integrating functional cns observations into toxicology studies: preliminary results from an...
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Integrating functional CNS observations into toxicology studies: Preliminary Results from An Industry
Survey
Simon Authier, DVM, MBA, PhD
Director - Safety Pharmacology and Veterinary Science
CIToxLAB North America
Agenda Introduction Preliminary results from an Industry Survey Expert panel presentations
– Pros: Mary Jeanne Kallman, PhD (Covance)– Cons: Will Redfern (AstraZeneca)
Open discussions Closing remarks
Introduction: Methodologies Functional Observation Battery in Rodents: Widely accepted Functional Observation Battery in Large Animals:
– Canines Gad SC & Gad SE. A functional observational battery for use in canine toxicity studies: development
and validation. Int J Toxicol. 2003 Nov-Dec;22(6):415-22. Tontodonati M et al. A canine model used to simultaneously assess potential neurobehavioural and
cardiovascular effects of candidate drugs. J Pharmacol Toxicol Methods. 2007. Sep;56(2):265-75
– Non human primates Authier S. et al., Functional observation battery in nonhuman primates with continuous intracerebral
infusion. J Pharmacol Toxicol Methods. 2012 Sep-Oct;66(2):162. Gauvin DV, Baird TJ. A functional observational battery in non-human primates for regulatory-required
neurobehavioral assessments. J Pharmacol Toxicol Methods. 2008 Sep;58(2):88-93.
– Minipigs van der Laan JW, et al.; RETHINK Project. Regulatory acceptability of the minipig in the development of
pharmaceuticals, chemicals and other products. J Pharmacol Toxicol Methods. 2010 Nov;62(3):184-95. Authier S et al., Safety Pharmacology in the Göttingen minipig: Cardiovascular, Respiratory and
Neurological Investigations. Annual Meeting of SOT 2012, San Francisco
Preliminary Industry Survey Results
I routinely perform the safety phar-macology
component of these stud-
ies
I routinely design or in-terpret the safety phar-macology
component of these stud-
ies
I develop or supply
technology used to conduct safety
pharmacol-ogy studies
I am respon-sible for the
safety pharmacol-ogy disci-
pline in my company
I am respon-sible for the toxicology
discipline in my company
0%
10%
20%
30%
40%
50%
What is your role? (please check all that apply)
Total of 361 participants
Preliminary Industry Survey Results
Preliminary Industry Survey Results
Preliminary Industry Survey Results
Funct
ional o...
Funct
ional ob...
020406080
100120140160180200
39 35
249
109
37
21
7
If you have conducted CNS safety pharmacology investigations by adding endpoints to regulatory toxicology studies what species have
you used?
Mouse
Rat
Canine
Nonhuman primate
Mini-pig
Minipig 2
Preliminary Industry Survey Results
Respiratory CNS CV Renal GI50%
55%
60%
65%
70%
75%
80%
61%
74%
68%
55%
69%
Based on your opinion, S7A safety pharmacology endpoints in toxicology studies are generally ap-
propriate for:
Preliminary Industry Survey Results
Allowed you to manage safety risk more effec-
tively
Data contributed to the halting the progression
of a compound
Data addressed a spe-cific concern and sup-
ported the continuation of a compound
0%10%20%30%40%50%60%70%80%90%
77.8%
22.2%
54.3%
In your organization, has the ability to add safety pharma-cology endpoints onto regulatory toxicology studies had any
of the following consequences? (check all that apply)
Preliminary Industry Survey Results
Slides of expert panel members
Questions for open discussions
Based on your opinion, S7A safety pharmacology endpoints in regulatory toxicology studies are generally appropriate for:
– CNS safety pharmacology for small molecules ?
– CNS safety pharmacology for large molecules ?
– As a standalone study?
Questions for open discussions
In your organization, has the ability to add safety pharmacology endpoints onto regulatory toxicology studies had any of the following consequences?
– Allowed you to manage safety risk more effectively?
– Data contributed to the halting the progression of a compound?
– Data addressed a specific concern and supported the continuation of a compound?
Questions for open discussions
Based on your experience, please state any disadvantages of safety pharmacology investigations in toxicology studies?
Based on your experience, please state any advantages of safety pharmacology investigations in toxicology studies?
Questions for open discussions
Have you received regulatory feedback on inclusion of respiratory safety pharmacology in toxicology studies?
Thank you for your time and participation!
Looking forward to see you in Phoenix for the 2012 Annual SPS meeting
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