Letter from the FDA to the IHGT

Below is the letter from the Food and Drug Administration to Philip J. Cross at the Intitute for Human Gene Therapy. It refers to BB-INDs 5139, 5613, 6274, 6301, 6624, 7552, 8384 and 8410. It was dated January 21, 2000

Dear Mr. Cross:

Subsequent to an FDA inspection for BB-IND 6624, conducted from November 30, 1999 through January 19, 2000, that disclosed numerous serious deficiencies in the procedures in place for oversight and monitoring of the clinical trials conducted by investigators as outlined in 21 CFR 312.50 and 21 CFR 312.56, your studies under the above referenced INDs have been placed on clinical hold effective today.

Your INDs are on clinical hold because the nature and scope of the deficiencies in oversight of the clinical studies raise substantial concerns that similar deficiencies in oversight of the above referenced INDs under the sponsorship of the Institute for Human Gene Therapy may exist and that the subjects enrolled in the proposed clinical investigations would be exposed to a significant and unreasonable risk [21 CFR 312.42(b)(1)(i)]. Appropriate oversight by the Institute for Human Gene Therapy should diminish risks to patients by, among other things, ensuring the following: conduct of the study in accordance with the clinical protocols that are contained in the IND; obtaining adequate informed consent from subjects prior to participation in a study of an investigational agent or performance of invasive procedures; compliance with reporting protocol changes and adverse events to the responsible IRB; filing of safety reports as outlined in 21 CFR 312.64; and maintenance of complete and accurate records.

Please submit the following information to each applicable IND:

  1. Provide a detailed description of the monitoring plan for oversight of the conduct of clinical studies. The plan should include an organizational chart, identifying each individual responsible for oversight of clinical studies and list their duties, and should include a copy of the procedures to be followed for all aspects of study monitoring. This plan should demonstrate your ability, as a sponsor, to comply with all obligations outlined in 21 CFR 312, Subpart D. If you choose to transfer some or all of these obligations to a contract research organization, as outlined in 21 CFR 312.52, please describe the monitoring plan as requested above.
  2. For each study submitted under these INDs, please provide a statement that you have reviewed all aspects of the clinical trial(s) and have determined that the clinical investigators have conducted the study in accordance with the protocol as submitted to the INDs and are also in compliance with all clinical investigator obligations, including those outlined in 21 CFR 312.60 through 21 CFR 312.69. Alternatively, report all deficiencies in the conduct of the clinical trials and specify the corrective action which has been taken.

You may not continue or initiate clinical trials under the above referenced INDs until your response to the above deficiencies has been received and reviewed by FDA, and you are informed that the response is satisfactory. When you respond to all of the above issues, please identify your response as a "CLINICAL HOLD COMPLETE RESPONSE" and submit this information in triplicate to the IND. In addition, FAX a copy of the Form 1571, cover letter, and delivery tracking number to Ms. Andrea Wright at 301-827-5397. For additional information, please refer to the FDA Guidance: Submitting and Reviewing Complete Responses to Clinical Holds--5/14/98 (http://www.fda.gov/cber/gdlns/clinhold.pdf - link no longer available).

If you have any questions, please contact the Regulatory Project Manager, Andrea Wright, at (301) 827-5101.

Sincerely yours,

Glen D. Jones, Ph.D., Director,

Division of Application Review and Policy,

Office of Therapeutics Research and Review,

Center for Biologics Evaluation and Research

Almanac, Vol. 46, No. 18, January 25, 2000