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10 BioPharm International ® Manufacturing and Facilities eBook November 2024 www.biopharminternational.com Bioprocessing Page Header_ Toward the 'Facility of the Future' Simultaneously, the next generation of technologi- cally advanced manufacturing facilities, or "Facility of the Future," is being described and characterized. These facilities aim to improve efficiency, agility, and quality. They integrate automation, real-time data analytics, and digital technologies, and leverage in- novative approaches such as continuous manufactur- ing, modular designs, and real-time process control. Linked to the ability to run continuously, closed systems emerge as a key component to achieve this vision. The uninterrupted product stream requires the ability to manage continuous input. Single-use components may undergo prolonged use or require frequent change-outs and should be evaluated for po- tential contamination risks, as any contamination could affect a large amount or product. A control strategy should be put in place to ensure the integ- rity of single-use equipment is maintained during use (Figure 3). It becomes clear that adoption of closed processes will occur gradually, with the aim of achieving a closed processing environment. Each step toward CNC will be made possible by different technologies and motivated by different objectives (Table I). Conclusion Closed systems represent a key tool for advancement in the biopharmaceutical industry, offering tangible economic and operational benefits primarily due to the abilit y to declassif y production environment. This, in turn, is linked to advancement in facilit y design, evolving to ballroom production suites even- tually being controlled non-classified. Challenges remain in the implementation of closed systems, particularly regarding products, technol- ogy, and facility design. Despite these challenges, ef- forts are made to lay down a clearer path for practical implementation. The gradual adoption of closed sys- tems, and the innovative factory hosting them, will enable the "Facility of the Future" to emerge, where processes will be increasingly integrated, controlled, and optimized for superior pharmaceutical product quality and supply. References 1. ISPE. Baseline Guide Vol. 6: Biopharmaceutical Manufac- turing Facilities, 2nd Edition (November 2013). 2. BioPhorum. Closed Systems in Controlled Non-Classi- fied (CNC) Space. biophorum.com/workspace (accessed Oct. 16, 2024). 3. Estapé, D.; Walker, A.; Orichowskyj, S.; et al. Proof of Closure: Life Cycle of Closed Systems. Pharm. Eng. 2017, 37 (5) 51–56. 4. EC. Guideline, The Rules Governing Medicinal Products in the European Union, Volume 4: EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Final Version (Aug. 22, 2022). 5. ICH. Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, Step 4 version (ICH, 2000). 6. FDA. Guidance for Industry, Sterile Drug Products Pro- duced by Aseptic Processing – Current Good Manufactur- ing Practice (CDER, September 2004). 7. WHO. Technical Report Series 996, Annex 3 – Good Man- ufacturing Practices: Guidelines on Validation, Replace- ment/Revision (April 2016). 8. ICH. Q9 Quality Risk Management, Step 4 version (2005). 9. BioPhorum, Closure Playbook – Introduction; BioPho- rum, September 2023. 10. BioPhor u m, A ccelerat ing Mult i-P roduct Biophar- maceutical Manufacturing Facilit y P roject Lifecycle Through Modular Design; BioPhorum, June 2022. ■ TABLE I. Toward a fully closed process. Critical steps closed Most briefly open or functionally closed Steps functionally closed, some fully closed Closed process and dismantling Existing Today—New facilities Future Technology Single-use technologies used to close critical steps Adapted technologies and aseptic connectors used to close steps Fit-for-purpose closed processing technologies Key driver Contamination risk mitigation Reduced cleanroom requirements Multi-product and platform manufacturing Facility Separate rooms, traditional cleanroom classification and environmental controls Ballroom concept cleanroom, fully closed unit ops in CNC space Majority of unit ops in CNC space, very limited cleanroom footprint Manufacturing Campaign strategy, multi-product manufacturing Multi-product manufacturing; labor intensive product changeover still required Concurrent multi-product and/or multi-platform manufacturing possible