GMP News No. 390
23 February 2004
New FDA Requirements on Filter Validation
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.
Our events always include the current draft
guidances. Thus, the relevant contents, e.g. the FDA Draft Guidance "Sterile Drug Products
Produced by Aseptic Processing," are also part of the following
Dr Ulrich Herber
Source: FDA Draft Guideline "Sterile Drug Products Produced by Aseptic Processing"