Open vs. Closed Aseptic Processing Systems Analysis
Our client required an aseptically controlled environment to produce their autologous and allogeneic therapeutics. Facing challenges in achieving sterility assurance for their biomanufacturing processes, they turned to Genesis AEC to aid them with the expedited transfers of biological materials, gene manipulation, decontamination cycles, and regulatory compliance needs.
Genesis evaluated their initial production suite which operated with traditional manual-focused manufacturing operations within a designated Grade A BSC, set against a Grade B background.
After thoroughly evaluating their unit operations which included initial apheresis processing, thaw/wash/incubation operations, sorting/sampling, expansion/harvest, and cryopreservation, we determined that they could transition to a Grade C cleanroom facility with a Grade A closed system for cost and operational efficiencies. We outlined the following risk mitigation strategies: closing their primary operations, reducing their environmental classifications, optimizing the air handling unit design, and minimizing gowning requirements.
Our recommendations included comprehensive operator training on new equipment, the development of updated procedures, and the optimization of their facility layout design to align with new area classification requirements.
To move forward, our improvements indicated that an optimized design would feature Grade C or Grade D suites with Grade A closed system isolators which would provide enhanced operator and patient safety, reduced HVAC and operational costs (e.g., fewer classified spaces, limited shutdowns, and decreased solid waste handling), and simplified facility maintenance and validation processes; as well as an increased probability of acceptance from cGMP regulatory authorities, US FDA and EU EMA, and other global agencies in the future.
Specifically, while this risk mitigation effort would mean an initial increase in equipment costs and qualification/validation costs, it would yield the following cost reduction outcomes:
- Reduction of nearly 1,000 SF of classified environment space
- Elimination of nearly 5,000 SF of Grade B-classified space
- Removal of multiple Grade B airlocks
- 35% Reduction of air handling unit sizing
- Reduction of overall facility qualification costs by $250,000
- Reduction of environmental monitoring costs by $1.5 million
Financial Analysis Highlights Client’s Return on Investment (ROI)
A five-year projected ROI analysis (below) revealed the new closed equipment design’s impact on capital costs, equipment costs, facility costs, validation costs, and annual operating costs if they were to move baseline open manufacturing controls with the new closed design.
The risk-driven exercise demonstrated that implementing a closed system led to lower facility costs, reduced environmental classifications, annual operations costs, overall space footprints, and simplified day-to-day operations. Despite challenges, the financial benefits and operational efficiencies make a compelling case for using process closure as a manufacturing risk mitigation strategy.
Genesis demonstrated to the client how strategic shifts in facility design, coupled with risk mitigation measures, can significantly enhance the efficiency, safety, and cost-effectiveness of biomanufacturing processes. The transition to a closed system not only meets regulatory standards but also positions the facility for long-term success in the evolving landscape of biomanufacturing.