Pathways of Antimicrobial Resistance Emergence and Dissemination Associated with Biopharmaceutical Manufacturing

Abstract

Antimicrobial resistance (AMR) is a worldwide One Health emergency, but the contribution of biotherapeutic manufacturing to the selection and dissemination of resistant microorganisms is not well appreciated. This review compiles available interdisciplinary evidence on biopharmaceutical production environments as hotspots for AMR selection, where industrial activities are associated with environmental and public health threats. We consider the primary sources of contamination, the biological factors driving resistance development, and the routes by which the spread of various pathogens can connect manufacturing activities to neighbouring ecosystems. Data derived from culture-based studies, quantitative molecular assays, whole-genome sequencing, and shotgun metagenomics illustrate how pharmaceutical water systems, reusable processing equipment, biofilms, antimicrobial residues (such as antibiotic active pharmaceutical ingredients), and waste streams provide settings conducive to the enrichment and persistence of resistance. Sub-lethal antimicrobial exposure, plasmid-mediated horizontal gene transfer, biofilm-related persistence, and co-selection by metals and biocides all serve to magnify resistance genes. Illustrative case studies, particularly those from low- and middle-income countries, demonstrate the persistence of multidrug resistance organisms and clinically meaningful resistance genes in pharmaceutical effluents, sludge, and downstream environments. Here, we present an integrated roadmap that combines next-generation molecular surveillance, design-based advancements in facilities and processes, waste management strategies, and coordinated regulatory governance options. Recognizing the potential risks of AMR in biopharmaceutical production is essential to ensure product integrity, minimize environmental spread, and reduce the global burden of AMR.