Attachment III - Page 7 
BUREAU OF DRUGS 
GUIDE 
BD 4831.1 
ATTACHMENT A 
f. Study may not proceed because the serious potential toxicity of 
the drug outweighs any possible benefit. 
9. Deficiency/Problem List . A listing of deficiencies or problems in 
the submitted protocol or in the IND itself. They may indicate a 
need for required changes in, or additions to, the protocol or for 
additional studies, clinical or pre-clinical, that must be carried 
out. On the other hand, problems/deficiencies may lead to 
suggestions for modifications in the protocol or the IND that do not 
represent requirements, at least at the present time. 
Deficiencies/problems should be clearly, concisely stated and 
appropriately referenced to a particular point in the submission. 
The recommended solution (an additional measurement, a new study, 
etc.) should be stated if it is not clearly implied. 
Deficiencies/problems will be listed verbatim in the letter to the 
sponsor. A clear statement of the implications of the 
problem/deficiency should also be included and will also go into the 
letter to the sponsor. The nine choices below will cover most 
situations, (letters are for in-house use) 
a. This is a suggestion for improving the study but not a 
requirement. 
b. This is a deficiency that must be corrected before an NDA can be 
approved. 
c. This is a deficiency that must be corrected before Phase III 
studies are started. 
d. This is a deficiency that must be corrected before Phase II 
studies are started. 
e. This is a deficiency that should be corrected before Phase I 
studies are started. 
f. This is a deficiency that should be corrected during the present 
study if possible but the study may proceed. 
g. This is a deficiency that must be corrected during the present 
study (within days) or the study must be terminated (or, 
alternatively, no new patients may be added, etc.). 
h. This is a deficiency that must be corrected before the proposed 
study is started but the correction need not be reviewed by the 
Agency before starting the study. 
BD 80-23 (8714/80) 
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