For gamma presterilised single-use systems, where the filter manufacturer has already validated that gamma irradiation does
not compromise filter integrity, the risk of filter damage during sterilisation appears even more remote. The primary risk
of product loss due to integrity failure of gamma-sterilised filters in a single-use filtration system would most probably
be from filter damage incurred after sterilisation, for instance, during shipping, handling, and system installation. The
lower risk of filter damage and product loss in this case may be further ameliorated if the process is a bulk filtration and,
in the event of post-use filter integrity failure, refiltration is qualified and documented in the SOP.
Alternatively, a redundant filtration scheme may be used to minimise risk of product loss in the event of a filter integrity
failure discovered only postuse. Finally, the cost of the drug product or process fluid may be sufficiently low that an infrequent
disposal is considered inconsequential (e.g., buffers and inexpensive small-molecule drug products).
Although the potential for product loss due to filter nonintegrity may be very low, the effect can be great if the product
is expensive and cannot be refiltered, such as with biopharmaceuticals and vaccines. Avoiding catastrophic batch loss, as
well as possible product shortages, is a justifiable reason to perform pre-use, poststerilisation filter-integrity testing
on single-use filtration systems.
Another advantage of single-use systems compared with stainless steel is that versatile system designs can readily accommodate
the necessary flushing to prewet filters before the pre-use integrity test. Stainless-steel tanks for the supply and collection
of wetting liquid, which must be cleaned and steam sterilised in place, or autoclaved and aseptically connected, can be easily
replaced with preassembled flush supply and collection bags that are gamma sterilised in place. Sterilisation validation is
provided by the supplier. Where product is used to prewet the filter for integrity testing, even the side-flush collection
bag can be eliminated in some cases. Additional schemes are also available to enable flushing the filter to reduce leachables
and any particles that may be present on the downstream side of the filter, along with wetting them for pre-use integrity
testing. Filters can be flushed with product to wet the filter, reducing filter leachables and potential particles while recovering
the product to maximise yield.
Jerold Martin is senior vice-president of Global Scientific Affairs at Pall Life Sciences, Port Washington, NY (US), and chairman of the
Board and Technology Committee at Bio-Process Systems Alliance. Tel. +1 516.801.9086 jerold_martin@pall.com
.
References
1. FDA, Sterile Drug Products Produced by Aseptic Processing —Current Good Manufacturing Practice (Rockville, MD, Sept. 2004).
2. EC, Guide to GMP, Annex I — Manufacture of Sterile Medicinal Products (Brussels, Belgium, revised Feb. 2008, effective Mar. 2009).
3. J. Wood, presentation at the IBC Single-Use Conference (San Francisco, CA, Jun. 4–6, 2012).
4. J. Martin, presentation at the IBC Single-Use Conference (San Francisco, CA, Jun. 4–6, 2012).
5. E. Mahajan et al., Pharmaceutical Engineering,
32 (3), 54–56 (2012).
6. K. Lear, presentation at the IBC Single-Use Conference (San Francisco, CA, Jun. 4–6, 2012).
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