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:
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).