Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Zalmoxis: genotox, carcinogenicity and repro: done or skipped?
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cells
Genotoxicity
Not conducted; in vitro retroviral integration site analysis instead
“Genotoxicity studies have not been submitted.”
Carcinogenicity
Not conducted in vivo (species-specific product); in vitro clonality, integration, IL-2 dependence, RCR
“Therefore, no specific in vivo carcinogenicity studies were performed for the MM-TK to date.”
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
In vitro clonality, insertional pattern, growth-factor independent growth and RCR studies
“The in vitro studies pertain 1) evaluation of clonality of the transduced cell population, 2) characterisation of the insertional pattern, 3) evaluation of growth-factor independent growth, and 4) assessment of break out of replication competent retroviruses (RCR).”
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
Not conducted; justified
“The lack of studies on reproductive and development toxicity is justified.”
Safety pharmacology
Not submitted; agreed given product type
“There are no specific studies on secondary pharmacodynamics and safety pharmacology, which is agreed considering the type of product.”
Genotox: Ames
Not conducted (cell therapy)
“Genotoxicity studies have not been submitted.”
Genotox: in vitro mammalian
Not conducted (cell therapy)
“Genotoxicity studies have not been submitted.”
Genotox: in vivo
Not conducted (cell therapy)
“Genotoxicity studies have not been submitted.”
Carcinogenicity model
No in vivo study; in vitro clonality, insertion-site profile, growth-factor-independent growth and RCR assessments
“The in vitro studies pertain 1) evaluation of clonality of the transduced cell population, 2) characterisation of the insertional pattern, 3) evaluation of growth-factor independent growth, and 4) assessment of break out of replication competent retroviruses (RCR).”
Carcinogenicity timing
Not required: species-specific product, standard rodent/NHP carcinogenicity studies not appropriate; in vitro oncogenic-risk studies instead
“The MM-TK DP is a species specific product and therefore standard carcinogenicity studies using rodents or non-human primates as described in the ICH guidelines are not appropriate.”
hERG / QT
Not conducted; no safety pharmacology studies, agreed for product type
“There are no specific studies on secondary pharmacodynamics and safety pharmacology, which is agreed considering the type of product.”
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
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Done: ISO-10993 battery (bacterial, mammalian cell, mouse micronucleus on device extracts), negative
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
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Done for residual UM171 only (Ames, CHO micronucleus negative) plus cytogenetics of treated cells; none for cells