Disposable Filling Lines in Fill–Finish

According to Millipore's Robert Blanck, disposable filling systems will change the way fill–finish is done. They will allow faster filling-line implementation, easier validation, and improved sterility. The disposal of product contact surfaces will reduce downtime between filling campaigns and provide added product safety. The operator intervention in aseptic connections and components is eliminated up to the tip of the filling needle. This is particularly relevant for filling cytotoxic or biohazard components. Such disposable components can be installed in 15 minutes, compared with conventional filling operations, where set-up times may exceed eight hours. For R&D or clinical-fill operations requiring the fast development of products, or production "fill-and-finish" operations requiring improved filling efficiency and enhanced product safety, disposable filling technologies are expected to expand.

Fill–finish for Non-sterile Environments

Reduced Operator Training and Oversight

Disposables may permit lower staffing and training requirements in biopharmaceutical operations. Pall Life Sciences' Pora believes that the risk to expensive production batches due to operator errors can be reduced by decreasing the number of connection points associated with the use of sterile connection technology.

Simplified Biopharmaceutical Cleanroom and Facility Design

As disposable technologies expand, they will have a greater impact on facility planning and design. Cleanroom operations for biopharmaceutical companies and contract manufacturers must manage contamination, yet maximize operations such as fill and finish. This becomes a design issue and the use of disposables must be part of facilities design considerations today. Whether for final product storage, sterile formulation, or mixing, barrier isolator technology that limits personnel interaction with exposed product must be considered.

Producing Otherwise Uneconomical Drug Candidates

The economics of biopharmaceutical drug candidates that appear to be difficult to commercialize may change and disposables may permit the further development and possible commercial-scale production of such drugs. Disposables may permit the development of such "marginal" biologics because disposables work well at smaller batch sizes.

Other Areas of Future Opportunity

Some other effects of using disposables may include:

• Reducing water for injection (WFI) requirements, permitting production in areas where costly WFI usage may impact decisions for building facilities.
• Pasteurization of products at the ≥500 L scale may be conducted in the future, or potentially outsourced. This is not currently being done.
• Semidisposable products may be used for certain campaigns, reducing costs and providing the benefits of both disposable and fixed systems.

STAYING ON TRACK

To achieve their maximum potential, the work on R&D and developments for disposables continues. Some of the areas that require additional work may include:

• Addressing leachables and extractables from a manufacturing, regulatory, and analytical perspective.
• Identifying ways to reduce costs and enhance the overall value of disposables to increase adoption at the process development stage.
• Improving disposable systems to ensure scalability from process development to large-scale manufacturing for all products, including buffers, bags, reactors, tank liners, etc.
• Creating bag systems with options for easy customization. The cost and time-lag associated with customization is high. Given the infinite variety of configurations at a manufacturing facility, bags need to be easier to customize.
• Establishing standards for bags and connectors and reducing concerns regarding reliance on single-source vendors.
• Increasing product safety by reducing risks of rupture. Fixed tanks can have rupture controllers. Such products are being developed and marketed for disposables. These may be needed to enhance the robustness of existing disposables and broaden market acceptance.
• Creating systems that can help address "zero failure tolerance" situations. Certain applications cannot tolerate failure (e.g., human pathogens, some cytotoxics).
• Moving from a "batch mentality." Many safety concerns in the biopharmaceutical industry stem from a focus on batch production. Several innovations in the pharmaceutical industry came from the food industry, which has moved away from batch production. The pharmaceutical industry may need to move in this direction too.
• Reducing waste solvents in biopharmaceutical manufacturing is a factor in disposable equipment usage. Products should be developed that support these environmental considerations.
• Improving disposable downstream technologies. For example, one technology uses a rotary drum filter for laboratory applications. This uses media that may not suit all applications. Filtration media suppliers will need to expand offerings to meet current and future needs.
• Membrane chromatography, currently in use by many in the upstream analytical phases, has benefits over columns, including good flow rates, high capacities, and newer membranes that have produced sharper resolutions. These need to be further developed.

As single-use components in biopharmaceutical manufacturing processes continue to prove their economic, operational, environmental, and regulatory mettle, we will see greater diversification and increased usage in larger applications. Users and vendors will continue to explore the potential for disposables over the next 10 years. But it seems clear that the products are accepted as effective, useful tools to be considered within each manufacturer's system. They are seen as alternatives, for which economic models and end-user creativity will drive future applications.

Eric S. Langer is the president and managing partner of BioPlan Associates, Inc., Rockville, MD, 301.921.9074, elanger@bioplanassociates.com

Brandon Price, PhD, is the president of Falcon Ridge Associates, Inc., Cary, NC.