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A validatible porosimetric technique for verifying the integrity of virus-retentive membranes
1Advanced Separations Research Department, Millipore Corporation, Bedford MA 01730, USA.
Abstract:
The verification of membrane integrity for filtration processes specifically designed for the removal of adventitious virus from biotherapeutics is of the utmost importance to both biomanufacturers and regulatory agencies. Although conventional bubble-point and air-diffusion tests are widely accepted for integrity testing of bacteria-retentive membranes, these tests have severe limitations in their ability to assess the integrity of virus-retentive membranes. A novel membrane integrity test based upon liquid-liquid porosimetric principles (CorrTest) has been specifically designed to correlate and predict the virus retention capabilities of Viresolve virus removing membranes. To optimize test sensitivity for both Viresolve/70 and Viresolve/180 membrane types, two distinct porosimetric correlations at different transmembrane pressures have been developed. Based upon an 80% prediction interval, an integrity test performed at either test pressure can reliably predict the ability of Viresolve membranes to remove the bacteriophage phi X174 to within 0.4 log removal value (LRV) units. To maintain test sensitivity and provide greater flexibility for conducting the liquid-liquid intrusion integrity test, appropriate pressure- and temperature-correction equations have been established. The two immiscible fluids employed in the developed technology are easily flushed from the membrane structure and are generally regarded as acceptable, non-toxic reagents for pharmaceutical applications. Consequently, the CorrTest integrity test can reliably and non-destructively measure both pre- and post-use membrane integrity to verify virus removal performance with the Viresolve module.
Insights
A new liquid-liquid porosimetry test (CorrTest) reliably verifies virus removal in biotherapeutic filtration membranes. This method accurately predicts membrane integrity and virus retention capabilities, ensuring product safety.
Area of Science:
- Biopharmaceutical Manufacturing
- Filtration Technology
- Membrane Science
Background:
- Membrane integrity testing is critical for adventitious virus removal in biotherapeutics.
- Conventional tests (bubble-point, air-diffusion) are inadequate for virus-retentive membranes.
- Ensuring membrane integrity is vital for regulatory compliance and patient safety.
Purpose of the Study:
- To introduce and validate a novel liquid-liquid porosimetry test (CorrTest) for virus-retentive membranes.
- To correlate CorrTest results with the virus removal performance of Viresolve membranes.
- To establish optimized testing parameters for different Viresolve membrane types.
Main Methods:
- Development of a liquid-liquid porosimetric test (CorrTest) using immiscible fluids.
- Optimization of transmembrane pressures for Viresolve/70 and Viresolve/180 membranes.
- Establishment of pressure- and temperature-correction equations for the integrity test.
Main Results:
- CorrTest reliably predicts virus removal (phi X174) to within 0.4 LRV units with 80% prediction interval.
- Two distinct porosimetric correlations were developed for different Viresolve membrane types.
- The test demonstrated flexibility and reliability across different conditions.
Conclusions:
- CorrTest provides a reliable, non-destructive method for verifying virus removal performance of Viresolve membranes.
- The developed integrity test ensures both pre- and post-use membrane integrity.
- This technology enhances biomanufacturing safety and regulatory confidence.