Evaluation of a sterile filtration process for viral vaccines using a model nanoparticle suspension

Abstract

There is growing interest in the development of new vaccines based on liveattenuated viruses (LAVs) and virus-like particles. The large size of these vaccines, typically 100-400 nm, significantly complicates the use of sterile filtration. The objectives of this study are to examine the performance of several commercial sterile filters for filtration of a cytomegalovirus vaccine candidate (referred to as the LAV) and to develop and evaluate the use of a model nanoparticle suspension to perform a more quantitative assessment. Data obtained with a mixture of 200-and 300-nm fluorescent particles provided yield and pressure profiles that captured the behavior of the viral vaccine. This included the excellent performance of the Sartorius Sartobran P filter, which provided greater than 80% yield of both the vaccine and model particles even though the average particle size was more than 250 nm. The particle yield for the Sartobran P was independent of filtrate flux above 200 L/m 2 /h, but increased with increasing particle concentration, varying from less than 10% at concentrations around 10 7 particles/ml to more than 80% at concentrations above 10 10 particles/ml due to saturation of particle capture/binding sites within the filter. These results provide important insights into the factors controlling transmission and fouling during sterile filtration of large vaccine products.

Evaluating Nanoparticle Hydrophobicity Using Analytical Membrane Hydrophobic Interaction Chromatography

“…One of the distinct advantages of MHIC is that the hydrophobicity can be evaluated in the presence of surfactants, something that is typically not possible in two-phase partitioning since the surfactant itself will partition unequally between the phases. In order to explore the effects of surfactants on NP hydrophobicity, data were obtained in the presence of CTAB (a cationic surfactant) and two nonionic surfactants, Poloxamer 188 and Tween 20 (Polysorbate 20), all of which are commonly used in vaccine formulations. , Figure shows the elution profiles for 200 nm PS in CTAB, Poloxamer 188, and Tween 20 at concentrations of 0.9 mM, 0.1%, and 0.01%, respectively. All of the surfactant concentrations were above their respective critical micelle concentrations.…”

“…In order to explore the effects of surfactants on NP hydrophobicity, data were obtained in the presence of CTAB (a cationic surfactant) and two nonionic surfactants, Poloxamer 188 and Tween 20 (Polysorbate 20), all of which are commonly used in vaccine formulations. 27,28 Figure 4 shows the elution profiles for 200 nm PS in CTAB, Poloxamer 188, and Tween 20 at concentrations of 0.9 mM, 0.1%, and 0.01%, respectively. All of the surfactant concentrations were above their respective critical micelle concentrations.…”

Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application

“…Once the immunogen is in its free form, the material can be purified using one of the following methods: sterile filtration [346], solvent extraction [347], alcohol precipitation [348], ultrafiltration [349], gel permeation chromatography [350], zonal centrifugation [351], formaldehyde inactivation [352], diafiltration [353], detergent precipitation [354] and various other methods of chromatography. Depending on the selected nanocarrier delivery strategy an appropriate encapsulation method is utilised.…”

Pressure‐dependent fouling behavior during sterile filtration of mRNA‐containing lipid nanoparticles

“…Sterile filtration of LNPs, as well as other large viral and nonviral delivery vehicles, can be challenging because these products can be similar in size to the 0.2 µm pore size rating of sterilizing‐grade filters (Wright et al, 2020). For example, Taylor et al (2021) examined the sterile filtration of a live attenuated viral vaccine with mean particle size ranging from 100 to 400 nm through a range of sterile filters, including both single‐ and dual‐layer filters, with the vaccine transmission ranging from less than 2% to more than 80%. Emami et al (2021) reported a high yield (>95%) but more than a sevenfold difference in capacity during sterile filtration of different glycoconjugate serotypes even though these glycoconjugate vaccines differed by less than a factor of two in their measured particle size.…”