A modular approach for the ultra-scale-down of depth filtration

• Novel micro-scale device enabling eight parallel depth filtrations at constant flux.
• Cross-sectional area of 0.2 cm2 enables filter screening with 4 mL/run.
• Qualified device with two single-layer and one double-layer media from two vendors.
• Demonstrated scalability to commercially-available lab-scale devices.
• Several micro-scale clarity measurements were competitively evaluated.

Depth filtration is employed in the production of many biological products. Although high throughput process development is available for most purification operations, options for high throughput depth filtration are limited. In this report, we describe the development and qualification of an ultra scale-down (USD) device for high throughput depth filtration. The system enables the parallel evaluation of eight single- or multi-layer depth filters approximately 0.2 cm2 in cross-sectional area, greater than two logs smaller than the smallest commercially available devices. To assess precision, scalability, modularity, and media heterogeneity in USD depth filtration, several types of adsorbent media were qualified in the USD device, with filtration performance compared to lab-scale devices (cross-sectional area: 23–25 cm2). The performance was further investigated with several high throughput clarity measurements, including particle characterization of filtrate fractions. Historically, depth filtration development has been limited by the amount of material required to run lab-scale filters. The described high throughput technology enables the screening of filter media early in development, optimization of operating parameters, and coupling of upstream operations to filtration performance. These high throughput capabilities will create efficiencies for development and manufacturing that were unattainable previously and create an important tool for screening novel biological entities.