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Depth Filtration

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Advancing bioprocessing with clarity and confidence

At Thermo Fisher Scientific, we understand that harvest and clarification have become more demanding as bioprocessing shifts toward higher cell densities, higher titers, and evolving feed strategies. These conditions can increase the amount and variability of solids that must be addressed during clarification. Clarification strategies are evaluated early to anticipate differences in solids load, viscosity, and impurity profiles that emerge during upstream processing. Depth filtration solutions are one of several clarification approaches used to remove cells, cell debris, and fine insoluble particulates. 

The role of depth filtration in the harvest workflow

Depth filtration can be implemented at multiple points in the harvest workflow, depending on process objectives and feed stream characteristics. It may be applied as a primary clarification step to remove cells and cell debris and prepare the process stream for downstream purification. In workflows that incorporate upstream centrifugation to reduce bulk solids, depth filtration can also function as a secondary clarification step to manage fine debris and remaining particulates.

 

Decisions around where and how depth filtration is deployed are guided by solids burden, throughput requirements, facility constraints, and downstream process sensitivity. Zeta Plus depth filtration solutions support process-specific clarification strategies from process development through commercial manufacturing.

Reliable performance across complex harvest streams

Depth filtration media are engineered with a porous, three-dimensional matrix that enables particle capture throughout the depth of the media. Zeta Plus depth filter media are available in a wide range of grades, including single- and dual-layer configurations designed to manage complex harvest streams with broad particle size distributions. The dual-layer structure supports staged retention within a single device, helping balance contaminant holding capacity and throughput. Media chemistry options further enable charge-based and adsorptive interactions, with grade selection evaluated during process development to address variability in solids composition and impurity profiles.

Format options to optimize your facility fit

Depth filtration solutions, including Zeta Plus depth filters, are available in capsule, cartridge, and sheet formats. These solutions enable clarification strategies to be applied across process development and manufacturing using the same underlying media. Format selection typically reflects process scale, facility design, handling preferences, and system closure requirements. As processes progress, formats may be reevaluated to align with manufacturing needs.

Capsules for single-use clarification

Zeta Plus depth filter capsules are available from 25 cm² to 2.5 m², enabling lab-scale screening through production with consistent media. Production capsules feature a self-guiding locking mechanism, dual handles, and alkaline-resistant options to support closed clarification workflows.

Cartridges for reusable system integration

Depth filter cartridges, such as Zeta Plus depth filters, integrate into stainless steel housings and support clarification within established reusable infrastructure. Cartridges can enable higher flow rates or pressure tolerance as required, as part of clarification systems.

Sheets for filter press operations

Zeta Plus depth filter sheets are designed for use in filter press systems and support clarification in facilities with press infrastructure. Offered in consistent media grades across formats, sheets enable solids management and staged clarification in high-load or legacy operations.

Media and layer configurations for process needs

Depth filtration media and layer configurations should align with process-specific solids load, impurity profiles, and throughput requirements. Media characteristics and single- or dual-layer designs are considered when evaluating contaminant holding capacity and impurity retention within the filter structure.

SP depth filters

Zeta Plus SP depth filters offer the widest nominal pore size range within the portfolio. They can be applied across a range of clarification conditions, including primary and secondary clarification, to accommodate differences in solids load and particle size distribution.

ZB depth filters

Zeta Plus ZB depth filters feature higher charge levels and smaller nominal pore sizes than SP or LA media. They combine mechanical retention with strong electrostatic interactions to reduce negatively charged impurities, supporting processes where impurity profiles extend beyond insoluble solids. 

LA depth filters

Zeta Plus LA depth filters are designed for low extractable performance, including reduced aluminum levels. They are often selected for processes sensitive to inorganic and organic extractables.


 

Specialized application media

Depth filtration portfolios also include application-specific media designed to address clarification requirements beyond standard harvest workflows.

  • Zeta Plus SLP activated carbon filters are used when decolorization or targeted reduction of specific contaminants is required, eliminating the need for handling bulk carbon powder. 
  • Zeta Plus VR depth filters are applied in bioprocessing workflows where viral burden reduction is evaluated as part of a broader clarification or downstream strategy.
  • Zeta Plus DEL depth filters are used in processes requiring selective reduction of lipids or hydrophobic substances and are positioned for targeted applications. 
  • Zeta Plus CP depth filters are used in plasma fractionation workflows.

Evaluate nominal pore sizes

A range of depth filtration formats, configurations, and media types are available to support clarification needs across different process conditions. Nominal pore size is commonly used as a guide during media selection to align clarification steps with solids load and impurity profiles. Pore size evaluation is considered alongside media chemistry and layer design during process development.

Chart of Zeta Plus Depth Filter Media

Table 1. Coarse and fine grades across filtration media

 

Media Course Fine
ZB N/A 60ZB05A, 90ZB08A, 120ZB08A
SP 05SP01A, 10SP02A, 30SP02A 60SP02A, 60SP03A, 60SP05A
LA N/A 90LA

Scaling clarification from process development to production

Zeta Plus depth filter solutions are designed to support scalable clarification. The same media chemistry is available across capsule, cartridge, and sheet formats from 25 cm² to 2.5 m² production capsules. This format continuity allows small-scale development insights to translate directly into manufacturing configuration decisions. As a result, scale-up can proceed with reduced revalidation risk while maintaining clarification performance.

Infographic of Zeta Plus and encapsulated scalability

Depth filtration in plasma-derived therapeutics

In plasma fractionation, Zeta Plus depth filters are applied at multiple downstream stages with many processes transitioning to cartridge or single-use formats. These formats are fully scalable and based on differentiated media technologies established in the plasma industry. Zeta Plus depth filters, including LA, SP, VR, and CP, are available in sheet, cartridge, and single-use capsule formats to support scalable implementation from pilot to commercial manufacturing. We collaborate with plasma processors to refine clarification strategies, aligning media selection and format configuration with changing process and facility requirements.

Enhancing clarification with chromatographic filtration

When additional impurity control is required, the Emphaze AEX hybrid purifier can be integrated as an enhanced clarification step to reduce negatively charged soluble and insoluble impurities, including host cell DNA, host cell proteins (HCP), endotoxin, and fine debris, through combined anion exchange and size-based mechanisms. By lowering impurity and turbidity levels prior to capture chromatography, it helps protect Protein A (ProA) columns, improve downstream process performance, and reduce required sterilizing filter area. It also supports a more consistent, clarified feed quality while maintaining product recovery in a scalable, single-use format.

Supporting consistent performance and process control

Zeta Plus depth filter media are manufactured under defined product specifications with documented lot traceability from raw materials through finished product. Media performance characteristics, including nominal retention and extractable release specifications, are defined and tested as part of manufacturing controls.

 

When integrated into established workflows, depth filtration supports process characterization, comparability assessments, and sustained process control across process development and manufacturing.

Frequently asked questions

In many bioprocesses, depth filtration is introduced during harvest and clarification as either a primary clarification step or a secondary clarification step. It is commonly evaluated following centrifugation or similar separation steps to manage remaining cells and insoluble material. Placement and configuration are determined during process development, taking into account harvest composition, facility constraints, and how clarification interfaces with downstream operations.

Format selection usually depends on how a process is operated at a given stage rather than on a single configuration. During development or scale-up, single-use capsules may be evaluated for flexibility, while cartridges or sheets are often used in facilities with existing reusable infrastructure. Scale, handling approach, and integration with surrounding unit operations are reviewed during process design.

High-density cultures can introduce higher solids levels, increased debris, and changes in fluid viscosity that affect clarification behavior. Impurity profiles may also shift as titers increase, influencing how media interact with process streams. During process development, these factors are evaluated together to inform media grade and layer configuration. In some cases, these factors may prompt exploration of modified clarification strategies to accommodate high-titer process demands.

Depth filtration can support scale-up when clarification strategies are explored early and revisited as processes advance. Evaluating the same media across scalable formats allows development-stage learnings to inform later configuration decisions. Format selection and media choices are commonly reassessed during tech transfer to align clarification steps with manufacturing-scale equipment and downstream process requirements.

Depth filtration may be combined with additional clarification or polishing technologies when process streams present higher impurity loads or increased variability. In these cases, depth filtration can be paired with approaches, such as chromatographic clarification or membrane-based steps, to further condition the stream. Decisions to combine technologies are typically made during process development based on impurity profiles, downstream sensitivity, and overall workflow design.

Explore related clarification technologies

Depth filtration is one component of a broader clarification strategy that may include additional technologies as process requirements change. Fiber chromatographic clarification can be evaluated alongside depth filtration to address charged impurities and fluid variability earlier in the workflow.

Discover filtration resources

Explore optional resources designed to support a deeper understanding of bioprocess filtration topics and decision-making considerations. Available materials include technical documents, webinars, and educational content that address practical applications, emerging trends, and process challenges across bioprocessing workflows. 

Explore the School of Purification

Gain practical insights into filtration, purification strategy, technology transfer, and emerging therapeutic applications.

 

Whether you are strengthening foundational knowledge or evaluating approaches for process development and manufacturing, the School of Purification supports ongoing learning across bioprocessing workflows.

Bring clarity and control to your harvest workflow

Intended use of the products mentioned on this page vary. For specific intended use statements, please refer to the Instructions for Use for the product.