Biopharmaceutical manufacturers continue to face many challenges amid increasing demand for critical therapeutics and pressure to advance sustainability goals. Although the therapeutics industry has evolved over the past few decades, manufacturers are still looking for ways to efficiently scale and increase production.

Due to the large number of patients and the demand for large quantities of product, commercial scale manufacturing of stainless steel bioproduction dominated the market even after the first production took place. Single-use bioreactor (SUB) It appeared in the late 1990s. The adoption of single-use technologies (SUTs) was initially delayed due to skepticism and concerns regarding sustainability, leachables and extractables, operational equivalence, and scale limitations.

However, today's SUTs offer several advantages in terms of flexibility, capital costs, reduced downtime, and can be scaled up or down quickly to accommodate rapid changes in production volumes. In addition, the SUT's single-use elements can be quickly assembled and disassembled, reducing downtime required for cleaning, sterilization, and maintenance, enabling faster delivery times, leading to shorter production cycles and increased productivity.

The choice between SUTs and stainless steel bioreactors (SSBs) depends on each biomanufacturer, including molecule type, titer range, cell density, and stage of demand (preclinical, early stage, late clinical, commercial stage, etc.) depends on your unique scenario. , number of patients, single-product versus multi-product facilities, product volume, and facility type (new facility, existing facility, etc.).

As SUTs continue to grow and evolve, biomanufacturers are gaining a better understanding of how SUTs fit with stainless steel in terms of sustainability, flexibility and scalability, quality and cost, and are looking to find the right fit for their company. You need to choose a method. Here we outline and compare the capabilities offered by SUTs and stainless steel systems, with a focus on the flexibility of SUT implementation.

Promoting sustainability in biomanufacturing

As companies develop and formalize their environmental, social, and governance (ESG) goals and determine their respective paths to achieving them, choosing the right manufacturing technology is critical.

In addition to facility footprint, including energy and HVAC requirements, liquid and solid waste are of critical importance.

SUBs have been shown to significantly reduce water consumption and facility energy usage compared to SSBs. However, the disposal of single-use components raises concerns regarding waste generation and potential environmental impact. A life cycle assessment (LCA) comparing SUB and SSB shows that the environmental impact of both systems is highly dependent on manufacturing conditions and disposal methods.

Introducing circular economy concepts such as recycling and reusing single-use components can reduce the negative environmental impact of single-use technologies. From materials to packaging to local manufacturing and distribution, great strides have been made in SUT sustainability.

SUB is shown as 37% reduction in consumables costsWhen compared to stainless steel. Disposable centrifuges also offer significant water savings benefits compared to devices that utilize depth filtration, a requirement for SSB (Figure 1). There are still opportunities to improve the sustainability and recyclability of single-use components such as bags used in the process.

Figure 1. Yield comparison: water, buffer, and NaOH reduction. Credit: Thermo Fisher Scientific

Achieve your goals with flexibility and scalability

Scalability is important as processes are further developed and large quantities of molecules are required for clinical or commercial manufacturing. Additionally, flexibility is essential for manufacturers producing a variety of products for commercialization.

SUTs increase flexibility for biomanufacturers, including faster setup times, reduced cleaning requirements, and easier customization of reactor size and configuration. This allows for better volume forecasting, especially for companies that focus on research and development and do not always plan for the commercialization phase.

Because SUTs are modular, they offer a unique way to add flexibility and scalability to the timing of facility construction, reducing the time needed to get a facility up and running. This may make it easier to adjust and adapt to new technologies in the future.

Stainless steel is an established choice in large-scale, commercial-scale biopharmaceutical production. However, SSBs require significant up-front investment, and because of their installation challenges and enormous size requirements, it may take some time for biomanufacturers to begin to see a return on their investment.

Overall, SUTs are useful in facilities that produce a large number of products in varying quantities and where flexibility and scalability are paramount. However, for the largest commercial scale manufacturers, the economic benefits of SSB exceed those of his SUT.

quality process management

Existing quality process controls can be implemented using either SUTs or SSBs depending on the needs of individual manufacturers.

With SSB, end users must control and update their own processes and components, whereas SUT suppliers own the quality and documentation components of their products, including multi-sourcing of reactors and single-use components. This relieves this burden from the end user. user.

SUTs offer significant quality advantages, including supplier-centric change control, no batch-to-batch production contamination, no soil carryover, and consistent product contact materials. SSB also provides benefits through existing documentation and processes, end-user-centric change management, and consistent product communications.

Overall cost improvement

The choice of manufacturing method can have a significant impact on a biomanufacturer's spending. Stainless steel technology has strict sterilization and maintenance guidelines in addition to requiring separate space for each unit, whereas SUT allows for more flexibility in cleanroom space requirements and and eliminates the need for gown changes and other process requirements.

SUTs improve overall workflow efficiency, allowing facilities that utilize SUTs to better utilize resources and reduce labor costs. Additionally, manufacturers can take advantage of cost savings in consumables compared to using depth filtration (Figure 2). At the 5,000L scale, it is possible to reduce consumables costs by 37% and overall costs by up to 33%.

Figure 2. Harvesting batch costs comparing the Thermo Scientific DynaSpin single-use centrifuge and depth filtration at various capacities. Credit: Thermo Fisher Scientific.

Despite lower initial capital expenditures (CAPEX) due to lower infrastructure requirements for SUTs compared to SSBs, manufacturers experience higher operating expenditures (OPEX) due to higher costs of consumables that must be disposed of. There is likely to be.

Although SSB has a higher initial cost, it has established durability and can potentially save you more money in the long run. However, his OPEX is also correspondingly higher due to increased water usage, labor costs, training, and other preparation and hygiene requirements.

There are many new advances in SUT to improve affordability. Next-generation technologies are also introducing automation tools that can reduce contamination and improve process control.

The path manufacturers should take

The choice between using SSB or SUT for bioproduction ultimately depends on the needs of each biomanufacturer in terms of economic and environmental considerations.

Stainless steel technology will continue to be a viable option for a variety of large manufacturers. However, SUT has come a long way since its inception. To keep up with the changing treatment environment it's necessary Further process intensification results in lower volumes, higher production yields, and increased manufacturing flexibility.

these Flexibility, scalability, performance benefits and improved sustainability make SUTs desirable for biomanufacturers looking for ways to increase yields and improve efficiency while achieving ESG goals more easily and cost-effectively. It is an option.

About the author:

John P. Puglia received his PhD in polymer science from the University of Massachusetts Lowell. John currently serves as Senior Director of Research and Development for Thermo Fisher Scientific's Bioprocessing business with a focus on single-use technologies. Puglia's research history includes plastics engineering, composite materials, cell culture, chromatography, sustainable engineering and high-purity manufacturing.

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