Designing GLP-Compliant Preclinical Cohorts
Good Laboratory Practice (GLP) preclinical studies have specific requirements for group sizes that vary by study type and regulatory authority:
Regulatory minimums: The minimum number of animals per sex per dose group is set by guidelines such as FDA Redbook 2000, OECD Test Guidelines (407, 408, 451–453), EPA OPPTS, and ICH S-series. Using fewer animals than the minimum can invalidate the study for regulatory submission.
Satellite/TK groups: For repeat-dose studies, toxicokinetic (TK) satellite animals provide pharmacokinetic data (Cmax, AUC) without disturbing the main toxicology cohort. ICH S3A recommends TK sampling at multiple time points. Satellite groups are typically 3–5 animals per sex per group.
Recovery groups: Recovery animals continue through a treatment-free period (usually 2–4 weeks for subchronic, 4 weeks for chronic) to assess reversibility of findings. This is increasingly expected by FDA and EMA for novel therapeutics.
Replacement reserves: Order 10–15% extra animals to account for losses during acclimatization, health screening failures, or early-study attrition. Replacements must be from the same supplier lot and age-matched.
Combination studies (OECD TG 453): Combined chronic/carcinogenicity studies use 50/sex/group for the carcinogenicity arm and 20/sex/group for the chronic arm, sharing the vehicle control.