Ramesh Raju Mavuleti*, rrajum@gmail.com, is head of operations, Validation Services India, at Merck Life Sciences Pvt, Ltd.

Ramesh Raju Mavuleti

The adoption of single-use technologies (SUTs) in biopharmaceutical manufacturing reduces manufacturing costs, increases the manufacturing line flexibility, and improves the speed and efficacy of the line changeovers or the batch turnaround times. The closed manufacturing systems also facilitate production of a safe and regulatory-compliant product. SUTs are used throughout the biopharma manufacturing process flow, the single-use filter capsules, tubing, and connectors being the most widely used in the final fill/finish applications of the injectable preparations. The single-use bioreactor bags and buffer storage bags are used for upstream applications. This paper reviews the drivers for adoption of SUTs and how the risks from the use of these technologies can be overcome in a planned, proactive, and compliant manner. 

Review of SUT Adoption in Biopharma Manufacturing

 Pharmaceutical Technology’s Quality and Regulatory Sourcebook 2024

The adoption of single-use components emerged from the mid-1980s. Initially, blood bags replaced glass bottles and soon became available with a plastic tube or two as well as connectors, valves, and vials for taking biological samples. The polyvinyl chloride blood bags used for blood donations were more than just bags. Evolving from these examples are the current single-uses systems (SUS) that are gaining wider use in the biopharmaceuticals industry, especially for the production of specialized and/or small-batch biopharmaceutical drugs. These SUS are the alternatives to the systems made of relatively inflexible stainless-steel vessels and reactors, hard piping, 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 sampling 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 filtration, 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 assemblies (1,2).

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 industry survey (3). The leading reasons cited in the survey as being “very important” for the adoption of SUS include a decrease in the risk of cross-product contamination, cited by 46.2% survey respondents; eliminating cleaning requirements, cited by 41.2% of respondents; reducing time to get facility up and running, cited by 44.1% of respondents; and reduction in capital investment in facility and equipment, cited by 40.4% of respondents.

A study found that SUTs, when adopted, required 87% less water (primarily by reducing steaming in place [SIP], cleaning, and changeover between batches), 21% less labor (primarily by reducing cleaning 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 energy 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 market faster by increasing throughput and making scalability 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).

1. Rathore, A. S.; Agarwal, H.; Sharma, A. K.; Pathak, M.; Muthukumar, S. Continuous Processing for Production of Biopharmaceuticals. 

 (8), 836–849. DOI: 10.1080/10826068.2014.985834.
2. Klutz, S.; Magnus, J.; Lobedann, M.; et al. Developing the Biofacility of the Future Based on Continuous Processing and SUT. 

, 120–130. DOI: 10.1016/j.jbiotec.2015.06.388
3. Langer, E. S.; Rader, R. A. Biopharmaceutical Manufacturing is Shifting to SUS. Are the Dinosaurs, the Large Stainless-Steel Facilities, Becoming Extinct? 

 online, Oct. 23, 2018.
4. Lim, J.; Cox, S.; Leveen, L.; Monge, M.; Sinclairm A. The Environmental Impact of Disposable Technologies. 

.
5. Single Use Support. Pioneering Biopharma. 

 (accessed Jan. 21, 2024).
6. Das, S. The Appeal of Single-use Tech. 

Ramesh Raju Mavuleti*, rrajum@gmail.com, is head of operations, Validation Services India; Subhasis Banerjee, PhD, is principal technical application expert, Bioprocessing APAC; and Tathagata Ray, is consultant, Global Strategy Deployment; all at Merck Life Sciences Pvt, Ltd.; K. Vasantakumar Pai, PhD , is professor and chairman, PG Department of studies & research in Industrial Chemistry, Kuvempu University; K. Sreedhara Ranganath Pai, PhD, is professor, epartment of Pharmacology, Manipal Academy of Higher Education; and Somasundaram Gopalakrishnan, is senior consultant, Global Biopharm Center of Excellence, Merck Pte. Ltd.

*To whom all correspondence should be addressed.

When referring to this article, please cite it as Mavuleti, R. R.; Pai, K. V.; Pai, K. S. R.; et al. Review of SUT Adoption in Biopharma Manufacturing. 

Pharmaceutical Technology Quality and Regulatory Sourcebook

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