Quality management systems in modern manufacturing are at a critical inflection point. Traditional Design Control frameworks including Design Development Plans (DDP), Design History Files (DHF), Verification and Validation (V&V), Design Inputs and Outputs, and Design Control Plans (DCP) are largely document-centric, reactive, and siloed from real-time production intelligence. While ISO 9001:2015 and regulatory standards such as FDA 21 CFR Part 820 provide robust compliance architectures, their implementation remains labor-intensive, error-prone, and disconnected from emerging digital manufacturing ecosystems. This paper introduces the Autonomous Quality Intelligence (AQI) Framework, a novel, first-of-its-kind architecture that unifies Generative Artificial Intelligence (GenAI), Industrial Digital Twin (IDT) technology, and real-time compliance orchestration engines into a single, self-adaptive Design Control system. AQI redefines how organizations manage Design Inputs, Design Outputs, DDP, DHF, V&V cycles, and DCP transforming static documentation into living, AI-governed, sensorsynchronized quality artifacts. The framework introduces three original constructs: (1) the Compliance Generative Layer (CGL) for automated, regulation-aware documentation synthesis; (2) the Dynamic Verification Engine (DVE) for continuous, twin-based validation; and (3) the Predictive Risk Intelligence Module (PRIM) for AI-augmented FMEA and risk scoring aligned with ISO 14971 and ISO 9001 Clause 6.1. A case study from a transit infrastructure manufacturing environment (Aventura Corporation, MTA New York) demonstrates AQI implementation outcomes: 40% reduction in design-related nonconformances, 97% first-pass verification success rate, 100% regulatory submission acceptance, and a 35% decrease in quality-related costs. The AQI Framework is proposed as a universal, cross-industry standard applicable to medical devices, aerospace, automotive, and high-tech manufacturing sectors, with direct alignment to ISO 9001:2015, ISO 13485:2016, and FDA 21 CFR 820.30 requirements. 1