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Key considerations for implementing single-use components or platforms when moving from research to process development.
The adoption of single-use systems in biopharmaceutical production originated with the desire to minimize cleaning and associated validation. Before long, bioprocessors recognized the value of flexibility, reduced capital costs, and faster campaign turnaround times attainable through disposable bioprocess equipment. Single-use technologies have evolved from a supporting role for upstream operations (e.g., media storage and cell harvest) to near-complete platform processes that include all downstream processing steps except chromatography.
Numerous technical advances have contributed to the attractiveness of single-use equipment across the range of production scales, such as improvements in materials and quality of construction and connectivity. Another positive factor has been suppliers’ increased commitment to providing a robust regulatory package. Vendors have taken on the burden of documenting their products’ suitability and safety, which had previously fallen to a large extent on end-users. Moreover, the 5- to 10-fold improvement in product titers for monoclonal antibodies over the past 15 years has nearly eliminated arguments against single-use based on scale. Bioprocessors can now generate production-scale batches in what were once pilot-scale volumes.
With many technical hurdles overcome, the focus has shifted to maximizing the operational and economic advantages of single-use bioprocessing. As the case continues to build for end-to-end disposable bioprocessing, bioprocessors should be aware of the key factors associated with implementing single-use components or platforms. Potential adopters must focus on which criteria to consider as their plant’s manufacturing capacity evolves away from multi-use unit operations to disposable components and systems.
Bioprocessors have successfully deployed single-use equipment at nearly every conceivable production scale. Yet, the decision to “go disposable” is significant. It involves considering the product, scale, process, and corporate objectives that include the value of legacy stainless-steel equipment. Decisions made early in process development and scaleup will affect the trajectory of manufacturing at successive production scales. Employing best practices when selecting single-use products during process development can ease the transition from clinical to commercial production, and maximize the overall benefit of single-use systems. Based on shared and observed experiences in single-use bioprocessing, the principal factors to consider when embarking on a new single-use deployment include materials of construction, components, system design, and vendor support. Neglecting these considerations can result in costly delays and an uncertain pathway to commercial scale-up.
Materials of construction constitute a principal factor when specifying single-use bioprocess equipment. At the most basic level, materials must meet stringent biological and chemical guidelines. Bioprocessors should settle for nothing less than fully compliant materials from proven suppliers with established reputations.
Consistency and availability of materials of construction directly affect the quality and supply of single-use products. End-users should expect availability of the same or equivalent materials of construction, of equal or higher quality, for the duration of a development and/or manufacturing campaign. To meet these requirements, suppliers should maintain a redundant or backup supply chain for their raw materials. Customers should inquire about a vendor’s contingency plan in the event of a supply interruption.
Frequent change notices from single-use system suppliers altering materials of construction carry potential quality implications that may delay program timelines and add to quality assurance costs. Consider the frequency of a vendor’s change notices, or whether the vendor is providing notifications at all. New materials introduced to existing systems can lead to validation issues and delay a product’s time-to-market.
Components are the building blocks of single-use systems that are, in essence, only as robust as their weakest link. Users should specify components that are consistent with overall facility practices. For example, if commercial production relies on sterile welders and sealers, users should specify compatible tubing that meets material requirements.
Proprietary components not generally available to the market at competitive prices will almost certainly add to cost and reduce customer choice. Bioprocessors can strengthen their long-term supply position by specifying components
from suppliers that trade freely with other single-use system assemblers. Only by evaluating both performance and marketing practices can a user make the best selection decisions. Also important is the component supplier’s
reliability and delivery history.
Delaying a development program or manufacturing campaign due to an unreliable supplier can be a real issue. Delays occur when a crucial component of a single-use system has a very long lead time. Because the assembler cannot produce the system without this component, system delivery times will be dictated by the long-lead item. To avoid this pitfall, assess potential suppliers by the experience of users who have previously worked with them.
Bioprocessors will commonly use any component on hand during preclinical development. By the time a product reaches clinical testing, processors will have a much better idea of what the process looks like. By Phase III, the process
becomes “locked.” As integral components of manufacturing processes, single-use components and systems should parallel biopharmaceutical development in terms of maturity. When processes become established, so should the components.
The decision to replace a multi-use unit operation with its single-use equivalent depends on the product, the process, and the organization’s business objectives. Some reasons include the need to eliminate a processing bottleneck (e.g., cleaning and cleaning validation), process issues such as frequent contamination failures, or to realize the calculated benefits that stem from cost, time, and product quality.
Best-in-class single-use system suppliers possess expertise that customers can use to help select components and systems most suitable to their business needs. The best designs are often minimal in terms of materials and accessories. Products such as single-use bags with unused ports, tubing, and fittings, which are commonly found in off-the-shelf systems, add nothing but excess cost and waste, thus reducing the advantages of single-use systems.
The vendor’s job is to produce and ship precisely the system a bioprocessor requires. The system should arrive with the required regulatory documentation, ready to use. At one time, bioprocessors made routine modifications to single-use systems at their facilities. These days, it is best to avoid changes at a facility, particularly those that might compromise sterility.
Because the business relationship between supplier and customer may last many years, vendor qualification is crucial. Top vendors view customer interactions as opportunities to improve their products and services. Conversely, a vendor’s lack of expertise, poor communication, or reluctance to collaborate with or on behalf of the customer can limit the benefits of single-use bioprocesses.
Suppliers should be prepared to play an ongoing support role for every single-use system sale, and for the product’s entire lifecycle. End-users should ask for specific examples of a proposed vendor’s ability and willingness to provide support, process expertise, and technical advice that add value to the business relationship.
The customer-vendor relationship should be capable of feedback that results in system optimization, thus, creating significant value for both parties. Because flexibility and ease of modification are key advantages of single-use systems, end-users should seek vendors that are adept at maximizing these advantages.
Customers must assess the value associated with every aspect of vendor contact. This process need not be difficult. If the vendor consistently assists in problem-solving, improving processes, and educating their clients, then the time is well spent. Vendors should demonstrate competence in their clients’ bioprocessing niche, and be eager to point out how changes in equipment or operations will improve the process. Suppliers who do not provide this level of value should be avoided as time spent with them offers no tangible return.
Choices made when specifying single-use equipment can have cascading and lifecycle-long effects on process throughput, cost, efficiency, and risk. Adopting disposable bioprocessing by jumping on the bandwagon is not the way to go. Bioprocessors must first analyze benefits and risks for their specific situation, keeping in mind their expression system, process, product, and corporate objectives.
After determining the suitability of single use, bioprocess organizations must consider the practical aspects of “going disposable.” Examining the impact of materials, components, systems, and the vendor relationship at each stage and at every level will help customers make good decisions. Value should always be the bottom line: Does deploying a single-use device improve your process, and thereby your product? Will adoption drive key business objectives such as improved quality, shorter timelines, and cost savings in a concrete, quantifiable way? Will your relationship with your supplier be a two-way street, supportive, and mutually value-driven, or does the vendor’s responsibility end with the sale? Bioprocessors who follow the decision process outlined here are in the best position to benefit from the considerable promise of single-use systems.
About the Author
John Schmitz, director of strategy and business development, life sciences, Saint-Gobain Performance Plastics.