Single-use filter capsules and integrated systems with disposable containers, tubing, and connectors are used throughout bioprocessing
operations. Disposable unit operations are employed for a variety of direct-flow filtration operations including depth filtration,
prefiltration, sterilizing, and virus filtration, as well as for chromatographic separation applications, including contaminant
removal (DNA, host cell proteins, viruses, endotoxins) and capture (plasmids, viruses, proteins).
These disposable systems provide both upstream and downstream benefits. Stainless steel is expensive and in limited supply.
Its use can be reduced or eliminated completely with a disposable system, resulting in cost savings and faster installation.
Furthermore, hard-piped systems require cleaning and cleaning validation, both of which can be greatly reduced or eliminated
by employing a single-use system. Cleaning validation, in particular, can require considerable effort and is often an important
driver for the selection of a single-use system over a hard-piped system. Disposable systems only require initial cleaning
validation, and ongoing validation activities are typically limited to operator training and routine monitoring. Additional
validation testing is required when there is a change in product, process, procedure, or equipment.
Steam-in-place (SIP) sterilization, required for many traditional systems, requires process time as well as validation efforts.
Some operations require one or more shifts to assemble, steam, and cool down process equipment. Errors in processing can create
even longer delays, making disposable systems — presterilized by gamma irradiation and ready to use immediately out of box
— a time saver.
Bioprocess operations also involve gas stream handling. There are many applications for disposables in gas filtration.
Membrane SelectionMembranes used for sterile filtration of gas streams are typically made of hydrophobic materials, such as polytetrafluoroethylene
(PTFE). Hydrophobic membranes, which do not spontaneously wet with water, are desirable in gas applications because hydrophilic
filters can become wet and clogged.
While PTFE is often used for vent and gas filtration applications in hard-piped systems, it cannot be subjected to the level
of gamma irradiation required for sterilization — typically a 25 kGy minimum dose. However, hydrophobic polyvinylidenefluoride
(PVDF) filter capsules, which can be gamma irradiated, are available for gas applications.
Table 1: Time required for use of a vent filter in disposable capsule and stainless steel housing
Tank Vent Applications Disposable systems often include flexible containers (typically, fluid contact is with polyethylene) that replace stainless
steel tanks in hard-piped operations, as well as smaller, rigid containers or carboys. A 0.2 mm sterilizing-grade vent filter
is typically used to fill and empty rigid containers. Since disposable containers (bags) are empty before they are filled,
a vent filter is not required — a further cost savings and operation simplification.
For applications that require an SIP-sterilized stainless steel tank, a hybrid system incorporating a capsule filter with
a PTFE membrane can be used. The filter capsule housing is constructed of a specially engineered plastic (polyetherimide)
that can be subjected to multiple SIP cycles.
The use of a capsule can reduce capital costs associated with stainless steel filter housings, as well as the labor required
for filter assembly. Table 1 illustrates the steps required to assemble a gas filter on a tank. The overall time savings when
a capsule is used is 3.3 hours. Given a labor rate of $75 per hour, this is a cost reduction of approximately $250 per change-out.
If there are 500 filters used per year, the cost reduction is approximately $125,000. Approximately 42 40-hour weeks of process
time is also saved.