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Nowhere is this more evident than in tier I safety assessment of the central nervous system (CNS). The CNS and peripheral nervous system have multiple behavioral units of general activity. A complete picture of the motor control neural pathways cannot be measured by any one single approach. The CNS safety protocols under International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use S7A are required to be conducted in accordance with Good Laboratory Practices by trained technical staff. The CNS safety assessments necessitate the inclusion of a thorough and detailed behavioral analysis of home cage activity, the response to handling, and transportation to and observations within an open-field apparatus with ancillary measures of basal muscle tone, muscle strength, and tremor in a functional observation battery, as well as quantitative measurements of 3-dimensional activity in an automated photobeam arena. Cost-cutting initiatives or a radical application of the \u201creduce use\u201d principle of the 3 Rs only jeopardize the spirit, intent, and predictive validity of tier I safety testing assays dictated by current drug safety guidelines.<\/jats:p>","DOI":"10.1177\/1091581819864836","type":"journal-article","created":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T00:12:07Z","timestamp":1567210327000},"page":"339-356","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["CNS Safety Screening Under ICH S7A Guidelines Requires Observations of Multiple Behavioral Units to Assess Motor Function"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-7731","authenticated-orcid":false,"given":"David V.","family":"Gauvin","sequence":"first","affiliation":[{"name":"Director, Neurobehavioral Sciences Department, CRL Laboratories, Inc, Mattawan, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary J.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Neurobehavioral Sciences Department, CRL Laboratories, Inc, Mattawan, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill A.","family":"Dalton","sequence":"additional","affiliation":[{"name":"Director, Safety Pharmacology Department, CRL Laboratories, Inc, Mattawan, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore J.","family":"Baird","sequence":"additional","affiliation":[{"name":"Senior Director Drug Safety, CRL Laboratories, Inc, Mattawan, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary-Jeanne","family":"Kallman","sequence":"additional","affiliation":[{"name":"CEO, VP, Kallman Preclinical Consulting, Greenfield, IN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,8,30]]},"reference":[{"key":"bibr1-1091581819864836","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. 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