Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Encelto: genotox, carcinogenicity and repro: done or skipped?
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)
Genotoxicity
Done: ISO-10993 battery (bacterial, mammalian cell, mouse micronucleus on device extracts), negative
“No genotoxicity was observed in these studies.”
Carcinogenicity
Not conducted (waived based on toxicological risk assessments)
“Studies to evaluate the carcinogenicity/tumorigenicity of ENCELTO were not conducted.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
No substitute; ISO-10993 device genotoxicity battery on NT-501 instead of cell-specific assessment
“A battery of genotoxicity studies was conducted to support licensure of NT-501 in keeping with ISO-10993, guidance for biological evaluation of medical devices.”
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Four DART studies of SC rhCNTF in rats and rabbits; no teratogenicity; exemption for device via margin of exposure
“There were no rhCNTF-related teratologic changes reported in the fetuses.”
Safety pharmacology
Not stated as separate studies; ERG assessments for intraocular implants in pharmacology
“Electroretinographic (ERG) Assessments for Intra-Ocular Implantation of”
Genotox: Ames
Negative: bacterial reverse mutation assay of device extract (no 2-fold increase in revertants)
“There were no instances of a 2-fold or greater increase in the mean number of revertants of tester strains.”
Genotox: in vitro mammalian
Negative: in vitro mammalian cell clastogenicity assay of device extract, with and without activation
“Under the conditions of this assay, the test article extract was not considered genotoxic to in the presence or absence of metabolic activation.”
Genotox: in vivo
Negative: mouse bone marrow micronucleus study
“mouse bone marrow micronucleus study, and a Kligman maximization test. No genotoxicity was observed in these studies.”
Carcinogenicity model
Not conducted; waived via toxicological risk assessments for rhCNTF and ENDO medium
“The applicant provided TRAs conducted by to support waivers for carcinogenicity/tumorigenicity studies for rhCNTF and the medium used within the device, human Endothelial-SFM medium (ENDO medium).”
Carcinogenicity timing
Not required (waiver rationale accepted by reviewer)
“This reviewer agrees with the rationale provided in the TRAs for not conducting carcinogenicity/tumorigenicity studies.”
hERG / QT
Not conducted (no safety pharmacology studies with NT-501)
“No safety pharmacology studies with NT-501 were conducted.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCNot conducted; cell-based product does not interact with DNA
Amtagvi
lifileucel · TIL therapyNot conducted (not warranted given product characteristics and biological activity)
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNot conducted (third-generation SIN lentiviral vector, release criterion, long-term clinical monitoring for insertional mutagenesis)
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNot conducted (traditional); lentiviral integration site mapping instead
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TNot conducted (classical); lentiviral integration site analysis instead
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNot conducted (per cell-based product guideline)
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsNot conducted (ICH S6(R1)); non-genetically engineered cells
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNot conducted (nature of product and clinical experience)
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNot conducted (classical); in vitro karyotype analysis of cells
Kymriah
tisagenlecleucel · CD19 CAR-TNot conducted (classical); lentiviral integration site analysis on 14 donor products
Lantidra
donislecel · Allogeneic pancreatic isletsNot conducted
Laviv
azficel-T · Autologous fibroblastsNot conducted (autologous nature, prior human experience)
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesNot conducted on cells; four studies on collagen membrane were non-mutagenic
Omisirge
omidubicel · Expanded cord blood HPCNo standard genotox; cytogenetic/karyotype analyses of CF and NF showed no clonal aneuploidy
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Not conducted (autologous nature of product)
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNot conducted
Ryoncil
remestemcel-L · Allogeneic BM-MSCNot conducted (not warranted)
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNot conducted (per cell-based product guideline)
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNot conducted
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNot conducted (traditional); vector integration site analysis performed instead
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TNot conducted (no test models or relevant species); integration site analysis showed polyclonal products, no selective insertion
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNot conducted
Yescarta
axicabtagene ciloleucel · CD19 CAR-TNot conducted; literature review of retroviral-transduced T-cell transformation risk instead
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsNot conducted; in vitro retroviral integration site analysis instead
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Done for residual UM171 only (Ames, CHO micronucleus negative) plus cytogenetics of treated cells; none for cells