Optimizing Vaccine Adjuvant Filtration - The viscosity of oily emulsions can reduce filter capacity and bacterial retention. - BioPharm International

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Optimizing Vaccine Adjuvant Filtration
The viscosity of oily emulsions can reduce filter capacity and bacterial retention.


BioPharm International Supplements


Bacteria Retention Affected by Plugging and Interactions

Sterilizing-grade filters are used to ensure product sterility and are designed to remove all bacteria present in a process stream. Regulatory requirements dictate that processes involving sterile filtration must be validated to remove at least 107 bacteria per square centimeter of filter area under worst-case processing conditions. ASTM F838-83 outlines the standard method for determining the bacteria retention of a membrane using Brevundimonas diminuta (ATCC 19146).6 Using our model stream, we investigated mechanisms that affect bacteria retention; our testing followed this ASTM test method. In our study, two primary factors influenced retention: the suspected interaction among the oil emulsion, the bacteria, and the membrane, and the impact of plugging.

The coating of bacteria on the membrane with emulsion is likely one of the contributing factors that makes bacterial retention less robust in the presence of the emulsions than in typical aqueous solutions. Scanning electron microscope (SEM) imaging was used to evaluate bacteria size. Our analysis did not show bacteria to decrease in size on exposure to the oil emulsion; however, the bacteria did appear to be coated with emulsion. Additional studies showed that the emulsion did not affect bacteria viability. Other properties, such as motility and flexibility, have not been evaluated yet in detail, but to date, no evidence has been observed to support the suggestion that bacterial retention is affected by changes in their properties.

Pore blockage, the primary flow decay mechanism, also affects retention. Similar to the phenomenon observed in virus filtration, retention in the presence of the emulsion decreases as the membrane plugs. This behavior is exacerbated by the presence of the oily emulsion coating the bacteria, which produces a worst-case environment for retention, even in the absence of membrane plugging.

The study also assessed the effect of temperature on retention and found better retention at higher temperatures—approximately 1 log higher at room temperature than at cold temperatures. We are conducting further investigation to determine the reasons behind this finding.

Improved Understanding Will Lead to Improved Solutions

In our study, using a model oil-in-water emulsion, we found that capacity limitations are primarily the result of pore blockage, coupled with low initial flux. Additionally, process conditions, such as inlet pressure, can further reduce membrane capacity. These factors also affect bacteria retention and are exaggerated by temperature effects and the interaction of the oil and the bacteria.

Based on improved understanding of the mechanisms involved in filter capacity and retention in the presence of an emulsion, there are a number of variables that can be manipulated to optimize process performance. Processing conditions, filter selection, and feed stream properties affect on filtration performance. Temperature, pressure, membrane selection particle size, and loading can all be manipulated to improve process efficiency and ensure product sterility. Combinations of the various options present the potential for further improvements.

Early process development work coupled with early prescreening before validation is recommended to ensure a robust process under worst-case conditions for temperature, pressure, and particle load.

Christina Carbrello is a development engineer and Marc Rogers is a senior microbiological scientist, both at Millipore Corporation Billerica, MA,
, 781.533.2141.

REFERENCES

1. Allison AC. Squalene and squalene emulsions as adjuvants. Methods. 1999;19:87–93.

2. Schultze V, D'Agosto V, Wack A, Novicki D, Zorn J, Hennig R. Safety of MF59 adjuvant. Vaccine. 2008;26:3209–3222.

3. Bolton G, LaCasse D, Kuriyel R. Combined models of membrane fouling: Development and application to microfiltration and ultrafiltration of biological fluids, J Membr Sci. 2006;(277):75–84.

4. Grace HP. Structure and performance of filter media. AICHE J. 1956;2(3):307–36.

5. Hermia J. Constant pressure-blocking fluids. Transactions of the Institute of Chemical Engineers. 1982;60(3):183–187.

6. American Society for Testing and Materials. Standard method for determining bacterial retention of membrane filters utilized for liquid filtration. ASTM F838-83. 2005. Philadelphia, PA: American Society for Testing and Materials.


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