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A J DiLeo

Publications and source records attributed to A J DiLeo.

5 recordsLinked to original sources
PubMed1996

A validatible porosimetric technique for verifying the integrity of virus-retentive membranes.

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.

Bacteriophage phi X 174↗
PubMed1993

Size exclusion removal of model mammalian viruses using a unique membrane system, Part I: Membrane qualification.

We have previously described a new class of composite membrane that has the capability to efficiently remove particles, including viruses, from protein solution. The qualification of this membrane requires that it reproducibly and predictably remove model mammalian viruses. Using the Viresolve/70 membrane, the mammalian viruses polio, Simian virus-40, Sindbis, reovirus type 3 and Rauscher murine leukemia virus are shown to be reproducibly removed via a sieving mechanism. Mammalian virus retention increases constantly with virus diameter independent of virus class or type, increasing from 3.5 logs with polio virus to greater than 6.8 logs with murine leukemia virus. Consistent with a sieving mechanism, mammalian virus retention with the Viresolve/70 membrane is independent of virus concentration. These results are shown both in the presence and absence of protein in solution. The presence of protein in solution is shown to increase the virus retention coefficient of each virus above that measured in phosphate buffered saline. The model virus retention is shown to be well predicted by hard particle retention reported previously for this membrane. In addition, the hard particle retention is shown to predict the worse case performance expected of the membrane in the presence of protein.

Animals↗
PubMed1993

Size exclusion removal of model mammalian viruses using a unique membrane system, Part II: Module qualification and process simulation.

The performance of a fabricated device may be influenced by the characteristics of the fluid management within the device and reproducibility with which the device is manufactured. The performance of the Viresolve/70 membrane is not diminished when incorporated into a fabricated module. The Viresolve/70 fabricated modules are shown to reproducibly retain viruses via a sieving mechanism, independent of virus type or character, in excellent agreement with the base membrane retention coefficients reported previously. The retention coefficients measured for the Viresolve/70 modules are shown to increase with increased recirculation flow rate within the module. Mammalian virus spiked protein solutions processed through the Viresolve/70 system show that mammalian viruses can be removed from solution in accordance with the apparent membrane retention coefficients. The retained virus is recoverable on the upstream side of the membrane. Process clearance factors for murine leukemia virus is in excess of 6.7 LRV and that of human immunodeficiency virus I is 8.5 LRV.

Animals↗
PubMed1992

High resolution removal of virus from protein solutions using a membrane of unique structure.

We describe a new class of membrane that has the capability of removing particles such as viruses from solution with resolution and reproducibility superior to that of conventional membranes. This composite membrane is composed of a pre-formed microporous membrane plus a thin asymmetric, finely porous retentive layer that is quite different from conventional ultrafilters. The protein sieving characteristics of this membrane are nearly equivalent to, but slightly less than, that of conventional 100,000 Dalton cut-off ultrafiltration membranes. This membrane uniquely shows particle retention characteristics that increase monotonically from 3 to 8 logs as a function of particle diameter in the range of 28 to 93 nm. The performance of this membrane in both a single stage and a two stage system show that 4 to 6 log overall removal of virus particles in the size range 30 to 70 nm is possible with simultaneous high recovery of product protein. Clearance factors exceeding 6 logs are possible with viruses larger than 78 nm. In addition, the performance of process systems containing this membrane is predictable in accordance with the general membrane properties and equilibrium mass balance models. This membrane system is fully validatable and can be used in conjunction with other validated operations in a down-stream process to reliably achieve an over-all reduction of 12 logs of known or putative virus particles.

Bacteriophage phi X 174↗