Techno-Economic Evaluation and Contamination Risk Investigation of Isolator versus RABS Technologies in Aseptic Pharmaceutical Filling Operations

Aseptic pharmaceutical manufacturing is essential for patient safety, particularly for sterile drug products that cannot undergo terminal sterilization. In such cases, sterility assurance depends on robust process design, strict environmental control, and effective contamination risk management. Restricted Access Barrier Systems (RABS) and isolators are widely used to limit human intervention and reduce microbial contamination during aseptic filling operations. However, a comprehensive comparative evaluation integrating technological performance, contamination risk, regulatory expectations, and long-term economic impact remains limited. This thesis presents a comparative techno-economic and risk-based assessment of isolator and RABS technologies applied to aseptic pharmaceutical filling lines. The analysis examines key technological aspects, including classified area requirements, gowning practices, decontamination regimes, line setup procedures, and environmental monitoring strategies, with reference to EU GMP Annex 1 and FDA guidance on aseptic processing. Contamination risk is quantitatively assessed using a structured methodology considering facility design, aseptic setup complexity, intervention frequency, and filling operations. In parallel, an economic analysis evaluates capital and operational expenditures (CAPEX and OPEX), including utilities, labor, and environmental monitoring costs. Results indicate that isolator technology provides higher sterility assurance due to its fully enclosed design, automated decontamination, and reduced operator intervention. Downgraded background environments enable long-term cost savings despite higher initial investment. RABS technology, while offering greater flexibility, presents higher contamination risk due to increased human interaction and stricter background requirements. Overall, this study supports informed technology selection in aseptic pharmaceutical manufacturing.