment and thus minimize the risk of biocontamination and reduce environmental control requirements, which is important in a regulatory framework. Using one container from post-thawing to surgical handover also minimizes cell losses.

[0126] 2. Easy to use

[0127] There is no reliance on operator pipetting skills. The only process operations are centrifuge and needle injection or aspiration, designed to be easy.

[0128] 3. Scalability

[0129] Suitable for use in research, development, clinical or GMP environments. Simple automated operation is envisioned for future large-scale use.

[0130] 4. Addressing growing unmet needs

[0131] Cell and gene therapies will increasingly target solid tissues and organs and will therefore require low-volume reconstitution during the therapeutic delivery phase.

[0132] It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All these different combinations constitute different alternative aspects of the invention.

Claims

1. A processing device for a therapeutic product or a biological sample, the processing device being provided with a proximal end and a distal end and comprising a first compartment and a second compartment, the processing device comprising a first substantially tubular portion, wherein: The first compartment is in fluid communication with the second compartment via a filter opening arranged in or along the first substantially tubular portion.

2. The processing device according to claim 1, wherein: The first substantially tubular portion defines a side wall of the first compartment, wherein the filter opening is disposed on the side wall.

3. The processing device according to claim 1 or 2, wherein: The filter opening is elongated, with the elongated extent of the filter opening being oriented generally aligned with the longitudinal direction of the first substantially tubular portion.

4. A processing device as claimed in any one of the preceding claims, wherein: The first generally tubular portion has a cross-section, and the centroid of the cross-section is offset from a central longitudinal axis of the treatment device along at least a portion of the length of the first generally tubular portion.

5. The processing device according to claim 4, wherein: For at least a portion of the length of the first substantially tubular portion, the cross-sectional area of ​​the cross section decreases towards the distal end.

6. A processing device as claimed in any one of the preceding claims, wherein: A portion of the first generally tubular portion toward the distal end is skewed toward one side of the treatment device.

7. The processing device of claim 6, further comprising: A first needle guide is at least substantially aligned with the skewed portion of the first generally tubular portion.

8. The processing device according to claim 6 or 7, wherein: The filter opening preferably faces towards another side of the treatment device to face a void within the treatment device, the void forming part of the second compartment.

9. A processing device as claimed in any one of the preceding claims, wherein: The length of the filter opening is at least half the length of the first substantially tubular portion.

10. A processing device as claimed in any one of the preceding claims, wherein: The first compartment and the second compartment include an inner compartment and an outer compartment, respectively, wherein the inner compartment is at least partially disposed within the outer compartment.

11. A processing device as claimed in any one of the preceding claims, wherein: The volume of the first compartment is greater than the volume of the second compartment.

12. The processing device according to claim 8, wherein: A second needle guide and / or an outlet port is disposed at or near the void for selectively removing filtrate from the second compartment.

13. A processing device as claimed in any one of the preceding claims, wherein: The processing device further comprises a second closure for the second compartment, the second closure comprising a sealable closure, such that the second sealable closure allows the filtrate to be drawn through the sealable closure.

14. A processing device as claimed in any one of the preceding claims, wherein: The first generally tubular portion forms part of an inner portion which is generally tubular and is at least partially received within the generally tubular outer portion, and the second compartment is defined between the inner portion and the outer portion.

15. The processing device according to claim 14, wherein: The inner portion protrudes proximally beyond the outer portion.

16. The processing device according to claim 14 or 15, wherein: The inner portion and the outer portion are permanently connected or integrally formed such that the inner portion and the outer portion are interconnected at a proximal region thereof.

17. A processing device as claimed in any one of the preceding claims, wherein: The proximal end of the device is closed by a first closure member.

18. A treatment device as claimed in any preceding claim, further provided with a vent.

19. A kit comprising components assemblable to define a treatment device as claimed in any preceding claim.

20. A kit for a processing device for processing a therapeutic product or a biological sample, the kit comprising assemblable components for defining a first compartment and a second compartment, such that in the assembled processing device, the first compartment is in fluid communication with the second compartment via a filter opening, wherein the filter opening is arranged in or along a first basic tubular portion of the device.

21. A method of using a processing device or kit as claimed in any one of the preceding claims for processing a therapeutic product or a biological sample using centrifugation, wherein: The method includes: delivering the product or sample to the first compartment, removing filtrate from the second compartment; and The processed product is recovered from the first compartment.

22. A processing device for a therapeutic product or a biological sample, the processing device comprising a first compartment and a second compartment, wherein: The first compartment is in fluid communication with the second compartment via a filter opening, wherein the first compartment and the second compartment are defined by permanently connected or integrally formed container portions.

23. The processing device according to claim 22, wherein: The container portion includes a generally tubular inner portion and a generally tubular outer portion, the inner portion at least partially defining the first compartment and the second compartment being at least partially defined between the inner portion and the outer portion.

24. The processing device according to claim 22 or 23, wherein: The opposite end of the processing device is closed by a first elastically deformable closure member and a second elastically deformable closure member, wherein the first closure member is arranged for closing the first compartment and the second closure member is arranged for closing the second compartment.

25. A method of processing a therapeutic product or a biological sample using centrifugal separation using a processing device as claimed in any one of claims 22 to 24, wherein: The method includes: delivering the product or sample to the first compartment, removing filtrate from the second compartment; and The processed product is recovered from the first compartment.

26. A processing device for a therapeutic product or biological sample, the processing device comprising a substantially tubular inner portion and a substantially tubular outer portion, the inner portion being at least partially received or receivable within the outer portion such that at least a portion of the inner portion is offset from a central longitudinal axis or centerline of the substantially tubular outer portion.

27. The processing device according to claim 26, wherein: The processing device is adapted for centrifugal separation.

28. The processing device according to claim 26 or 27, wherein: The inner portion has a cross-section, and the centroid of the cross-section is offset from the central longitudinal axis of the treatment device along at least a portion of the length of the inner portion.

29. The processing device of claim 28, wherein: The inner portion and the outer portion define an inner compartment and an outer compartment, and the inner compartment is in fluid communication with the outer compartment via the filter opening.

30. The processing device according to any one of claims 26 to 29, wherein: The offset portion is at least substantially aligned with a first needle guide for sample delivery and / or retrieval.

31. The processing device of claim 30, wherein: The inner portion is closed by a first closure member, which is elastically deformable and on which a positioning mark is provided, wherein the mark is at least substantially aligned with the first needle guide.

32. A processing device as claimed in any one of claims 26 to 31, wherein: A gap is created within the outer portion by the offset portion, and the second needle guide is at least substantially aligned with the gap.

33. The processing device of claim 32, wherein: The outer portion is closed by a second closing piece, which is elastically deformable and on which a positioning mark is provided, which is at least substantially aligned with the gap.

34. A treatment device as claimed in any one of claims 26 to 33 provided in the form of a kit, wherein: The inner portion and the outer portion are assemblable discrete parts, wherein the inner portion is at least partially received within the outer portion.

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