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6 Pharmaceutical Technology ® Quality and Regulatory Sourcebook eBook March 2024 PharmTech.com Manufacturing valves, and so on. Such fixed systems must be cleaned and sterilized between batches, a relatively labor and energy-intensive operation. The adoption of aseptic connectors, tubing, mixers, storage bags, and sam- pling bags and usage of capsule filters in a wide range of applications in the late 1990s lead to the "plastic factory" concept in the 2000s. The technology was further expanded to the upstream and downstream unit operations in the biopharma industry, such as the bioreactors, chromatography, virus removal fil- 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- ta 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 ima r i ly by reducing stea m ing 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 organizations were the earliest adopters of SU Ts because of the ease-of-use and efficiency of these systems and devices when dealing with multiple products and processes that require quicker turn- around times; f lexible production capacities in terms of switching between product campaigns with the ability to manufacture a wider range of production scales; and abilit y 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. SU Ts suppor t f lexible current good manufacturing practice manufacturing, en- abling efficient adjustment of production scales, pro- duction schedules, and reconfigurations. SUTs also facilitate process tech transfer to other global sites or to contract manufacturers. These attributes also support the implementation of regulatory initiatives such as quality-by-design, process analytical tech- nology, and continuous processing. Furthermore, the technology practically eliminates the need for clean- ing and related validations, sterilization and related validations, and changeover qualifications. The abil- ity to use a similar configuration and materials for production equipment at the process development and commercial-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 review 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). A 2018 survey from BioPlan Associates (3) reports five downsides or potential problems with SUS as cited by more than 50% of respondents. These down- sides include breakage of bags and loss of produc- tion material, cited by 75% of sur vey respondents; extractables and leachables (E&L), cited by 73.3% of respondents; and high cost of disposables, cited