The primary considerations for any pharmaceutical manufacturer revolve around a few core tenets: risk reduction, speed, cost, flexibility, and product quality. Since the early 2000s, end-to-end disposable or single-use technology (SUT) has been gradually displacing stainless steel equipment in drug development and manufacturing due to its ability to positively impact each of these core tenets.
What is SUT—and Why is it Important?
SUT generally refers to the category of biopharmaceutical manufacturing (bioprocessing) equipment designed to be used once and then discarded. SUT typically consists of polymeric or plastic materials that are assembled and sterilized by suppliers using gamma irradiation prior to use. As of 2018, SUT was being used for ≥85% of pre-commercial scale (i.e., pre-clinical and clinical) biopharmaceutical manufacturing and is increasingly being adopted for commercial products manufacturing.
There are several well-established advantages to SUT versus “classical” stainless steel manufacturing facilities. The “plug and play” nature of SUT allows manufacturers to avoid the significant cost, time, and resources that would otherwise be required for stainless steel equipment cleaning, sterilization, cleaning validation, and product changeover activities. Variable cost and capital/infrastructure investment savings can be found in reduced reliance on utility systems (e.g., high purity water, clean steam) and equipment preparation space. Environmental risk can also be reduced with less reliance on high volumes of acidic and caustic solutions for large-scale equipment cleaning. SUT allows for the quicker start-up of facilities with less need for segregated unit operations (think “open ballroom” facility concept) and a potentially smaller overall carbon footprint.
However, SUT is not without its downsides. A 2018 BioPlan Associates survey of biopharmaceutical companies, mostly in the U.S. and Europe, revealed some interesting feedback around SUT adoption.
The leading reasons cited as “very important” resulting in the adoption of SUT were:
- 46.2% of survey respondents cited, “Decrease risk of cross-product contamination”
- 41.2% of survey respondents cited, “Eliminating cleaning requirements”
- 44.1% of survey respondents cited, “Reducing time to get the facility up and running”
- 40.4% of survey respondents cited, “Reduce capital investment in facility & equipment”
The top five downsides or potential problems with SUT were:
- “Breakage of bags and loss of production material” cited by 75.0%;
- “Leachables and extractables” cited by 73.3%;
- “High cost of disposables” 68.8%; and
- “Material incompatibility with process fluids” and “We do not want to become vendor-dependent (single-source issues)” tied at 56.7%.
When to Implement an SUT Program
Business leaders developing their manufacturing strategy often have an unenviable list of considerations in their quest to create a capable, agile, and efficient network. For high-volume commercial biologic products (e.g., requiring ≥5-10,000L bioreactor capacity), stainless steel facilities are still the most cost-effective option despite the advantages of SUT. These behemoth stainless steel facilities can attain more economies-of-scale and can provide products at costs as low as ≤$100/gram, the current lowest costs being attained in the biopharmaceutical industry. However, these facilities are typically the realm of the pharma giants, who have the capital and product pipeline needed to make these types of facilities a worthwhile long-term investment.
Due to its physico-mechanical constraints, SUT is primarily used for the ≤2,000L bioreactor scale. This scale is generally preferred for clinical manufacturing or low-volume commercial products. However, multiple SUT systems can be used in parallel to produce commercial products at costs that are still competitive and allow a considerable profit. To date, SUT adoption has been much more pronounced in the upstream and solution prep areas. Higher risk, questionable benefits, and lagging technology have limited downstream applications of SUT, but adoption is gradually increasing as suppliers have developed more appealing technologies in recent years.
Flexibility and speed (tech transfer, product changeover) are typically among the most important factors in an SUT decision. A great example of this impact is with contract manufacturers (CMOs), whose propensity for SUT adoption has been consistently high due to the flexibility and rapid changeover that SUT can provide. CMOs use SUT to build facilities quickly and change from product to product with relative ease, incorporating new technologies from suppliers as they are developed. Early engagement with CMOs in the drug development process can greatly accelerate tech transfer timelines and reduce testing needs upon commercialization if the developer and CMO can harmonize on SUT platforms.
Constructing an Effective SUT Program
Success in SUT program management revolves around forward-thinking core principles like scalability, sustainability, and standardization. Smaller manufacturers often push to get a facility operational as quickly, efficiently, and cost-effectively as possible, with little emphasis placed on long-term strategy. For big pharma, the challenge is typically in reducing the complexity associated with continuous M&A activity and highly diversified facilities and assets. In any scenario, building a program around scalability, sustainability, and standardization will set your organization up for minimal headaches down the road.
SUT Design Philosophy
An established SUT consumable design philosophy at the outset of program initiation provides a strong foundation for future network expansion—potentially greatly reducing tech transfer times and supply-chain risks. Constructing designs focused on simplicity, versatility, and modularity can help control the proliferation of highly customized SKUs that are challenging for vendors to supply consistently and that are less easily transferred between facilities and accompanying single-use equipment assets (hardware). Manufacturers should prioritize as much alignment with standard vendor offerings and preferred components as possible to ensure minimal risk to OTIF delivery. Additionally, a thorough evaluation of the landscape of suppliers and their offerings is necessary to decide on SUT platforms and supplier partnerships that will be sustainable and preferable long term.
Forward-looking data fundamentals and systems are the lifeblood of an SUT program. A vast amount of material-specific data exists, which should be well understood initially to ensure data systems are capable of providing visibility to it. Standards for material descriptions and technical drawings should be established to ensure consistency as an SUT material portfolio grows. There are three main categories of valuable SUT data:
- Procurement data
- Quality data
- Technical data
Users will benefit from the ability to easily visualize and report this data, with oversight of the material hierarchy from hardware to corresponding assemblies/components. ERP, EDMS, and QMS systems should be integrated (or linked) to consolidate data across all SUT materials, in as close to real time as possible. This data management program relies heavily on external supplier inputs, thus expectations around data structures/formats should be clearly communicated and regularly reinforced with suppliers.
SUT Introduction and Lifecycle
SUT introduction and lifecycle management require the ongoing coordinated collaboration of several functions. As with any cross-functional activity, things can get messy very quickly without the proper agreements up front. Manufacturers would do best to bring together all stakeholding functions to align on a lean business process that covers SUT introduction, implementation, and lifecycle from end-to-end. The business process should specify the ownership of key activities, stage/decision gates, deliverables (content & format), and time/resource allocations. This is a process that should be regularly iterated upon and improved.
Certain functions should own and build out sub-processes relevant for their aspect of the material ownership. For example, technical stakeholders may build out “SUT Qualification” into sub-processes around extractable/leachable evaluations, compendial data gathering, validation testing, etc., which they would own and for which they would generate procedures/requirements. All key deliverables should be supplemented with templates and required data packages that ensure traceability in the event of an audit. The overall business process owners should also detail out a vendor-initiated change management process that specifies communication pathways and ownership of key mitigation actions. Sustainability processes (e.g., material recycling, incineration, etc.), often one of the most overlooked areas of an SUT program, should be evaluated and implemented on an ongoing basis in order to reduce the environmental impact of a facility.
From a program effectiveness point of view, human resources can be the make-or-break aspect. Depending on the organization’s potential investment in SUT, business leaders should consider employing a dedicated SUT expert group, potentially as a subset of a larger materials management organization. Key experts in the procurement, quality, and technical functions should be identified for work primarily focused on SUT. Building and investing in internal material knowledge will be crucial to support ongoing SUT change management, qualification activities, discrepancy assessment, facility design, and new technology evaluation.
Contract or consultant resource support should also be considered for functions such as project and data management. Multi-site manufacturing organizations should consider best practice sharing network teams, especially in global environments where regulatory expectations and preferred suppliers/technologies may differ across sites. Multi-site organizations should also consider employing SUT experts at their sites, to facilitate network collaboration and act as primary contacts for site SUT-related issues and assessments. External relationships are critically important to the SUT program; internal experts should be expected to participate in industry consortia, develop relationships with SUT suppliers, contribute to regulatory agency forums, and consult with key external manufacturers. These relationships contribute to the organization’s SUT knowledge base and help align internal compliance and technology with the greater industry.
The Road Ahead
While traditional stainless steel facilities will still see the lion’s share of commercial biopharmaceutical product volume over the coming years, fewer new stainless steel facilities are being built, and the adoption of SUT is growing exponentially, particularly in clinical and low-volume commercial manufacturing. Projected annual sales revenue growth from 2018-2023 for stainless steel (non-SUT) bioprocessing systems is at 49%, versus 214% for SUT. New modalities in cell and gene therapy will only further fuel the fire. The trends are clear. How will your organization respond?
Langer, E.S., et al, 15th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan Associates, 511 pages, April 2018 (see www.bioplanassociates.com/15th).
Rader, R.A., “Biosimilars Paving The Way For Cost-Effective Bioprocessing,” Biosimilar Development, Aug. 23, 2017.
Contact Enterey Today
Enterey partners with life science organizations across every vertical to optimize compliance, efficiencies, and results. Schedule an appointment today with our team to learn more. Or, take our Process Improvement Plan assessment to identify potential gaps in your existing projects and programs.