Applications of re-use in liquid service
In addition to process conditions, the risk of re-use, including the criticality of the filtration process, should be assessed
for each application. Some processes may be considered less critical than others and may not require the highest levels of
sterilization assurance. Such processes use sterilizing-grade filters for particulate and/or bioburden control but do not
claim sterility of the effluent. In these applications, a user may consider re-use of those filters more aggressively. Other
processes require a reasonable level of sterilization assurance, suggesting greater risk in re-use. The most critical applications
require the highest levels of sterilization assurance achievable and are often done by combining sterilizing-grade filters
with effluent from bioburden control filters and, in some cases, use of serial filtration with double 0.2 μm, 0.2 μm to 0.1
μm, or double 0.1 μm sterilizing-grade filters. With such redundancy, there may be a balance between re-use of upstream filters
and single use of final filters, or re-purposing of prior batch final filters as upstream filters for subsequent batches.
In each case, any perceived economic advantage to re-use of the filters should be weighed against the risk of failure, which
can be caused by premature plugging, loss of integrity, increased leachable contamination, or bacterial penetration.
Examples of applications for sterilizing-grade filters used as either nonsterilizing particle or bioburden control filters
or as sterilizing filters, or both, include filtration of:
- Fermenter or cell-culture bioreactor culture media
- Fermenter or bioreactor additives
- Serum for cell culture media
- Process water
- Chromatography buffers
- Diafiltration buffers
- Solvents
- Disinfectants
- Intermediate product hold
- Nonsterile active pharmaceutical ingredients (APIs)
- Final bulk sterile APIs
- Sterile culture media for aseptic filling validation
- Terminally sterilized injectables
- Aseptically filled sterile injectables
- Aseptically filled sterile topicals and ophthalmics.
Each of these applications has its own requirements and risk factors for bioburden control and/or sterilizing filtration.
In addition to the conditions of re-use (rinsing, cleaning, resterilization, drying), each application for re-use should be
considered independently based on its criticality for sterilization assurance and any other influence on the filtered effluent.
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