System for providing cellular products

Abstract

The present invention addresses the problem of providing a system for finally providing a single cell product in a state of functioning as a cell product without mixing or confusing raw materials when producing a single cell product using two or more types of tissues derived from the same patient. According to the present invention, provided is a system for providing a cell product, the system comprising: an identification step for attaching an identification code indicating patient information to two or more types of raw materials originating from the same patient; a first conveyance step for conveying the two or more types of raw materials to which the identification code has been attached from the medical institution to the manufacturing station under the condition that the product of the temperature (DEG C) and the number of days during conveyance is within a prescribed numerical range; a production step for producing a cell product by recognizing the identification code and combining two or more types of respective raw materials into one type; and a second transport step for transporting the cell product from the manufacturing station to the medical institution.

Description

Technical Field

[0001] The present invention relates to a system for providing a cell product produced using two or more raw materials derived from the same patient. Background Art

[0002] In recent years, due to the progress of regenerative medicine technology and cell therapy technology, various cell therapies using autologous, allogeneic or xenogeneic cells and the development of cell products for research have been actively carried out. For example, mesenchymal stem cells (MSC) are expected to become a useful cell source for cell therapy. Mesenchymal stem cells can be extracted from various body tissues and can be isolated from bone marrow tissue, adipose tissue, muscle tissue, synovial tissue and periosteum tissue. In particular, it is reported that mesenchymal stem cells derived from synovium (also called synovial stem cells) have higher proliferation ability and cartilage formation ability than mesenchymal stem cells derived from various mesenchymal tissues such as bone marrow. Patent document 1 discloses a method for treating articular cartilage damage and meniscus damage using mesenchymal stem cells derived from synovium.

[0003] In addition, Patent Document 2 describes a human stem cell preservation solution containing at least human serum, wherein the volume ratio of human serum to the preservation solution as a whole is 0.70 or more, and is a preservation solution for preserving human stem cells at a temperature higher than 0°C, and a method for preserving human stem cells using the above-mentioned preservation solution.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent No. 5656183

[0007] Patent Document 2: International Publication No. WO2018 / 147457 Summary of the invention

[0008] Technical issues to be solved by the invention

[0009] Regarding therapeutic cells, the cells themselves are not completely uniform structures, and it is difficult to determine the characteristics of the cells. They have so-called viability characteristics (i.e., it is necessary to distinguish between living cells and dead cells). Therefore, through the development of cell products, people have realized that it is difficult to manage them as a completely specified object. In fact, even in the manufacture of cell products, it is necessary to control the characteristics of cell products by controlling the manufacturing process, rather than managing cells as final products. However, in reality, it is difficult to use cells appropriately for treatment only by controlling the manufacturing process of the manufacturer. Therefore, as a system for providing cell products, a system is needed to control the process from extracting the starting materials from the patient to administering the manufactured cell products to the patient.

[0010] In the past, cells have been isolated from patient-derived tissues in medical institutions and used for treatment. On the other hand, it is envisioned that two or more raw materials derived from the same patient may be used, and these two or more raw materials derived from the patient may be transported to a manufacturing plant outside the medical institution, and the two or more raw materials derived from the patient may be combined at the manufacturing plant to produce one type of cell product, and the produced cell product may be transported to the medical institution and administered to the patient.

[0011] The inventors of the present invention have focused on the following new problem: when two or more tissues originating from the same patient are used as described above, it is necessary to maintain the quality of the two or more raw materials originating from the same patient, and not to mix or confuse the raw materials, and finally to manufacture a cell product in a state where the cells are alive, and to transport the cells to a medical institution in a state where the cells are alive, and to provide the cell product in a state where the cell product functions (the cell survival rate in the cell product is 70% or more). That is, the problem to be solved by the present invention is to provide a system for providing a cell product in a state where the raw materials are not mixed or confused when manufacturing a cell product using two or more tissues originating from the same patient, and finally to provide a cell product in a state where the cell product functions.

[0012] Means for solving technical problems

[0013] As a result of in-depth research to solve the above-mentioned problem, the inventors found that the above-mentioned problem can be solved by attaching identification codes indicating patient information to two or more different raw materials from the same patient, transporting the two or more different raw materials with the identification codes from a medical institution to a manufacturing plant under prescribed appropriate conditions, identifying the identification codes after transport, and combining the two or more different raw materials into one to manufacture a cell product. The present invention was completed based on the above-mentioned findings.

[0014] According to the present invention, the following inventions are provided.

[0015] <1> A system for providing a cell product, the system comprising:

[0016] an identification step of adding identification codes indicating patient information to two or more respective raw materials derived from the same patient;

[0017] A first transport step is to transport two or more raw materials with identification codes respectively sealed in two or more packaging containers from a medical institution to a manufacturing plant, wherein at least one of the two or more raw materials is transported from the medical institution to the manufacturing plant under a condition where the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less;

[0018] a manufacturing process, after the first conveying process, comprising manufacturing a cell product by identifying the identification code and combining the two or more separate raw materials into one; and

[0019] The second transporting step is to transport the cell product from the manufacturing site to the medical institution after the manufacturing step.

[0020] <2> The system according to <1>, wherein a temperature in the first transport step is 1° C. to 27° C., and a transport period is 1 hour to 160 hours.

[0021] <3> The system according to <1> or <2>, wherein the manufacturing process further comprises the following steps:

[0022] Components are separated from the two or more raw materials, one of which is a cell, and the cells are cultured at a temperature of 30° C. or higher, and then determined whether they meet the quality standard of the cells.

[0023] <4> The system according to any one of <1> to <3>, wherein no biologically derived raw materials other than the patient-derived raw materials are used.

[0024] <5> The system according to any one of <1> to <4>, wherein the first conveying step and the second conveying step include: measuring and recording temperature, and tracking the temperature record.

[0025] <6> The system according to any one of <1> to <5>, wherein one of the two or more separate raw materials is blood.

[0026] <7> The system according to <6>, wherein a period of the first blood transfer step is 150 hours or less.

[0027] <8> The system according to any one of <1> to <7>, wherein one of the two or more separate raw materials is synovial tissue.

[0028] <9> The system according to <8>, wherein a period of the first transport step of the synovial tissue is 130 hours or less.

[0029] <10> The system according to any one of <1> to <9>, wherein the two or more raw materials include blood and synovial tissue.

[0030] <11> A system according to any one of <1> to <10>, wherein the interval between the dates on which the two or more raw materials are sent from the medical institution or the interval between the dates on which the two or more raw materials arrive at the manufacturing plant is 3 days to 2 weeks.

[0031] <12> The system according to any one of <1> to <11>, wherein a transport time in the second transport step is 1 hour to 90 hours, and a transport temperature is 30° C. or less.

[0032] <13> A system according to any one of <1> to <12>, wherein a second identification code linked to the identification codes attached to the above-mentioned two or more respective raw materials is attached to the cell product, and based on the above-mentioned second identification code, the cell product is allocated to a patient who is a source of the raw materials.

[0033] Effects of the Invention

[0034] According to the present invention, when one cell product is produced using two or more tissues derived from the same patient, one cell product can be provided in a state of functioning as a cell product without mixing or confounding the raw materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a schematic diagram showing an example of a system for providing the cell product of the present invention. DETAILED DESCRIPTION

[0036] Hereinafter, an example of an embodiment of the present invention will be described. However, the present invention is not limited to the following embodiments, and can be implemented by appropriately changing within the scope of the purpose of the present invention. In this specification, the numerical range represented by "to" refers to the range including the numerical values ​​recorded before and after "to" as the minimum value and the maximum value, respectively.

[0037] A system for providing a cell product of the present invention comprises:

[0038] an identification step of adding identification codes indicating patient information to two or more separate raw materials derived from the same patient;

[0039] A first transport step is to transport two or more raw materials with identification codes respectively sealed in two or more packaging containers from a medical institution to a manufacturing plant, wherein at least one of the two or more raw materials is transported from the medical institution to the manufacturing plant under a condition where the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less;

[0040] a manufacturing process, after the first conveying process, comprising manufacturing a cell product by identifying the identification code and combining the two or more separate raw materials into one; and

[0041] The second transporting step is to transport the cell product from the manufacturing site to the medical institution after the manufacturing step.

[0042] Cell therapy refers to the treatment (including prevention and relief) of a disease or injury in a subject by administering to the subject cells (e.g., mammals, preferably humans) processed in vitro and derived from the subject, the same species, or a different species. Cell products are products used for cell therapy (including prevention and relief), at least medicines containing cells. By administering living cells to a subject from in vitro, it is possible to treat or prevent a subject's disease based on the function of the cells in vivo. The cell product in the present invention is a product manufactured by combining two or more raw materials from the same patient.

[0043] In the system of the present invention, it is preferred to use two or more raw materials derived from a patient, but no raw material derived from a living organism other than the raw materials derived from the patient is used.

[0044] The system in the present invention may be a method for providing a cell product, or a mechanism for performing the method for providing the cell product, and the system includes the above-mentioned identification step, first conveying step, manufacturing step, and second conveying step.

[0045] <Identification process>

[0046] The identification step is a step of adding identification codes indicating patient information to two or more raw materials derived from the same patient. The identification step can be performed in a medical institution such as a hospital, a clinic, a doctor's office, or the like.

[0047] In the present invention, two or more raw materials derived from the same patient are used. The types of raw materials may be two or more, or three or more raw materials may be used. The upper limit of the number of types of raw materials is not particularly limited, but is usually 5 or less.

[0048] Examples of raw materials derived from patients include tissues or organs of the patient, such as synovium, blood (peripheral blood, etc.), bone marrow, periosteum, synovium, adipose tissue, muscle, dental pulp, placental tissue, umbilical cord tissue (umbilical cord blood), skin, etc., but are not particularly limited.

[0049] In one example of the present invention, one of the two or more separate raw materials is blood.

[0050] In one example of the present invention, one of the two or more separate raw materials is synovial tissue.

[0051] In one example of the present invention, the two or more separate raw materials are a combination of blood and synovial tissue.

[0052] The types of cells contained in the cell product of the present invention are not particularly limited, and examples thereof include mesenchymal stem cells (synovial stem cells, bone marrow stem cells, adipose stem cells, etc.), hematopoietic stem cells, embryonic stem cells, artificial pluripotent cells, neural cells, glial cells, non-glial cells, osteoblasts, osteocytes, osteoclasts, chondroblasts, chondrocytes, fibroblasts, keratinocytes, melanocytes, glandular cells, corneal cells, retinal cells, epithelial cells, platelets, thymocytes, lymphocytes, spheroids, macrophages, muscle cells, hepatocytes, kidney cells, urethral cells, cardiomyocytes, myoblasts and / or germ cells.

[0053] In the present invention, identification codes representing patient information are added to two or more different raw materials derived from the same patient. By adding identification codes representing patient information to two or more different raw materials derived from the same patient, in the manufacturing process described later, the two or more different raw materials are combined into one by identifying the identification code, thereby manufacturing a cell product composed of two or more raw materials derived from the same patient.

[0054] In the present invention, identification codes indicating patient information are attached to two or more different raw materials. Specifically, the two or more different raw materials can be contained in separate containers, and the identification codes indicating patient information are labeled on each container. Alternatively, separate containers with identification codes indicating patient information attached can be prepared in advance, and the two or more different raw materials can be contained in these containers.

[0055] There is no particular limitation on the method of the identification code representing the patient information, as long as the patient information can be identified. As an example, it can be a combination of 8 or more (e.g., 10) letters and numbers. In addition, a one-dimensional code or a two-dimensional code can be used. As a one-dimensional code, a barcode can be cited. As a two-dimensional code, stacked two-dimensional codes and matrix two-dimensional codes can be cited. As a stacked two-dimensional code, PDF417 can be cited. As a matrix two-dimensional code, QR code (registered trademark), DataMatrix, VeriCode can be cited. When using a one-dimensional code or a two-dimensional code, patient information can be managed more simply by using a code reading device in combination.

[0056] <First conveying step>

[0057] The first transport step in the present invention is a step of transporting two or more separate raw materials with identification codes from a medical institution to a manufacturing facility in a state where each is sealed in a two-layer or more packaging container. In the first transport step, at least one of the two or more separate raw materials is transported from a medical institution to a manufacturing facility under the condition that the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less. By transporting the raw materials from the medical institution to the manufacturing facility under the above conditions, a sufficient yield of the manufactured cells can be achieved.

[0058] For example, when blood and synovial tissue are used as two or more raw materials, at least one of the blood and synovial tissue may be transported from a medical institution to a manufacturing facility under the condition that the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less. Preferably, the blood can be transported from a medical institution to a manufacturing facility under the condition that the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less.

[0059] When the temperature fluctuates during transportation, the average temperature during transportation may be used as the temperature obtained by multiplying the temperature (° C.) by the number of days during transportation (days).

[0060] The product of the temperature (°C) and the number of days during the transportation period (days) may be 170 (°C × days) or less, and may preferably be 160 (°C × days) or less, 150 (°C × days) or less, 140 (°C × days) or less, 130 (°C × days) or less, 120 (°C × days) or less, 110 (°C × days) or less, 100 (°C × days) or less, 90 (°C × days) or less, 80 (°C × days) or less, 70 (°C × days) or less, 60 (°C × days) or less, or 50 (°C × days) or less. For example, when blood is transported, by setting the product of the temperature (°C) and the number of days during the transportation period (days) within the above range, blood can be transported while maintaining high quality, and as a result, by culturing synovial stem cells using the above blood, synovial stem cells can be obtained at a high yield. The lower limit of the product of the temperature (°C) and the number of days during the transportation period (days) is not particularly limited, but is usually 0.01 (°C×day) or more, 0.04 (°C×day) or more, 0.08 (°C×day) or more, or 1 (°C×day) or more.

[0061] The temperature in the first transport step is preferably 1°C to 35°C, more preferably 1°C to 30°C, further preferably 1°C to 27°C, further preferably 1°C to 25°C, particularly preferably 5°C to 25°C, and most preferably 10°C to 20°C.

[0062] The conveying period of the first conveying step is preferably 1 hour to 240 hours, more preferably 1 hour to 192 hours, further preferably 1 hour to 160 hours, further preferably 1 hour to 150 hours, further preferably 1 hour to 144 hours, further preferably 1 hour to 130 hours, further preferably 1 hour to 120 hours, further preferably 1 hour to 96 hours. It may be 1 hour to 72 hours, 1 hour to 48 hours, 1 hour to 36 hours, or 1 hour to 24 hours.

[0063] For example, when the raw material to be transported is blood, the duration of the first transport step is preferably from 1 hour to 150 hours, more preferably from 1 hour to 144 hours, further preferably from 1 hour to 130 hours, further preferably from 1 hour to 120 hours, further preferably from 1 hour to 96 hours. It may be from 1 hour to 72 hours, from 1 hour to 48 hours, from 1 hour to 36 hours, or from 1 hour to 24 hours.

[0064] As another example, when the raw material to be transported is synovial tissue, the duration of the first transport step is preferably 1 hour to 130 hours, more preferably 1 hour to 120 hours, and even more preferably 1 hour to 96 hours or less. It may be 1 hour to 72 hours, 1 hour to 48 hours, 1 hour to 36 hours, or 1 hour to 24 hours.

[0065] In the first conveying step, it is preferred to measure the temperature, record the temperature, and track the record. By measuring the temperature, recording the temperature, and tracking the record, it is possible to detect when the temperature exceeds a predetermined range.

[0066] The timings at which two or more kinds of raw materials are respectively sent from the medical institutions may be simultaneous, but in reality, it is assumed that the two or more kinds of raw materials are sent at different timings.

[0067] The interval between the dates on which two or more separate raw materials are sent from medical institutions, or the interval between the dates on which each of the two or more separate raw materials arrives at the manufacturer, is preferably 3 days to 2 weeks, more preferably 5 days to 10 days, further preferably 6 days to 8 days, and as an example, 7 days.

[0068] In the first conveying step, the raw material is conveyed in a packaged state. The packaging of the raw material is preferably a double-layer packaging. For example, when the raw material is blood, a blood collection bag (such as Cell-Aid (registered trademark)) or a blood collection tube can be used as a primary packaging, and a plastic bag or a plastic bag can be used as a secondary packaging.

[0069] As described above, the packaged raw materials are preferably transported in a state of being contained in a constant temperature transport device. The constant temperature transport device is a device configured to maintain the transported raw materials at a predetermined temperature, and is known to those skilled in the art. Commercially available products (e.g., TS500: Toho Pharmaceutical Co., Ltd.) can be used. A refrigerant, a cooler, etc. can also be used to maintain the temperature.

[0070] The transport distance in the first transport step is not particularly limited, and may be, for example, 100 m or more, 1 km or more, 10 km or more, or 10000 km or less or 1000 km or less.

[0071] The conveying mechanism in the first conveying step is not particularly limited, and the conveying may be carried by a person or by various transportation vehicles. The transportation vehicle is not particularly limited, and may be, for example, a railway, a truck, a bus, a car, a bicycle, a motorcycle, a ship, a helicopter, an airplane, or the like.

[0072] <Manufacturing process>

[0073] The manufacturing process of the present invention is a process that includes manufacturing a cell product by identifying an identification code and combining two or more separate raw materials into one after the first delivery process. In the present invention, by identifying an identification code and combining two or more separate raw materials into one, two or more separate raw materials from the same patient can be combined into one without confusion. The manufacturing process can be performed in a manufacturing facility, a factory, a research institute, etc.

[0074] In the manufacturing process, the raw materials may be inspected before combining two or more separate raw materials into one. Preferably, the manufacturing process further includes a step of separating components from the two or more separate raw materials, one of the components being cells, culturing the cells at a temperature of 30° C. or higher, and then determining whether the cells meet the quality standards.

[0075] For example, when the raw material is blood, an appearance inspection of the blood can be performed. As an appearance inspection of the blood, it can be evaluated from the perspectives of whether the state is maintained, whether a black change is observed, etc. If it is judged that the appearance inspection is suitable, serum can be prepared by separation work from blood tissue, and the serum can be used in combination with other raw materials.

[0076] For example, when the raw material is synovial tissue, the synovial tissue can be inspected for appearance, etc. Inspection of appearance, etc. can be evaluated from the perspectives of whether color change is observed, whether pH state is maintained, whether it is not dried but moist, and whether the required amount is contained.

[0077] The appropriate synovial tissue is finely cut and immersed in an enzyme solution containing serum confirmed to be derived from the same patient by an identification code, and a cell component can be produced by an enzyme reaction. The produced cell component is immersed in a culture solution containing serum confirmed to be derived from the same patient by an identification code, placed in a flask, and cultured in a sterile environment such as 37°C and 5% CO2, so that the synovial tissue and serum can be combined into one.

[0078] In the production process, the cell product is produced by combining two or more different raw materials into one. Preferably, the cell product can be produced by culturing a mixture obtained by combining two or more different raw materials into one.

[0079] As culture conditions for manufacturing cell products, normal cell culture conditions can be used, for example, culture under a sterile environment of 25 to 42°C (preferably 37°C) and 1 to 10% CO2 (preferably 5% CO2). Culture can be carried out using a culture dish, a culture plate, a culture bottle or a culture bag. The culture medium and conditions used when culturing cells can be appropriately set according to the cells used. Specifically, Eagle's Minimum Essential Medium (EMEM), Dulbecco's Modified Eagle's Medium (DMEM), α-MEM, Glasgow's MEM (GMEM), IMDM, RPMI1640, Ham's F-12 and their mixed culture media can be cited, but are not limited to this. In addition, culture media added with various growth factors, differentiation inducing factors, antibiotics, hormones, amino acids, sugars, salts, etc. can be used.

[0080] Preferably, the manufactured cell product can be subjected to a shipping inspection and final packaging of the cell product after cleaning.

[0081] As a shipping inspection, the cell count can be evaluated (e.g., shipping standard: 1.5×10 7 cells), cell survival rate (e.g., shipping standard: 70% or more) and cell purity. When the cell product is a product containing synovial mesenchymal stem cells, CD90 positivity and CD45 negativity can be used as the shipping standard of cell purity.

[0082] The manufactured cell product can preferably be attached with a second identification code linked to the identification codes of two or more different raw materials. In this case, after the cell product is transported from the manufacturer to the medical institution through the second transport process described later, the cell product can be distributed to the patient who is the source of the raw material based on the second identification code.

[0083] <Second conveying step>

[0084] The second transport step in the present invention is a step of transporting the cell product from the production site to a medical institution after the production step.

[0085] The temperature in the second transport step is preferably 30°C or lower, more preferably 1°C to 30°C, further preferably 2°C to 25°C, further preferably 2°C to 22°C, further preferably 2°C to 20°C, particularly preferably 10°C to 20°C.

[0086] The conveying time in the second conveying step is preferably from 1 hour to 90 hours, more preferably from 1 hour to 80 hours, further preferably from 1 hour to 72 hours, further preferably from 1 hour to 56 hours, further preferably from 1 hour to 48 hours, further preferably from 1 hour to 32 hours.

[0087] In the second conveying step, it is preferable to measure the temperature, record the temperature, and track the record. By measuring the temperature, recording the temperature, and tracking the record, the temperature can be maintained at a predetermined temperature.

[0088] In the second conveying process, the conveyed raw material is conveyed in a packaged state. The packaging of the raw material is preferably a double-layer packaging. When the cell product is attached with a second identification code linked to the identification codes of two or more separate raw materials, it is preferred that the second identification code is attached to the first layer of packaging (i.e., a primary container). In addition, "linked" means that there is no limitation on the method of linkage, indicating that the identification codes can be associated with each other, for example, a method of establishing association by specifying association rules in the process manual or by changing the branch number of the same code.

[0089] As described above, the packaged raw materials are preferably transported in a state of being contained in a constant temperature transport device. The constant temperature transport device is a device configured to maintain the transported raw materials at a specified temperature, is known to those skilled in the art, and a commercially available product (e.g., TS500: Toho Pharmaceutical Co., Ltd.) can be used.

[0090] The transport distance in the second transport step is not particularly limited, and may be, for example, 100 m or more, 1 km or more, 10 km or more, or 10000 km or less, or 1000 km or less.

[0091] The conveying mechanism in the second conveying step is not particularly limited, and the conveying may be carried by a person or by various transportation means. The transportation means is not particularly limited, and may be, for example, any of railways, automobiles, ships, or airplanes.

[0092] The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the examples.

[0093] Example

[0094] The following examples are based on Figure 1 The process shown is carried out according to an example of a system for providing a cell product according to the present invention. In a medical institution, blood is collected and an identification code is assigned, and synovium is extracted and an identification code is assigned. The blood assigned an identification code and the synovium assigned an identification code are transported to a manufacturer, respectively. In the manufacturer, serum is made from blood. The synovium is finely chopped and the serum from the same patient is treated with an enzyme together. The enzyme-treated synovium is cultured to manufacture a cell product. The manufactured cell product is transported to a medical institution after a shipment inspection. In the medical institution, the cell product is administered to the patient whose blood and synovium have been extracted.

[0095] <Example 1> Identification step and first transfer step of tissue (blood tissue) derived from the first type of patient

[0096] As a tissue derived from a patient, blood tissue was extracted from a patient at a university hospital. Specifically, a blood separation bag (Cell-Aid (registered trademark)) was used to extract 180 g of blood from the vein of the flexion of the forearm in each bag, and a total of 360 g of blood was separated from two bags. A patient identification code (a 10-digit number consisting of letters and numbers) was attached to the blood tissue, and a two-layer package (the first layer was Cell-Aid (registered trademark), and the second layer was a vinyl bag (plastic bag packaging)) was used, and it was placed in a transport box (equivalent to a constant temperature transport device (TS500: Toho Pharmaceutical Co., Ltd.)) that maintained a constant temperature and sealed. Through the transport box, the blood tissue was transported to the manufacturer in a state where the desired temperature was controlled between 1°C and 30°C. In addition, the delivery date was the same as the extraction date of the blood tissue. The transportation time (this is the time from extracting the sample and placing it in the constant temperature transport device until it arrives at the manufacturer) corresponds to 1 hour, 96 hours, 144 hours, and 192 hours.

[0097] <Example 2> Identification step and first delivery step of tissue (synovial tissue) derived from the second type of patient

[0098] Seven days after the blood tissue is extracted, synovial tissue is aseptically extracted from the knee as the second type of patient-derived tissue. The extracted synovial tissue is sealed in a primary container filled with a transport fluid. The primary container is affixed with a patient identification code, and the primary container is sealed in a secondary container and placed in an outer box. The second layer of packaging is now completed. The outer box is placed in a transport box (equivalent to a constant temperature transport device (TS500: Toho Pharmaceutical Co., Ltd.)) that maintains a constant temperature and is sealed. Through this transport box, the synovial tissue is transported to the manufacturer with the desired temperature controlled between 10°C and 22°C. In addition, the shipping date is the same as the extraction date of the synovial tissue. The times corresponding to this transport time are 1 hour, 120 hours, and 168 hours.

[0099] <Example 3> Blood separation process in a manufacturing plant

[0100] The seal of the temperature-controlled transporter transported to the manufacturing plant is unsealed, and the blood bag is transported to the clean manufacturing area in a double-packed state. In the clean manufacturing area, the packaging is opened and the blood is visually inspected.

[0101] The results of the blood appearance examination were evaluated according to the following criteria. The evaluation results are shown in Table 1 below.

[0102] A: Maintain status

[0103] B: Allowable range

[0104] C: Black variation

[0105] The patient identification code is determined and serum is prepared from the appropriate blood tissue through separation. The prepared serum is stored sterilely.

[0106] Example 4: Synovial membrane separation process in a manufacturing plant

[0107] The seal of the constant temperature transport device transported to the manufacturing plant is unsealed, and the synovial tissue is transported to the clean manufacturing area in a double-layer package. In the clean manufacturing area, the package is unpacked, the patient identification code is identified, and the appropriate synovial tissue is finely cut, and then immersed in the enzyme solution containing serum confirmed to be derived from the same patient by the identification code prepared in Example 1, and the cell components are produced by enzyme reaction. The produced cell components are immersed in the culture solution containing serum confirmed to be derived from the same patient by the identification code prepared in Example 1, and placed in a flask for culture and production at 37°C, 5% CO2, and a sterile environment. This process is a process of combining two raw materials derived from patients into one.

[0108] Example 5: Manufacturing and Shipping Inspection of Cultured Cell Products

[0109] The cell product was produced by culturing the mixture of synovial tissue and blood tissue obtained in Example 4 for 10 to 14 days at 37°C and 5% CO2 in a sterile environment. The produced cell product was recovered from the flask, washed, and then subjected to shipping inspection and final packaging of the cell product.

[0110] As a shipping inspection, the cell count (shipping standard: 1.5×10 7 cells), cell survival rate (shipping standard: more than 70%) and cell purity (shipping standard: CD90 positive, CD45 negative).

[0111] The standard yield of cell number (= the number of synovial stem cells returned from the manufacturer to the medical institution) is 1.5×10 7 Cells. A standard yield is enough cells to treat one person.

[0112] The evaluation criteria for the number of synovial stem cells are as follows.

[0113] A: More than twice the standard output

[0114] B: More than 1 times and less than 2 times the standard output

[0115] C: 0.5 times or more and less than 1 times the standard output

[0116] D: Less than 0.5 times the standard output

[0117] The evaluation criteria for the cell viability of synovial tissue are as follows.

[0118] A: 80% or more and 100% or less

[0119] B: 70% or more and less than 80%

[0120] C: less than 70%

[0121] The results of the above evaluation are shown in Tables 1 and 2. The purity of all cells met the shipping standard (CD90 positive, CD45 negative).

[0122] [Table 1]

[0123] Table 1: Blood tissue delivery time, delivery temperature and final synovial stem cell yield

[0124]

[0125] The upper panel shows the evaluation results of cell yield.

[0126] The middle section shows the evaluation results of the appearance inspection.

[0127] The lower part shows the product of the temperature (°C) and the number of days during the transportation (days).

[0128] [Table 2]

[0129] Table 2: Synovial tissue delivery time, delivery temperature, and final synovial stem cell yield (conditions for the first blood delivery step were 1 to 20°C and 96 hours)

[0130]

[0131] As shown in Table 1 above, when blood tissue transported under the condition of temperature × number of days (hours) of 170°C or less was used, a cell product that met the shipping standard was successfully obtained.

[0132] Example 6: Shipping from a manufacturing plant and transporting to a medical institution

[0133] As a shipping package, synovial stem cells obtained by culturing synovial tissue and blood tissue are suspended in serum and processed into a cell product form consisting of serum and synovial stem cells (5×10 7 cells / mL).

[0134] In one embodiment, the serum and synovial stem cells are aseptically sealed in a primary container (freezing tube) with an identification code, placed in a secondary container (Nipro Sergatch (registered trademark)), and further placed in an outer box and sealed (non-frozen form). The two-layer packaging is now completed. The outer box is placed in a transport box (equivalent to a constant temperature transport device (TS500: Toho Pharmaceutical Co., Ltd.)) that maintains a constant temperature and is sealed, and stored as a behavior corresponding to transportation. The storage temperature and time are shown in Table 3.

[0135] [Table 3]

[0136] Table 3: Transportation (storage) time, temperature and cell survival rate of cell products

[0137]

[0138] As shown in Table 3, the cell products were kept alive at a temperature of 2°C to 25°C and a time of 1 hour to 80 hours (survival rate of 70% or more). According to this result, the cell products can be transported from the manufacturer to the medical institution at a transport temperature of 2°C to 25°C and a transport time of 1 hour to 80 hours and kept alive. In addition, there is no problem with this temperature and time, but it is more preferable that the survival rate is 90% or more at 2°C to 20°C and less than 80 hours, which is known to be a more preferable condition for the system providing cells.

[0139] In another embodiment, in addition to the above-mentioned blood tissue and synovial stem cells, a structure containing 5% dimethyl sulfoxide (DMSO) is aseptically sealed in a primary container with an identification code attached, and placed in a secondary container, and frozen at -80°C or below. At this point, the two-layer packaging is completed. The frozen secondary container is placed in an outer box and sealed, and then placed in a frozen sample transport container (dry consignment) or a freezer filled with dry ice and sealed for storage. This is the behavior corresponding to transportation to a medical institution. At this time, if the storage temperature is below -60°C, or below -80°C and the transportation time is 1 hour to 1 month, the survival state of the cell product can be restored (survival rate of more than 70%) by thawing in a hot water bath at 37°C. From these results, it can be seen that if the transportation temperature is below -60°C or below -80°C and the transportation time is 1 hour to 1 month, the cell product can be provided to the medical institution in a state of cell survival by thawing in a hot water bath at 37°C after arriving at the medical institution. In addition, in this frozen delivery, the cell survival rate after thawing at -30°C for 1 month was less than 70%. From these results, it can be seen that the delivery system in the frozen form of -60°C or less for 1 hour to 1 month is preferable as a system for delivering viable cells.

[0140] Example 7: Use of cell products in medical institutions

[0141] The synovial stem cells provided in Example 6 are used in medical institutions to treat osteoarthritis and meniscus tears. In fact, it has been found that the use of synovial stem cells to treat knee osteoarthritis can improve clinical scores. And, it has been found that similarly by using it for meniscus tears, clinical scores are also improved. In addition, when used in a medical institution, the therapeutic cells composed of tissues (more than 2 types) derived from the patient's own body are confirmed by an identification code and then given to the patient's system.

[0142] As shown in Examples 1 to 7 above, by utilizing the therapeutic cell delivery system of the present invention, two or more raw materials originating from the same patient will not be mixed or confused, and can be transported from a medical institution to a manufacturing plant in a living state, and further manufactured into a living cell product combining the two or more raw materials originating from the same patient and sent to a medical institution.

Claims

1. A system for providing a cell product, the system comprising: an identification step of adding identification codes indicating patient information to two or more respective raw materials derived from the same patient; A first transport step, in which two or more kinds of raw materials with identification codes are respectively sealed in two or more layers of packaging containers and transported from a medical institution to a manufacturing plant, wherein at least one of the two or more kinds of raw materials is transported from the medical institution to the manufacturing plant under a condition where the product of the temperature (°C) and the number of days during the transport period (days) is 170 (°C × days) or less; a manufacturing process, after the first conveying process, comprising manufacturing a cell product by identifying the identification code and combining the two or more separate raw materials into one; and The second transporting step is to transport the cell product from the manufacturing site to the medical institution after the manufacturing step.

2. The system according to claim 1, wherein: The temperature of the first transport step is 1° C. to 27° C., and the transport period is 1 hour to 160 hours.

3. The system according to claim 1 or 2, wherein: The manufacturing process also includes the following steps: Components are separated from the two or more raw materials, one of which is a cell, and the cell is cultured at a temperature of 30° C. or higher, and then it is determined whether the cell meets the quality standard.

4. The system according to claim 1 or 2, wherein: No biologically derived raw materials other than those derived from the patient are used.

5. The system according to claim 1 or 2, wherein: The first conveying step and the second conveying step include: measuring and recording temperature, and tracking the temperature record.

6. The system according to claim 1 or 2, wherein: One of the two or more separate raw materials is blood.

7. The system according to claim 6, wherein: The duration of the first blood transfer step is 150 hours or less.

8. The system according to claim 1 or 2, wherein: One of the two or more separate raw materials is synovial tissue.

9. The system according to claim 8, wherein: The duration of the first delivery step of the synovial tissue is 130 hours or less.

10. The system according to claim 1 or 2, wherein: The two or more separate raw materials include blood and synovial tissue.

11. The system according to claim 1 or 2, wherein: The interval between the delivery dates of the two or more types of raw materials from the medical institution or the arrival dates of the two or more types of raw materials at the manufacturer is 3 days to 2 weeks.

12. The system according to claim 1 or 2, wherein: The transport time in the second transport step is 1 hour to 90 hours, and the transport temperature is 30° C. or less.

13. The system according to claim 1 or 2, wherein: A second identification code linked to the identification codes added to the two or more types of raw materials is added to the cell product, and the cell product is distributed to a patient who is a source of the raw materials based on the second identification code.

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