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Removing Viruses From Your Downstream mAb Process

A scientist is diligently working in a laboratory, engaged in the downstream processing of monoclonal antibodies.

Downstream processing in the production of monoclonal antibodies (mAb) reduces the levels of virus by either removal or inactivation. Regardless of the technology, biomanufacturers must demonstrate the clearance capabilities of different downstream steps as part of the viral safety assessment process. Downstream processing typically includes:

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Chromatography

To reach viral clearance targets, most downstream processes include at least two chromatography operations. A typical solution is protein A capture, followed by ion exchange chromatography (IEX), comprised of cation exchange chromatography (CEX) to reduce antibody aggregate levels and anion exchange chromatography (AEX) to remove residual host cell proteins and DNA. Under select conditions, both CEX and AEX can contribute to viral safety.

Chemical Treatment

Chemicals used for virus inactivation must meet the same high-quality standards as other raw materials. Selected chemicals should be manufactured or purified to GMP standards (based on the IPEC – PQG GMP guide for pharmaceutical excipients, 2006) for consistent high purity in order to assure process reliability. Chemicals with comprehensive testing and documentation packages simplify the compliance process.

Filtration

Removal of virus by filtration is typically based on size, with most mAb production processes relying on filtration to provide high levels of both enveloped and non-enveloped virus reduction. Virus filtration is regarded as a robust step for virus removal and is relatively insensitive to process conditions. However, the presence of protein aggregates and other trace fouling species can negatively impact the throughput performance of virus filters, resulting in increased filtration area requirements. For greater filtration efficiency, a prefiltration step to remove fouling species may be incorporated, leading to significant improvements in virus filter capacity, flux, and overall viral filtration costs.

Demonstrating Effectiveness

Manufacturers of biologics are required to evaluate their downstream manufacturing process for the ability of selected unit operations to inactivate or remove potential contaminants. Results of such clearance studies are required by regulatory authorities for investigational new drug (IND) submissions. Understanding these regulatory expectations is a key component of clearance study design, informing the manufacturer’s overall viral safety strategy.

Workflow

A scientist selects and pre-treats raw materials to safeguard downstream processes from potential adventitious viruses.

Preventing adventitious agent contamination

Careful selection and pretreatment of raw materials to prevent adventitious viruses from entering processes.

Scientists in a lab analyze samples using microscopes. The setting is modern and busy, and a colorful cell image on a monitor.

Testing for the presence of viruses and other adventitious agents in cell banks, raw materials, and process intermediates.

Three scientists engage in a focused discussion about Monoclonal antibody manufacturing, emphasizing both high therapeutic concentration and process safety.

Monoclonal antibody manufacturing is a highly templated approach used to produce mAb-based immunotherapies. Robust, scalable process solutions are required at every step to ensure high therapeutic concentration and process safety, while meeting speed-to-market and cost containment concerns.

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Provise™ Clearance Services
Our experienced team of process scientists can perform all virus inactivation and virus removal steps for you at our state-of-the-art facilities, keeping you informed at every step with seamless technology transfer and a QA-audited Final Report to support your regulatory filing.
Standard and Hybrid Clearance Services
Execute your viral clearance study at state-of-the-art facilities where you’ll have the flexibility to perform on-site clearance operations such as chromatography and VRF with expert support, or tailor your own hybrid approach in true collaboration with our team of process scientists.
Emprove® Program
Emprove® Program: The smart way to master compliance and control. Complementing our product portfolio, the Emprove® Program provides convenient access to reliable technical, regulatory and supply information in Emprove® Dossiers to support your risk assessment continuum.
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Flexible, easy-to-use filter holders are a key component for integration of the Viresolve® Pro Solution, enabling scalable virus filtration that meets your manufacturing demands.
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Viral safety is a key component of drug safety for patients. Virus filtration of cell culture media minimizes the risk of bioreactor contamination, while downstream virus filtration assures viral clearance. Learn how virus filtration reduces risk and enhances viral safety.
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Affinity Chromatography Resins
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Related Technical Resources

  • Viral Safety in Bioprocessing

    Viral safety in bioprocessing relies on a framework of (1) preventing contamination, (2) detecting contamination, and (3) removing or inactivating viral contaminants.

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