New FDA Requirements on Filter Validation

GMP News No. 390

23 February 2004

NewFDA Requirements on Filter Validation

Filtration is still considered to be the most unsafesterilisation method used in pharmaceutical processes. Therefore, it isunder close observation both within the pharmaceutical companies and bythe supervisory authorities.

In this context, it is of considerableinterest that the FDA Draft Guideline "Sterile ProductsProduced by Aseptic Processing" published in 2003 defines new requirementson the use of sterilising filters and their validation. These result among others from a stricter definition ofsterilising filters.

The guideline version from 1987, which is still in force, defines asterilising filter as "a filter which, when challenged with themicroorganism Pseudomonas diminuta [nowcalled: Brevundimonas diminuta], at a minimum concentration of 107organisms per cm2of filter surface, will produce a sterile effluent."

In contrast, last year's draft guideline defines a sterilising grade filteras "a filter that, when appropriately validated, will remove allmicroorganisms from a fluid stream, producing a sterile effluent."

Here, the draft shifts the emphasis from the model bacterium Brevundimonasdiminuta to microorganisms isolated from bioburden. The drafttext even points to this fact explicitly. 

This confronts the pharmaceutical industry with completely newchallenges. On the one hand, the industry is glad to have Brevundimonasdiminuta, a test microorganism that can be cultivated easily and in acontrolled way and that has been used for filter validation so far. On theother hand, those microorganisms that are critical for filtration and thatmight be isolated from bioburden will change their properties whencultivated to an adequate concentration and thus will not represent theoriginal worst case any more.

Nevertheless one has to ask the question in how far Brevundimonasdiminuta reflects the situation in the respective processes. It is tobe expected that in the future one will have to give a well-founded rationalefor using this microorganism in filter validation depending on the productand on the process.

This is why the draft contains the call for the trending of bioburdenbefore filtration.

Two further interesting points mentioned in the draft are the use offilters for only one batch of product and filtration by means of twosterilising filters arranged in series. These innovations will also forcemany users to have a close look at their filtration processes.  

Dr Ulrich Herber

Source: FDA Draft Guideline "SterileDrug Products Produced by Aseptic Processing"


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