Department of Health and Human Services
Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
January 11, 2001
Our Reference: BB-IND 5108
Cell Therapy Research Foundation
Attention: Peter K. Law, Ph.D., Chairman
1770 Moriah Woods Boulevard, Suite 18
Memphis, TN 38117
Dear Dr. Law:
Reference is made to Cell Therapy Research Foundation's (CTRF) Investigational New Drug Application (IND) for "Cultured Allogeneic Myoblasts, and Cyclosporin (Sandoz)." We also refer to our letter, dated October 16, 1998, in which the investigation of cultured allogeneic myoblasts for delay or prevention of severe disability and/or death in patients with Duchenne Muscular Dystrophy was designated as a Fast Track development program under section 506 of the Food, Drug, and Cosmetic Act (the act), 21 U.S.C. § 356. For the reasons stated below, the FDA finds that the requirements for Fast Track designation are no longer being satisfied and the Fast Track designation for your drug development program is withdrawn effective the date of this letter.
Under section 506(a)(1) of the act, upon the request of a sponsor, FDA designates a drug development program as fast track if the product is intended to treat a serious or life-threatening condition and demonstrates the potential to address an unmet medical need for the condition. Fast track designation may be withdrawn if a product does not continue to meet the criteria for designation over the course of drug development. As described in the "Guidance for Industry: Fast Track Drug Development Programs - Designation, Development, and Application Review," September 1998, a drug development program may no longer meet the criteria if the product no longer demonstrates a potential to address unmet medical needs or is not being studied in a manner that would show it is able to treat a serious or life threatening condition and meet unmet medical needs.
Based on FDA's inspection and your submissions to the IND, we have determined that the criteria for Fast Track designation are no longer being met. Specifically, the manufacture of the investigational product and the conduct of the clinical trials draws into question the reliability of clinical data submitted to demonstrate the potential of the product to meet an unmet medical need in the treatment of the designated condition.
The Agency's inspection of your establishment from July 12 - September 15, 1999, disclosed serious deficiencies in quality control and quality assurance of product manufacturing. During the inspection, the Agency found that the frozen allogeneic myoblasts in CTRF's inventory were not manufactured in conformity with current Good Manufacturing Practice (cGMP) regulations. The inspection findings included the improper use of reagents that were labeled as not for human use, the lack of documentation of required testing, and the clinical use of cells of questionable sterility or viability. The inspection also revealed a failure to conduct clinical studies according to the study protocols and the applicable regulations for protecting the rights and safety of human subjects, deficiencies in medical oversight of study procedures and failure to maintain adequate case report forms of data observations or to notify FDA and the IRB of adverse effects that may have been caused by the product.
Consequently, as described in our October 15, 1999, letter, all clinical studies under this IND were placed on clinical hold effective October 4, 1999, because there was insufficient information to assess the risks to subjects in the proposed investigation and because evidence indicated that the subjects would be exposed to unreasonable risk.
These facts establish that the clinical data submitted in support of the fast track designation are not reliable and thereby do not demonstrate the potential of the product to meet an unmet medical need. Furthermore, the product has not been and is not being studied in a manner that will evaluate the potential to treat a serious or life threatening condition and fulfill an unmet medical need. Accordingly, with this letter we are withdrawing the designation of this Fast Track drug development program. All references, on the internet and elsewhere, to the Fast Track designation should be removed. No representation should be made that this Fast Track designation is in effect. Furthermore, any description of this product that mentions the previous Fast Track designation should also clearly and prominently state that the designation has been withdrawn by FDA.
If you have any questions, please contact the Regulatory Project Manager, Jeanne Delasko, at (301) 827-5101.
--- signature ---
Jay P. Siegel, M.D., FACP
Office of Therapeutics Research and Review
Center for Biologics Evaluation and Research