Filtration

Evaluating Disposable Depth Filtration Platforms for MAb Harvest Clarification

At small to medium scales, single-use technology offers significant advantages over traditional reusable (e.g., stainless steel) manufacturing technology with regard to flexibility, cost of goods, implementation timelines, and maintenance. However, process design based on disposables does create new challenges. With traditional fed-batch processes, harvest clarification is usually achieved by centrifugation followed by depth filtration. For processes based entirely on disposables, the disc-stack centrifuge needs to be replaced by filtration alone. To extend its manufacturing capabilities and capacities, Rentschler decided to…

Scaling Up Normal-Flow Microfiltration Processes

    Scaling up biological processes from laboratory bench to process scale is complex and requires considering a number of factors to ensure process robustness. Due to variability among raw materials and processes, most process developers use generous safety factors to ensure that their systems are not undersized. Although that method can be reduce process risk, it is inefficient. To improve process efficiency and reduce risk, we conducted a study to identify and quantify key factors that contribute to variability…

Streamlining Downstream Process Development

Normal-flow filtration is used throughout downstream processes for biologics including depth, sterile, and viral filtration applications. Because of its ubiquity in large-scale biomanufacturing, using the most efficient normal-flow filter media area and type can lead to significant cost savings. To determine the most effective media type and area, developers use a scaled-down process model is used in bioprocess laboratories to minimize material requirements. Constant–flow-rate filter evaluations involve direct scale-down parameters that match manufacturing-scale process conditions. This type of evaluation can…

A Framework for Selecting and Working with a Normal-Flow Filtration Supplier

The biopharmaceutical market accounts for about 20% of the total market for pharmaceuticals, but its share continues to increase because of double-digit compound annual growth rates leading to projections that by 2014 eight of the top 10 best-selling drugs will be biologics (1). The industry faces many challenges and opportunities, as Jim Davies of Lonza Biologics explained to me: “Biomanufacturers have to contend with what is at present a dynamic technical and commercial landscape. Industry consolidation continues to occur as…

Predicting Virus Filtration Performance with Virus Spike Characterization

Evaluating a virus filter should, in theory, be a straightforward exercise. Membrane-based filtration is a robust virus reduction technology that plays an important role in virus safety for most drug production processes. An appropriate virus filter for a given process is generally selected through preliminary testing with relevant drug feed material. Data acquired during such tests are used to determine hydraulic performance targets such as expected flow rates and total throughputs. A virus clearance evaluation study is then performed in…

Single-Use Tangential Flow Filtration in Bioprocessing

    Single-use (SU) components are widely accepted in bioprocessing due in part to improvements in component design, a wider range of products, and increased scalability. Benefits driving their increased use include elimination of cleaning, improved system flexibility, and reduced risk of contamination. Nonetheless, companies now question how far disposables can be incorporated into bioprocessing unit operations. Results of the second annual survey of the bioprocessing market fo single-use solutions showed that >90% of respondents considered filtration well suited for…

How Pore and Fibrous Interstice Structure Influence Filter Performance

    When bioprocess liquids bearing suspended particles are filtered, retained particles can block and clog membrane filter pores. The pore size rating of a filter should be selected to retain objectionable particles by sieving, and the aptitude of its polymeric composition for adsorptive sequestration of those particulates also needs to be known. The quantity and nature of retained particles require accommodation if filtrative removal is to be considered successful. Too extensive a particle load will prematurely block a filter’s…

How Pore and Fibrous Interstice Structure Influence Filter Performance

    A common objective in pharmaceutical processing is the removal of solids from fluid suspensions through filtration. The usual purpose is the removal of the solid particles to a specified extent, within a given time interval, at the largest possible throughput. Attainment of those goals is managed by proper selection of filtration conditions: principally an adequate effective filtration area (EFA) as defined by filter porosity and a proper rate of flow as regulated by applied differential pressure (ΔP) over…

Using In-Line Disposable Pressure Sensors to Evaluate Depth Filter Performance

    Development of a recovery process for a fed-batch mammalian cell culture product involves several objectives: process scalability, robustness, maximizing product yield, elimination of subsequent purification steps, and low cost of goods. In an effort to achieve those objectives, we developed a three-stage primary recovery process to remove biomass and clarify the feed stream for downstream column chromatography (Figure 1). The initial stage involves removal of whole cells and larger cellular debris using a continuous disc-stack centrifuge. Depth filtration…

Investigating Flow Distribution and Its Effects on Scale-Up

Depth filtration is widely used in the biopharmaceutical industry to purify target proteins by removing whole cells, cellular debris, fines, aggregates, and colloidal particles from the fermentation broth (1,2). At large scale (>2,000 L), culture harvest from a bioreactor is typically processed with a disc-stack centrifuge to remove cells and cell debris. Although centrifugation is very effective for removing whole cells and larger debris, it cannot remove small-size particles, which remain suspended in the centrate. Depth filters are commonly used…