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20 BioPharm International ® Quality and Regulatory Sourcebook eBook March 2024 www.biopharminternational.com Manufacturing tration, concentration, and purification steps. This expansion has evolved over time to the current-day concept of closed continuous processing technology, which is almost completely based on SUTs and assem- blies (1,2). Adoption drivers Single-use or disposable bioprocessing equipment is now used for ≥85% of pre-commercial scale (i.e., preclinical and clinical) biopharma manufacturing and is increasingly being adopted for commercial product manufacturing, according to an industr y sur vey (3). The leading reasons cited in the sur vey as being "ver y important" for the adoption of SUS include a decrease in the risk of cross-product con- t a m i nat ion, cited by 46.2% sur vey respondent s; eliminating cleaning requirements, cited by 41.2% of respondents; reducing time to get facility up and running, cited by 44.1% of respondents; and reduc- tion in capital investment in facility and equipment, cited by 40.4% of respondents. A study found that SUTs, when adopted, required 87% less water (pr i ma r i ly by reduci ng stea m i ng in place [SIP], cleaning, and changeover bet ween batches), 21% less labor (primarily by reducing clean- ing in place [CIP] activities), 38% less space, and 29% less energy (4). According to industry sources (5), SUS lower operating costs by offering 46% water and en- ergy reductions, a 35% more favorable carbon dioxide footprint due to lower facility emissions, and a 40% lower initial investment cost. The technology allows biopharma manufacturers to push products to mar- ket faster by increasing throughput and making scal- ability easier (5). The availability of this technology has made new biopharma companies adopt SUS, as it requires less upfront capital investment and enables quick advancement of development efforts towards new products (6). The advantages of SUT drive its adoption in bio- pharma manufacturing. Contract manufacturing or- ganizations were the earliest adopters of SUTs because of the ease-of-use and efficiency of these systems and devices when dealing with multiple products and pro- cesses that require quicker turn-around times; flexible production capacities in terms of switching between product campaigns with the ability to manufacture a wider range of production scales; and ability to turn around manufacturing operations quickly. Another driver of adoption of SUTs is ease of scal- ing down a manufacturing process in biopharma modular facilities. SUTs support flexible current good manufacturing practice manufacturing, enabling ef- ficient adjustment of production scales, production schedules, and reconfigurations. SUTs also facilitate process tech transfer to other global sites or to con- tract manufacturers. These attributes also support the implementation of regulator y initiatives such as quality-by-design, process analytical technology, and continuous processing. Furthermore, the tech- nology practically eliminates the need for cleaning and related validations, sterilization and related vali- dations, and changeover qualifications. The ability to use a similar configuration and materials for produc- tion equipment at the process development and com- mercial-scale manufacturing phases also simplifies process scale-up. Meanwhile, single-use components and assemblies can be supplied pre-sterilized, and, when fastened with aseptic connectors, can potentially eliminate the requirement for classified environments for the manufacturing process and further reduce the risk of cross-contamination. SUTs further help companies avoid costly downtime and material waste. Another reason for increased adoption of SUTs can be found in the evolution of healthcare toward per- sonalized therapies such as cell and gene therapies, including chimeric antigen receptor T cell therapies, and messenger RNA vaccines. The small doses re- quired for such treatments cannot be processed in traditional large stainless-steel tanks, rather, sin- gle-use platforms offer a perfect solution in terms of adaptability and scalability. The risks and challenges While SUTs provide many benefits, they nevertheless carry risks that tend to be magnified on the commer- cial scale. These risks are of greater importance at the final drug manufacturing stages. The authors will re- view how most of these risks can be overcome with the recommendations given by guidance documents such as those provided by the International Society for Pharmaceutical Engineering (ISPE), Parenteral Drug Association (PDA), and BioPhorum (formerly BioPhorum Operations Group). The advantages of SUT drive its adoption in biopharma manufacturing.