In this context, it is of considerable
interest that the FDA Draft Guideline "Sterile Products
Produced by Aseptic Processing" published in 2003 defines new requirements
on the use of sterilising filters and their validation. These result among others from a stricter definition of
sterilising filters.
The guideline version from 1987, which is still in force, defines a
sterilising filter as "a filter which, when challenged with the
microorganism Pseudomonas diminuta [now
called: Brevundimonas diminuta], at a minimum concentration of 107
organisms per cm2
of filter surface, will produce a sterile effluent."
In contrast, last year's draft guideline defines a sterilising grade filter
as "a filter that, when appropriately validated, will remove all
microorganisms from a fluid stream, producing a sterile effluent."
Here, the draft shifts the emphasis from the model bacterium Brevundimonas
diminuta to microorganisms isolated from bioburden. The draft
text even points to this fact explicitly.
This confronts the pharmaceutical industry with completely new
challenges. On the one hand, the industry is glad to have Brevundimonas
diminuta, a test microorganism that can be cultivated easily and in a
controlled way and that has been used for filter validation so far. On the
other hand, those microorganisms that are critical for filtration and that
might be isolated from bioburden will change their properties when
cultivated to an adequate concentration and thus will not represent the
original worst case any more.
Nevertheless one has to ask the question in how far Brevundimonas
diminuta reflects the situation in the respective processes. It is to
be expected that in the future one will have to give a well-founded rationale
for using this microorganism in filter validation depending on the product
and on the process.
This is why the draft contains the call for the trending of bioburden
before filtration.
Two further interesting points mentioned in the draft are the use of
filters for only one batch of product and filtration by means of two
sterilising filters arranged in series. These innovations will also force
many users to have a close look at their filtration processes.
