MACI
autologous cultured chondrocytes on porcine collagen membrane
Species
RabbitOther
Longest study
53 wk
Genotox
Partial / alternative Partial / alternative
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Rabbit and horse, with analogous MACI (species-matched autologous cells on ACI-Maix)
“Studies conducted in horses and rabbits compared ACI-Maix or empty defects to analogous products consisting of ACI-Maix seeded with rabbit or horse cells.”
Why that species
Critical-sized knee/stifle defect models in load-bearing species; no further rationale stated
“Implantation of MACI secured with a commercially available fibrin sealant resulted in improved repair of critical-sized defects in the knee/stifle”
Surrogate molecule
Yes: analogous product using rabbit or horse autologous chondrocytes on the same membrane
“The products consisted of the same membrane as MACI with rabbit or horse cells, respectively.”
Study lengthopen answer page →
Longest pivotal study
53 weeks
“A definitive 53-week study was conducted in 27 horses (Study # GENZ-09-4417)”
Pivotal GLP studies
Combined GLP-type pharm/tox 53-week equine study (27 horses, stifle trochlear defect implant); 12- and 24-week rabbit studies
“A definitive 53-week study was conducted in 27 horses (Study # GENZ-09-4417) to evaluate the safety and the activity of MACI”
Route in tox
Surgical implantation into cartilage defect (intra-articular, fibrin sealant fixed)
“Implantation is performed using sterile surgical techniques and requires both the preparation of the defect bed and the application of fibrin sealant”
Skipped studiesopen answer page →
Genotoxicity
Not conducted on cells; four studies on collagen membrane were non-mutagenic
“Four studies ( in vitro and in vivo ) were conducted to assess the genotoxic potential of the collagen membrane.”
Carcinogenicity
Not conducted (avascular local site, differentiated cells, no systemic distribution)
“Studies to evaluate the carcinogenicity or impairment of fertility potential of MACI have not been performed.”
Reproductive & developmental
Not conducted (local administration, minimal systemic entry, mature autologous cells)
“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.”
Safety pharmacology
Not conducted
“No safety pharmacology studies were conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; no significant safety signals; mild transient inflammation, mild early lameness in horses recovered by 53 weeks
“There were no significant safety signals identified in the animals.”
Risksopen answer page →
Immune & cytokine safety
Inflammation likely due to defect creation and possible immune response to porcine membrane
“Inflammation was present in all knees, likely due to defect creation and possible immune response to the porcine membrane.”
Biodistribution & persistence
No systemic distribution of MACI, membrane or chondrocytes to lymph nodes or tissues in horses; membrane persisted to 53 weeks
“There was no indication of systemic adverse reactions or systemic distribution of MACI, ACI-Maix, or the seeded chondrocytes.”
Modality-specific risk
Local inflammation, graft failure/delamination, membrane persistence; tumorigenicity judged unlikely
“No tumors were detected in the one-year animal study, thus indicating that tumor formation is unlikely.”
Similar precedents
ChondroCelectcharacterised viable autologous cartilage cells · Autologous chondrocytesOther species · 53 wkSpheroxspheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsOther species · 39 wkHoloclarautologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNo relevant species · none