WO2023129565A1 - Medical device system and method for preparing a dose - Google Patents

Abstract

An apparatus including a first container including a first container outer body, a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container, and a first container-side valve configured to be activated, upon connection of a second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

Description

MEDICAL DEVICE SYSTEM AND METHOD FOR PREPARING A DOSE

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No. 63/294,851, filed on December 30, 2021, the entire contents of which is incorporated herein by reference.

BACKGROUND

[0002] The present disclosure relates in general to a medical device system and a method for preparing a dose of a formulated drug product. The formulated drug product can include a cellbased formulated drug product.

[0003] A process for preparing a dose of the cell-based formulated drug product can be performed by a highly trained technician. The process can include receiving a suspension of cells in a cryoprotectant, separating the cells from the cryoprotectant and introducing a cell delivery solution to the cells to produce the cell-based formulated drug product.

[0004] A need has been identified to provide improvements to the process for preparing doses of the cell-based formulated drug product. The improvements include, but are not limited to, preparing doses of the formulated drug product with a consistent volume and a cell concentration that meets a predetermined target concentration, and minimizing or eliminating a risk of contamination of the formulated drug product in different environments such as an operating room or an off-site location away from the operating room without access to a clean environment such as a biosafety cabinet or a cleanroom.

SUMMARY [0005] According to an embodiment, an apparatus comprises: a first container comprising: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container- side valve configured to be activated, upon connection of a second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

[0006] According to an embodiment, a medical device system comprises: a first container; and a second container, wherein the first container comprises: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container-side valve configured to be activated, upon connection of the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

[0007] According to an embodiment, a process for operating a medical device system comprising: a first container; and a second container, wherein the first container comprises: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container- side valve, and wherein the process comprises: aligning the first container and the second container; and connecting the second container to the first container outer body, wherein the first container- side valve is configured to be activated, upon connection of the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space. [0008] Further features as well as the structure and operation of various embodiments are described in detail below with reference to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar elements.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. 1 shows a medical device system including a first container, a second container, a second container loading module and a dose loading module according to one embodiment.

[0010] FIG. 2 shows features of the first container according to one embodiment.

[0011] FIG. 3 shows features of the first container according to one modified embodiment.

[0012] FIG. 4 shows a process for assembling the first container according to one embodiment.

[0013] FIG. 5 shows features of the second container according to one embodiment.

[0014] FIG. 6 shows a disconnected arrangement and a connected arrangement of the first container and the second container according to one embodiment.

[0015] FIG. 7 shows a process for assembling the second container according to one embodiment.

[0016] FIG. 8 shows features of a second container loading module according to one embodiment.

[0017] FIG. 9 shows a process for preparing a formulated drug product according to one embodiment.

DETAILED DESCRIPTION [0018] FIG. 1 illustrates an example of a medical device system 10 for implementing dose preparation according to one embodiment. The medical device system 10 may include a first container 100 (also referred to as a dose preparation tube), a second container 200 (also referred to as a wash tube) and a second container loading module 300 and a dose loading module 400.

[0019] First Container (Dose Preparation Tube)

[0020] The first container 100, that is an apparatus, will now be described with reference to FIG. 2. The first container 100 may include a first tube body 104. The first tube body 104 may extend along a first tube body axis A between a first end of the first tube body 104 and a second end of the first tube body 104.

[0021] The first tube body 104 may define a first interior space 106. The first interior space 106 may be connected to a first opening 104 A at the first end of the first tube body 104.

[0022] The volume of the first interior space 106 is not particularly limited. For example, the volume of the first interior space 106 may be selected based on a target dose volume of a dose to be prepared. As an example, the volume of the first interior space 106 may be selected to hold the target dose volume and to account for some additional dead volume (e.g., approximately 50 pl).

[0023] In some embodiments, the target dose volume may be at least about 1 microliter, at least about 2 microliters, at least about 3 microliters, at least about 4 microliters, at least about 5 microliters, at least about 6 microliters, at least about 7 microliters, at least about 7.2 microliters, at least about 7.4 microliters, at least about 7.6 microliters, at least about 7.8 microliters, at least about 8 microliters, at least about 8.1 microliters, at least about 8.2 microliters, at least about 8.3 microliters, at least about 8.4 microliters, at least about 8.5 microliters, at least about 8.6 microliters, at least about 8.7 microliters, at least about 8.8 microliters, at least about 8.9 microliters, at least about 9 microliters, at least about 9.5 microliters, at least about 10 microliters, at least about 11 microliters, at least about 12 microliters, at least about 13 microliters, at least about 14 microliters, at least about 15 microliters, at least about 20 microliters, at least about 30 microliters, at least about 100 microliters, at least about 1 mL, at least about 10 mL, at least about 100 mL, at least about 500 mL, or at least about 800 mL.

[0024] In some embodiments, the target dose volume may be less than or equal to about 1000 mL, less than or equal to about 800 mL, less than or equal to about 500 mL, less than or equal to about 100 mL, less than or equal to about 10 mL, less than or equal to about 1 mL, less than or equal to about 100 microliters, or less than or equal to about 100 microliters, or less than or equal to about 90 microliters, or less than or equal to about 80 microliters, or less than or equal to about 70 microliters, or less than or equal to about 60 microliters, or less than or equal to about 50 microliters, or less than or equal to about 40 microliters, or less than or equal to about 30 microliters, or less than or equal to about 20 microliters, or less than or equal to about 15 microliters, or less than or equal to about 12 microliters, or less than or equal to about 10 microliters, or less than or equal to about 9.9 microliters, or less than or equal to about 9.8 microliters, or less than or equal to about 9.7 microliters, or less than or equal to about 9.6 microliters, or less than or equal to about 9.5 microliters, or less than or equal to about 9.4 microliters, or less than or equal to about 9.3 or less than or equal to about 9.2 microliters, or less than or equal to about 9.1 microliters, or less than or equal to about 9 microliters, or less than or equal to about 8.8 microliters, or less than or equal to about 8.2 microliters, or less than or equal to about 8 microliters, or less than or equal to about 7 microliters, or less than or equal to about 6 microliters, or less than or equal to about 5 microliters.

[0025] Combinations of the above referenced ranges are also possible. For example, in some embodiments, the target dose volume is 1 mL to about 1000 mL, or about 10 mL to about 800 mL, or about 100 mL to about 500 mL, or about 1 microliter to about 100 microliters, or about 2 microliters to about 60 microliters, or about 3 microliters to about 30 microliters, or about 4 microliters to about 20 microliters, or about 5 microliters to about 18 microliters or about 6 microliters to about 16 microliters or about 7 microliters to about 14 microliters or about 8 microliters to about 10 microliters or about 8.5 microliters to about 9.5 microliters or about 8.9 microliters to about 9.1 microliters, or about 9 microliters to about 9.1 microliters.

[0026] As an example, the first tube body 104 may include a first container outer body 108 and a first container barrel 110 arranged within the first container outer body 108.

[0027] A material or materials for forming the first container outer body 108 is not particularly limited. Examples of the material or materials for forming the first container outer body 108 may include resins such as polypropylene and polycarbonates.

[0028] The first container outer body 108 may have a geometry or structure for directly or indirectly connecting the first container 100 to the second container 200. A surface of the first container outer body 108 may include a first part 112 of a connection or coupling mechanism to directly or indirectly connect the first container 100 to a second container. The connection or coupling mechanism is not particularly limited. As an example, the first part 112 of the connection or coupling mechanism may include one part of a threaded connection, while the second container 200 may include another part of the threaded connection that detachably connects to the one part of the threaded connection to connect the second container 200 to the first container 100. The one part of the threaded connection can be a one of a male thread (as shown in FIG. 2) and a female thread, while the another part of the threaded connection provided to the second container 200 may be the other of the male thread and the female thread.

[0029] The first container outer body 108 may have a geometry or structure that allows the first container 100, when attached to the second container 200, to be fitted within a compartment of a centrifuge as described in more detail below.

[0030] The first container barrel 110 may be arranged within the first container outer body 108 along the first tube body axis A. The first container barrel 110 may define the first interior space 106. The first container barrel 110 may be open-ended on a side closer to the first end of the first tube body 104 to connect the first interior space 106 to the first opening 104A of the first tube body 104. The first container barrel 110 may be close-ended on a side closer to the second end of the first tube body 104.

[0031] The dimensions of the first container barrel 110 is not particularly limited. For example, a length of the first container barrel 110 along the first tube body axis A and an inner diameter of the first container barrel 110 in a direction perpendicular to the first tube body axis A may be selected based on the target dose volume of the dose to be prepared.

[0032] The first container barrel 110 may be formed as a unitary structure or an assembly of a plurality of structures. A material or materials for forming the first container barrel 110 is not particularly limited. The material or materials for forming at least an interior surface and any other cell contacting surface of the first container barrel 110 may be a biocompatible material or materials such as a biocompatible polymer. The material or materials for forming the first container barrel 110 may be selected to minimize cell adhesion to the interior surface and any other cell contacting surface of the first container barrel 110. Examples of the materials or materials for forming the first container barrel 110 may include resins such as polypropylene and polycarbonate.

[0033] Referring to FIG. 1, the medical device system 10 may include a first flow path control module 124 for controlling a flow between the second container 200 and the first container 100.

[0034] Referring to FIG. 2, the first container 100 may include a first portion of the first flow path control module 124. The first portion of the first flow path control module 124 is configured to be activated from a normally closed position to an activated position, and to be deactivated from the activated position to the normally closed position. In the normally closed position, a flow into and out of the first interior space 106 through the first opening 104A is reduced relative to the activation position or completely restricted. In the activated position, a flow into and out of the first interior space 106 through the first opening 104 A is increased relative to the normally closed position.

[0035] The structure and geometry of the first portion of the first flow path control module 124 is not particularly limited. One example of the first portion of the first flow path control module 124 is described in detail below.

[0036] The first flow path control module 124 may include a valve system. The first portion of the first flow path control module 124 may include a first container- side valve 126. The first container- side valve 126 may be provided to the first end of the first tube body 104. The first container- side valve 126 may include a first valve casing 128 attached to the first container outer body 108. Although the first container- side valve 126 is described as a separate structure from other parts of the first container 100 such as the first container outer body 108, portions of the first container- side valve 126 such as the first valve casing 128 may be formed as a unitary structure with the first container outer body 108.

[0037] The outer surface of the first valve casing 128 may have a geometry or structure for directly or indirectly connecting the first container- side valve 126 of the first container 100 to a third container. The outer surface of the first valve casing 128 may include a first part of a connection or coupling mechanism for directly or indirectly connecting the first container 100 to the third container. An example of the first part of the connection or coupling mechanism may include one part of a threaded connection, while the third container may include another part of the threaded connection that detachably connects the third container to the first container- side valve 126 of the first container 100. The third container may include a medical device such as a syringe for receiving a dose of a formulated drug product from the first container 100 and delivering the dose to a subject. The third container may include a connector to the medical device through which the dose can be moved from the first container 100 to the medical device such as the syringe.

[0038] An interior surface of the first valve casing 128 may define a first valve casing interior space 130 leading to the first opening 104A of the first tube body 104. The first container-side valve 126 may include a first seal 132 arranged within the first valve casing interior space 130 of the first valve casing 128. The first seal 132 is configured to provide the normally closed position and the activated position of the first container-side valve 126. The structure of the first seal 132 is not particularly limited. An example of the first seal 132 is a self-sealing seal.

[0039] The first seal 132 may be arranged in the first valve casing interior space to control a flow through the open end of the first container barrel 110 into the first interior space 106. For example, the open end of the first container barrel 110 may extend along the first tube body axis A into the first valve casing interior space 130 to abut the first seal 132.

[0040] The first seal 132 may have a normally closed position that relatively reduces or completely restricts flow through the first seal 132. The normally closed position of the first seal 132 may be a sealed position of the self-sealing seal.

[0041] The first seal 132 may be activated from the normally closed position to an activated position. The activated position of the first seal 132 allows for relatively increased flow through the first seal 132 and the open end of the first container barrel 110 into the first interior space 106 of the first container barrel 110 (and the first tube body 104). For example, the first seal 132 may be activated from the normally closed position to the activated position by deforming the self-sealing seal to provide a pathway for flow through the first seal 132. The first seal 132 may be activated by a valve stem to be described below.

[0042] The first seal 132 may be made of a resilient material such as rubber, silicone rubber, a flexible plastic or other resilient polymer.

[0043] Referring to FIG. 2, the first container outer body 108 may have a geometry or structure for connecting the first portion of a first flow path control module 124 to the first container outer body 108 will be described.

[0044] To aid in the assembly of the first container 100, the first container outer body 108 may be provided as a plurality of parts. For example, the first container outer body 108 may include a first outer body part 108A and a second outer body part 108B. The first outer body part 108A and the second outer body part 108B may be arranged sequentially along the first tube body axis A such that the first outer body part 108A is arranged closer to the first end of the first tube body 104 and the second outer body part 108B is arranged closer to the second end of the first tube body 104 along the first tube body axis A.

[0045] The second outer body part 108B may define an interior space extending along the first tube body axis A. For example, the second outer body part 108B may have a tubular inner surface that defines the interior space of the second outer body part 108B. The interior space of the second outer body part 108B may be dimensioned to allow the first container barrel 110 to be arranged therein. The first container barrel 110 may be connected to the tubular inner surface of the second outer body part 108B by, for example, press fitting the first container barrel 110 within the tubular inner surface of the second outer body part 108B and/or, for example, adhering the cylindrical outer surface of the first container barrel 110 to the tubular inner surface of the second outer body part 108B.

[0046] The first outer body part 108 A and the second outer body part 108B may have geometries or structures that cooperate to connect the first container outer body 108 to the first containerside valve 126.

[0047] The first outer body part 108 A may define an interior space extending along the first tube body axis A. For example, the first outer body part 108A may have a tubular inner surface that defines the interior space of the second outer body part 108B. The first valve casing 128 may have a cylindrical outer surface having an outer diameter that matches an inner diameter of the tubular inner surface of the first outer body part 108A such that the first valve casing 128 is coaxially arranged within the interior space defined by the tubular inner surface of the first outer body part 108A. The first valve casing 128 may be connected to the tubular inner surface of the first outer body part 108A by, for example, press fitting the first valve casing 128 within the tubular inner surface of the first outer body part 108 A and/or, for example, adhering the cylindrical outer surface of the first valve casing 128 to the tubular inner surface of the first outer body part 108A. [0048] An outer surface of the first valve casing 128 may include a first valve casing flange 128A. The first outer body part 108A may include a first sandwiching surface 108A1, and the second outer body part 108B may include a second sandwiching surface 108B 1. Further, the first sandwiching surface 108A1 and the second sandwiching surface 108B 1 may be separated by a gap in which the first valve casing flange 128A may be arranged to be sandwiched by the first sandwiching surface 108A1 and the second sandwiching surface 108B 1. Still further, the first outer body part 108A and the second outer body part 108B may have corresponding surfaces that can be connected by, for example, press fitting and/or adhesive while the first valve casing flange 128A is sandwiched by the first sandwiching surface 108A1 and the second sandwiching surface 108B1 to thereby connect the first container outer body 108 to the first container- side valve 126. In this connected state, when the first seal 132 is activated from the normally closed position to the activated position, flow from the second container 200 into the first interior space 106 within the second outer body part 108B, or flow from the first interior space 106 within the second outer body part 108B into the third container may occur.

[0049] Although the first container 100 is described above as including a plurality of separate parts such as the first outer body part 108A, the second outer body part 108B, the first valve casing 128 and the first container barrel 110, two or more of the plurality of separate parts may be provided as a single structure.

[0050] The dimensions of the first container 100 is not particularly limited. For example, a length of the first container 100 along the first tube body axis A and an outer diameter of the first container 100 in a direction perpendicular to the first tube body axis A can be selected to allow the first container 100, together with the second container, to be fitted within the compartment of the centrifuge, as described below.

[0051] First Container (Dose Preparation Tube) - Modification

[0052] A modified embodiment of the first container 100 will now be described with reference to

FIG. 3. The modified embodiment of the first container 100 is similar to the first container 100 described above. In the modified embodiment, a portion of the second outer body part 108B of the first container outer body 108 and a portion of the first container barrel 110, as described above, may be replaced with a malleable material. The malleable material may be selected to be squeezed to decrease the volume of the first interior space. As an example, the malleable material may include fluorinated ethylene propylene, a polyimide material such as Kapton®, polyvinyl chloride, polypropylene, silicone, polyurethane or any suitable material.

[0053] Process for Assembling First Container (Dose Preparation Tube)

[0054] Next, a process for assembling the first container 100 will be described with reference to FIG. 4.

[0055] The process for assembling the first container 100 may include a step S102 of arranging first seal 132 in the first valve casing interior space 130 of the first valve casing 128 of the first container- side valve 126.

[0056] The process for assembling the first container 100 may include a step S104 of connecting the first container barrel 110 to the tubular surface of the second outer body part 108B by, for example, press fitting the first container barrel 110 within the tubular inner surface of the second outer body part 108B and/or for example, adhering the cylindrical outer surface of the first container barrel 110 to the tubular inner surface of the second outer body part 108B.

[0057] The process for assembling the first container 100 may include a step S106 of connecting the first container- side valve 126 to the first container barrel 110. The step S 106 may include arranging the first seal 132 to the first container barrel 110 such that when the first seal 132 is activated from the normally closed position to the activated position, the activated position of the first seal 132 allows for relatively increased flow through the first seal 132 and the open end of the first container barrel 110 into the first interior space 106 of the first container barrel 110.

[0058] The first container-side valve 126 may be connected to the first container barrel 110 by connecting the first valve casing flange 128A of the first valve casing 128 to the second sandwiching surface 108B1 of the second outer body part 108B.

[0059] The process for assembling the first container 100 may include a step S108 of connecting the first outer body part 108A to the second outer body part 108B. For example, the corresponding surface of the first outer body part 108 A and the second outer body part 108B may be connected by, for example, press fitting and/or adhesive. In connecting the first outer body part 108A to the second outer body part 108B, the first valve casing flange 128A may be sandwiched between the first sandwiching surface 108 Al and the second sandwiching surface 108B1.

[0060] The process for assembling the first container 100 may include a step S 110 of loading a predetermined volume of cell delivery solution or transplantation media into the first interior space 106 of the first container barrel 110. The cell delivery solution or transplantation media may be loaded into the first interior space 106 through the first container- side valve 126 that is activated from the normally closed position to the activated position. The predetermined volume of the cell delivery solution or transplantation media to be loaded into the first interior space 106 may be selected based on target dose volume to be prepared. For example, the predetermined volume of the cell delivery solution or the transplantation media may be selected to be the same as the volume of the first interior space 106. By selecting the predetermined volume of the cell delivery solution or the transplantation media to be the same as the volume of the first interior space 106, any additional loading of cells from the second container 200 into the first interior space 106 may displace the same or substantially the same volume of the cell delivery solution or the transplantation media such that the first interior space 106 having the cells and the cell delivery solution or the transplantation media (together to be considered a prepared dose) will occupy the entirety or substantially the entirety of the first interior space 106. In another example, the predetermined volume of the cell delivery solution or the transplantation media may be selected such that the predetermined volume of the cell delivery solution or the transplantation media with a predetermined volume of the cells loaded from the second container 200 into the first interior space 106 will occupy the entirety or substantially the entirety of the first interior space 106.

[0061] The process for assembling the first container 100 is described as including steps S102 to S 110 performed in the described order. However, the steps S 102 to S 110 may be performed in different orders.

[0062] The above-described process for assembling the first container 100 may occur in an aseptic environment or near aseptic environment to eliminate or minimize contamination of the first interior space 106 after the first container 100 is fully assembled.

[0063] Second Container (Wash Tube)

[0064] Returning to FIG. 1, the medical device system 10 may include the second container 200 (also referred to as a wash tube).

[0065] Referring to FIG. 5, the second container 200, that is an apparatus, may include a second tube body 204. The second tube body 204 may extend along a second tube body axis C between a first end 204A of the second tube body 204 and a second end 204B of the second tube body 204.

[0066] The dimensions of the second container 200 is not particularly limited. For example, a length of the second container 200 along the second tube body axis C and an outer diameter of the second container 200 in a direction perpendicular to the second tube body axis C can be selected to allow the second container 200 with the first container 100 connected thereto be fitted within the compartment of the centrifuge.

[0067] The second tube body 204 may include a second container outer body 208. The second container outer body 208 may have a geometry or structure that allows the second container 200, when connected to the first container 100, to be fitted within a compartment of a centrifuge as described in more detail below. [0068] A material or materials for forming the second container outer body 208 is not particularly limited. Examples of the material or materials for forming the second container outer body 208 may include resins such as polypropylene and polycarbonates

[0069] Referring to FIG. 5, the second container outer body 208 may include a first section 208A, a second section 208B and a third section 208C arranged in the recited order from the first end 204 A of the second tube body 204 to the second end 204B of the second tube body 204. The first section 208A and the second section 208B may be formed as a single structure. The first section 208A and the second section 208B may define a second interior space 206 between a first opening (that is also the first end 204 A) and a second opening. Further, the third section 208C may be a separate structure connected to the second section 208B . The third section 208C may be connected to the second section 208B such that a portion of the third section 208C is arranged in the second interior space 206.

[0070] The first section 208A of the second container outer body 208 may have a geometry or structure for directly or indirectly connecting the second container 200 to the first container 100, as described above. A surface of the first section 208A of the second container outer body 208 may include a second part of the connection or coupling mechanism to directly or indirectly connect the second container 200 to the first container 100. As an example, an inner surface of the first section 208A of the second container outer body 208 may include a female thread (as shown in FIGS. 5 and 6) configured to be connected to the male thread (as shown in FIGS. 2 and 6) of the first part 112 of the first container outer body 108.

[0071] Referring to FIG. 5, the third section 208C of the second container outer body 208 may define a second container barrel interior space 212. The third section 208C may extend along the second tube body axis C between a first end of the third section 208C and a second end of the third section 208C. The third section 208C may define a first opening 212A along the second tube body axis C between the first end 204A of the second tube body 204 and the second end 204B of the second tube body 204. The third section 208C may define a second opening 212B along the second tube body axis C closer to the second end 204B of the second tube body 204 than the first opening 210A of the second container barrel 210.

[0072] The volume of the second container barrel interior space 212 is not particularly limited. For example, the volume of the second container barrel interior space 212 may be selected based on the target dose volume of the dose to be prepared in the first container 100 and a volume of therapeutic substance in wash buffer to be loaded in the second container barrel interior space 212. In some embodiments, the therapeutic substance to be delivered are cells, or other particles having a certain diameter. It should be appreciated, however, that the therapeutic substance is not limited to cells or particles. Wherever discussed hereinafter, “cells” may be substituted with any other therapeutic substance, as appropriate.

[0073] In some embodiments, the cells are dopaminergic neuron cells, and, in some embodiments, may be iPSC-derived dopaminergic neuron cells. It should be appreciated however, the types of cells are not particularly limited. Other type of cells, such as mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells or induced pluripotent stem cells, red blood cells, platelets, chondrocytes, skin cells, immune cells (e.g. tumor infiltrating lymphocytes, viral reconstitution T cells, dendritic cells, regulator T cells, macrophages), neural crest stem cells, neurons, glia, smooth muscle, cardiac tissue, chondrocytes, osteocytes, glial restricted progenitors, astrocytes, oligodendrocytes, neuroblast cells, megakaryoblasts, megakaryocytes, monoblasts, monocytes, macrophages, myeloid dendritic cells, proerythroblasts, erythroblasts, normoblasts, reticulocytes, thrombocytes, myeloblasts, progranulocytes, neutrophilic myelocytes, neutrophilic band cells, neutrophils, eosinophilic myelocytes, eosinophilic band cells, eosinophils, basophilic myelocytes, basophilic band cells, basophils, committed lymphoid projenitors, pre-NK cells, NK lymphoblasts, NK cells, thymocytes, T-lymphoblasts, T-cells, plasmacytoid dendritic cells, pre-B cells, B -lymphoblasts, B cells, plasma cells, osteoblasts, chondrocytes, myoblasts, myotubes, fibroblasts, adipocytes, mesoderm, ectoderms, primordial germ cells, sperm, eggs, definitive endoderm, myeloid progenitor cells, microglial cells, myeloid cells or any other suitable type of cell may be processed. [0074] The third section 208C may have a geometry or structure for directing a displacement of the cells in the wash buffer by centrifugal force applied by the centrifuge towards the first opening 212A of the third section 208C. The geometry or structure of the third section 208C is not particularly limited. For example, the third section 208C may include a first part 212C, a second part 212D and a third part 212E arranged in the recited order along the second tube body axis C from the second opening 212B of the third section 208C and the first opening 212A of the third section 208C. The first part 212C may have a cylindrical shape having a first diameter. The second part 212D can be a conical shape having a varying diameter that reduces along the second tube body axis C in a direction from the second opening 212B towards the first opening 212A from the first diameter to a second diameter. The third part 212E may be a cylindrical shape having the second diameter.

[0075] Referring to FIG. 5, the second container 200 may include a cover 230 configured to be connected to the third section 208C to cover the second opening 212B of the third section 208C. The cover 230 and the second tube body 204 each have portions of a connection or coupling mechanism to directly or indirectly connect the cover 230 to the second tube body 204. As an example, the third section 208C may include one part of a threaded connection, while the cover 230 may include another part of the threaded connection that detachably connects the cover 230 to the second container outer body 208. The one part of the threaded connection can be one of a male thread (as shown in the drawings) and a female thread, while the another part of the threaded connection provided to the cover 230 may be the other of the male thread and the female thread (as shown in the drawings).

[0076] Referring to FIG. 5. The second container 200 may include a second flow path control module 232 arranged to the cover 230. The second flow path control module 232 may include a luer valve that may be activated from a normally closed position to an activated position to permit flow into the second container barrel interior space 212, and to be deactivated from the activated position to the normally closed position to reduce to eliminate flow into the second container barrel interior space 212. [0077] Referring to FIG. 5, the second container 200 may include a second portion of the first flow path control module 124. The second portion of the first flow path control module 124 is configured to be activated from a normally closed position to an activated position, and to be deactivated from the activated position to the normally closed position. In the normally closed position, a flow out of the second container barrel 210 through the first opening 212A of the third section 208C is relatively reduced or completely restricted. In the activated position, a flow out of the third section 208C through the first opening 212A is increased relative to the normally closed position.

[0078] As described above, the first flow path control module 124 may include the valve system. The second portion of the first flow path control module 124 may include a second containerside valve 220. The second container- side valve 220 may be provided in the second section 208B of the second container outer body 208, as described below.

[0079] The second container- side valve 220 may include a valve cap 222, a valve stem 224 and a second seal 226.

[0080] The valve cap 222 may include a cylinder 222A and an attachment surface 222B. The cylinder 222A may be arranged within the second section 208B of the second container outer body 208. An inner surface of the second section 208B of the second container outer body 208 is sized to limit movement of the cylinder 222A to movement along a predetermined range of the second tube body axis C in the direction from the first end 204A of the second tube body 204 toward the second end 204B of the second tube body 204.

[0081] The valve stem 224 may be connected, at an intermediate portion of the valve stem 224 along the length of the valve stem 224, to the attachment surface 222B. A first portion 224A of the valve stem 224 on a side of the attachment surface 222B facing the third section 208C of the second container outer body 208 is exposed while being surrounded radially by the cylinder 222A of the valve cap 222, and a second portion 224B of the valve stem 224 on a side of the attachment surface 222B facing the first end 204A is also exposed. The valve stem 224 is connected by the attachment surface 222B to the cylinder 222A such that when the cylinder 222A moves along the predetermined range of the second tube axis C, the valve stem 224 also moves along the second tube axis C. A portion of the valve stem 224 including a first end of the valve stem 224 may have a tapered geometry that reduces an outer diameter of the portion of the valve stem 224 in a direction approaching the first end of the valve stem 224. A portion of the valve stem 224 including a second end of the valve stem 224 may have a tapered geometry that reduces an outer diameter of the portion of the valve stem 224 in a direction approaching the second end of the valve stem 224. The tapered geometries of the portions of the valve stem 224 including the first end and the second end of the valve stem 224 may improve the ability of the valve stem 224 to activate the first seal 132 and the second seal 226 as described in detail below.

[0082] The second seal 226 may be arranged to be connected to the third part 212E of the third section 208C of the second container outer body 208. The second seal 226 is configured to provide a normally closed position and an activated position of the second container-side valve 220. An example of the second seal 226 is a self-sealing seal.

[0083] The second seal 226 has the normally closed position that relatively reduces or completely restricts flow through the second seal 226. The second seal 226 may be activated from the normally closed position to the activated position. The activated position of the second seal 226 allows for relatively increased flow through the second seal 226. For example, the second seal 226 may be activated from the normally closed position to the activated position by deforming the self-sealing seal to provide a pathway for flow through the second seal 226. The second seal 226 may be activated by the valve stem 224 as described below.

[0084] Referring to FIG. 6, activation of the first container-side valve 126 and the second container- side valve 220 by the valve stem 224 through connection of the first container 100 and the second container 200 will be described.

[0085] As described above, the first container outer body 108 may include the male thread, and the first section 208A of the second container outer body 208 may include the female thread. The first container 100 and the second container 200 may be connected by aligning the first tube body axis A and the second tube body axis C, and engaging the male thread of the first container outer body 108 with the female thread of the first section 208 A of the second container outer body 208 through rotation of the first container 100 relative to the second container 200 to advance the first container- side valve 126 towards the second container-side valve 220. As the first container- side valve 126 continues to advance towards the second container- side valve 220, the tapered portion of the valve stem 224 closest to the first seal 132 advances past the first valve casing 128 to contact and activate the first seal 132 from the normally closed position to the activated position.

[0086] As the male thread of the first container outer body 108 continues to engage the female thread of the first section 208A to advance the first container-side valve 126 towards the second container- side valve 220, the first valve casing 128 of the first container-side valve 126 may be brought into contact with the valve cap 222. For example, the first valve casing 128 may be brought into contact with the attachment surface 222B of the valve cap 222. A force in a direction of the first container 100 towards the second container 200 resulting from the advancement of the first container- side valve 126 towards the second container- side valve 220 may be transferred from by the first valve casing 128 to the valve cap 222 to move the valve cap 222 having the valve stem 224 attached thereto along the predetermined range of the second tube body axis C in the direction of the second end 204B of the second tube body 204 towards the second seal 226. As the valve cap 222 is moved towards the second seal 226, the tapered portion of the first portion 224A of the valve stem 224 may contact and activate the second seal 226 from the normally closed position to the activated position. In a state where the valve cap 222 is moved to an end of the predetermined range closest to the second end 204B of the second tube body 204, the tapered portions of the valve stem 224 contact the first seal 132 and the second seal 226, respectively, to activate the first container- side valve 126 and the second container-side valve 220 to form a pathway for flow from the second interior space 206 of the second tube body 204 to the first interior space 106 of the first tube body 104.

[0087] Referring to FIG. 6, deactivation of the first container-side valve 126 and the second container- side valve 220 through disconnection of the first container 100 the second container 200 will be described.

[0088] The first container 100 and the second container 200 may be disconnected by disengaging the male thread of the first container outer body 108 from the female thread of the first section 208 A of the second container outer body 208 through counter-rotation of the first container 100 relative to the second container 200 to retract the first container- side valve 126 away from the second container-side valve 220. As the first container- side valve 126 continues to retract from the second container- side valve 220, the tapered portion of the second portion 224B of the valve stem 224 that activated the first container- side valve 126 is retracted away from the first seal 132 to deactivate the first seal 132 from the activated position to the normally closed position to thereby reduce or completely eliminate flow through the first seal 132 of the first container- side valve 126.

[0089] Process for Assembling Second Container (Wash Tube)

[0090] Next, a process for assembling the second container 200 will be described with reference to FIG. 7.

[0091] The process for assembling the second container 200 may include a step S202 of arranging the valve cap 222 and the valve stem 224 connected to the valve cap 222 in the second section 208B of the second container outer body 208. The valve cap 222 and the valve stem 224 may be inserted through the second opening of the single structure including the first section 208 A and the second section 208B to be arranged in the second interior space 206. The valve cap 222 and the valve stem 224 may be arranged in the second interior space 206 such that the first portion 224A of the valve stem 224 faces the third section 208C of the second container outer body 208 and such that the second portion 224B of the valve stem 224 faces the first opening 104A of the second tube body 204.

[0092] The process for assembling the second container 200 may include a step S204 of arranging the second seal 226 to the third part 212E of the third section 208C of the second container outer body 208.

[0093] The process for assembling the second container 200 may include a step S206 of connecting the third section 208C of the second container outer body 208 to the second section 208B such that a portion of the third section 208C is arranged in the second interior space 206. For example, the third section 208C may be connected to the second section 208B such that the third part 212E (having the second seal 226 arranged to the third part 212E) and a portion of the second part 212D of the third section 208C are arranged in the second interior space 206.

[0094] The third section 208C may be connected to the second section 208B to define the predetermined range along which the cylinder 222 A of the second container- side valve 220 moves. Further, second container-side valve 220 is in the normally closed position at the position at which the third section 208C is connected to the second section 208B.

[0095] The process for assembling the second container 200 may include a step S208 of connecting the cover 230 having the second flow path control module 232 arranged to the cover 230 to the third section 208C of the second container outer body 208 to cover the second opening 212B of the second container barrel interior space 212.

[0096] The above-described process for assembling the second container 200 may occur in an aseptic environment to minimize or eliminate contamination of the second container barrel interior space 212 and the second interior space 206 after the second container 200 is fully assembled.

[0097] Second Container Loading Module

[0098] Referring to FIG. 1, the medical device system 10 may include a second container loading module 300 for loading a plurality of cells and a cell wash solution into the second container barrel interior space 212 of the second container 200. [0099] The second container loading module 300 will be described with reference to FIG. 8. The second container loading module 300 may include a flow regulator 302, an adapter 304 and a cell vial 306. The cell vial 306 may hold a mixture of a predetermined number of cells and cryoprotectant. The flow regulator 302 may fluidly connect a source of wash solution to the adapter 304. The adapter 304 may fluidly connect the flow regulator 302 to the cell vial 306. The adapter 304 may separately fluidly connect the cell vial 306 to the second container 200.

[00100] The flow regulator 302 may regulate the flow of wash solution to the cell vial 306 via the adapter 304 to, for example, 1 drop (approximately 50 microliters) per second to prevent osmotic shock to the cells contained in the cell vial 306.

[00101] The adapter 304 may fluidly direct the wash solution, the flow of which is regulated by the flow regulator 302, to the cell vial 306. Further, the adapter 304 may be directly or indirectly connected to the second flow path control module 232 to fluidly direct a mixture of the cells, the cryoprotectant and the wash solution from the cell vial 306 through the second flow path control module 232 into the second container barrel interior space 212 of the third section 208C of the second container outer body 208.

[00102] Process for Preparing a Formulated Drug Product

[00103] A process for preparing a formulated drug product such as a cell-based formulated drug product will be described with reference to FIG. 9.

[00104] The process for preparing the formulated drug product may include a step S302 of regulating, by the flow regulator 302, a flow of wash solution from the source of wash solution to the cell vial 306 holding a mixture of cells and cryoprotectant. The wash solution may serve to wash the cells that were previously cryopreserved in the cryoprotectant. Regulation of the wash solution may serve to prevent osmotic shock to the cells contained in the cell vial 306. [00105] The process for preparing the formulated drug product may include a step S304 of fluidly directing a mixture of the cells, the cryoprotectant and the wash solution from the cell vial 306 through the second flow path control module 232 into the second container barrel interior space 212 of the third section 208C of the second container outer body 208.

[00106] The process for preparing the formulated drug product may include a step S306 of connecting the first container 100 and the second container 200. Connecting the first container 100 and the second container 200 may include aligning the first tube body axis A and the second tube body axis C, and engaging the male thread of the first container outer body 108 with the female thread of the first section 208A of the second container outer body 208 through rotation of the first container 100 relative to the second container 200 to advance the first container- side valve 126 towards the second container-side valve 220. As the first container- side valve 126 continues to advance tow ards the second container- side valve 220, the tapered portion of the valve stem 224 closest to the first seal 132 advances past the first valve casing 128 to contact and activate the first seal 132 from the normally closed position to the activated position.

[00107] As the male thread of the first container outer body 108 continues to engage the female thread of the first section 208A to advance the first container-side valve 126 towards the second container- side valve 220, the first valve casing 128 of the first container-side valve 126 may be brought into contact with the valve cap 222. For example, the first valve casing 128 may be brought into contact with the attachment surface 222B of the valve cap 222. A force in a direction of the first container 100 towards the second container 200 resulting from the advancement of the first container- side valve 126 towards the second container- side valve 220 may be transferred from by the first valve casing 128 to the valve cap 222 to move the valve cap 222 having the valve stem 224 attached thereto along the predetermined range of the second tube body axis C in the direction of the second end 204B of the second tube body 204 towards the second seal 226. As the valve cap 222 is moved towards the second seal 226, the tapered portion of the first portion 224A of the valve stem 224 may contact and activate the second seal 226 from the normally closed position to the activated position. In a state where the valve cap 222 is moved to an end of the predetermined range closest to the second end 204B of the second tube body 204, the tapered portions of the valve stem 224 contact the first seal 132 and the second seal 226, respectively, to activate the first container- side valve 126 and the second container-side valve 220 to form a pathway for flow from the second interior space 206 of the second tube body 204 to the first interior space 106 of the first tube body 104.

[00108] It is noted that prior to connecting the first container 100 and the second container 200, the first interior space 106 of the first container 100 is pre-loaded with a predetermined volume of cell delivery solution or transplantation media according to step SI 10, as described above.

[00109] The predetermined volume of the cell delivery solution or transplantation media to be loaded into the first interior space 106 may be selected based on target dose volume to be prepared. For example, the predetermined volume of the cell delivery solution or the transplantation media may be selected to be the same as the volume of the first interior space 106. By selecting the predetermined volume of the cell delivery solution or the transplantation media to be the same as the volume of the first interior space 106, any additional loading of cells from the second container 200 into the first interior space 106 may displace the same or substantially the same volume of the cell delivery solution or the transplantation media such that the first interior space 106 having the cells and the cell delivery solution or the transplantation media (together to be considered a prepared dose) will occupy the entirety or substantially the entirety of the first interior space 106. In another example, the predetermined volume of the cell delivery solution or the transplantation media may be selected such that the predetermined volume of the cell delivery solution or the transplantation media with a predetermined volume of the cells loaded from the second container 200 into the first interior space 106 will occupy the entirety or substantially the entirety of the first interior space 106.

[00110] The process for preparing the formulated drug product may include a step S3O8 of applying a centrifugal force to the connected first container 100 and second container 200. The step S3O8 may include loading the connected first container 100 and second container 200 into a centrifuge in an orientation such that during, the spinning operation of the centrifuge along a spin axis, at least a portion of the cells in the second container 200 move outward in the radial direction of the spin axis from the second container 200 to the first container 100. Since the first container- side valve 126 and the second container- side valve 220 are each in the activated position after the step S306, the at least a portion of the cells in the second container 200 is moved from the second container barrel interior space 212 through the second seal 226 that is in the activated position, through the valve stem 224, through the first seal 132 that is in the activated position and into the first interior space 106 defined by the first container barrel 110 to form a dose of a formulated drug product.

[00111] In the step S308, the centrifuge can be controlled to operate for at least a predetermined length of time, to operate at a predetermined speed, or both to ensure that a sufficient number of cells are separated from the cryoprotectant and wash solution in the first container 100 and moved to the first interior space 106 of the first container barrel to produce a dose having a cell concentration that meets a predetermined target concentration. The sufficient number in addition to the predetermined volume of cell delivery solution or transplantation media would form a dose of consistent volume between repeated preparation of doses of the formulated drug product.

[00112] The process for preparing the formulated drug product described above may be modified to include other steps. For example, after step S304 directing the mixture of cells, cryoprotectant and wash solution from cell vial 306 into the second container barrel interior space 212 and before performing step S306 of connecting the first container 100, the process for preparing the formulated drug product may include a step of applying centrifugal force to the mixture of the cells, cryoprotectant and wash solution contained in the second container 200 to separate the cells from the cryoprotectant and wash solution. The cells, separated from the cryoprotectant and wash solution, may be formed as a pellet primarily in a portion of the second container barrel interior space 212 in the third part 212E of the third section 208C of the second container outer body 208. After forming the pellet of cells in the third part 212E of the third section 208C of the second container outer body 208, the step S306 is performed to apply centrifugal force to transfer the cells from the second container 200 to the first container 100 via the first flow path control module 124 having the first container- side valve 126 in the activated position and the second container- side valve 220 in the activated position. Performing the step of applying centrifugal force to the mixture of the cells, cryoprotectant and wash solution contained in the second container 200 before perform the step S308 may minimize the amount of cryoprotectant and wash solution transferred to the first container 100 in the step S308 and may increase the number of cells transferred to the first container 100 in the step S3O8 to thereby increase the likelihood that a cell concentration of the dose prepared in the first container 100 meets a predetermined target concentration.

[00113] The process for preparing the formulated drug product may include a step S310 of disconnecting the first container 100 from the second container after the step S3O8 to deactivate the first container- side valve 126 and the second container-side valve 220. The first container 100 and the second container 200 may be disconnected by disengaging the male thread of the first container outer body 108 from the female thread of the first section 208 A of the second container outer body 208 through counter-rotation of the first container 100 relative to the second container 200 to retract the first container- side valve 126 away from the second container- side valve 220. As the first container- side valve 126 continues to retract from the second containerside valve 220, the tapered portion of the second portion 224B of the valve stem 224 that activated the first container- side valve 126 is retracted away from the first seal 132 to deactivate the first seal 132 from the activated position to the normally closed position to thereby reduce or completely eliminate flow through the first seal 132 of the first container- side valve 126.

[00114] Upon completion of the step S310, a dose of cell-based formulated drug product including the mixture of the cells and cell delivery solution or transplantation media are enclosed in the first interior space 106 of the first container barrel 110 by the first container-side valve 126 in the normally-closed position.

[00115] According to the process for preparing the formulated drug product, the cells originally cryopreserved in the cryoprotectant and held by the cell vial 306 are washed and transferred from the cell vial 306 to the second container 200 and further to the first container 100 in a flow path that minimizes or eliminates a risk of contamination of the formulated drug product through contact with an external environment. Therefore, the formulated drug product can be considered to be aseptic or near aseptic.

[00116] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[00117] The corresponding structures, materials, acts, and equivalents of all means or step plus function elements, if any, in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the invention. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.

Claims

CLAIMS What is claimed is:

1. An apparatus comprising: a first container comprising: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container- side valve configured to be activated, upon connection of a second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

2. The apparatus according to claim 1, wherein the second container comprises a second container-side valve, and wherein upon connection of the second container to the first container outer body, the first container- side valve is brought into contact with the second container- side valve.

3. The apparatus according to claim 2, wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the second containerside valve from the normally closed position to the activated position.

4. The apparatus according to claim 2, wherein the second container comprises: a second container outer body that defines a second container barrel interior space connected a first opening of the second container, wherein the second container- side valve is configured to be activated, upon connection of

29 the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the second container, from a normally closed position that relatively reduces flow through the first opening of the second container into the second container barrel interior space to an activated positon that relatively increases flow through the first opening of the second container into the second container barrel interior space, and wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the second containerside valve from the normally closed position to the activated position and the second containerside valve is configured to be activated from the normally closed position to the activated position to communicate the second container barrel interior space with the first interior space.

5. The apparatus according to claim 4, wherein the second container- side valve comprises a valve stem, and wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the valve stem from the normally closed position to the activated position and the second container- side valve is configured to be activated from the normally closed position to the activated position to communicate the second container barrel interior space with the first interior space through the valve stem.

6. A medical device system comprising: a first container; and a second container, wherein the first container comprises: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container- side valve configured to be activated, upon connection of the second container to the first container outer body, from a normally closed position that relatively

30 reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

7. The medical device system according to claim 6, wherein the second container comprises a second container-side valve, and wherein upon connection of the second container to the first container outer body, the first container- side valve is brought into contact with the second container- side valve.

8. The medical device system according to claim 7, wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the second containerside valve from the normally closed position to the activated position.

9. The medical device system according to claim 7, wherein the second container comprises: a second container outer body that defines a second container barrel interior space connected a first opening of the second container, wherein the second container- side valve is configured to be activated, upon connection of the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the second container, from a normally closed position that relatively reduces flow through the first opening of the second container from the second container barrel interior space to an activated positon that relatively increases flow through the first opening of the second container from the second container barrel interior space, and wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the second containerside valve from the normally closed position to the activated position and the second containerside valve is configured to be activated from the normally closed position to the activated position to communicate the second container barrel interior space with the first interior space.

10. The medical device system according to claim 9, wherein the second container- side valve comprises a valve stem, and wherein upon connection of the second container to the first container outer body, the first container- side valve is configured to be contacted by and activated by the valve stem from the normally closed position to the activated position and the second container- side valve is configured to be activated from the normally closed position to the activated position to communicate the second container barrel interior space with the first interior space through the valve stem.

11. A process for operating a medical device system comprising: a first container; and a second container, wherein the first container comprises: a first container outer body; a first container barrel, arranged within the first container outer body, that defines a first interior space connected to a first opening of the first container; and a first container- side valve, and wherein the process comprises: aligning the first container and the second container; and connecting the second container to the first container outer body, wherein the first container- side valve is configured to be activated, upon connection of the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the first container into the first interior space to an activated position that relatively increases flow through the first opening of the first container into the first interior space.

12. The process according to claim 11, wherein the second container comprises a second container-side valve, and wherein the process comprises: in connecting the second container to the first container outer body, bringing the first container- side valve into contact with the second container- side valve.

13. The process according to claim 12, comprising: in bringing the first container-side valve into contact with the second container-side valve, activating, by the second container- side valve, the first container-side valve from the normally closed position to the activated position.

14. The process according to claim 12, wherein the second container comprises: a second container outer body that defines a second container barrel interior space connected a first opening of the second container, and wherein the process comprises: activating the second container- side valve, upon connection of the second container to the first container outer body, from a normally closed position that relatively reduces flow through the first opening of the second container, from a normally closed position that relatively reduces flow through the first opening of the second container from the second container barrel interior space to an activated positon that relatively increases flow through the first opening of the second container from the second container barrel interior space, to communicate the second container barrel interior space with the first interior space.

15. The process according to claim 14, wherein the second container- side valve comprises a valve stem, and wherein the process comprises, upon connection of the second container to the first container outer body: bringing the valve stem into contact with the first container- side valve to activate the first container- side valve from the normally closed position to the activated position and the second container-side valve from the normally closed position to the activated position to communicate the second container barrel interior space with the first interior space through the valve stem.

33

16. The process according to claim 14, further comprising: pre-loading the first interior space of the first container with a cell delivery solution.

17. The process according to claim 16, further comprising: loading a mixture comprising a plurality of cells and a wash solution in the second container barrel interior space.

18. The process according to claim 17, further comprising: after communicating the second container barrel interior space with the first interior space, applying a centrifugal force to the medical device system to move the plurality of cells from the second container barrel interior space through the second container- side valve in the activated position and the first container- side valve in the activated position into the first interior space.

19. The process according to claim 11, further comprising: pre-loading the first interior space of the first container with a cell delivery solution.

34