Understanding Single-Use Facility Design in Life Sciences: The Basics for Success
Single-use technology (SUT) has transformed biopharmaceutical manufacturing. With significant advantages over traditional stainless-steel facilities—reduced cleaning validation burden, faster turnaround, and greater operational flexibility—single-use is a significant design approach for many new life sciences facilities.
The choice to manufacture with single-use comes with design and operational challenges that are frequently underestimated, however. Unlike a traditional facility where fixed piping is installed once and remains in place indefinitely, a single-use manufacturing process may need to be rebuilt from scratch with every batch. Hundreds of individual components must be sourced, stored, inspected, assembled, and ultimately properly disposed of each time a process is run.
Based on experience designing and operating multiple single-use facilities, we have identified recurring themes that, when not addressed early in the design phase, can turn into significant schedule delays and operational gaps.
In this article, we’ll discuss the critical design considerations for single-use facilities and explain why early, deliberate planning is the single most important factor in a successful facility start-up.
Understanding the scale of single-use complexity
The equipment used in single-use biopharmaceutical manufacturing covers a wide range of components: single-use bioreactor bags, single-use mixers, depth filtration assemblies, chromatography skids, and Tangential Flow Filtration (TFF) skids (whose fluid pathways are themselves single-use). Every connection made to this equipment, every length of tubing, every filter, every pump head, every bag and container, is in fact a single-use component.
To get an idea of the scale of this challenge, a comprehensive count of all the single-use components required to physically assemble and run a single process at a facility can be a thousand individual pieces or more. Every one of those pieces must be sourced from a qualified supplier, received into the warehouse, inspected, and tracked. And when the process is complete, each piece has to discarded, and the entire assembly must be rebuilt for the next batch.
This is the fundamental operational reality that distinguishes a single-use facility from a stainless-steel facility. In a traditional facility, the piping is built once and does not change. In a single-use facility, the process infrastructure is, almost by definition, changeable. Understanding this from the outset shapes every aspect of how such a facility must be designed and operated.
Design phase considerations
Several design-phase decisions directly affect facility readiness and ongoing operations. The following areas have to be top of mind during design early in the process, not as an afterthought.
Manifold design is not typically in the A&E scope. Architecture and engineering firms that design biopharmaceutical facilities do not typically take on the design of single-use tubing and manifold systems. Single use component design drawings are largely the responsibility of the SUT supplier. The component design is a collaboration between the owner and the SUT supplier; the owner is responsible for approval of any design or drawing change. Additionally, any change notices in SUT parts will be cascaded from the original manufacturer through the SUT supplier to the owner throughout the component’s lifecycle.
An A&E firm can be involved in the original development of the manifold design, but this must be discussed early in the project lifecycle. Owner companies that have a dedicated person with single use design experience on their design team early will avoid the scramble that occurs as the facility approaches commissioning and start-up.
Manifold supplier selection must happen early. Single-use manifolds are not standard, off-the-shelf products. They are custom-designed assemblies, unique to each facility's process requirements. Selecting a supplier early in the design process is essential because manifold design drawings require formal review and approval by both the supplier and the facility owner, which is a process that is more time-consuming than most organizations imagine.
Manifold design also requires careful thought about the physical reality of the process: How many lines need to run where, what lengths are required, what connector types are specified at each end, and what cleaning and flushing sequences must the assembly support. Sodium hydroxide and other caustic cleaning agents will run through the same tubing as the product, and the manifold design and plans for flushing the cleaning agents must account for this.
Working through all of these variables, obtaining a supplier drawing, and completing the approval cycle is a process that, if started from scratch, could realistically take six to nine months.
Vendor connector compatibility must be resolved at the design stage. Each equipment vendor in a single-use facility may specify a proprietary connector type. When two pieces of equipment from different vendors must interface, the connectors are likely not going to match. The solution may need to be a custom manifold that bridges the two connector standards. These bridging manifolds must themselves be designed, fabricated, and gamma irradiated for sterilization before use. To avoid costly delays, it’s important to understand and resolve these possible conflicts during design, rather than discovering them during commissioning.
Materials management systems have regulatory requirements. Regulatory agencies such as the US Food & Drug Administration (USFDA) or the European Medicines Agency will inspect any facility whose products are sold in their markets. In particular, they will expect to see materials management systems used in facility operations. These systems cover the receipt, inspection, organization, traceability, storage, expiry, and controlled handling of single-use tubing and manifold assemblies.
As SUT materials are moved from the warehouse to the floor, they will pass through material airlocks for changes in air classification, which require a wipe-down and a dwell time for disinfection effectiveness. The sizes of airlocks will need to be designed to accommodate the quantity of materials they will need to hold during the disinfectant contact time.
Tubing management systems are expected by regulatory agencies. Unlike stainless steel construction, which is physically installed and secured, single use tubing and components need to be physically supported during the assembly of the components prior to the batch and during the manufacturing process.
During facility inspections, regulatory authorities will expect to see structured tubing management systems used in facility operations. Tubing management systems assure that tubing is supported (off the floor), can accommodate different routings as required, and can be easily cleaned to maintain the room classification.
As with manifold design, tubing management system development is not typically in the A&E scope. An A&E firm can provide this service but it will need to be specified by the owner early in the design process. Appropriate tubing management system design will meet regulatory agency expectations, eliminate safety issues and improve the work environment for the manufacturing associates.
Warehousing requirements are larger than expected. Storing single-use components can be a substantial warehousing and logistical burden. Depending on the scale of production, the inventory of single-use materials (including bags, tubing, filters, connectors, and all associated components) can take up 50 percent or more of an organization’s total warehouse space.
This figure routinely surprises companies in the early stages of facility planning, but it is a hard fact of the process. Depending on the process and/or the facility, it may be beneficial to pre-assemble single use components in a controlled environment kitting/assembly room, away from the manufacturing suite. Space planning for single-use inventory, movement and assembly must be considered in facility design from the beginning, not added after the fact.
Operational considerations that begin at design
Several operational challenges in single-use facilities are best addressed during the design phase. Two areas in particular deserve early attention.
Supply chain planning and procurement timelines. Single-use component orders may have lead times that will extend the timeline for facility readiness. Assembling a complete Bill of Materials (BOM) for all single-use components, understanding the procurement timelines associated with each item, and placing orders on a schedule that ensures components are available before construction is complete must all begin earlier than most organizations expect. Possible supply chain disruptions compound the risk. If single use components are unavailable when needed, production cannot begin, no matter how ready the facility may be otherwise.
Planning for component failures. Single-use components are subject to quality defects. Integrity failures, contamination events, and inspection-related discards are routine realities of operating a single-use facility. Production planning must account for these kinds of failures. Maintaining a buffer stock of critical components could help hedge against supplier delays and unexpected failures, even if they tax your available warehouse space. This is particularly important for organizations that run lean inventories of single-use materials. These companies could find their production runs disrupted by events that could have been dealt with if they had supplies in reserve.
The timeline reality: Start earlier than you think
Based on my experience with single-use facility design and operation, the most important piece of advice companies should take to heart is to start early. They must begin their single-use design work far earlier than the project schedule might suggest. The moment a project transitions from conceptual design into detailed design, single-use manifold and tubing work should begin in parallel.
Why? Simply because facility construction is likely to be done before the single-use design work is complete, unless the two are started concurrently. The process of identifying the manifold supplier, working through the design of every assembly, completing the drawing review and approval cycle, placing procurement orders, and receiving and inspecting components can take nine to twelve months even in the best case. Delays in supplier selection or single use material deliveries will extend that timeline.
Organizations that have gone through this process before (for example, those that may be adapting an existing process to a new facility, or are scaling up from a development-scale operation) have an advantage here. The manifold designs and supplier relationships they’ve already established give them a strong starting point. Organizations building a single-use facility for the first time, or transitioning from a stainless-steel operating environment, should treat nine to twelve months as a minimum planning timeline, running in parallel with detailed design and construction.
Biopharmaceutical facility design conversations tend to focus on the physical structure: the cleanrooms, the HVAC systems, the utility infrastructure, and the capital equipment. For single-use facilities this conversation has to extend to process infrastructure, including the manifolds, tubing assemblies, and inventory systems that make it possible to actually run product through the facility once it is built.
Regulatory agencies treat these elements as part of the product quality. Operators depend on them for every campaign. Procurement teams are constrained by them in ways that affect production schedules months before a product is ever made. To ensure that a single-use facility will start up on schedule, the design process needs careful and diligent management on the owner side, with thorough communication between the owner and the A&E team.
The logistics of single-use manufacturing can be unforgiving. Unlike the piping in a stainless-steel facility, which is permanent, the process infrastructure in a single-use facility effectively disappears the moment a batch is complete. Building it back again, reliably and on schedule, every time, is the operational challenge that good design work makes manageable.
