Recombinant DNA Advisory Committee - 01/14/93 
Dr. Woodcock stated that the FDA encourages access to these drugs; however, the FDA 
discourages access before the agent has been tested in a Phase I trial because of 
uncertainties about the dose/toxicity profile of the drug. Many drugs that seem 
promising in the preclinical development phase are abandoned following a Phase I trial 
due to toxicity. However, the FDA still receives occasional requests for exceptions from 
patients who have exhausted all other therapies, do not fit the inclusion/exclusion 
criteria of the protocol, do not have geographic access to the protocol, or for other 
various reasons. In these rare cases, the FDA tries to work with the patient's physician 
and the investigator to provide some exception. Most of these cases are time-limited 
situations due to the life-threatening status of the patient. 
Dr. Woodcock explained that the emergency use situation is more of a medical 
emergency in which there is insufficient time to perform the required paperwork. 
Physicians can call the FDA and request clearance for emergency use. Emergency use 
would ordinarily occur when there is some known effectiveness information about the 
agent, and there is a clear indication why the physician made the determination that the 
particular agent was needed. 
COMMITTEE'S DISCUSSION 
Dr. Walters inquired as to the particular section of the FDA regulations that 
encompasses the single patient use category. Dr. Woodcock responded that the correct 
terminology is single patient IND which is found in section 312 of the 21 Code of Federal 
Regulations. An IND application exempts the sponsor from the general requirement to 
use an approved drug. 
Dr. Parkman asked if the requirement for the submission of preclinical data is different 
for single patient protocols than for multiple patient protocols. Dr. Woodcock explained 
that virtually the same standards for submission data are required for both types of 
requests. However, the FDA statutory and regulatory regulations do not apply the same 
standards of preclinical rationale that the RAC requires. 
As a point of clarification, Dr. Post inquired whether the FDA has granted first time use 
of investigational protocols on a single patient basis. Dr. Woodcock answered that the 
FDA has granted first time single patient use; however, these instances have been 
extremely rare. 
Dr. Post explained that many of the RAC members are concerned that Dr. Royston's 
protocol was approved based on the documentation that was submitted to NIH. He 
asked Dr. Woodcock to provide the committee with qualitative information about the 
kinds of data that the FDA considered before granting approval of this request. Dr. Post 
stated that the members of the RAC would have more confidence in this decision if they 
Recombinant DNA Research, Volume 17 
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