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A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

Abstract：

INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. METHODS:The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. RESULTS:The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. DISCUSSION:The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B.

journal_name

J Pharmacol Toxicol Methods

journal_title

Journal of pharmacological and toxicological methods

authors

Ewart L,Milne A,Adkins D,Benjamin A,Bialecki R,Chen Y,Ericsson AC,Gardner S,Grant C,Lengel D,Lindgren S,Lowing S,Marks L,Moors J,Oldman K,Pietras M,Prior H,Punton J,Redfern WS,Salmond R,Skinner M,Some M,Stanto

doi

10.1016/j.vascn.2013.04.008

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

30-43

issue

eissn

1056-8719

issn

1873-488X

pii

S1056-8719(13)00248-7

journal_volume

pub_type

杂志文章,多中心研究

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A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.