Biomedical Engineering Reference
In-Depth Information
operators to make sterile connections between these presterilized disposable
systems and stainless steel bioreactors for aseptic transfer of media.
Similarly, disposable tubing assemblies may be used to transfer inocu-
lum between bioreactors using either a peristaltic pump or headspace
pressure. Such transfer lines can reduce the number of reusable valves
required for transfer and eliminate problem areas for CIP and SIP valida-
tion. Terminating each presterilized transfer line with a disposable SIP con-
nector provides sterility assurance equal to that of traditional fixed piping
at lower capital costs.
As disposable bioreactors are beginning to appear, companies are using
them for both seed trains and small-scale production. These systems are
connected to a cell culture media storage bag (either by aseptic welding or
aseptic connectors such as Colder Products' AseptiQuik
®
) using flexible tub-
ing. Flexible tubing with aseptic connectors is used as transfer lines between
each reactor in the process.
There are also instances when liquids are transferred from a higher-ISO
environment to a lower-ISO environment, and assurance is needed that
it does not result in cross-contamination; to ensure this, a conduit can be
installed in the walls connecting the two areas, with the cleaner room having
a higher pressure. A presterilized tube is then inserted from the lower ISO
class side to the higher ISO class side and connected to the vessels between
which the liquid is transferred by a peristaltic pump; upon completion of
transfer, the tube is pulled into the higher-ISO class area and discarded. This
method allows connection between downstream and upstream areas with-
out the risk of transferring any contamination to a lower-ISO class area such
as a downstream area.
Tubing
Flexible tubes are an essential part of all disposable systems and are sub-
ject to the safety concerns described in an earlier chapter with regard to
the leachables and extractables. Several attributes of flexible tubing require
evaluation such as their heat resistance, operating temperature range, chemi-
cal resistance, color, density, shore hardness, flexibility, elasticity, surface
smoothness, mechanical stability, abrasion resistance, gas permeability, vis-
ible and ultraviolet (UV) light sensitivity, composition of layers, weldability,
sealability, and sterilizability by gamma radiation or in an autoclave.
All tubes used in bioprocessing conform to USP Class VI classification,
FDA 21 CFR 177.2600, and EP 3A Sanitary Standard. For cGMP manufactur-
ing, these are classified as bulk pharmaceuticals. The most common materi-
als are used for the tubing include
