TECHNOLOGY EXPLAINER
Autologous and Allogeneic
— whose cells they are reshapes the entire factory and supply chain
Medicines made from cells come in two kinds: autologous products, made from the patient's own cells, and allogeneic products, made from another person's cells (a healthy donor's). The difference goes well beyond immunology. One lot per patient, or one large lot? How many days from collection to administration? Can the product be made in advance? The design of manufacturing and logistics changes from the ground up. This article follows those differences in numbers, using the prescribing information of approved products and regulators' documents.
- What autologous and allogeneic mean (the short version)
- "Autologous" and "allogeneic" in approved products
- Two manufacturing models — scale-out and scale-up
- Autologous logistics — how many days from collection to administration
- A materials engineer's view (1): collection kits and shipping containers are part of the product
- Allogeneic and off-the-shelf — what making in advance means, and the exceptions
- Rejection, immunosuppression and HLA
- Cryopreservation and "usable time"
- A materials engineer's view (2): cryoprotectants, temperature and containers
- Strengths, weaknesses and challenges of autologous and allogeneic products
- Glossary / References / Claim-to-source audit
Sourced = stated in published material, prescribing information or a peer-reviewed paper (link given)
Our calculation = a figure this article derived, with the assumptions spelled out
Not yet confirmed = at the planning or research stage, with no confirmed track record
Structural summaries and readings about materials and processes are marked separately as Commentary.
This is a technology explainer written from the angle of manufacturing and logistics, not a treatment recommendation or medical advice. Product names are given only as examples of manufacturing approaches, as described in primary sources. No comparison of therapeutic effect is intended.
1. What autologous and allogeneic mean (the short version)
- Autologous: cells are taken from the patient, processed and returned to the same patient. Example: CAR-T cell products. The FDA prescribing information describes Yescarta as a product in which "the patient's own T cells are harvested and genetically modified ex vivo"Sourced
- Allogeneic: made from another person's cells, such as a healthy donor's, and used for many patients. Example: Ryoncil is described as "mesenchymal stromal cells isolated from the bone marrow of healthy adult donors and expanded in culture"Sourced
- What changes: an autologous product means one manufacturing lot per patient, and collection to administration takes several weeks. An allogeneic product can potentially be made in advance (off the shelf), but rejection has to be dealt with (this article's summary)
Allogeneic does not automatically mean "can be made in advance". One of the allogeneic iPS cell-derived products approved in Japan has a shelf life of 31 hours and is manufactured for each operationSourced. Whether a product can be made in advance is decided not by where the cells come from but by process design: whether it can be frozen, and at what stage the process can be paused (our commentary).
2. "Autologous" and "allogeneic" in approved products
Many regenerative medicine products in Japan state "human (autologous)" or "human (allogeneic)" in their non-proprietary names, so the origin of the cells can be read from the name. The table below picks out examples from PMDA's lists of approved products (PMDA is Japan's Pharmaceuticals and Medical Devices Agency) in which differences in manufacturing approach can be seenSourced.
| Type | Brand name (year of approval or partial change) | What PMDA's list says (summarised) |
|---|---|---|
| Autologous | JACE (partial change 2016, among others) | Epidermal cells from a piece of the patient's own skin are co-cultured and expanded using 3T3-J2 cells from mouse embryos as feeders, formed into a sheet and shipped immersed in a preservation solution. A container (including tissue transport solution) for shipping skin tissue to the manufacturing site is a secondary component |
| Autologous | HeartSheet (conditional and time-limited approval, 2015) | The main component is the patient's own skeletal myoblasts, cultured, expanded and cryopreserved. It includes instruments and other items for forming the sheet at the medical institution as secondary components |
| Autologous | Stemirac Inj. (conditional and time-limited approval, 2018) | Mesenchymal stem cells from the patient's own bone marrow aspirate, cultured, expanded and cryopreserved. It includes a blood collection kit and a bone marrow collection kit for taking the patient's peripheral blood and marrow and transporting them to the manufacturing site as secondary components |
| Autologous | JACC (partial change 2025) | Autologous cultured cartilage: chondrocytes isolated from the patient's own cartilage tissue, embedded in atelocollagen gel and cultured |
| Autologous | Kymriah and other CAR-T cell products (2019 onward) | T cells from the patient's peripheral blood with a CAR introduced by a viral vector |
| Autologous + allogeneic | Sakracy (2022) | A cell sheet made by seeding and culturing the patient's own oral mucosal epithelial cells on an amniotic membrane substrate made from human allogeneic amnion |
| Allogeneic | Temcell HS Inj. (2015) | Human (allogeneic) bone marrow-derived mesenchymal stem cells obtained by expansion culture of nucleated cells isolated from healthy adult bone marrow aspirate |
| Allogeneic | Alofisel Inj. (2021) | A cell suspension of human (allogeneic) mesenchymal stem cells from the subcutaneous adipose tissue of healthy adults |
| Allogeneic | Vyznova (2023) | A cell suspension made by culturing human (allogeneic) corneal endothelial cells isolated from donor corneas |
| Allogeneic | Reheart, Amchepry (conditional and time-limited approval, 2026) | Cardiomyocyte sheets derived from human (allogeneic) iPS cells; aggregates of dopaminergic neural progenitor cells derived from iPS cells made from the peripheral blood mononuclear cells of a healthy adult |
| Allogeneic | Allostem Sheet (2026) | A human (allogeneic) mesenchymal stem cell sheet in which mesenchymal stem cells from the subcutaneous adipose tissue of healthy adults are formed into a sheet |
All Sourced (PMDA lists of approved products for each fiscal year [Refs. 1 to 6 and 23]). The table picks out examples of manufacturing approaches and is not a complete list of approved products. A "partial change" is an approved change to an already-approved product. Conditional and time-limited approval is a Japanese pathway for regenerative medicine products: approval is granted with conditions and a time limit when efficacy is presumed and safety confirmed, and the company must reapply within the term.
Lined up this way, one thing stands out: autologous products come with secondary components such as "collection kits", "transport containers" and "instruments for forming the sheet at the hospital"Sourced. The round-trip logistics of collecting cells from the patient, shipping them to the factory and bringing them back are built into the design of the product itself (our commentary).
3. Two manufacturing models — scale-out and scale-up
Autologous: one patient = one lot (scale-out)
According to the FDA prescribing information, for Yescarta the patient's peripheral blood mononuclear cells are collected by apheresis; the T cells are enriched, activated, transduced with a retroviral vector, expanded in culture, washed, formulated and frozen. The product is shipped as a frozen suspension in a patient-specific infusion bag, after passing sterility testingSourced. The receiving hospital must confirm that the patient identifiers on the cassette and infusion bag match the patientSourced.
In other words, for an autologous product a manufacturing lot is started for one patient, and the product cannot be used for anyone else. As patient numbers grow, the same process has to be run many times in parallel. This is called scale-out (our commentary).
Allogeneic: one donor (one bank) = many patients (scale-up)
Ryoncil consists of mesenchymal stromal cells isolated from the bone marrow of healthy adult donors and expanded in culture; each vial holds about 25 million (25×10⁶) frozen cellsSourced. The CiRA Foundation's iPS cell stock, 27 lines built from seven donors, has likewise been used in more than ten clinical studiesSourced.
Because many patients' doses can be made from the same starting material, a process can be designed around making it all at once in large vessels (scale-up). Quality testing may also be done per lot rather than per patient (our commentary).
4. Autologous logistics — how many days from collection to administration
The defining feature of an autologous product is that the patient has to wait. The FDA prescribing information gives the number of days seen in the clinical trialsSourced.
| Product (trial) | Apheresis to product delivery or availability (median) | Apheresis to administration (median) | What is said about manufacturing failure |
|---|---|---|---|
| Yescarta (ZUMA-1) | 17 days (14 to 51) | 24 days (16 to 73) | Under 1% in the clinical trial (1 of 111 patients not treated because of manufacturing failure) |
| Yescarta (NCT03391466) | 18 days (13 to 49) | 26 days (16 to 52) | — |
| Breyanzi (NCT03575351) | 26 days (19 to 84) | 36 days (25 to 91) | Risk stated as 11% |
| Carvykti (CARTITUDE-1) | 32 days (27 to 66) | — | 18% (17 of 97 patients) |
| Kymriah | — | — | Up to 9% of manufacturing attempts |
All Sourced (FDA prescribing information [Refs. 7 to 9 and 11]). The labels use "delivery" for some products and "availability" for others. "—" means no corresponding statement could be found in the prescribing information this article consulted.
The prescribing information also states that if manufacturing fails, a second manufacturing attempt may be made, and that while patients wait for their product additional anticancer treatment (bridging therapy) may be neededSourced. In the Carvykti trial, 75% of patients received bridging therapy during manufacturingSourced.
In routine practice it can take longer still. A real-world study at two US centres reported a median of 62 days from referral for CAR-T therapy to infusion (decision-to-vein) and 32 days from collection to infusion (vein-to-vein), and found that factors other than manufacturing, such as insurance approval, contributed to the delaysSourced.
In Yescarta's ZUMA-1 trial the median time to delivery was 17 days and the median time to administration 24 daysSourced. The gap is 24 − 17 = 7 daysOur calculation. Likewise it is 8 days in trial NCT03391466 and 36 − 26 = 10 days in Breyanzi's trial NCT03575351Our calculation.
Assumptions and limits: these are differences between medians, not the median of individual patients' days. The Yescarta prescribing information asks that availability of the product be confirmed before starting the lymphodepleting conditioning regimenSourced. This interval presumably includes the conditioning schedule, but a breakdown of the days could not be confirmed in the prescribing information. The calculation is meant to show that shortening "manufacturing days" alone does not necessarily shorten collection-to-administration time by the same amount (our commentary).
5. A materials engineer's view (1): collection kits and shipping containers are part of the product
Read PMDA's lists of approved products and it is clear that autologous products are not complete with the cells alone.
- Stemirac Inj. includes a blood collection kit and a bone marrow collection kit for taking the patient's peripheral blood and marrow and transporting them to the manufacturing site as secondary componentsSourced
- JACE has as a secondary component a container (including tissue transport solution) for shipping the skin tissue taken from the patient to the manufacturing site, and the finished sheet is shipped immersed in a preservation solutionSourced
- HeartSheet includes instruments and other items for forming the sheet at the medical institution as secondary componentsSourced
What this suggests is that an autologous product cannot have an incoming inspection of its raw material. A chemical plant can send back a lot of raw material that is out of specification. The raw material of an autologous product is the patient's own cells, and there is no substitute. The temperature, the time, the container material and the composition of the transport solution between collection and arrival at the manufacturing site become the quality of the starting material (our commentary).
That is why, on this reading, kits and transport containers are controlled as components of an approved product. The plastic of the collection bag, the anticoagulant, the transport solution, the coolant — these are not "accessories" but the starting point of quality (our commentary).
One more point: as with JACC's atelocollagen gel, Sakracy's amniotic membrane substrate made from allogeneic human amnion and JACE's mouse-derived 3T3-J2 feeder cellsSourced, even when the cells are autologous, the substrate or support is often a material of other origin. "Autologous" describes where the cells come from; it does not mean every material in the product comes from the patient (our commentary).
6. Allogeneic and off-the-shelf — what making in advance means, and the exceptions
Off-the-shelf means ready to take off the shelf and use at once: a state in which products that have already been manufactured and quality-tested are held in stock and can be delivered to the patient who needs them when they need them (our commentary). A peer-reviewed paper describes the genome-edited allogeneic CAR-T cells UCART19 as a product "available for immediate clinical use"Sourced.
The typical case: frozen stock
Ryoncil is shipped directly to hospitals in a liquid nitrogen dry shipper (at or below −135 °C), and must be kept in the vapour phase of liquid nitrogen at or below −135 °C until thawed just before administrationSourced. Each vial contains about 25×10⁶ cells, and the recommended dose is 2×10⁶ cells per kg of body weight, given twice a week for four weeks, eight infusions in allSourced.
- Assumption: body weight of 30 kg (our assumption)
- Per infusion: 2×10⁶ cells × 30 = 6×10⁷ cells
- In vials: 6×10⁷ ÷ 2.5×10⁷ = 2.4 vials, which means thawing 3 vials per infusion
- Over eight infusions: 3 vials × 8 = 24 vials (in cells, 6×10⁷ × 8 = 4.8×10⁸)
Assumptions and limits: the 30 kg body weight is our assumption. The actual number of vials, how part-vials are handled and how doses are prepared follow the instructions in the prescribing information, and this calculation is no substitute for themOur calculation. It is only meant to show the order of magnitude: tens of vials for a single patient. For an autologous product, that many would have to be made for one patient every time (our commentary).
The exception: allogeneic products that are not (or cannot be) made in advance
The two iPS cell-derived products that received conditional and time-limited approval in Japan in March 2026 are both from healthy donors (allogeneic), yet neither is a frozen-stock productSourced.
- Amchepry (Parkinson's disease): a non-frozen product with a shelf life of 31 hours, manufactured for each operation. A Ministry of Health, Labour and Welfare (MHLW) document states that "supply is limited because manufacturing starts from the iPS cell differentiation step for each patient"Sourced
- Reheart (severe heart failure): frozen cells are thawed and cultured to form the sheet, which is transported without freezing. The company explains that its proprietary transport solution allows the sheet to be transported while keeping its shape for about two days at room temperatureSourced
On this reading, the allogeneic advantage stops at being able to make the starting material (the iPS cell stock) in advance, and the final product is made to order for each patient. For cell forms that do not survive freezing and thawing (aggregates, sheets), the origin of the cells alone does not make a product off-the-shelf (our commentary).
7. Rejection, immunosuppression and HLA
To the patient's immune system, allogeneic cells carry markers that say "someone else". The main one is HLA (human leukocyte antigen), carried by almost every cell and acting as a marker that tells self from non-self and from abnormal cellsSourced. When allogeneic cells are transplanted, immune reactions in two directions can be a problem (this article's summary).
| Direction | What happens | How primary sources handle it (examples) |
|---|---|---|
| Patient → transplanted cells (rejection) | The patient's immune system attacks the transplanted cells from another person as foreign | Reheart: three immunosuppressants for 90 days after transplantation. Amchepry: tacrolimus for about one year, then tapered and stopped over 12 weeks (extended if needed) |
| Transplanted cells → patient (GVHD) | Donor T cells contained in the graft attack the patient's body (graft-versus-host disease) | The Ryoncil prescribing information explains that acute GVHD occurs when "alloreactive donor-derived T cells in the transplanted tissue" trigger an immune response |
All Sourced (MHLW documents [Refs. 15 and 16]; Ryoncil prescribing information [Ref. 10]). Dividing the reactions into two directions is this article's own framing.
Matching HLA: the iPS cell stock
The CiRA Foundation has built an iPS cell stock of 27 lines from seven donors who are homozygous at the three loci that matter most for immune rejection, HLA-A, -B and -DR, and says it matches about 40% of the Japanese populationSourced. The idea is to lower the risk of rejection by matching HLA types, so that a starting material made in advance can be used for many patients. Even so, immunosuppressants are used with both approved products, and matching HLA does not make immunosuppression unnecessary (see the table above).
The problem with allogeneic T cells: GVHD
When the T cells themselves are made allogeneic, as with CAR-T cells, GVHD, in which the donor's T cells attack the patient, becomes a major issue. In two Phase 1 trials of the genome-edited allogeneic CAR-T cells UCART19 (21 patients), grade 1 acute skin GVHD was seen in two patients (10%)Sourced. By contrast, a trial giving HLA-mismatched cord blood-derived CAR-NK cells to 11 patients reported no cases of GVHDSourced. These were small early-stage trials, and no approval of an allogeneic CAR-T or CAR-NK product could be found in the FDA's list of approved products (updated 17 September 2026)Not yet confirmed.
8. Cryopreservation and "usable time"
Whether autologous or allogeneic, many cell products are shipped frozen and thawed just before administration. From the FDA prescribing information, we have extracted storage temperatures, cryoprotectant concentrations and how long the product can be used after thawingSourced.
| Product (type) | Cryoprotectant (DMSO) | Storage and shipping | Time after thawing |
|---|---|---|---|
| Kymriah (autologous) | 7.5% (v/v) | At or below −120 °C (e.g. in the vapour phase of liquid nitrogen) | Administer within 30 minutes of reaching room temperature |
| Breyanzi (autologous) | 75% CryoStor CS10 (containing 7.5% DMSO) | Vapour phase of liquid nitrogen (at or below −130 °C) | Administer within 2 hours of removal from frozen storage |
| Carvykti (autologous) | 5% | Stored and shipped below −120 °C | Finish administration within 2.5 hours at room temperature after thawing |
| Yescarta (autologous) | 5% | Shipped in a dry shipper (at or below −150 °C), kept at or below −120 °C at the site. Storage at −80 °C once only, for up to 90 days, is also allowed | Up to 3 hours at room temperature after thawing |
| Ryoncil (allogeneic) | 10% (v/v) | At or below −135 °C in a dry shipper and in the vapour phase of liquid nitrogen | Administer within 5 hours of starting to thaw the first vial |
All Sourced (FDA prescribing information [Refs. 7 to 11]). The starting point for "time after thawing" (start of thawing, end of thawing, reaching room temperature, removal from storage) differs by product; the table follows the wording of each label.
9. A materials engineer's view (2): cryoprotectants, temperature and containers
Read the table in Section 8 through a materials lens and it becomes clear that the storage of cell products rests on three materials elements.
- Cryoprotectant: the DMSO concentration differs by product: 5%, 7.5% and 10%Sourced. DMSO has been used for many animal cells since the early days of cryopreservation, but its toxicity in patients has been debated and the search for less toxic alternatives continuesSourced. The prescribing information also notes that hypersensitivity reactions may be due to DMSOSourced
- Temperature: storage is cryogenic, at or below −120 °C to at or below −150 °CSourced. Yescarta may be stored at the hospital at −80 °C once only, for up to 90 days, and the label states explicitly that it must not then be returned to −120 °C or belowSourced. The temperature history is managed as a one-way street (our commentary)
- Container: infusion bags are held individually in metal cassettes (Yescarta), and Kymriah requires closed, break-resistant, leak-proof containers for transport within the facilitySourced. There is also a step to check the bag for cracks and other damage before thawingSourced
At cryogenic temperatures around −150 °C, plastic bags are in the glassy state and vulnerable to impact. Each freeze and thaw imposes thermal shrinkage and embrittlement on the bag material, the welds, the ports and the adhesive of the labels. The line in the prescribing information, "check for cracks before thawing", shows that the low-temperature properties of container materials bear directly on product quality (our commentary).
And the "usable time" after thawing is 30 minutes to 5 hoursSourced. Hospital staff are asked to set the time to start thawing by working back from the planned time of administration (Yescarta, Carvykti, Ryoncil)Sourced. Lowering cryoprotectant toxicity, extending post-thaw survival, making containers that do not crack at low temperature — all of these are ways to relax the time constraint from the materials side (our commentary).
10. Strengths, weaknesses and challenges of autologous and allogeneic products
(1) The autologous challenge: time, and manufacturing failure
In the trials of approved CAR-T products, the median time from collection to product delivery or availability was 17 to 32 days, and the median time from collection to administration 24 to 36 daysSourced. The risk of manufacturing failure stated in the prescribing information ranges from under 1% to 18%Sourced. Reasons given for manufacturing failure include not meeting the product's release specificationsSourced, but how far the condition of the patient's cells contributes could not be confirmed in the prescribing information this article consulted.
(2) The allogeneic challenge: immunity, and the limits of making in advance
Even though they are allogeneic, the two approved iPS cell-derived products use immunosuppressantsSourced. And for products in forms not designed to be frozen, such as cell aggregates or sheets, the final product is manufactured for each patient even when the cells are allogeneicSourced.
(3) Allogeneic CAR-T and CAR-NK
CAR-T cells made allogeneic by genome editing, and CAR-NK cells built on NK cells, which are said to be less likely to cause GVHD, are being researched as ways around the "waiting time" and "manufacturing failure" problems of autologous CAR-T. The UCART19 paper says the approach could offer treatment to patients who cannot receive autologous CAR-T, or whose disease is progressing rapidlySourced. At the time of writing, however, no allogeneic CAR-T or CAR-NK product could be found in the FDA's list of approved products, and when they will reach practical use is not yet knownNot yet confirmed.
- Autologous is a "round trip" of one lot per patient; allogeneic is a "one-way street" from one donor to many patients, and the manufacturing models (scale-out versus scale-up) differ at the root (our commentary)
- For autologous CAR-T, collection to product delivery takes a median of 17 to 32 daysSourced. The gap to the median time to administration was 7 to 10 daysOur calculation
- In autologous products, collection kits and transport containers are secondary components of the approved productSourced
- Making allogeneic products in advance assumes frozen stock. Ryoncil is stored at or below −135 °C and administered within 5 hours of starting to thawSourced
- Some allogeneic products cannot be made in advance. Amchepry has a shelf life of 31 hours and is manufactured for each operationSourced
- Materials specifications — cryoprotectant (DMSO 5 to 10%), cryogenic temperature and container — determine how long a cell product remains usable (our commentary)
11. Glossary
- Autologous
- Using the patient's own cells. The processed cells are returned to the same patient.
- Allogeneic
- Using another person's cells, such as those of a healthy donor.
- Off-the-shelf
- Manufactured and tested in advance, held in stock and usable at once when needed.
- Scale-out
- Raising output by adding small production units in parallel. Typical of autologous products.
- Scale-up
- Raising the amount made at once by using larger vessels. Potentially possible for allogeneic products.
- Apheresis
- A collection method that takes only particular components of blood, such as white blood cells, and returns the rest to the body.
- Vein-to-vein
- The time from collecting cells from the patient to administering the product.
- Bridging therapy
- Treatment given to hold the disease in check while the product is being manufactured.
- Secondary component
- In a Japanese regenerative medicine product, a component other than the cells, such as a collection kit or transport container.
- HLA
- Human leukocyte antigen. A marker that tells self from non-self and is involved in rejection.
- GVHD (graft-versus-host disease)
- Donor T cells contained in a graft attacking the patient's body.
- DMSO
- Dimethyl sulfoxide. A cryoprotectant used in freezing cells.
- Dry shipper
- A shipping container that keeps cryogenic temperatures with liquid nitrogen soaked into an absorbent, so no liquid can spill.
- Vapour phase of liquid nitrogen
- The layer of cold vapour above liquid nitrogen. Used to store cells at cryogenic temperature without immersing them in the liquid.
12. References
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2015 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2016 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2018 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2021 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2022 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2025 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
- U.S. FDA "YESCARTA (axicabtagene ciloleucel) Prescribing Information", revised 07/2026 — fda.gov
- U.S. FDA "KYMRIAH (tisagenlecleucel) Prescribing Information", revised 6/2025 — fda.gov
- U.S. FDA "BREYANZI (lisocabtagene maraleucel) Prescribing Information", revised 2/2026 — fda.gov
- U.S. FDA "RYONCIL (remestemcel-L-rknd) Prescribing Information" — fda.gov
- U.S. FDA "CARVYKTI (ciltacabtagene autoleucel) Prescribing Information", revised 10/2025 — fda.gov
- U.S. FDA "FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease", 18 December 2024 — fda.gov
- CiRA Foundation "Paper summarising ten years of the iPS cell stock project published", 17 November 2022 (in Japanese) — cira-foundation.or.jp
- Hu B, et al. "Real-World Analysis of Barriers to Timely Administration of Chimeric Antigen Receptor T Cell (CAR T) Therapy in Diffuse Large B-cell Lymphoma", Transplant Cell Ther 30(11):1082.e1-1082.e10, 2024 — doi.org
- Medical Device Evaluation Division, Pharmaceutical Safety Bureau, Ministry of Health, Labour and Welfare "Conditional and time-limited approval of three regenerative medicine products", Central Social Insurance Medical Council (Chuikyo) general meeting, material 11, reference 2, 8 April 2026 (PDF, in Japanese) — mhlw.go.jp
- Ministry of Health, Labour and Welfare "Handling of regenerative medicine products (Amchepry)", Chuikyo general meeting, material 11-4, 8 April 2026 (PDF, in Japanese) — mhlw.go.jp
- Cuorips "Reheart (iPS cell-derived cardiomyocyte sheet)" product page (in Japanese) — cuorips.co.jp
- Sumitomo Pharma "Notice on receipt of marketing approval in Japan for Amchepry, allogeneic iPS cell-derived dopaminergic neural progenitor cells", 6 March 2026 (in Japanese) — sumitomo-pharma.co.jp
- Benjamin R, et al. "Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia", Lancet 396(10266):1885-1894, 2020 — doi.org
- Liu E, et al. "Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors", N Engl J Med 382(6):545-553, 2020 — doi.org
- U.S. FDA "Approved Cellular and Gene Therapy Products" (updated 17 September 2026) — fda.gov
- Awan M, et al. "Dimethyl sulfoxide: a central player since the dawn of cryobiology, is efficacy balanced by toxicity?", Regen Med 15(3):1463-1491, 2020 — doi.org
- Pharmaceuticals and Medical Devices Agency (PMDA) "List of products approved in FY2026 (regenerative medicine products)" (PDF, in Japanese) — pmda.go.jp
13. Claim-to-source audit
| Claim in the text | Basis | Label |
|---|---|---|
| The entries for Temcell HS Inj. (allogeneic bone marrow-derived mesenchymal stem cells, expansion culture of nucleated cells from healthy adult bone marrow aspirate, 2015) and HeartSheet (autologous skeletal myoblasts cultured and cryopreserved, instruments for forming the sheet at the medical institution as secondary components, conditional and time-limited approval in 2015) | PMDA list of products approved in FY2015 — Reference 1 https://www.pmda.go.jp/files/000228179.pdf | Sourced |
| The entry for JACE (the patient's own epidermal cells co-cultured with mouse embryo-derived 3T3-J2 feeder cells, shipped immersed in preservation solution, with a container and tissue transport solution for skin tissue as secondary components) | PMDA list of products approved in FY2016 — Reference 2 https://www.pmda.go.jp/files/000228178.pdf | Sourced |
| The entries for Stemirac Inj. (autologous bone marrow-derived mesenchymal stem cells cultured and cryopreserved, blood and bone marrow collection kits as secondary components, conditional and time-limited approval in 2018) and Kymriah (CAR introduced into T cells from the patient's peripheral blood, approved in 2019) | PMDA list of products approved in FY2018 — Reference 3 https://www.pmda.go.jp/files/000231456.pdf | Sourced |
| The entries for Alofisel Inj. (allogeneic adipose-derived mesenchymal stem cells, 2021) and Sakracy (autologous oral mucosal epithelial cells cultured on an amniotic membrane substrate from human allogeneic amnion, 2022) | PMDA list of products approved in FY2021 — Reference 4 https://www.pmda.go.jp/files/000246141.pdf | Sourced |
| The entry for Vyznova (a cell suspension of cultured allogeneic corneal endothelial cells from donor corneas, 2023) | PMDA list of products approved in FY2022 — Reference 5 https://www.pmda.go.jp/files/000252078.pdf | Sourced |
| The entries for JACC (autologous chondrocytes embedded in atelocollagen gel and cultured, partial change in 2025) and Reheart and Amchepry (derived from allogeneic iPS cells, conditional and time-limited approval on 6 March 2026) | PMDA list of products approved in FY2025 — Reference 6 https://www.pmda.go.jp/files/000280052.pdf | Sourced |
| The entry for Allostem Sheet (a human (allogeneic) mesenchymal stem cell sheet formed from mesenchymal stem cells from the subcutaneous adipose tissue of healthy adults, approved in 2026) | PMDA list of products approved in FY2026 — Reference 23 https://www.pmda.go.jp/files/000282058.pdf | Sourced |
| That Yescarta is made by harvesting the patient's own T cells and genetically modifying them ex vivo with a retrovirus; the manufacturing flow (apheresis, T cell enrichment, activation with anti-CD3 antibody and IL-2, transduction, expansion, washing, formulation, freezing); shipment in a patient-specific bag after passing sterility testing; matching of patient identifiers; in ZUMA-1, 17 days to delivery and 24 days to administration (medians), and one patient not treated because of manufacturing failure; in NCT03391466, 18 and 26 days; manufacturing failure risk under 1%, a second manufacturing attempt, additional treatment while waiting, and confirming the product is available before starting conditioning; DMSO 5%, dry shipper at or below −150 °C, at or below −120 °C at the site, −80 °C once for up to 90 days, up to 3 hours at room temperature after thawing, metal cassette, checking the bag for damage before thawing, and the instruction to time thawing to administration | FDA YESCARTA prescribing information — Reference 7 https://www.fda.gov/media/108377/download | Sourced |
| That Kymriah is an autologous T cell product and that manufacturing failure is stated as up to 9% of manufacturing attempts; DMSO 7.5%, storage at or below −120 °C, administration within 30 minutes of reaching room temperature, use of closed, break-resistant, leak-proof containers for transport within the facility, and confirmation of patient identity | FDA KYMRIAH prescribing information — Reference 8 https://www.fda.gov/media/107296/download | Sourced |
| For Breyanzi (NCT03575351), 26 days to availability and 36 days to administration (medians); manufacturing failure risk of 11%; 75% CryoStor CS10 (containing 7.5% DMSO); vapour phase of liquid nitrogen at or below −130 °C; administration within 2 hours of removal from storage | FDA BREYANZI prescribing information — Reference 9 https://www.fda.gov/media/145711/download | Sourced |
| That Ryoncil consists of allogeneic mesenchymal stromal cells isolated from the bone marrow of healthy adult donors and expanded in culture; about 25×10⁶ cells per vial; DMSO 10%; shipped and stored at or below −135 °C in a dry shipper; recommended dose of 2×10⁶ cells/kg twice weekly for 4 weeks, 8 infusions in all; within 5 hours of starting to thaw the first vial; no more than 4 vials thawed at once; the explanation of acute GVHD; and the possibility of hypersensitivity due to DMSO | FDA RYONCIL prescribing information — Reference 10 https://www.fda.gov/media/184603/download | Sourced |
| For Carvykti (CARTITUDE-1), 32 days to availability (median); 75% received bridging therapy; manufacturing failure of 18% (17 of 97, including failure to meet release specifications); DMSO 5%; stored and shipped below −120 °C; administration completed within 2.5 hours at room temperature after thawing | FDA CARVYKTI prescribing information — Reference 11 https://www.fda.gov/media/156560/download | Sourced |
| That Ryoncil is an allogeneic bone marrow-derived MSC therapy approved on 18 December 2024, with cells isolated from the bone marrow of healthy adult donors | FDA press release — Reference 12 https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host | Sourced |
| That the CiRA Foundation's iPS cell stock comprises 27 lines from seven donors, matches about 40% of the Japanese population (HLA-A, -B and -DR) and has been used in more than ten clinical studies; and the explanation of HLA | CiRA Foundation announcement — Reference 13 https://www.cira-foundation.or.jp/j/news/2022/11/17-000302.html | Sourced |
| In routine practice, a median decision-to-vein time of 62 days and vein-to-vein time of 32 days, with insurance procedures contributing to delays | Hu et al., Transplant Cell Ther 2024 — Reference 14 https://doi.org/10.1016/j.jtct.2024.09.007 | Sourced |
| Three-drug immunosuppression for 90 days after transplantation with Reheart; Amchepry's shelf life of 31 hours, manufacture for each operation, and supply limited because manufacture starts from the differentiation step for each patient | MHLW Chuikyo material — Reference 15 https://www.mhlw.go.jp/content/10808000/001687611.pdf | Sourced |
| Tacrolimus with Amchepry (for about one year, then tapered and stopped over 12 weeks, extended if needed) | MHLW Chuikyo material (Amchepry) — Reference 16 https://www.mhlw.go.jp/content/10808000/001687606.pdf | Sourced |
| That Reheart is made by thawing and culturing frozen cells into a sheet and transported without freezing, and that the proprietary transport solution allows about two days' transport at room temperature | Cuorips product page (the company's own description) — Reference 17 https://www.cuorips.co.jp/riheart | Sourced |
| That Amchepry is a non-frozen product made from iPS cells from a healthy donor (non-self) | Sumitomo Pharma news release — Reference 18 https://www.sumitomo-pharma.co.jp/news/20260306.html | Sourced |
| That UCART19 is an allogeneic CAR-T product "available for immediate clinical use"; grade 1 acute skin GVHD in 2 of 21 patients (10%); and the statement that it could offer treatment to patients who cannot receive autologous CAR-T, among others | Benjamin et al., Lancet 2020 — Reference 19 https://doi.org/10.1016/S0140-6736(20)32334-5 | Sourced |
| That HLA-mismatched cord blood-derived CAR-NK cells were given to 11 patients with no GVHD | Liu et al., N Engl J Med 2020 — Reference 20 https://doi.org/10.1056/NEJMoa1910607 | Sourced |
| That no allogeneic CAR-T or CAR-NK product appears in the FDA's list of approved products (updated 17 September 2026) | FDA Approved Cellular and Gene Therapy Products — Reference 21 https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products | Sourced |
| That DMSO is a cryoprotectant long used in cryopreservation, that its toxicity has been debated and that alternatives are being sought | Awan et al., Regen Med 2020 — Reference 22 https://doi.org/10.2217/rme-2019-0145 | Sourced |
| The gaps between the medians to administration and to delivery (7, 8 and 10 days); the Ryoncil vial count for a 30 kg patient (3 vials per infusion, 24 in all, 4.8×10⁸ cells) | Our calculation. Differences between medians, not individual patients' days. The 30 kg body weight is our assumption, and actual vial use follows the prescribing information | Our calculation |
| Approval and timing of practical use of allogeneic CAR-T and CAR-NK products | No approval could be confirmed at the time of writing (September 2026); they are at the research stage (this article's judgement) | Not yet confirmed |
| How far the condition of the patient's cells contributes to manufacturing failure; the breakdown of the time from product delivery to administration | Not stated because they could not be confirmed in the prescribing information this article consulted (commentary) | Commentary |
| Framing autologous as a "round trip" and allogeneic as a "one-way street"; the scale-out versus scale-up contrast; the possibility of lot-by-lot quality testing; the reading that secondary components are the starting point of quality; the caution that "autologous" does not describe the origin of every material; the reading that process design decides whether a product can be made in advance; dividing immune reactions into two directions; the link between the low-temperature properties of container materials and quality; and the summary of strengths and weaknesses | This article's summary and commentary based on published content. Not views expressed by the companies or institutions | Commentary |
| That Figs. 1 to 6 are explanatory drawings rather than real process or facility drawings, and that the hero image is an AI-generated image | Our note | Commentary |
Last updated 23 September 2026. Sources are limited to primary material (PMDA lists of approved products; FDA prescribing information, approved-product list and press releases; MHLW documents; the CiRA Foundation; official company announcements; and peer-reviewed papers). Because the article includes structural summaries and readings about materials and processes, those are marked as Commentary and kept separate from sourced fact. Product names are given as examples of manufacturing approaches, not as a comparison of therapeutic effect or a recommendation. The relationship between manufacturing failure and the condition of the patient's cells, the breakdown of time from product delivery to administration, and when allogeneic CAR-T and CAR-NK products will reach practical use are not stated here because no published primary source could be confirmed. All figures are explanatory concept graphics. Figs. 1 to 6 are vector drawings and the hero image is an AI-generated image; none of them shows a real process, facility or product.