Integrating functional CNS observations into toxicology studies: Preliminary Results from An Industry Survey Simon Authier, DVM, MBA, PhD Director - Safety

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




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


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:


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)


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?


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?


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?


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

Documents

Integrating functional CNS observations into toxicology studies: Preliminary Results from An Industry Survey Simon Authier, DVM, MBA, PhD Director - Safety