Drugs and the pharmaceutical sciences

316 Meltzer et al.
Advantages and Disadvantages of Bubble Point Testing
As for every test methodology, there are benefits but also limitations to the bubble point
test. This certainly is also valid for the other described integrity test methods.
Advantages
The bubble point test can be directly correlated to membrane pore size. It detects the
largest pore by forcing the liquid from such pores and creating a bulk air flow which can
be detected. It is relatively easy to perform on small to medium scale filters. It is the only
test, which can be performed on small scale filtration devices, which cannot be tested via
the diffusive flow measurement or the pressure hold test. The test duration can be brief
due to short stabilization periods and faster pressure rises. The correlation between the
bubble point and the bacteria challenge, as well as the water wetted bubble point and the
product-wetted bubble point is reliably and easy to establish. Temperature influences are
not as critical as for the diffusive flow or pressure hold test. The temperature influence
restricts itself to the surface tension of the wetting medium. Usually a temperature
increase of the air upstream volume does not have such an effect as in diffusive flow or
pressure hold testing.
Disadvantages
When performing a manual bubble point test, one has to manipulated the downstream,
i.e., filtrate side of the filter, which one wants to avoid. Furthermore, a high degree of
the test person’s subjectivity is involved, when the test is performed manually. Both
such disadvantages can be avoided, using automated integrity test machines. The
sensitivity of the bubble point test decreases with increasing filtration area, due to the
fact that the diffusive flow may complicate the bubble point’s detection. The use of
the bubble point becomes more critical with smaller pore size rated filter membranes.
The bubble point values of such pore size ratings may exceed the maximum differential
pressure that such membranes can sustain, or may be above the allowable operating
pressure of the filter. Bubble point measurement does not take the membrane thickness
into account. This can be critical for the retentive capabilities of such membranes (Pall
and Kirnbauer, 1978).
DIFFUSIVE FLOW TEST
Fick’s Law of Diffusion
The diffusive airflow is an expression of Fick’s law of diffusion (Reti, 1977;
Waibel et al., 1996; Jornitz et al., 1998):
N ¼ DHðP1 P2Þ =L
where N is the permeation rate, D is diffusivity of the gas in the liquid, H is solubility
coefficient of gas in the liquid, L is the membrane thickness; (P 1 – P 2) is the differential
pressure; is total porosity.
The diffusive flow permeates the pores of all sizes, large and small. It should be
noted that the sizes of the pores do not enter into the equation; in their aggregate they
comprise L, the thickness of the liquid layer, the membrane being some 80% porous. The
critical measurement of a flaw is the thickness of the liquid layer. Therefore, a flaw or an
oversized pore would reflect the thinning of the liquid layer due to the elevated test