Remestemcel-L: The First FDA-Approved MSC Product

By Benn Bluestein-Veyra, M.Sc. Organic Chemistry · Updated 20 October 2026

Remestemcel-L, licensed by FDA on December 18, 2024 through a biologics license application, is the first mesenchymal stromal cell product approved in the United States.^[1][2] FDA approved it under section 351(a) of the Public Health Service Act as remestemcel-L-rknd, proprietary name RYONCIL, for the pediatric indication in FDA’s approved labeling.^[1][3]

This reference reads the public approval record as FDA wrote it: the license, the product description, the regulatory history, and the potency and manufacturing questions that shaped the review.^[4][5] Each statement is attributed to an FDA document or to the peer-reviewed literature on MSC manufacturing and regulatory science.

Identifying remestemcel-L in the FDA approval record

The approval letter from the Center for Biologics Evaluation and Research (CBER) issued U.S. License No. 2140 to Mesoblast, Inc. under STN BL 125706/0 and approved manufacture at Lonza Bioscience Singapore Pte Ltd.^[1] The application was received on January 31, 2020, and FDA’s 2024 list of biological license approvals records the action date as December 18, 2024 (Fig. 1).^[1][6]

FDA’s approved labeling describes the active ingredient as culture-expanded MSCs isolated from the bone marrow of healthy adult human donors.^[3] FDA’s summary lists orphan drug, fast track and priority review designations in the regulatory history.^[4] The ISCT MSC committee described the approval as ending a long wait for an approved MSC product in the United States.^[2] CBER’s product page gathers the approval letter, package insert, Summary Basis for Regulatory Action and review memoranda in one place.^[7]

Bone marrow MSCs of this kind were first characterized by Pittenger and colleagues, who isolated them from volunteer donors’ marrow aspirates and induced them toward adipocytic, chondrocytic and osteocytic lineages.^[8] FDA’s summary records that product development began under an investigational new drug application filed by the product’s original developer.^[4]

Distinguishing a 351 biologics license from a 361 HCT/P

A human cell or tissue product is regulated solely under section 361 and 21 CFR Part 1271 when it meets all four criteria in 21 CFR 1271.10(a): minimal manipulation, homologous use, no combination with another article, and either no systemic effect and no dependence on the metabolic activity of living cells, or an autologous, close blood relative or reproductive use.^[9] The 361 versus 351 reference on this site quotes the criteria in full and walks through each one.

For cells, minimal manipulation means processing that does not alter the relevant biological characteristics of the cells, as defined in 21 CFR 1271.3(f).^[10] Culture expansion exceeds minimal manipulation, which places culture-expanded MSCs on the 351 pathway. That pathway runs from an investigational new drug application to a biologics license application (Fig. 2).^[4][9]

Under 42 U.S.C. 262(a)(2)(C), FDA approves a biologics license on a demonstration that the product is safe, pure and potent, and that its facility meets standards designed to keep it so.^[11] Under 21 CFR 601.2(d), approval is a determination that the establishment and the product meet the requirements that ensure continued safety, purity and potency.^[12]

FDA scientists Mendicino, Bailey, Wonnacott, Puri and Bauer described MSC-based proposals reaching the agency with growing variability in donor and tissue sources, manufacturing processes, proposed mechanisms and characterization methods.^[13] That variability is the setting in which the remestemcel-L record was built.

Describing the product as FDA’s labeling presents it

The package insert describes remestemcel-L as a frozen cell suspension in a cryogenic vial whose active ingredient is culture-expanded MSCs isolated from the bone marrow of healthy adult donors.^[3] The cells are formulated in Plasma-Lyte A with human serum albumin and dimethyl sulfoxide, then thawed and combined with Plasma-Lyte A as the labeling describes.^[3]

The approval letter sets a dating period of 60 months from the date of final fill when stored at or below −135 °C in liquid nitrogen vapor.^[1] The package insert states that the product ships in a liquid nitrogen dry shipper and stays frozen in the vapor phase until it is thawed for use.^[3]

FDA’s summary outlines the process: MSCs are isolated from bone marrow aspirate, culture-expanded and cryopreserved as a donor cell bank, and the contents of a single bank bag are thawed and expanded three further passages before harvest, formulation and fill.^[4] Lot release covers identity by cell surface markers, potency, viability, cell concentration, appearance, residual trypsin and bovine serum albumin, sterility, mycoplasma and endotoxin.^[4]

Reading identity against the ISCT marker panel

The commercial specification table in FDA’s summary lists CD166, CD105 and CD45 under identity.^[4] The ISCT panel published by Dominici and colleagues defines MSCs by plastic adherence, expression of CD105, CD73 and CD90, absence of hematopoietic markers including CD45, and trilineage differentiation in vitro.^[14]

CD105 is endoglin, one of the three positive markers in that panel (Fig. 3).^[14] Viswanathan and colleagues, for the ISCT MSC committee, recommended naming MSCs with their tissue source and pairing them with a matrix of functional assays chosen for the intended mode of action.^[15]

Tracing the regulatory history FDA documents

FDA’s summary lists the milestones: an investigational new drug application in October 1998, orphan drug designation in December 2005, fast track designation in February 2017, a pre-BLA meeting in April 2019 and filing with priority review in March 2020 (Fig. 4).^[4] An FDA advisory committee met on August 13, 2020, and its morning session addressed chemistry, manufacturing and controls (CMC) questions.^[4]

FDA issued complete response letters on September 30, 2020 and August 1, 2023, each listing clinical and CMC items for the sponsor to address.^[5] Mesoblast resubmitted on January 31, 2023 and on July 8, 2024, and FDA’s summary describes the history as several cycles of BLA submissions and complete response actions.^[4]

CBER inspected the Singapore drug product facility from May 11 to 19, 2023, issued no Form FDA 483, and classified the inspection No Action Indicated.^[4] The summary records that the July 2024 resubmission addressed the CMC items by implementing two complementary potency assays that support lot release and shelf-life determination.^[4]

Defining potency for a living cell product

Federal regulation defines potency as the specific ability or capacity of the product, indicated by appropriate laboratory tests or adequately controlled clinical data, to effect a given result.^[16] Under 21 CFR 610.10, potency tests are in vitro or in vivo tests designed specifically for each product.^[17] FDA’s 2011 guidance on potency tests for cellular and gene products expands on both rules.^[18]

The first complete response letter addressed an analytical potency assay that measured TNFR1 in the cells.^[5] FDA asked for a demonstrated relationship between that attribute and a product-specific biological activity, and both the sponsor and FDA read 2020 knockdown experiments as showing that suppression of activated T cell proliferation in vitro was independent of TNFR1.^[5]

The second letter reviewed a modified bioassay measuring inhibition of IL-2Rα, a T cell activation marker, and asked for data linking its acceptance criterion to the potency of lots used in clinical studies.^[5] It also asked for stability studies with at least one quantitative potency test, citing 21 CFR 211.137(a) and 211.166(a)(3) on reliable, meaningful and specific test methods.^[5]

Placing the record within MSC potency science

Bravery and colleagues, reviewing industry experience for ISCT, described a potency assay as the basis for lot release, stability and comparability after process changes such as site transfer or a new donor.^[20] Galipeau and colleagues proposed an assay matrix combining quantitative RNA analysis, flow cytometry of functional surface markers and secretome protein assays, measured after in vitro licensing.^[21]

Krampera and colleagues, for the ISCT MSC committee, put forward standardized immune assays for MSC characterization.^[22] Dutch regulators de Wolf, van de Bovenkamp and Hoefnagel reported that in vitro inhibition of T cell proliferation was the release assay most often proposed for MSC medicinal products, with biological relevance substantiated by product-specific data.^[23]

Bloom and colleagues built a reproducible assay of CD4+ T cell suppression and found values from 27% to 88% across eleven MSC products from three centers.^[24] Ketterl and colleagues pooled responder leukocytes to reduce assay variability and reported marked donor variation in MSC immunomodulatory capacity.^[25]

In FDA’s own laboratories, Klinker and colleagues found that MSC morphology after IFN-γ stimulation predicted the immunosuppressive capacity of MSC lines from different donors and manufacturing conditions.^[26] Chinnadurai and colleagues reported that thawed MSCs suppressed T cell proliferation across a transwell membrane, and that IFN-γ licensing before banking supported post-thaw function in co-culture.^[27]

Capelli and colleagues reviewed potency assays across cell-based advanced medicinal products and the biomarkers proposed to complement complex functional tests.^[28] The extracellular vesicle potency reference on this site applies the same principles to vesicle preparations.

Controlling manufacturing consistency across lots and sites

FDA’s summary lists five elements of the control strategy: raw material and reagent qualification, chain of identity and custody, in-process monitoring, process validation and release testing.^[4] Donor screening and eligibility determination open the strategy at the bone marrow aspirate, and segregation of lots, equipment and personnel prevents mix-ups at the Singapore facility.^[4]

The record also documents manufacturing transfers. Drug product manufacture moved from the original developer to Lonza Walkersville and, in 2014, to Lonza Singapore, which began production in 2015 from donor cell bank material made in 2008.^[4] The first complete response letter noted that new donor cell banks would call for a comparability exercise supported by attributes associated with potency.^[5]

The literature shows why these controls matter. Stroncek and colleagues sent aliquots of the same marrow to five laboratories and found that the manufacturing center contributed more to MSC transcriptome variability than the source material did.^[29] Liu and colleagues surveyed seven GMP centers, found that no two used the same method, and reported differences in bone formation in vivo across their products.^[30]

Fekete and colleagues compared five GMP-compliant protocols using platelet lysate and obtained products meeting the ISCT minimal criteria.^[31] A German consensus led by Wuchter set out quality criteria for bone marrow MSC production, including immunophenotype, medium composition, aging and immunosuppressive potential.^[32]

Stultz and colleagues at FDA used spectral karyotyping across ten donors and recommended karyotypic monitoring of MSCs during expansion.^[33] Marklein and colleagues showed that early morphological profiles predicted later mineralization capacity across donors and passages.^[34] Lipsitz, Timmins and Zandstra argued for quality-by-design principles that link measurable cell attributes to final product quality.^[35]

Robb and colleagues built a matrix of genes, secreted factors and morphometric features to define putative critical quality attributes, and found that culture process parameters drove immunomodulatory fitness.^[36] These approaches give manufacturers quantitative handles on the consistency that FDA’s review emphasized.

Reading the postmarketing obligations in the approval letter

The approval letter requires CBER lot release: the sponsor submits protocols with results of all applicable release tests, and distributes a lot only after the Director of CBER notifies release.^[1] Changes in manufacturing, testing, packaging, labeling or facilities are submitted for approval under 21 CFR 601.12, and biological product deviations are reported under 21 CFR 600.14.^[1]

One postmarketing requirement under section 505(o) asks for completion of a cumulative leachables study across manufacturing and storage, with a toxicological assessment and a final report scheduled for October 31, 2030.^[1] Three CMC postmarketing commitments cover an additional potency assay, an assay suitability study and an in-use stability study of critical quality attributes after simulated formulation, with final reports due December 31, 2027.^[1]

Interpreting what the approval documents for the MSC field

The record shows a culture-expanded allogeneic MSC product completing the full 351 pathway, from an investigational application to a U.S. license with CBER lot release.^[1][4] It also places potency control at the center of the CMC review, settled with two complementary assays and a commitment to a further one.^[4] FDA’s 2023 draft guidance on potency assurance points the field toward an integrated potency strategy.^[19]

Where to go from here

The 361 versus 351 reference explains the classification at the start of this record, and the ISCT minimal criteria reference covers the marker panel behind identity testing. The MSC source tissues reference compares bone marrow with perinatal and adipose sources, and the perinatal tissue donor eligibility reference describes how donors are qualified.

The extracellular vesicle potency reference carries the potency discussion into vesicle preparations, and the MSC immunobiology reference explains the HLA, IDO and PGE2 biology that many assays measure. ExaVeyra Sciences has no affiliation with remestemcel-L or its manufacturer; this page summarizes the public regulatory record.

This article summarizes publicly available FDA records and federal regulation for licensed practitioner education. It is not legal advice, medical advice, or regulatory guidance, and it does not establish that any particular product or practice is compliant. Confirm current federal and state obligations with qualified counsel.