Processing Equipment

Abstract

The therapeutic product or biological sample treatment device (10) has a proximal end (12b) and a distal end (12a). The device includes first and second compartments (40, 42) and a first generally tubular portion (20). The first compartment (40) is in fluid communication with the second compartment (42) through a filtering opening (28) disposed in or along the first generally tubular portion (20). The treatment device (10) may be provided in the form of a kit. Methods of using the treatment device (10) or kit are also disclosed.

Description

[Technical field]

[0001]

[0001] The present invention relates to a treatment device for therapeutic products or biological samples. In particular, but not exclusively, the present invention relates to a treatment device intended for use in a centrifuge. One specific application of the treatment device is the reconstitution of a thawed cell therapy product in a therapeutic setting. Although the present invention is described with a particular application to the reconstitution of a thawed cell therapy product, the treatment device may have applications outside of the therapeutic field. The treatment device may also be applied to other fields where centrifugation is required. [Background technology]

[0002]

[0002] Typically, the prior art process for reconstitution of frozen cellular therapy products requires the product to undergo a process of thawing, removal of cryopreservatives, washing and final concentration to a therapeutic dose before handover to the surgical team.

[0003]

[0003] Figure 1 shows the workflow for reconstitution of a frozen cell therapy product. As shown in Figure 1A, frozen cells are delivered into the cryopreservative DSMO in a freezing container 1. As shown in Figure 1B, the cells are thawed in the freezing container 1.

[0004] As shown in FIG. 1C, a pipette 2 is used to aspirate the contents of the freezing container 1 and deliver it to a spin tube 3. Such spin tubes, also known as PCR tubes, are known in the art. Typically, they comprise a closed container with a hinged lid. During centrifugation, the top of the spin tube 3 is located radially inward and the bottom of the spin tube is located radially outward. For convenience, the radially inward is referred to as the "proximal" and the radially outward is referred to as the "distal".

[0005]

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

[0006]

[0006] As shown in Figure 1F, a pipette 2 delivers a fresh suspension for the therapeutic product, for example Ringer's. The liquid is agitated to disperse the cells into the fresh suspension, as shown in Figure 1G. The spin tube 3 is then placed in a centrifuge, as shown in Figure 1H. The supernatant is then removed from the spin tube 3 using a pipette, as shown in Figure 1I. This washing cycle is repeated several times.

[0007]

[0007] Next, excess suspension is removed from the spin tube 3 via pipette 2, as shown in Figure 1J. The amount of suspension removed depends on the desired concentration of the therapeutic product. The therapeutic product is then ready for handover to the surgical team.

[0008]

[0008] There are several problems with the current approach. First, the use of pipettes requires a skilled laboratory technician to carry out the process. This is manual intensive and therefore an obstacle. Second, the need for skilled laboratory personnel creates an obstacle to scalability. Second, the use of openable spin tubes (which need to be opened every time a pipette is used) is dangerous from a biosafety perspective. This imposes high environmental control requirements and increases costs and complexity. Third, the use of pipettes poses the risk of pumping up therapeutic cells or instead leaving valuable cells behind.

[0009]

[0009] Thus, current approaches cannot be scaled beyond initial research use, limiting their usefulness.

[0010]

[0010] It is therefore an object of the present invention to overcome or ameliorate at least one of the above-mentioned disadvantages. It is an alternative object of the present invention to provide the public with a useful alternative over known processing devices.

[0011]

[0011] The reference to any prior art in this specification is not an admission or suggestion that this prior art forms part of the common general knowledge in any jurisdiction, or that this prior art would be understood by, considered relevant, and / or could reasonably be expected to be combined with other prior art by a person skilled in the art. Summary of the Invention

[0012]

[0012] According to a first aspect of the present invention, there is provided a processing device for a therapeutic product or biological sample having a proximal end and a distal end, including a first compartment and a second compartment, and including a first generally tubular portion, the first compartment being in fluid communication with the second compartment through a filtration opening disposed within or along the first generally tubular portion.

[0013] The processing device may be configured for use in a centrifuge. Thus, the processing device may incorporate features that facilitate use in a centrifuge, such as any commercially available benchtop centrifuge. For example, the processing device may be insertable into a regular 15 ml centrifuge tube, with or without an insert for fixation. Thus, the processing device includes a proximal end and a distal end, the proximal end being positioned radially inward from the distal end during centrifugation.

[0014]

[0014] The first generally tubular portion may define a sidewall of the first compartment. Accordingly, a filtering opening may be provided in the sidewall. The filtering opening is preferably elongate. The elongate extension of the filtering opening is preferably oriented generally or substantially aligned with a longitudinal direction of the first generally tubular portion. The elongate extension of the filtering opening may be oriented in a longitudinal direction of the sidewall.

[0015]

[0015] The sidewall may be a cylindrical sidewall. Alternatively, the sidewall may be tapered. Preferably, the sidewall tapers in a distal direction. The first generally tubular portion may decrease in cross-sectional area along at least a portion of its length. This may include a gradual or stepwise decrease, or a combination of a gradual and stepwise decrease. Preferably, the cross-sectional area decreases in a distal direction along its length. The sidewall may be conical, or the first generally tubular portion may include a frusto-conical or semi-frusto-conical portion.

[0016]

[0016] The first generally tubular portion may be of a complex shape. In a most preferred form of the invention, the decreasing cross-sectional area along its length is such that the centerline of the cross-sectional area progressively deviates from the central longitudinal axis of the processing device. In other words, the first generally tubular portion has a transverse cross-section, the center of gravity of which deviates from the central longitudinal axis of the processing device over at least a portion of the length of the first generally tubular portion. Thus, the first generally tubular portion preferably slopes to one side of the processing device along its length in the distal direction.

[0017]

[0017] When the first generally tubular portion is angled towards one side of the treatment device, the filtration opening preferably faces the other side of the treatment device and thus faces a cavity within the treatment device that defines a portion of the second compartment.

[0018]

[0018] The filtration opening preferably comprises a filter for filtering the therapeutic product or biological sample. The filter may comprise any commercially available filter material, media or single media suitable for centrifugal filtration. For example, the filter material, media or single media may comprise a tightly woven fabric, paper, non-woven fabric, metal screen or porous media. Preferably, the filter is operable as a liquid filter to screen cells and retain them in the first compartment. For example, the filter material may have a pore size up to 20 μm, or in the range of 10 to 20 μm. Smaller sizes, including small protein filter sizes in the kDalton scale, can also be used.

[0019]

[0019] The filter and / or filtering opening may be disposed in a shaped, e.g. curved or flat, wide area of ​​the sidewall of the first generally tubular portion. The filter and / or filtering opening may extend to a distal end of the first generally tubular portion. The filter and / or filtering opening is preferably elongated, preferably having a length less than its width. The filter and / or filtering opening preferably extends over a substantial proportion of the length of the first generally tubular portion. Preferably, the length of the filter and / or filtering opening is about half the length of the first generally tubular portion. In an alternative version, the first generally tubular portion may comprise more than 2 / 3 of the length of the first generally tubular portion, optionally more than 3 / 4 of the length of the first generally tubular portion.

[0020]

[0020] The first compartment may have a working volume of about 5mL at a maximum fill level. The volume of the first generally tubular portion of the first compartment preferably comprises about 1mL. The filter and / or filtration opening may extend from the base of the first compartment to a position corresponding to more than 100μL. The first compartment may include indicia indicating the liquid level.

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

[0022]

[0022] The filter may be replaceable for reuse of the treatment device, or preferably the treatment device is disposable.

[0023]

[0023] Preferably, the first and second compartments each include an inner compartment and an outer compartment, the inner compartment being at least partially disposed within the outer compartment. In this configuration, the second compartment surrounds the first compartment. When the first generally tubular portion is angled, a cavity within the second compartment defines a convenient location for aspiration of filtrate.

[0024] In a preferred form of the device, a needle guide and / or an outlet port may be provided in or next to the cavity 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 for aspiration of filtrate through the sealable closure. For example, the second sealable closure may comprise an elastically deformable material that allows the passage of a pierceable closure member, e.g. a needle, while allowing closure of the passage due to the elastic properties of the material upon withdrawal of the needle. For example, the elastically deformable material may be a plastic material such as synthetic rubber or natural rubber.

[0025]

[0025] A needle guide may be provided to ensure proper and at least substantial alignment of the needle upon insertion into the second compartment. The needle guide may be used in conjunction with the second closure member.

[0026]

[0026] The first compartment may also include a second generally tubular portion disposed proximally relative to the first generally tubular portion. The second generally tubular portion may comprise the remaining portion of the working volume of the first compartment, i.e., approximately 4 mL. The first and second generally tubular portions preferably form a single container, such as an integrally formed container.

[0027]

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

[0028] In a preferred form of the invention, the inner generally tubular portion of the processing device includes at least a first and a second generally tubular portion. The inner generally tubular portion may be at least partially received within the outer generally tubular portion. The second compartment is preferably defined between the inner generally tubular portion and the outer generally tubular portion. Preferably, the first compartment is larger in volume than the second compartment. This avoids the passage of all liquid from the first compartment to the second compartment during centrifugation, thereby retaining a residual amount of liquid in the first compartment to retain cells / proteins / biological samples immersed in the liquid. To this end, the inner generally tubular portion may protrude proximally beyond the outer generally tubular portion.

[0029]

[0029] The inner and outer generally tubular portions may be permanently connected or integrally formed. For example, the inner and outer generally tubular portions may be interconnected at their proximal end regions. For example, the inner generally tubular portion may be fused to the outer generally tubular portion. For example, the inner and outer portions may be melted together. This, together with the first and second closure portions as described above and below, provides the processing device as a closed system in which the first and second compartments are not easily accessible. The inner and outer generally tubular portions are preferably corresponding in shape at their proximal end regions.

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

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

[0032]

[0032] The inner and outer generally tubular portions may be formed of a pyrogen-free plastic material. Preferably, the inner and outer generally tubular portions are formed of a transparent plastic material. Preferably, the treatment device is sterilized prior to use.

[0033]

[0033] The proximal end of the device may be closed by a first closure. Preferably, the processing device includes a first sealable closure for the first compartment. Preferably, the sealable closure allows for injection of a therapeutic product or biological sample through the sealable closure. For example, the sealable closure may comprise an elastically deformable material that allows the passage of a pierceable closure member, such as a needle, while allowing closure of the passageway due to the elastic properties of the material upon withdrawal of the needle.

[0034]

[0034] Preferably, a delivery / return port is provided at the proximal end region of the processing device. In the most preferred form, the delivery / return port is realized 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. There may be more than one needle guide to separate delivery from return to avoid contamination of the needle.

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

[0036]

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

[0037]

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

[0038]

[0038] The processing device may further be provided with an air vent, which is necessary in an otherwise sealed processing device to allow the evacuation of air during injection of a therapeutic product or biological sample and / or the introduction of air during aspiration of a therapeutic product or biological sample.

[0039]

[0039] The vent is preferably in the form of a peripheral vent. Preferably, the vent is provided in a protruding portion of the inner generally tubular portion that protrudes beyond the outer generally tubular portion. The vent may include a filter to allow gas exchange but prevent the passage of pathogens and / or contaminants. 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 prevent the passage of pathogens.

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

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

[0042]

[0042] Cell processing may include cell reconstitution, including cell washing, cell filtration and cell concentration.

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

[0044] According to another aspect of the invention, there is provided a kit comprising components which can be assembled to form a processing apparatus as described above or below in relation to the other aspects.

[0045]

[0045] According to an embodiment related to the first aspect of the present invention, there is provided a kit for a processing device for processing a therapeutic product or biological sample, the kit including assemblable components defining a first compartment and a second compartment, wherein in the assembled processing device the first compartment is in fluid communication with the second compartment via a filtration opening, the filtration opening being disposed within or along a first generally tubular portion of the device.

[0046] According to a related aspect of the first aspect of the present invention, there is provided a method of processing a therapeutic product or biological sample using centrifugation, the method comprising: Delivering a product or sample to a first compartment; removing the filtrate from the second compartment; Recovering the treated product from the first compartment; Includes.

[0047]

[0047] According to a second aspect of the present invention, there is provided a processing device for a therapeutic product or biological sample, the processing device comprising a first compartment and a second compartment, the first compartment being in fluid communication with the second compartment via a filtration opening, the first compartment and the second compartment being defined by a container portion that is permanently connected to or integrally formed with the first compartment.

[0048] For example, the processing device may be formed by an inner generally tubular portion and an outer generally tubular portion. The inner generally tubular portion may at least partially define the first compartment. The second compartment may be defined, at least partially, between the inner generally tubular portion and the outer generally tubular portion.

[0049]

[0049] The inner and outer generally tubular portions may be formed separately and permanently connected in a subsequent processing step. The inner and outer generally tubular portions may be permanently connected at their proximal end regions.

[0050]

[0050] Furthermore, the processing device may be closed at both ends by elastically deformable closure members. A first closure member may be provided for closing the first compartment. A second closure member may be provided for closing the second compartment.

[0051]

[0051] The container portion may be formed by an additive manufacturing process, for example 3D printing.

[0052] According to a related aspect of the second aspect of the present invention, there is provided a method of processing a therapeutic product or biological sample using centrifugation, the method comprising: Delivering a product or sample to a first compartment; removing the filtrate from the second compartment; Recovering the treated product from the first compartment; Includes.

[0053] Any of the features discussed above in relation to the first aspect of the invention or the other aspects below may also be applied to this aspect of the invention.

[0054]

[0054] According to a third aspect of the present invention, there is provided a processing device for a therapeutic product or biological sample, the processing device including a generally tubular inner portion and a generally 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 generally tubular outer portion.

[0055]

[0055] Preferably, the processing device is adapted for centrifugation.

[0056]

[0056] Furthermore, the inner and outer tubular portions may be closed by closure members. In a preferred embodiment of the present invention, the inner and outer tubular portions are closed by respective closure members. The closure members may be disposed at both ends of the processing device. The closure members may be elastically deformable closure members.

[0057]

[0057] Preferably, the inner and outer generally tubular portions define an inner compartment and an outer compartment. Preferably, the inner compartment is in fluid communication with the outer compartment via the filtering opening. A first closure member may be provided for closing the first compartment. A second closure member may be provided for closing the second compartment.

[0058]

[0058] Preferably, the offset of the inner generally tubular portion is at least substantially aligned with a needle guide for sample delivery and / or retrieval. Additionally or alternatively, a positioning indicia on one of the closure members may indicate a preferred needle entry point.

[0059]

[0059] Preferably, the cavity is created by offsetting the inner generally tubular portion within the outer generally tubular portion. Preferably, a needle guide for fluid aspiration is at least substantially aligned with the cavity. Additionally or alternatively, a positioning indicia on the elastically deformable closure member may be at least substantially aligned with the cavity.

[0060]

[0060] The processing device may be provided in the form of a kit.

[0061]

[0061] Any of the features described above in relation to other aspects of the invention may also be applied to this aspect of the invention.

[0062]

[0062] As used in this specification, unless the context requires otherwise, the term "comprise", as well as variations of that term, such as "comprising", "comprises" and "comprised", are not intended to exclude further additional, components, integers or steps.

[0063] Further aspects of the invention and further embodiments of the aspects described in the previous paragraphs will become apparent from the following description, given by way of example and referring to the accompanying drawings, in which:

[0064] In order that the invention may be more fully understood, an embodiment will now be described, by way of example, with reference to the following drawings, in which: [Brief description of the drawings]

[0065] [Figure 1] FIG. 1 is a schematic diagram of a prior art process for reconstituting a small volume cell therapy product. [Figure 2A] 1 is a side view of a processing apparatus according to a preferred embodiment of the present invention; [Figure 2B] FIG. 2B is a side view of the processing apparatus shown in FIG. 2A in relation to additional features. [Figure 2C] FIG. 2B is a detailed view of a portion of FIG. 2A. [Figure 3A] FIG. 2B is a side view of the processing apparatus shown in FIG. 2A in conjunction with some additional features. [Figure 3B] 3C is a side view of a processing apparatus similar to that shown in FIG. 2A, taken along section AA of FIG. 3C. [Figure 3C] FIG. 3C is a cross-sectional view taken along line AA in FIG. 3B. [Figure 3D] FIG. 3C is a side view of the processing apparatus shown in FIG. 3B in conjunction with some additional features. [Figure 3E] FIG. 3B is a cross-sectional view of BB in FIG. 3D. [Figure 3F] FIG. 3D is a cross-sectional view of CC in FIG. 3C. [Figure 4] FIG. 2B is a schematic diagram of a process for reconstituting a small volume of cell therapy product using the device of FIG. 2A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0066]

[0076] As shown in Figure 2A, a processing device 10 according to a preferred embodiment of the present invention is generally in the form of a sealed container 12. The sealed container 12 is for use in centrifugation. As such, the sealed container 12 has a distal end 12a and a proximal end 12b. The proximal end 12b is intended to be located radially inward of the distal end 12b during centrifugation.

[0067]

[0077] The hermetic container is comprised of a generally tubular inner portion 14 (hereinafter, "inner tubular body 14") and a generally tubular outer portion 16 (hereinafter, "outer tubular body 16"). The inner tubular body 14 is received mostly within the outer tubular body 16. The inner tubular body 14 and the outer tubular body 16 may be manufactured separately from suitable plastic materials and then fused together. The outer tubular body 16 is generally frusto-conical in shape and has an opening at the proximal end 12b. The outer tubular body 16 may have an opening at the distal end 12a (but is closed by an elastically deformable closure member 34, as described below). The outer tubular body 16 may include a needle guide 52 (as described in connection with Figures 3A and 3F).

[0068]

[0078] The proximal end region 18 of the inner tubular body 14 has an outer shape that corresponds to the internal shape of the outer tubular body 16. Thus, the inner tubular body 14 seats within the outer tubular body 16 by virtue of the distally tapering cross-sectional area of ​​both the inner tubular body 14 and the outer tubular body 16. The two portions thus have a tapered fit. As a result, the inner tubular body 14 nests within the outer tubular body 16. The inner tubular body 14 and the outer tubular body 16 may be fused together in this configuration by heat melting or a similar process.

[0069]

[0079] The inner tubular body 14 includes a first generally tubular section 20 and a second generally tubular section 22. The first tubular section 20 is disposed distally of the second tubular section 22. Both the first tubular section 20 and the second tubular section 22 are defined by a sidewall that extends from the proximal end 12b to the distal end 12a and decreases in cross-sectional area from the proximal end 12b to the distal end 12a. Along portions of the length, the cross-sectional area decreases gradually, while other portions along the length may have a step-like change in cross-sectional area, as shown in the figures.

[0070]

[0080] The first tubular section 20 has a proximal portion 24 that has a gradually decreasing cross-sectional area in a distal direction, except that the cross-sectional area decreases such that the center of each cross-section moves progressively to one side (to the left as shown in FIG. 2A).

[0071]

[0081] The first tubular portion 20 also has a distal portion 26 extending distally from the proximal portion 24 toward the distal end of the first tubular portion 20. The distal portion has a decreasing cross-sectional area along at least a portion of its length. The distal portion 26 continues distally in an offset trajectory established by the angled proximal portion 24 such that the first tubular portion 20 extends down one side of the container 12. A straight line is maintained along the first tubular portion 20 on one side (the left side in FIG. 2A). Thus, the longitudinal centerline of the first tubular portion 20 is offset from the central longitudinal axis of the outer tubular body 16, and for that matter, the central longitudinal axis of the container 12.

[0072]

[0082] 3E, the distal portion 26 is molded into a shell 21 that is C-shaped in cross section. The filter material 28 extends across the outer edge of the C-shaped shell 21. The C-shaped shell 21 approximates the cylindrical inner circumference of the outer tubular body 16' on the side adjacent (left side in the figure) the inner tubular body 14'.

[0073]

[0083] As shown in Figure 2A, the most distal end of distal portion 26 is closed by end wall 15. As shown in the variants of Figures 3D and 3F, the most distal end of distal portion 26 has an internal bevel 23. This guides cells 68 towards filter 28 and ensures that cells 68 avoid dead zones where they do not receive washing.

[0074]

[0084] Filters and partitions The other side of the distal portion 26 (right side in FIG. 2A ) is provided with a filtering opening 28. The filtering opening 28 is elongated and extends the entire length of the distal portion 26. Having a large filtering opening minimizes clogging of the filter material 28. The filter is preferably a 20 μm or smaller filter molded into the sidewall of the first tubular section 20. For example, the inner tubular body 14 may be formed in a process of overmolding onto an existing filter piece.

[0075]

[0085] As shown in FIG. 2A, the filtering opening 28 faces a cavity 30 formed in the container 12 by the offset first tubular portion 20 .

[0076]

[0086] The inner tubular body 14 is closed at its proximal end 12b by an elastically deformable closure member 32. The outer tubular body 16 may be closed at its distal end 12a by an elastically deformable closure member 34.

[0077]

[0087] The inner and outer tubular bodies 14, 16 together with the closure members 32, 34 define a sealed container 12. Within the sealed container 12, the inner tubular body 14, the end wall 15 and the closure member 32 define an inner compartment 40. An outer compartment 42 is defined between the inner and outer tubular bodies 14, 16, the end wall 15 and the closure member 34. The outer compartment 42 at least partially surrounds the inner compartment 40.

[0078]

[0088] The distal end wall 15 of the inner tubular body 14 terminates short of the distal end of the outer tubular body 16, while the proximal end of the inner tubular body 14 protrudes beyond the proximal end of the outer tubular body 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 the volume of the outer compartment 42.

[0079]

[0089] Ventilation openings 2B and 2C show a peripheral vent 46 provided on the container 12. The peripheral vent 46 is located in the protruding portion 36 of the proximal end region 18. However, the vent 46 can also be located in the closure member 32. The vent 46 allows the escape of air during injection of a sample or therapeutic product into the container 12 and also allows the aspirating of air into the container when filtrate and / or residue is aspirated from the container 12. This allows pressure equalization during delivery of the sample / product into the sealed container and during aspirating of the filtrate / residue / recovered product from the sealed container. Preferably, the vent is a filter in the form of a hydrophobic membrane with a pore size of 0.2 μm that allows gas exchange but prevents pathogens from exiting the container 12 and / or contaminants from entering the container 12. Since the therapeutic product to be injected should be sterile, the function of the vent is to allow pressure equalization during injection / aspiration but prevents the entry of pathogens from the outside.

[0080]

[0090] Furthermore, as shown in FIG. 2B, the vent 46 is located above a "max fill" line 47, which indicates the maximum operating volume of the inner tubular body 14 (5 mL in this example). Between the vent and the max fill line 47, a vent protector 48 is provided. The vent protector 48 has the form of a peripheral groove formed by a side wall 49 of the inner tubular body 14. The groove may extend next to the vent 46. The extension of the groove may substantially correspond only to the extension of the vent 46. Alternatively, the groove may be circumferential.

[0081]

[0091] Additionally, the inner tubular body 14 is marked to indicate the fill level. Of the inner tubular body 14's maximum working volume of 5 mL (marked), 1 mL is allocated to the first tubular portion 20 and the remaining 4 mL is allocated to the second tubular portion 22. To ensure that the maximum fill level is below the vent 46, the maximum marked fill volume is 5 mL, however, overall the inner tubular body 14 has a volume of more than 5 mL.

[0082]

[0092] capacity The working volume of the inner compartment 40 of the inner tubular body 14 (5 mL in this case) is greater than the volume of the outer compartment 42 (4.5-4.9 mL in this case). This ensures that after centrifugation, a residual amount of liquid must remain in the inner compartment 40. Thus, if the liquid undergoing centrifugation contains biological cells, these cells remain in the liquid at the end of the centrifugation. By varying the volume difference between the inner and outer compartments, the processing device can be adjusted to retain different volumes of residual liquid in the inner compartment. This is functionally very convenient, since in some applications a final volume of, for example, 0.1-0.5 ml may be desired. For other applications other generic dimensions are envisaged. Various versions of the processing device are available and various volumes of residual liquid in the inner compartment can be proposed depending on the version. There can be small, medium and large versions.

[0083]

[0093] closure part FIG. 3A shows the configuration of the closure members 32, 34. The closure members 32, 34 are in the form of compressed synthetic material commonly known as "plugs". These closure members 32, 34 are formed of elastically compressible material to allow penetration by needles for product / sample delivery and aspiration, as will be described later. The closure members 32, 34 are further provided with needle guides 50, 52. The closure members 32 incorporating the needle guides 50, 52 can be any of several known brands commonly used as needle ports for IV bags. For example, a suitable proprietary needle entry port 32' is provided by Medidose (https: / / www.medidose.com / injection-port4.aspx). See, for example, the right side of FIG. 3A.

[0084]

[0094] Thus, closure members 32, 34 serve multiple functions: firstly, as closure members for container 12, secondly, as delivery and aspiration ports for syringe delivery and aspiration from the container, and thirdly, as needle guides for the syringe needles.

[0085]

[0095] Needle guide 2A and 3A, the needle guide 50 is aligned with the offset axis of the first tubular portion 20. During sample / therapeutic product delivery, as described below, the delivery needle is angled toward the left as shown, allowing it to enter the inner compartment 40 without hitting the side wall of the first tubular portion 20. Additionally, during retrieval, the inserted needle is directly aligned with the distal portion 26 to retrieve cells and / or other residual liquid that have not passed through the filter 28.

[0086]

[0096] Conversely, distal needle guide 52 is located within or facing cavity 30, thereby providing space for the entry of an injection needle to remove filtrate from cavity 30.

[0087]

[0097] Preferably, the inner tubular body 14 and the outer tubular body 16 are transparent to allow the technician / surgeon to see the contents of the container 12 as well as the passage of the delivery and retrieval needles (although the process can also be automated).

[0088]

[0098] 3B and 3C show an alternative form of treatment device 10' in which needle guide 50 is integrated into container 12, specifically inner tubular body 14'. In this form of the invention, needle guide 50' is not integrated into closure member 32. Instead, needle guide 50' is joined to inner tubular body 14'. Specifically, a sidewall of inner tubular body 14' has a radially inwardly extending protrusion 55 by which needle guide 50' is supported. Sidewall of inner tubular body 14', protrusion 55 and needle guide 50' may be integrally formed, e.g., molded from a plastic material.

[0089]

[0099] 3B and 3C also show the configuration of the peripheral vent 46 in an arc shape.

[0090]

[0100] Similarly, Figures 3E and 3F show cross sections through the planes BB and CC, respectively, of Figure 3D. The needle guide 52' is integrated into the container 12, specifically into the outer tubular body 16'. The needle guide 52' is joined to the outer tubular body 16'. The sidewall of the outer tubular body 16' has a protrusion 56 extending radially inwardly, by which the needle guide 52' is supported. The sidewall of the outer tubular body 16', the protrusion 56 and the needle guide 52' may be integrally formed.

[0091]

[0101] It will be understood that like reference numerals are used to indicate like parts, however, the addition of the designation (') indicates where a part has been modified to accommodate a variation or second embodiment.

[0092]

[0102] Workflow So that the invention may be more fully understood, a workflow for using the processing device 10, 10' is described with reference to Figure 4. Figure 4 shows a workflow from start to finish for the reconstitution of a frozen cell therapy product that is thawed, washed to remove cryopreservatives, and concentrated into a therapeutic dose for handover to the surgical team. This is a particular preferred implementation. However, the invention extends beyond this particular implementation and may have many other applications in workflows that require centrifugation.

[0093]

[0103] As shown in Figure 4A, frozen cells are delivered in a cryopreservative such as DSMO in a freezing container 58 (shown is just one of many commercially available small volume cryovials). As shown in Figure 4B, the cells are thawed within the freezing container 58.

[0094]

[0104] As shown in FIG. 4C, a syringe 60 is used to aspirate the contents of the cryocontainer 58 and deliver them to the processing device 10. The syringe 60 may be part of an autosampler. The needle of the syringe 60 pierces the closure member 32 and enters the inner compartment 40 within the inner tubular body 14. The contents of the syringe 60 are thus deposited within the inner compartment 40. The needle is typically a 20 gauge needle.

[0095]

[0105] The processing device 10 is then placed in a centrifuge 62, as shown in Figure 4D. The effect of the centrifugation is to force a portion of the cryopreservation agent through the filtration openings 28 and into the outer compartment 42.

[0096]

[0106] As shown in FIG. 4E, the cryopreservative can then be removed using a syringe 64, the needle of which is inserted through the distal closure member 34 and into the cavity 30. Additionally, because the therapeutic product cells 68 have migrated to the distal region of the inner compartment 40, excess cryopreservative can be removed by a syringe 66, the needle of which is inserted into the inner compartment 40, so that excess cryopreservative can be removed from the inner compartment 40 without disturbing the cells 68. As shown, the outer compartment 42 is depleted of cryopreservative prior to the introduction of fresh suspension in FIG. 4F. While complete removal is not possible, this step and further washes have the intended functional effect of diluting the DMSO to an acceptable very low concentration (usually required by regulators / pharmacopoeias depending on the target tissue or organ).

[0097]

[0107] 4F, a syringe 70 delivers a fresh suspension for a therapeutic product, such as Ringer's, through a needle inserted through the proximal closure 32, the proximal needle guide 50 and into the inner compartment 40.

[0098]

[0108] The processing device 10 is then placed in a centrifuge, as shown in FIG. 4G. After centrifugation, a portion of the suspension passes through the filtration opening 28 into the outer compartment 42. The therapeutic product cells 68 remain in the inner compartment 40. A distal syringe 74 is then inserted through the distal closure 34 and distal needle guide 52 to expel the waste suspension from the cavity 30. As shown in FIG. 4, this wash cycle is repeated a number of times as determined by one of skill in the art depending on the therapeutic product, the level of residual removal required, the particular cryopreservative concentration to be achieved, etc.

[0099]

[0109] As shown in FIG. 4J, excess suspension is then 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. By using the same processing equipment 10 to hand over to the surgical team, the use of a separate container is avoided, minimizing additional steps, container waste, and reducing the possibility of contamination. Additionally, fusing the inner tubular body 14 and the outer tubular body 16 means that the inner tubular body 14 and the outer tubular body 16 are inseparable, which also reduces the risk of contamination or tampering.

[0100]

[0110] Syringes 60, 64, 66, etc. may be separate sterile syringes or may be the same syringe that is sterilized between processing steps as known in the art. Syringes may be dedicated to the delivery / removal of each respective liquid.

[0101]

[0111] Advantages of the preferred embodiment include: 1. Sealed cell management The precious cells never come into contact with the external environment, thus minimizing the risk of biocontamination and reducing the environmental control requirements that are important in regulatory frameworks. The need for a single container from post-thaw until surgical handover also minimizes cell loss. 2. Easy to use There are no operator dependent pipetting skills. The only processing operations are centrifugation and needle injection or aspiration, which are facilitated by the design. 3. Scalability It is applicable in research, development, clinical or pharmaceutical Good Manufacturing Practice (GMP) situations. Simple automated operation is envisioned for future field use. 4. Addressing growing unmet needs As cell and gene therapies are increasingly targeted to solid tissues and organs, small volume reconstitution at the therapeutic delivery stage is required.

[0102]

[0112] It will be understood that the invention disclosed and defined herein extends to all alternative combinations of two or more of the individual features mentioned or evident in the text or drawings, all of which different combinations constitute various alternative embodiments of the invention.

Claims

1. A processing apparatus for therapeutic products or biological samples, wherein the processing apparatus comprises a proximal end and a distal end, includes a first section and a second section, includes a first substantially tubular section, the first section is in fluid communication with the second section via a filtration opening, and the filtration opening is located within or along the first substantially tubular section.

2. The apparatus according to claim 1, wherein the first substantially tubular portion defines the side wall of the first compartment, and the filtration opening is provided in the side wall.

3. The apparatus according to claim 2, wherein the filtration opening is elongated, and the elongated extension of the filtration opening is oriented to be generally aligned with the longitudinal direction of the first substantially tubular portion.

4. The apparatus according to claim 3, wherein the first substantially tubular portion has a cross-section, and the center of gravity of the cross-section deviates from the central longitudinal axis of the apparatus over at least a portion of the length of the first substantially tubular portion.

5. The apparatus according to claim 4, wherein the cross-sectional area of ​​the cross-section decreases toward the distal end with respect to at least a portion of the length of the first substantially tubular portion.

6. The apparatus according to claim 2, wherein a portion of the first substantially tubular portion is inclined toward the distal end toward one side of the apparatus.

7. The apparatus according to claim 6, further comprising a first needle guide at least substantially aligned with the inclined portion of the first substantially tubular portion.

8. The apparatus according to claim 6, wherein the filtration opening faces the other side of the apparatus so as to face a cavity within the apparatus, and the cavity forms part of the second section.

9. The apparatus according to claim 2, wherein the length of the filtration opening is at least half the length of the first substantially tubular portion.

10. The processing apparatus according to claim 2, wherein the first section and the second section each include an inner section and an outer section, and the inner section is at least partially located within the outer section.

11. The apparatus according to claim 2, wherein the first section has a larger volume than the second section.

12. The apparatus according to claim 8, wherein a second needle guide and / or outlet port is provided in or adjacent to the cavity for selectively removing filtrate from the second compartment.

13. The apparatus according to claim 2, wherein the apparatus further includes a second closure for the second compartment, the second closure comprising a sealable closure, and the second sealable closure enabling the aspiration of filtrate through the sealable closure.

14. The apparatus according to claim 2, wherein the first substantially tubular portion forms a part of a substantially tubular inner portion that is at least partially received within the substantially tubular outer portion, and the second compartment is defined between the inner portion and the outer portion.

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

16. The apparatus according to claim 14, wherein the inner portion and the outer portion are permanently connected or integrally formed such that they are interconnected at their proximal end regions.

17. The apparatus according to claim 2, wherein the proximal end of the apparatus is closed by the first closing part.

18. The apparatus according to claim 2, further comprising a ventilation opening.

19. A kit comprising an assemblyable component for forming the apparatus according to any one of claims 1 to 18.

20. A kit for an apparatus for processing therapeutic products or biological samples, wherein the kit includes an assemblyable component for defining a first compartment and a second compartment, and in the assembled apparatus, the first compartment is in fluid communication with the second compartment via a filtration opening, and the filtration opening is located in or along a first substantially tubular section of the apparatus.

21. A method for processing a therapeutic product or biological sample using centrifugation, using the processing apparatus described in any one of claims 1 to 18 or the kit described in claim 20, The steps include delivering the product or sample to the first compartment, The steps include removing the filtrate from the second compartment, The steps include: recovering the processed product from the first section, A method that includes this.

22. A processing apparatus for therapeutic products or biological samples, wherein the processing apparatus includes a first compartment and a second compartment, the first compartment being in fluid communication with the second compartment via a filtration opening, and the first compartment and the second compartment being defined by a permanently connected or integrally formed container portion.

23. The apparatus according to claim 22, wherein the container portion includes a substantially tubular inner portion and a substantially tubular outer portion, the inner portion at least partially defines the first section, and the second section is at least partially defined between the inner portion and the outer portion.

24. The apparatus according to claim 22, wherein the apparatus is closed at both ends by first and second elastically deformable closing portions, the first closing portion being provided for closing the first compartment, and the second closing portion being provided for closing the second compartment.

25. A method for processing a therapeutic product or biological sample using centrifugal separation, using the processing apparatus described in any one of claims 22 to 24, The steps include delivering the product or sample to the first compartment, The steps include removing the filtrate from the second compartment, The steps include: recovering the processed product from the first section, A method that includes this.

26. Apparatus for therapeutic products or biological samples, wherein the apparatus comprises a substantially tubular inner portion and a substantially tubular outer portion, wherein the inner portion is at least partially received or can be received within the outer portion such that at least a portion of the inner portion is offset from the central longitudinal axis or centerline of the substantially tubular outer portion.

27. The apparatus according to claim 26, wherein the apparatus is adapted for centrifugal separation.

28. The apparatus according to claim 26, wherein the inner portion has a cross-section, and the center of gravity of the cross-section deviates from the central longitudinal axis of the apparatus over at least a portion of the length of the inner portion.

29. The apparatus according to 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 through a filtration opening.

30. The apparatus according to claim 29, wherein the offset portion is at least substantially aligned with a first needle guide for sample delivery and / or retrieval.

31. The apparatus according to claim 30, wherein the inner portion is closed by an elastically deformable first closing portion, the first closing portion is provided with a positioning mark, and the mark is at least substantially aligned with a first needle guide.

32. The apparatus according to claim 29, wherein the offset portion creates a cavity within the outer portion, and the second needle guide is at least substantially aligned with the cavity.

33. The apparatus according to claim 32, wherein the outer portion is closed by an elastically deformable second closing portion, and a positioning mark is provided on the second closing portion so as to be at least substantially aligned with the cavity.

34. The apparatus according to any one of claims 26 to 33, provided in the form of a kit, wherein the inner portion and the outer portion are separate parts, and the inner portion is assembled to be at least partially received within the outer portion.

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