Design GLP studies

• Assure optimal dose and species selection
• Anticipate potential toxicity based on known data and enhance efficiency of resource utilization to optimize evaluation of the toxicity

Benefit: Optimal study design will expedite toxicity evaluation and reduce the need for repeat studies

• Provide an integrated assessment of in life, anatomic and clinical pathology findings to fully characterize the toxicity
• Factor out known animal toxicities that have little or no human relevance
• Evaluate comparison of animal to human exposure to determine relevance of the animal toxicity to humans

Benefit: Provides a scientific basis for assessing the relevance of the animal toxicity to potential successful development of a drug

• Complete peer review of GLP and non-GLP toxicity studies, including in-life, anatomic, and clinical pathology correlation and interpretation.
• Histologic review of specific target organs, with hepatotoxicity as a specialty (JP)
• Provide advice on special morphologic technical approaches to enhance understanding of a toxicity
• Histologic review and interpretation of specific carcinogenicity questions
• Histologic review and interpretation of aquatic toxicology studies: single chemical and mixtures (medaka, guppy)

Benefit: An accurate, detailed characterization of tissue effects enhances decision-making concerning human relevance, and assists in the recognition and validation of cross-species biomarkers.

• Fully characterize toxicity issue based on all species evaluated
• Assess available information on toxicity based on literature review
• Provide advice on the probability that the issue can be satisfactorily addressed within time and resource constraints
• Provide advice on approaches to address toxicity issue
• Interpret results from studies utilized to understand the toxicity

Benefit: The development of an appropriate strategy to address animal toxicity may allow successful development of molecules that might otherwise be stopped

• Evaluate clinical and regulatory concerns based on animal toxicity
• Propose approaches to understand animal toxicity and predict human relevance
• Interpret results from any special evaluations or studies related to animal toxicity
• Interact with clinicians or regulatory agencies to provide reassurance of human safety

Benefit: Aggressive attention to clinical and regulatory concerns based on animal toxicity can reduce drug development delays and failures

• Review toxicology sections of INDs, NDAs and position papers in response to regulatory questions related to toxicity
• Assure that documents are clear, concise, complete, and scientifically accurate
• Assure that documents fully utilize available information from animal studies and the literature

Benefit: Complete, well-written regulatory documents can avoid delays in drug development related to multiple interactions with regulatory agencies on a single point

• Evaluate the completeness of toxicology studies performed
• Assess toxicity study findings that may impact further development and regulatory acceptance
• Provide advice on potential additional work required to address toxicity findings
• Assess feasibility of successful continued development or regulatory filings

Benefit: Critical evaluation of available toxicology data reduces the possibility of delayed completion of development or registration