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
AAIPharma's Karras also feels that because disposables offer faster changeovers and require less-dedicated equipment trains,
they make sense in fill–finish applications for parenteral manufacturing. "We may see a greater move toward disposable filling
needles and small product contact change parts; these are tough to track and harder to clean (thus harder to maintain in a
state of compliance)."
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
- Semidisposable products may be used for certain campaigns, reducing costs and providing the benefits of both disposable and
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
- 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
- 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, firstname.lastname@example.org
Brandon Price, PhD, is the president of Falcon Ridge Associates, Inc., Cary, NC.