The Proper Use of 47-mm Flat Disc Filters in Filter Sizing Studies - Why staining is crucial in flow decay studies. - BioPharm International

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The Proper Use of 47-mm Flat Disc Filters in Filter Sizing Studies
Why staining is crucial in flow decay studies.


BioPharm International
Volume 22, Issue 9

USING PREASSEMBLED 47-MM FLAT DISC FILTERS


Figure 3. Disposable test filter with 48-mm diameter or 18.4 cm2 filtration area
A pre-assembled, disposable unit containing a "47-mm" diameter flat disc filter is available. The pre-assembly offers the attractive advantage of disposability. It is likely that users assume that its EFA is that of a 47-mm disc. However, the membrane used for these devices is actually 50 mm in diameter, a common filter size. The staining technique using acridine yellow reveals its effective diameter to be 48 mm (Figure 3), which means it has an EFA of 18.4 cm2 . Its throughput, however, is being ascribed to that of a smaller EFA—the assumed EFA of the 47-mm disc ordinarily used, namely, 17.4 cm2 . The discrepancy in EFA is even larger if the stained 13.2 cm2 area of an actual 47-mm diameter filter disc is used in the comparison (Figure 4).


Figure 4. Typical 47-mm test filter used in a stainless steel holder
The flow emanating from the 18.4 cm2 EFA of the 48-mm diameter disc filter may mistakenly be ascribed to the actual 13.2 cm2 EFA of an O-ring sealed 47-mm diameter filter. If so, the extrapolation exercise will lead to a numerical multiplier that will indicate that a smaller EFA is needed for processing than would result if the multiplier were based on the smaller (stained) value of 13.2 cm2 . The result will be a low EFA that is insufficient for batch processing needs. This may cause a mid-process filter change-out, which the use of the flat disc filter sizing aims to avoid.

INDUSTRY USE OF STAINING TECHNIQUES

Even though the use of 47-mm flat disc filters is widespread in flow decline work, the operational details of these studies may differ among users, because the method is not standardized. It is not known what EFA values the many users of 47-mm disc filters actually use in their sizing protocols, because these numbers are seldom reported. Measuring filter EFAs by acridine yellow or other staining does not seem to be a widely discussed or published procedure. Clearly, its application to the use of 47-mm discs in filter sizing studies is not universal.

It is recommended that the staining technique be used to determine the exact diameter of the disc being used, so that its actual EFA can be calculated from that diameter. This practice would minimize the risk of underestimating the EFA needed for processing a batch operation, and reduce the possibility of needing mid-process filter replacements.

CONFIRMATORY ASSESSMENTS

Even if staining techniques are used to improve the accuracy of filter sizing studies, the extrapolations from 47-mm flat disc filters to 10-inch cartridges are beset by the uncertainties derived from suspended matter. At best, flow decline assessments based on 47-mm flat disc filters constitute indicator trials.

Therefore, it is best to follow up these indicator trials with verification trials using larger-area pleated filter devices, (commonly 1.5 ft2 ).7,8 Indeed, when costly drug preparations are involved and properly defined filtration area scaling is needed, the use of full-scale filters in assurance trials is recommended. Full-scale trials ensure that the filtration system will be large enough to filter the required batch volume without being oversized, thus minimizing product yield losses.


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