Local tissue compatibility determines whether implants integrate successfully or trigger inflammatory responses leading to fibrous encapsulation, chronic pain, or device failure - yet predicting local reactions requires sensitive in vivo testing beyond simple cytotoxicity. Intracutaneous reactivity testing following ISO 10993-23 evaluates local tissue compatibility through intradermal injection of polar and non-polar extracts in rabbit models, providing sensitive detection of irritation potential required for all medical devices per ISO 10993-1. The test protocol involves precise 0.2 mL intradermal injections at five sites per extract along the rabbit's dorsal surface, with erythema and edema scored at 24, 48, and 72 hours using standardized Draize criteria enabling comparison across studies. Regulatory requirements mandate intracutaneous testing for all implants regardless of duration where direct tissue contact demands demonstrated local compatibility, externally communicating devices beyond limited exposure, and blood path indirect devices where extractables could cause vascular irritation. The dual extraction approach using both polar and non-polar vehicles ensures detection of all potentially irritating substances regardless of solubility, capturing water-soluble irritants and lipophilic compounds causing tissue reactions. For devices with antimicrobial coatings, intracutaneous testing reveals whether therapeutic agents elute at levels causing tissue damage, supporting dose optimization balancing efficacy against local toxicity. The time-course observation distinguishes between immediate reactions suggesting acute irritation and delayed responses indicating potential sensitization requiring additional testing. Manufacturing validation confirms processing reduces extractable irritants, sterilization doesn't generate reactive degradation products, and aging doesn't increase irritation through material breakdown.