Re-use of sterilizing grade filters - Really ?!

Recently a question about the re-use of sterilizing grade filters came up again. The question, can it be done and what are the regulators thinking about it ? Well, it certainly depends on the application, in very few application sterilizing grade filters are re-used. These are for examples large volume parenterals, which are terminally sterilized after filtration, API, which often do not claim sterility, and in instances blow-fill-seal application, which though are multi-batch applications, not necessarily multi-use. In any case, running costs are driven down by the re-use of a $200 filter, but is it really worthwhile ? This certainly will need to be answered by the filter end-user.
Personally, I hope I will not receive an injection of a drug product which run through a re-used sterilizing grade filter. Why? Because, not only do I not kow how much the performance might have been influenced by multiple steam sterilizations, cleaning cycles, possible pressure pulsations etc., but has all previous filtration residue and debris been removed ? Is that cleaning cycle validated and how thorough is it ? Has the polymeric structure been compromised and sheds particulates ? Are the support fleeces lost its stabilizers and become brittle ?
A multitude of questions, which require answers because one wants to re-use a sterilizing grade filter, one better does understand the possible consequences. Again, is all the validation work worthwhile, the supposedly savings ?
Now are sterilizing grade filter designed to withstand multiple uses. Yes, current filter designs can cope with a lot of stresses, but one should not believe that these are withstanding any abuse. Manufacturers put processing or operating limits on their filters for reasons. These need to be observed !
Again, sterilizing grade filters can be, for very specific applications, re-used. In the majority of applications, though, don't !

Science versus Sales...Why ?!?

The unfortunate truth is, there are many "filtration scientists" out there who care more about the top line than supporting the industry using filtration.
Here a prime example from a PDA Interest Group Meeting (also supposed to science based):
"XYZ company tested a variety of its own and competitors’ filters, and Mr. X offered the following suggestions for addressing the surface tension issue. Consider, he said:
a tighter filter (0.1 µm if possible, he said)
serial (bioburden reduction) filtration
double sterilizing grade filtration
filtration prior to product formulation"


Three suggestions, which just will increase the sales of the filter vendors. How about showing the surface tension results, determining why surface tension increase the risk of microbial penetration, determine the critical process parameters and list them. The filtration industry should use meetings like this to synchronize their data and find robust solutions to filtration problems. A similar, one voice, approach requires to be found for other discussion points. For example, post-sterilization integrity testing causes an elevated risk. Why though are some vendors in denial, because they offer a magic test kit, which will solve all the associated problems, including meeting sales target. For me, just a disturbing sight.

Rather take this approach: http://www.americanpharmaceuticalreview.com/images/article/9_Jornitz.pdf

The myth of the "healing filter"

A 2007 Q&A by the EMA used the supposedly blocking of a flaw or defect within the filter membrane of a sterilizing grade filter as a reason for the need of a pre-use/post-sterilization integrity test. The filter, being damaged during steam sterilization, would pass the post-use integrity test, due to the fact that the filter flaw is blocked by contaminants. This, "healed" filter would not be detected by the current integrity tests, like diffusion flow or Bubble Point. Questions posted to the agency has not revealed any evidence or data that this truly happened. Filter vendors stated so far that they have not seen such occurrence.
To be sure that this does not happened, tests are performed now with 10" filter elements used in production processes. Around 30 tests of slightly failed filters utilizing different blocking grade of up to 95% showed that such heavily blocked filters will still fail the integrity test. The tests so far have not shown that a filter will "heal" during filtration and post-use testing will be able to find failed filters.
More tests like these are needed to stop speculative regulatory enforcement as it happens with Annex I, paragraph 113 and the 2007 Q&A.

New PES sterilizing filter from Cuno

Yet another sterilizing grade filter with a PES (Polyethersulfon) membrane has been launched. Cuno, as all other filter manufacturer, claim it is the best performing filter. It probably has a great performance due to the asymmetric membrane structure of PES, but also a unique pleat structure, which increases the filter area within the same 10" filter dimension.
The question one has to post, after the launch of now 20 new sterilizing grade membrane filters, 19 of them with a PES membrane and 1 with a hybrid structure of PES/PVDF, is PES becomeing the standard membrane polymer ? Probably, drift to PES will be prevalent as the membrane material is robust and can be modified easily. However, different membrane polymers are needed for different applications.

Pre-use/post-sterilization integrity testing of sterilizing filter

The topic of pre-use/post-sterilization integrity testing of sterilizing grade filters has become a hot button due to misinterpretation of EU Annex I, paragraph 113 and sporadic, unnecessary enforcement of such test. The test should be applied only after risk assessment, as the manipulation of the sterile downstream side due to the applied integrity test after sterilization can elevate the risk of the filtrate side. Risk assessment by the filter users is the right choice, not generic enforcement.
Check for two papers on the topic in American Pharmaceutical Review and Pharma.