January 19, 2014

Best Practices in Adopting Single-Use Systems

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.


Tags: disposable bioprocess equipment, biosimilars, single use