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www.biopharminternational.com Manufacturing and Facilities eBook November 2024 BioPharm International ® 7 Bioprocessing ration or decontamination (difficult to run in a closed mode); and integrity testing solutions to identify breach of closed systems. Furthermore, the market study shows a balance be- tween implementation in new and existing facilities. However, the latter are often dedicated to a single or limited number of products and may require costly modifications. Nevertheless, participants expect to achieve signifi- cant financial savings by implementing closed systems (Figure 1). Endeavor to quantify the value of closed processing A model was developed to quantify benefits of imple- mentation. It covers a typical fed-batch monoclonal antibody process in single-use from seed train to for- mulation, excluding media and buffer preparation as well as final filtration and filling. It quantifies the cost of transitioning to a closed state (i.e., running the same step in an open versus closed mode). It addresses sustainability aspects, including electrical consumption and gowning. Capital expen- ditures and waste streams treatment were excluded. The below summarizes the drivers and their con- tribution to the impact of adopting closed processing (Figure 2). Reduced risk of contamination Segregation through closed systems mitigates the risk of contamination associated with open manipula- tions. It reduces the need for environmental controls, sampling, and room cleaning. When moving from tra- ditional (open) processing to closed processing, the con- tamination risk was estimated to be reduced by 47%. Enabling multi-product manufacturing and multi-modal facilities Segregation at the process and product level removes the need for segregation at the level of the manufac- turing suite. Concurrent manufacturing of different products could then take place, increasing produc- tivity and facility utilization. Energy, labor, and cost savings can be substantial, as well as simplification of facility infrastructure and f loorplans. Reduction in gowning requirements, time, and energy consumption As contamination risk and room classification de- crease, gowning requirements can be lowered. Gown- ing procedures are lightened, associated time reduced by 55%, and cost by 81%. Declassifying and reducing manufacturing suites segregation decreases electricity consumption over- all, not to mention environmental monitoring and testing. It has been estimated that the combination of closed processing with declassification can lower energy consumption by up to 65% and environmen- tal control cost by up to 88%. Regulatory references and scope T h e m a j or i t y o f r e s p on d e n t s i n d i c a t e d t h a t a f ra mework f rom reg u lator y aut hor it ies def in ing t he bounda r ies a nd requirements for closed pro- cesses would be beneficial for them to confidently implement it. As early as 2000, t he Internationa l Counci l for Harmonisation (ICH) Q7 guideline made mention of declassification thanks to processing in a closed mode. The guideline states, "where the equipment itself (e.g., closed or contained systems) provides adequate protect ion of t he mater ia l, such equip- ment can be located outdoors" (5). In 2004, i n t he context of cel lu la r t herapy a nd cel l-der ived products, FDA g uida nce adv ised t he u se of closed s ystem s wherever possible du r i ng manufact uring, upstream of f ina l f i l l operations FIGURE 2. Value created by implementing closed processes.