The FDA's guidance document on the use of living autologous cellsmanipulated ex vivo intended for structural repair and reconstruction(MAS cells), published last week, said the products are subject tolicensure as biologics.
But the agency is offering flexible approaches for gaining approval ofsuch products and is giving companies already marketing them 18months to be under an active investigational new drug application oran approved biologics license application (BLA). One companyaffected by the guideline is Genzyme Corp.'s Tissue Repair Division.
Genzyme, of Cambridge, Mass., already is providing a service calledCarticel, which uses a process to grow patients' own cartilage cellsfor implantation to correct cartilage damage in the knee. Thecompany, anticipating the new policy, submitted a BLA in March1996 and expects a review to be completed within a year.
Therapies using MAS cells should demonstrate safety andeffectiveness, the agency said, but added a flexible approach may befeasible because of certain attributes of structural defects and MAScell therapies. They include the persistence of defects when leftuntreated; the possibility of short-term benefit; the frequentavailability of imaging or biopsy evidence of structural repair withthe high likelihood of predicting clinical benefit; and the lowprobability of systemic toxicities.
The agency said short-term endpoints (one year or less) directlymeasuring clinical benefit may be sufficient evidence of efficacy if afavorable risk-benefit evaluation has been established and long-termsafety issues are low. Evidence of normal or repaired structure maybe accepted as evidence of efficacy if it's likely to produce clinicalbenefit. The agency will allow comparative evaluations withhistorical data bases to show effectiveness rather than controlledstudies if compelling differences can be shown.
Screening of large numbers of patients for systemic toxicity generallywill not be required in the premarketing phase. Therapies usingmanipulated autologous cells for structural repair won't have todemonstrate superiority to existing therapies.
The FDA's Center for Biologics Evaluation and Research hasprimary jurisdiction for the premarket review and regulation of MAScells products.
Those interested in commenting on the proposed rules have 90 daysto submit written comments, which may be considered before finalpublication.
Cheryl Greenhouse, public relations associate for Genzyme, said,"The key point is the FDA is being very flexible in what it isrequiring to comply, especially during this transition period."
Genzyme began offering the Carticel service in March 1995, whenthe FDA had no regulations in place covering the procedure.Submission of the BLA was the only step Genzyme needed to be incompliance with the new rules, she said.
As of April 8, 1996, 106 Carticel patients had been treated in theU.S. and 540 surgeons trained to do the procedure, Greenhouse said.The procedure is done by taking biopsies from patients, sending themto Genzyme Tissue Repair where cells are grown before being sentback for implantation into an area of the femur. The idea then is thatcells will integrate back into the surrounding tissue and mature intonormal cartilage, thus restoring proper movement to the knee.
Greenhouse said Genzyme has not disclosed results from any Carticelprocedures done in the U.S. The company reported revenues of $1.7million from the service in the first quarter of this year.
Lars Peterson, the orthopedic surgeon who developed the procedureat the University of Gotenborg, Sweden, reported at a meeting inFebruary on the treatment of 308 cartilage defects in 251 patients. Ofthose treated for more than two years, Peterson reported an 81percent success rate in 31 defects of the femoral condyle, the part ofthe knee formed by the end of the thigh bone, and an 87 percentsuccess rate in 15 defects of the knee cap. n
-- Jim Shrine
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