Safety pharmacology investigations on the nervous system: An industry survey.
The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address non-clinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing.
CiToxLAB North America, 445 Armand Frappier, Laval, QC H7V 4B3, Canada. Electronic address: authiers@ca.citoxlab.com.
Simon
S
Authier
Department of Neuroscience, Albert Einstein College of Medicine, USA; Department of Neurology, Albert Einstein College of Medicine, USA.
Joseph
J
Arezzo
Division of Anesthesia, Analgesia and Addiction Products (DAAAP), CDER, U.S. Food & Drug Administration, Silver Spring, MD, USA.
Marcus S
MS
Delatte
Kallman Preclinical Consulting, Greenfield, IN 46140, USA.
Mary-Jeanne
MJ
Kallman
Discovery Sciences Support, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Carrie
C
Markgraf
CiToxLAB North America, 445 Armand Frappier, Laval, QC H7V 4B3, Canada.
Dominique
D
Paquette
Department of Toxicology, Purdue Pharma L.P., Cranbury, NJ 08512, USA.
Michael K
MK
Pugsley
Safety Pharmacology COE, Pfizer, United States, Groton, CT 06340, USA.
Sian
S
Ratcliffe
Drug Safety & Metabolism, AstraZeneca, 310 Cambridge Science Park, Cambridge CB4 0WG, UK.
William S
WS
Redfern
Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
Joanne
J
Stevens
Non-Clinical Development, UCB-Biopharma, Belgium.
Jean-Pierre
JP
Valentin
Integrated Discovery and Safety Pharmacology, Amgen, Inc., Thousand Oaks, CA, USA.
Hugo M
HM
Vargas
Cardiovascular Division, Faculty of Life Sciences & Medicine, King's College London, Rayne Institute, St Thomas' Hospital, London, SE17EH, UK.
Michael J
MJ
Curtis
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004345:Drug Industry / Q000706:statistics & numerical data*; D064420:Drug-Related Side Effects and Adverse Reactions; D004569:Electroencephalography / Q000187:drug effects; D006801:Humans; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D012449:Safety; D012640:Seizures / Q000139:chemically induced; D012890:Sleep / Q000187:drug effects; D019966:Substance-Related Disorders; D011795:Surveys and Questionnaires
Abuse; EEG; Neurological functional observation battery; Safety pharmacology; Seizure; Sleep