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
0% 5%
10% 15% 20% 25% 30% 35% 40% 45% 50%
I routinely perform the
safety pharmacology component of these studies
I routinely design or
interpret the safety
pharmacology component of these studies
I develop or supply
technology used to conduct
safety pharmacology
studies
I am responsible for the safety
pharmacology discipline in my
company
I am responsible for the
toxicology discipline in my
company
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
39 35
24 9
109
37
21
7
0
20
40
60
80
100
120
140
160
180
200
Fu
nctio
na
l o
bse
rva
tio
n
ba
tte
ry N
CE
Fu
nctio
na
l o
bse
rva
tio
n
ba
tte
ry
Bio
log
ics
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
61%
74%
68%
55%
69%
50%
55%
60%
65%
70%
75%
80%
Respiratory CNS CV Renal GI
Based on your opinion, S7A safety pharmacology endpoints in toxicology studies are generally
appropriate for:
Preliminary Industry Survey Results
77.8%
22.2%
54.3%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
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
In your organization, has the ability to add safety pharmacology 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
