Which nonclinical studies did approved cell therapies skip?

“No traditional genotoxicity assays and carcinogenicity assessments were performed for bb2121.”

“No carcinogenicity or tumorigenicity studies were conducted for bb2121. However, the applicant evaluated IL-2 independent growth in Study #10.”

“No animal reproductive and developmental toxicity studies were conducted for bb2121 which is acceptable based on the product characteristics.”

“Genotoxicity studies are not applicable for the product, considering the cell-based nature of the product, which precludes interaction directly with DNA or other chromosomal material.”

“In in vivo tumourigenicity tests, nude mice administered a subcutaneous injection of eASC at various population doubling levels, equal to levels of product for clinical use, all survived to scheduled sacrifice and no tumour-formation was observed.”

“Reproductive and developmental toxicity studies have not been performed for Alofisel because preclinical biodistribution studies indicated no migration and integration of eASC into reproductive organs”

“No genotoxicity studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”

“No tumorigenicity studies were conducted for AMTAGVI. This is acceptable since Studies #3 and #4 provided evidence that the expanded human TIL cultures in the studies were free of tumor cells.”

“No DART studies were conducted for AMTAGVI. Given the characteristics and biological activity of AMTAGVI, this omission is acceptable.”

“No nonclinical genotoxicity studies were conducted with obe-cel based on the genotoxic risks associated with the third-generation self-inactivating lentiviral vector used to produce obe-cel, acceptable release criterion, and inclusion of long-term clinical monitoring for insertional mutagenesis and clonality.”

“Carcinogenicity studies are not needed for indications falling under ICH S9 scope (advanced cancer). In addition, there is no cross-reactivity of the CD19-CAR T cells from Aucatzyl with the murine antigen.”

“DART studies are not needed for indications falling under ICH S9 scope (advanced cancer) and no pharmacologically relevant animal species is available.”

“Traditional genotoxicity assays and carcinogenicity assessments were not performed for JCAR017.”

“Consistent with regulatory guidance under “Nonclinical Evaluation for Anticancer Pharmaceuticals” (ICH S9, 2009) carcinogenicity studies were not conducted.”

“JCAR017 does not survive in immunocompetent rodents and induces graft-versus-host disease in immunocompromised mice; therefore, traditional DART studies were not conducted.”

“No classical genotoxicity studies have been performed.”

“As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat advanced cancer.”

“Therefore, traditional DART studies were not conducted.”

“The omission of genotoxicity studies in the development program for ChondroCelect is in line with EMEA/CHMP/410869/2006.”

“In view of these results, the absence of standard carcinogenicity studies was considered to be acceptable.”

“the omission of reproductive and developmental toxicity studies in the development program for ChondroCelect is acceptable”

“In accordance with ICH S6(R1), genotoxicity studies with tabelecleucel were not conducted.”

“standard carcinogenicity bioassays are generally inappropriate for”

“Due to the highly species-specific nature of the pharmacology associated with tabelecleucel, nonclinical reproductive/developmental toxicity studies were not submitted with this application.”

“No genotoxicity was observed in these studies.”

“Studies to evaluate the carcinogenicity/tumorigenicity of ENCELTO were not conducted.”

“There were no rhCNTF-related teratologic changes reported in the fetuses.”

“The toxicology study designs as discussed in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and”

“were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”

“were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”

“The analysis demonstrated a consistent karyotypic profile throughout the tested cell cultures.”

“While conventional carcinogenicity studies have not been performed, the potential for transformation and formation of tumours by the human corneal epithelial cells in Holoclar was investigated in in vitro assays.”

“As no systemic exposure was to be expected and since the product was autologous in nature, the risk for product-related toxicity to the reproductive system was considered to be negligible”

“Genotoxicity Studies: Classical genotoxicity studies were not conducted. The provided LV integration site analysis may be relevant for evaluation of potential genotoxicity.”

“Genotoxicity assays and carcinogenicity studies in rodents are not appropriate to assess the risk of insertional mutagenesis for genetically modified cell therapy products.”

“No preclinical reproductive studies were conducted with CTL019 to assess whether it can cause fetal harm when administered to a pregnant woman.”

“No genotoxicity studies with LANTIDRA were conducted.”

“Thus, the carcinogenic risk of LANTIDRA in transplanted patients is considered low.”

“No DART studies with LANTIDRA were conducted.”

“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”

“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”

“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”

“Four studies ( in vitro and in vivo ) were conducted to assess the genotoxic potential of the collagen membrane.”

“Studies to evaluate the carcinogenicity or impairment of fertility potential of MACI have not been performed.”

“Per the applicant, studies were not conducted to evaluate this safety endpoint because the product is administered locally in the knee with minimal to no product entry systemically.”

“The genomic integrity was evaluated using cytogenic and karyotype analysis. Results showed no difference in the occurrence of chromosomal abnormalities between the CF, NF, and control cells and no evidence of clonal aneuploidy.”

“No carcinogenicity/tumorgenicity studies were conducted with the test article and were not warranted based on the known safety profile.”

“Per the applicant, developmental and reproductive toxicology studies were not conducted because there were no test article-related toxicity findings in reproductive organs as assessed by histopathological analyses”

“Toxicology studies, as described in the International Conference on Harmonization (ICH) Safety (‘S’) guidelines”

“No genotoxicity, reproductive toxicity, mutagenicity and carcinogenicity studies were provided”

“No genotoxicity, reproductive toxicity, mutagenicity and carcinogenicity studies were provided”

“No genotoxicity studies were conducted.”

“No carcinogenicity/tumorigenicity studies were conducted.”

“No DART studies were conducted.”

“Genotoxicity, carcinogenicity and reproductive and developmental toxicity studies were not performed for remestemcel-L.”

“There was no evidence of neoplastic tissue formation attributable to ceMSC over the six-week duration of the study.”

“Genotoxicity, carcinogenicity and reproductive and developmental toxicity studies were not performed for remestemcel-L.”

“No genotoxicity, conventional carcinogenicity and reproductive- and developmental toxicity studies were performed”

“No genotoxicity, conventional carcinogenicity and reproductive- and developmental toxicity studies were performed”

“Reproductive and developmental toxicity studies were not conducted.”

“No genotoxicity studies were conducted.”

“No tumor formation was observed for the 20-week study duration.”

“No DART studies were conducted.”

“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”

“No carcinogencity/tumorigenicity studies were conducted.”

“No animal reproductive and developmental toxicity studies were conducted with KTE-X19, which is acceptable based on the product characteristics and safety profile.”

“Conventional genotoxicity studies were not conducted with afamitresgene autoleucel, due to the lack of appropriate test models and pharmacologically relevant species.”

“Afamitresgene autoleucel is a human TCR engineered T-cell product, therefore conventional carcinogenicity studies were not performed due to the lack of relevant animal models.”

“MAGE-A4 is known to be expressed in testes and placenta, and so there is a theoretical risk of embryotoxicity or toxicity to the testes.”

“No nonclinical studies were conducted to evaluate genotoxicity of TREGZI.”

“No nonclinical studies were performed to evaluate the effect of TREGZI on carcinogenesis, mutagenesis, or impairment of fertility.”

“No animal reproductive and developmental toxicity studies have been conducted with TREGZI to assess whether it can cause fetal harm when administered to a pregnant woman.”

“No in vitro and in vivo genotoxicity and carcinogenicity assessments for KTE-C19 were conducted.”

“The data suggest that T cells are relatively resistant to malignant transformation by retroviral vectors.”

“Developmental and Reproductive Toxicology Studies (DART) No DART studies were conducted.”

“Genotoxicity studies have not been submitted.”

“Therefore, no specific in vivo carcinogenicity studies were performed for the MM-TK to date.”

“The lack of studies on reproductive and development toxicity is justified.”

“An AMES and a micronucleus test were conducted to assess the genetic safety of UM171”

“Carcinogenicity studies were not submitted, which can be agreed.”

“No reproductive and developmental toxicity studies were presented.”