Attachment III - Page 3 
BUREAU OF DRUGS 
GUIDE 
BD 4831.1 
ATTACHMENT a 
(2) 
Excretion - Fraction of absorbed dose eliminated by 
routes. 
various 
(3) 
Distribution - Is there accumulation in particular 
exclusion from others. 
tissues, 
(4) 
Metabolism: Identify metabilites, whether active 
and how they are excreted, if known. 
or not 
c. Toxicology 
(1) Subacute and Chronic: Positive findings only and range of 
dosing causing them. If no findings, so state and give 
highest dose used. 
(a) General toxicology; 
(b) Reproduction and toxicology; 
(c) Carcinogenicity. 
d. Conclusions (after conference with pharmacologist). 
(1) Special observations needed during clinical studies on the 
basis of pre-clinical findings; 
(2) Maximum duration and dosage of drug administration 
supported by pre-clinical data; 
(3) Further data or studies needed (and implications, i.e., may 
studies proceed while they are being obtained? May 
clinical studies go beyond Phases I or II or III, etc?). 
5. Clinical Background 
a. Previous similar human studies and their results (including 
foreign studies). 
b. Literature references that are especially appropriate (summarize 
the data from each of these published reports). 
c. Important Information from related IND's and NDA's. This 
section should be pertinent to study design, precaucions needed, 
etc. It may thus be very long or very short, depending on the 
availability of useful data. 
0TN0 - BD 80-23 (8/14/80) 
3 
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t'Aiit 
