Time savings and flexibility
Perhaps the biggest benefit to be gained by implementing a single-use filling line is the savings in time gained by eliminating
the cleaning and validation steps. Nathan Beyeler, process engineer at Merck Sharp and Dohme, cited the decrease in changeover
time as being an important factor in the decision to implement a single-use fill line. "Market pressure and good business
sense dictate that we need to use our filling assets for manufacturing product, not for getting ready to manufacture product,"
he says. "The need to get the most product out of the process is increasingly critical to the business. That said, the paradigm
of a few blockbuster vaccines allowing for long campaign operation and few product-to-product changeovers is under pressure
as products portfolios become more focused on multiple (lower annual volume) biologics. This means that a production facility
is faced with the challenge of more frequently changing the facility and equipment over to process different products. The
reduction of changeover time has therefore become one of the primary influences in our decision to implement single-use technology
for current filling facilities."
Indeed, Beyeler reported a reduction in changeover time from 16 hours to two hours when switching to a single-use line. In
addition, a recent report produced by authors from Millipore demonstrated a similar reduction in total processing time, from
19 hours to 1.5 hours, when switching from a stainless system to a single-use system (3).
On average, biotech companies outsource 81% of their fill-and-finish requirements. Biotech and pharmaceutical companies with
in-house capabilities outsource 40% of their requirements (4). This means that CMOs are handling a large variety of filling
operations, and can benefit from the flexibility afforded by single-use systems to handle multiple products. Althea's Duffy
notes, "Stainless equipment requirements vary from client to client. When not in use, these must be stored and when they
are placed back into service must be cleaned again." The ability to quickly reconfigure the line to accommodate different
size runs, different biosafety requirements, or different product containers adds greater flexibility to the filling operation.
Evolving equipment requirements
It is often the case that equipment evolves to fill an unmet need, and this is the case with disposables for fill-finish.
At its simplest, a filling line can consist of a product container bag, a pump and a filling needle, all connected by plastic
tubing. Disposable filling lines, suitable for smaller-scale fills are available as "plug-and-play" systems, where the line
comes fully assembled and presterilized, ready to be used. Such systems are adequate for small-scale fills, but do not operate
at high speed and may not be suitable for high-viscosity products.
Pump technology has improved to the point where disposable filling lines are feasible, but further improvements are possible.
Peristaltic pumps have only recently achieved the accuracy required for fill applications. They are still limited by speed,
and the tubing that runs through the pump is subject to degradation and deformation over time. Plastic, disposable, rolling-diaphragm
pumps are currently available and offer an alternative. However, more rigorous applications requiring high volume, high speed,
or high pressure, may be places where stainless steel continues to be the better choice.
There is plenty of room for new technology to adapt to these challenges. Beyeler says, "At the moment, I think what has been
offered is that which is the easiest and least risky to develop from the equipment vendors, a single-use version of what is
already on the market. Some equipment suppliers for upstream processing have innovated beyond the 'also in single-use' type
of approach and have developed specifically new technologies. As vendors increasingly see the potential competitive advantages
for single-use technologies I am looking for them to specifically invest R&D in developing innovative filling technologies."
The requirements for speed and cost-effectiveness in multiproduct manufacturing will drive the development of new disposable
technologies for fill-finish operations.
References
1. Biotechnology Medicines in Development. PhRMA (September, 2011).
2. M. Hoffman, "Bioprocessing and Sterile Manufacturing" supplement to Pharm. Tech. 35, s6 (2011).
3. E. Jenness and V. Gupta, supplement to BioProcess Int.
9 (s2), 22–25 (2011).
4. J. Hartingan and W. Downey, GEN
31(10), (2011).
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