If there is one operation that is ubiquitous throughout biopharmaceutical production, it is the process of making connections.
Common connection points occur between two fluid pathways or between stainless steel equipment and media bags. Hundreds of
these connections are made every day during full-scale vaccine production, accounting for many hours of labor. Disposable
aseptic connection devices that are used to connect two fluid pathways, as well as single-use, steam-in-place connectors that
allow fluids to pass from the media bag into the bioreactor and vice versa, can significantly reduce the time and number of
steps required to establish these connections. They also reduce bottlenecks in manufacturing environments.
These devices differ from traditional connection methods, such as "quick connectors" and tubing welders, in that they enable
a connection to be made in a non-controlled environment in a matter of seconds. By contrast, quick connectors require assembly
under a laminar flow hood, and tubing welders mandate the use of a welding device. It generally takes 15-to-20 minutes to
set up a laminar flow hood, plus the time required to make the actual connections. Similarly, connections using tubing welders
take approximately 5-to-10 minutes to perform, and like laminar flow hoods, they require validation and record-keeping.
These newer aseptic connection methods allow connections to be made in seconds, because they do not require the use of a laminar
flow environment or tubing welder. Single-use aseptic connectors can be supplied pre-sterilized by gamma irradiation or can
be autoclaved up to 130 °C. Disposable steam-in-place connections can be gamma irradiated, steamed up to 130 °C, or autoclaved
up to 128 °C.
The use of disposable sterilizing grade filters also plays an important role in increasing the speed and safety of egg-based
flu vaccine manufacture. Because filter capsules are available in a variety of configurations, they can be used to support
processes as they are scaled up. Ideally, these differently sized capsules contain identical filter media and hardware materials.
This helps ensure that scale-up and scale-down studies yield relevant information and minimum requalification for various
batch sizes. These filters form the core of fully-integrated single-use systems that are available pre-sterilized by the supplier.
Aside from eliminating cleaning and cleaning validation, the reduced set-up time associated with these systems is critical
to the time-sensitive demands of vaccine manufacture.
A STEP TOWARDS DISPOSABLES
The role that disposable technologies play in helping bridge the gap between egg-based methods and conventional cell-based
processes will only increase as flu pandemic concerns mount. The fact that disposable technologies are being used for many
vaccines that are currently in development reinforces the growth potential of this processing approval. Government and non-governmental
agencies are increasing efforts to advance the cause of better vaccine production methods, and many drug companies are following
suit by applying greater resources to developing new production methods and optimizing older ones. Despite the challenges
facing manufacturers, the life-saving potential and vast market that exists for vaccines will continue to drive innovation
in this critical area.
Hélène Pora is marketing director, Pall Lifes Sciences, Pall France, 3 rue des Gaudines - B.P. 5253, 78175 Saint Germain-en-Laye Cedex-France, tel 33.1.3061.32.20, .fax 22.214.171.124.57.08,
1. Smith A. A bird flu vaccine without eggs? French drug maker Sanofi and others working on a flu vaccine sans oeufs, CNN
Money, Oct. 21, 2005; http://