Disposable Processing Gains You a Competitive Edge: Enhancing Manufacturing Capacity with Disposable Filters, Connectors, and Membrane Chromatography

The traditional sequential mode of "design-build-validate" project management, the mainstay of the last century, is now a suicidal strategy.
Oct 01, 2003
Volume 16, Issue 10

The biotechnology and pharmaceutical industries have some overriding concerns, namely regulatory and compliance issues, insufficient manufacturing capacity, and the economic challenges of producing niche drugs and therapies. Disposable systems can favorably impact the last item and provide some relief to the others as well.

Disposable systems improve the economic feasibility of producing niche drugs by enabling faster and cost-effective product changeovers. Manufacturing capacity is gained by simplifying scale up, eliminating process steps, and maximizing throughput. Because these systems are sterile and remain sterile, positive regulatory reviews are facilitated. Any technology this good surely deserves a closer look, and that is what follows.

Manufacturing costs generally make up 18% to 20% of a pharmaceutical company's operating costs (1). Maximizing productivity from manufacturing assets is critical in terms of maintaining a sustainable competitive advantage. This requires fast turnaround and cleaning procedures, especially when operating multi-product facilities and minimizing shutdown time for modification and maintenance. Of course, optimizing product recovery presents an additional opportunity to favorably impact costs. We will show that to maximize overall process efficiency, a holistic approach is needed from the outset, whereby downstream processing is directly matched with bioreactor performance.

Figure 1. A single-use aseptic connector between flexible tubings requires no laminar flow hood or specialized equipment.
Where Are Disposables Used Today? A wide range of biopharmaceuticals such as vaccines, monoclonal antibodies, and patient-specific treatments are already being made with disposable products in certain filtration, purification, and separation applications. Small-scale tangential flow filters (TFF), direct-flow filters (DFF) of all sizes, and membrane chromatography units are available and adapted for single-use systems. In addition, capsules can be bundled with bioprocessing bags, tubing, valves or clamps, and connection devices to form fully- integrated single-use filtration systems. Disposable filters can also be manifolded together to maximize processing capacity.

Disposable products are available in a range of sizes, making them ideal for use in every stage of drug development. Single-use products composed of the same materials of construction minimize re-validation requirements when a new process is scaled up.

The tubing used in these systems is usually clear and the capsule filters are typically designed with clear or translucent housings. This design feature allows operators to observe fluid levels and flow, as well as to detect fluid discoloration and air pockets, thereby enabling problems to be identified immediately and isolated from the rest of the process (if required).

Who Stands to Benefit? High-growth biotechnology companies, large pharmaceutical companies, and contract manufacturers stand to gain significant speed, safety, and cost-saving benefits by using disposable systems. A disposable processing approach is especially cost-effective and efficient for start-up biotech companies that do not have hard-piped processing systems already in place. As many biotech start-ups have not fully defined their operating parameters, single-use products can save them from making premature investments in capital equipment.

When funding is scarce, single-use products can provide an effective cost- and labor-saving strategy. Additionally, the timeliness of making a batch for clinical trials can be crucial for the development timeline, and disposable systems can be assembled much faster that a comparable hard-piped system.

Table 1. Comparison of set-up times between a single-use cartridge filter and a stainless steel housing.
Large pharmaceutical companies have a different motive for incorporating disposable systems into their drug processes. Cost, capacity, and compliance issues are the deciding factors. The time and labor spent to dismantle, clean, and re-sterilize stainless steel products is a considerable cost to large pharmaceutical companies. The time required to meet FDA's increasing calls for documentation of cleaning and cleaning validation procedures can be significantly reduced. Expansion of an existing process can be more cost-effective and faster if disposable system components are used. A further benefit for pharmaceutical companies is that it is possible to change an existing filtration process to a disposable process in order to reap the benefits of reduced cleaning, validation, and assembly requirements. This is a viable option since the same materials of construction are used for the filters formerly in stainless steel housings. As a result, extensive re-validation is generally not required.

Single-use products help contract manufacturers reduce cross-contamination risks, upfront equipment costs, space requirements, and complicated cleaning and cleaning validation procedures. This increases profit margin, enhances safety, and reduces compliance concerns, enabling them to be more competitive in a growing market.

The benefits of disposable processing can be profound. Disposable processing could increase the profitability of niche therapies and drugs, thereby making treatments for rare or unusual illnesses and diseases more readily available.

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