Integrity Testing
A critical in-process viral filtration control is the integrity test. A
filter integrity test is commonly performed to ensure the integrity of
the viral filter membrane and overall unit. Some tests can be performed
either before or after use while other tests may be destructive (e.g.
gold particle) and are therefore performed post use. Integrity tests are
commonly performed both by filter manufacturers and users. Viral filter
vendors typically provide data to support that the integrity test is
correlated to the virus retention of the device. However, some integrity
tests only provide indications of gross defects.
Typical viral filter integrity tests comprise:
- Gold Particle
- Leak
- Diffusive Air Flow
- Pressure Hold
- Liquid-Liquid Porosimeter
Each of these tests are described in detail elsewhere
(PDA 2008). The effects of the use of
nitrogen and alcohol, as opposed to air and water, on air-liquid
integrity tests are not discussed in detail in PDA TR41. The use of 30%
isopropyl alcohol will alter the solubility and diffusivity of nitrogen
and results in about an 8% reduction in diffusive gas flow, which does
not significantly impact the ability to detect defects
(Bolton, Cormier et al. 2006).
Filter vendors have described the use of binary gas filter integrity
tests. These tests utilize filters with wet pores and a mix of a fast
and slow diffusing gas. Any defects can be indicated by high flow (as
indicated by high concentration downstream) of the slow diffusing gas.
These tests are used successfully by filter manufacturers but less
commonly used by filter users (Giglia,
Caulmare et al. 2016).