How long were the pivotal tox studies for approved cell therapies?

“the observation period of the single dose studies described above were up to 12 weeks in mice, 14 weeks in sheep and 53 weeks in goats”

“These studies were non-GLP which is not in conformity with the pharmaceutical standards.”

“A definitive 53-week study was conducted in 27 horses (Study # GENZ-09-4417)”

“A definitive 53-week study was conducted in 27 horses (Study # GENZ-09-4417) to evaluate the safety and the activity of MACI”

“Grafts were harvested at 7, 14, 28, 56, 100, 180, 232, and 365 days after grafting.”

“The potential toxicity of Apligraf® was evaluated via studies that reflect the initial medical device framework (i.e., biocompatibility testing in conformance to ISO-10993 standards).”

“thymopoiesis was observed at the pre-specified time points (1 and 9 months”

“no nonclinical toxicology studies with RVT-802 were conducted.”

“The long term effects of the Spherox product cannot be fully evaluated from the in vivo data as the GLP compliant sheep study of 9 months duration failed due to loss of Spherox implants.”

“study Merino sheep was designed to evaluate local and systemic toxicity during 6 months of implantation of autologous spheroids in a femoral condyle defect.”

“An in vivo study was conducted to evaluate toxicity and BD in tumor-bearing mice receiving i.v. injection of CTL019 at 1, 5, and 20x106 cells/mouse and observed up to Day 217 post-injection (p.i.) with three terminal sacrifices.”

“The nonclinical toxicology studies were not conducted in compliance with Good Laboratory Practice (GLP), because there was no independent Quality Assurance (QA) audit of integral study parts and raw data storage was not applied in compliance with GLP regulations.”

“lack of normal splenic B cells was observed 63 days, 143 days, and 209 days (the last time point examined) after anti-murine CD19 CAR T-cell infusion”

“Therefore, no GLP-compliant formal toxicology studies were performed.”

“Some mice were followed out to Day 209. The publication reported no overt toxicity, but normal B cells were decreased (i.e., B cell aplasia).”

“No toxicology studies with KTE-C19 were conducted.”

“were not associated with any adverse histopathological changes to 28 weeks after administration of the cells.”

“Three male cynomolgus monkey were dosed with three consecutive IV doses (1 week apart) of 2.3, 23 and 230 µg/kg.”

“Animals were euthanised at 2 or 26 weeks after the final infusion.”

“Two repeat-dose toxicity studies were conducted with human eASC in male and female athymic nude rats (Crl:NIH-Foxn1rnu) via the perianal route”

“There was no evidence of systemic exposure to rhCNTF after ITV implantation of NT-501 in minipigs for up to 6 months or in rabbits for up to 9 months.”

“The effect of long-term ITV implantation of NT-501 was evaluated in a 3-part toxicology study”

“A six-month GLP study in baboons was performed using labeled allogeneic baboon ceMSC to evaluate the safety and immunogenicity following IV administration of 5x106 cells/kg on Day 1”

“In a GLP repeat dose toxicity study, rats received 2x106 , 10x106 or 20x106 rat ceMSC/kg administered in a 5mL/kg dosing volume by tail vein injection over a two-minute period”

“Two of 5 mice in each group had complete tumour regression and survived > 5 months after tabelecleucel treatment.”

“Studies conducted in immunodeficient animal models for EBV+ PTLD revealed no overt signs of toxicity (e.g. loss of activity or weight loss) associated with a single dose of tabelecleucel.”

“no apparent local or systemic toxicity was observed out to 140 days following topical application of STRATAGRAFT® to immunodeficient mice with an existing wound.”

“Minimum Eight Week Transdermal Subchronic Toxicity Study with STRATAGRAFT® Skin Tissue in Nude Mice”

“periods (0-100 days), in contrast with the control group (died by day 10-11).”

“In this light, traditional toxicity, including single and repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, and local tolerance studies were deemed of negligible utility and thus were not conducted.”

“Scheduled Sacrifice Time Points Day 98”

“The applicant performed one in vivo non-GLP toxicology pilot study in Cynomolgus monkeys using autologous CAR-T cells manufactured with the second/ third generation hybrid LV developed by Legend.”

“Day 85 = in-life completed.”

“No single or repeat-dose toxicity studies were conducted with ide-cel as traditional animal studies employing common toxicology study designs are not appropriate for ide-cel”

“Scheduled Sacrifice Time Points Day 1, Week 4, and Week 12 post-transplantation”

“The following toxicology study was conducted to evaluate the safety of the test article following administration in the NOD/SCID mouse.”

“On day 42, 4 rats from the control (unimmunised)”

“All pharmacological experiments were proof of concept studies that were non-GLP compliant.”

“Xenogenic GvHD incidence was monitored in all treated mice at week 1, 2, and 3 post-infusion”

“Single dose toxicity has been assessed in the immunodeficient animal models in the pharmacodynamic studies.”

“CAR T cells were present in peripheral blood as well as bone marrow two weeks post-injection.”

“The GLP tissue cross-reactivity study was conducted to determine potential binding of 1 or 3 μg/mL CAT19 to 42 normal human tissues and blood smears.”

“No toxicology studies were conducted for AMTAGVI.”

“No nonclinical pharmacology studies were performed for AMTAGVI.”

“in vivo studies in a homologous animal model were considered by the CAT not to be necessary”

“in order to investigate the proliferative capacity of the 3T3-J2 feeder cells, the applicant performed in vitro karyotype analysis and soft agar assays.”

“No toxicology studies with LANTIDRA were conducted.”

“The applicant provided publications assessing the overall safety of islet allografts following intraportal transplantation in Module 4 of the BLA.”

“Standard in vivo single-dose or repeat-dose toxicity studies were not conducted with afamitresgene autoleucel due to the lack of appropriate animal models for testing of human TCR engineered T-cells.”

“A comprehensive analysis of cross-reactivity was performed using a peptide library screen with single amino-acid substitutions at each position of the antigenic peptide sequence (X-scan) and peptides from MAGE family member proteins.”

“No preclinical studies were conducted with this product.”

“No toxicology studies were conducted for TREGZI.”