Safety pharmacology in 2022: Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment

TY - JOUR

T1 - Safety pharmacology in 2022

T2 - Taking one small step for cardiovascular safety assay development but one giant leap for regulatory drug safety assessment

AU - Pugsley, Michael K.

AU - Koshman, Yevgeniya E.

AU - de Korte, Tessa

AU - Authier, Simon

AU - Winters, Brett R.

AU - Curtis, Michael J.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/9/18

Y1 - 2022/9/18

N2 - The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the "comprehensive in vitro proarrhythmia assay" (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve?

AB - The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the "comprehensive in vitro proarrhythmia assay" (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve?

KW - hERG

KW - ICHE14/S7B

KW - QT correction

KW - Regulatory

KW - Safety pharmacology

UR - http://www.scopus.com/inward/record.url?scp=85138459272&partnerID=8YFLogxK

U2 - 10.1016/j.vascn.2022.107206

DO - 10.1016/j.vascn.2022.107206

M3 - Editorial

C2 - 35926772

AN - SCOPUS:85138459272

SN - 1056-8719

VL - 117

SP - 107206

JO - Journal of pharmacological and toxicological methods

JF - Journal of pharmacological and toxicological methods

M1 - 107206

ER -