Architectural Controls for Secure Retrieval-Augmented Generation in GxP-Regulated Pharmaceutical Research: A Compliance-Driven Framework for Protecting Biomedical Intellectual Property

Abstract

Pharmaceutical research and development organizations are adopting retrieval-augmented generation (RAG) systems for drug discovery knowledge retrieval, regulatory document analysis, and clinical literature synthesis — yet GxP-regulated deployments expose compliance vulnerabilities that general AI security frameworks leave unaddressed. Audit trail continuity under 21 CFR Part 11, cross-tenant intellectual property isolation between co-hosted research programs, and validated-system-state preservation impose obligations at each pipeline processing layer, not only at network perimeters. This paper develops a compliance-driven architectural control framework assigning discrete GxP controls to four RAG pipeline layers — ingestion, vector store, retrieval gate, and generation — and maps each control to the specific Part 11 provisions and ALCOA+ data integrity attributes it satisfies. Infrastructure as Code deployment patterns allow the complete pipeline to be qualified as a GxP computerized system under Computer Software Assurance principles. Layer-specific controls provide a more defensible regulatory posture than perimeter-only approaches precisely because GxP obligations bind to data provenance and audit trail continuity at the processing stage, not the access boundary.