Risk Management and Understanding the Potential

2 Risk Management and Understanding the Potential for Clinical TVanslation 

The potential for clinical translatabUity of preclinical findings of pancreatic toxicity needs to be determined on a case-by-case basis. Since pancreatic toxicity is a known risk factor for many approved drugs, it is clear that, if first identified early on in a drug development program, the risk does not necessarily preclude the further development of the drug candidate. However, such risk would need to be fuUy understood mechanistically, so that its potential for extrapolation to humans could be determined, successfully monitored and managed in the chnic, and balanced relative to the desired benefit of the proposed drug candidate for the patient population. 

PRECLINICAL SAFETY ASSESSMENT OF DRUG CANDIDATE-INDUCED PANCREATIC TOXICITY 

3 Interspecies and Interstrain Differences in Susceptibility to Pancreatic Toxicity 

Select major and minor differences exist between species at the gross anatomical, cellular, and molecular levels. For example, the pancreatic ducts in rodents open into the common bile duct, whereas, in the dog and human, the pancreatic duct or ducts open directly into the duodenum (Greaves, 2012). In the rat, part of the acinar blood supply 

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