Viral Clearance Validation

Studies that enable INDs all the way through commercial approval for a variety of biopharmaceuticals. Experience with column and filtration process removal and inactivation studies to name a few.

The Advanced Therapies Viral Clearance Database is a powerful tool allowing users to query for information related to general or specifi­c process step parameters and how those parameters affect viral clearance/inactivation. With database queries, clients are able to make informed decisions prior to or during critical process changes, which, in turn, permits ­fine-tuning of the processes – helping to avoid costly delays and the inclusion of unnecessary or non-ideal process steps in their viral clearance analysis. For example, a query might review the past results of a specifi­c process step prior to implementing a change or as an alternative to an existing process. Alternatively, the database could be mined to examine the performance and effectiveness of specifi­c conditions that could yield better viral clearance log reduction values.

Supported Products

• Recombinant proteins
• Monoclonal antibodies
• Tissue and plasma products
• Gene therapy vectors
• Vaccines
• Raw materials
• Devices

Features

• More than 3500 different viral clearance or inactivation studies
• Information tabulated from 20,000 data points and continuously expanding
• Log reduction values obtained over a 25-year span
• Extensive library of inactivation and removal process steps

Multiple Search Criteria

• Process step (AEX chromatography, solvent/detergent, nano¬ltration)
• Virus used (over 30 di erent types)
• Process step parameters (pH, flow rate, conductivity)
• Protein and viral load
• Infectivity or PCR detection methodology
• General scale-down parameters for individual processes

By testing large volumes of product material in viral clearance studies coupled with use of virus plaque assays (e.g., testing a level of fi­ltrate in quantities upwards of >200 ml), your program is best positioned to drive higher log-reduction claims through increasing the sensitivity of the assay so that a greater log reduction can be achieved.

The viral plaque assay is a true quantitative method, as it counts single infectious units. In contrast, TCID50 scores based on a percentage of cell death, with wells scored as positive or negative for viral infection. When a process step completely removes or inactivates virus (i.e. no virus detected), we’re able to increase plaque assay sensitivity and Log10 Reduction Value (LRV) for our client simply by plating and testing more sample volume.

Ultra-purified virus stocks reduce interference in process steps and ensure accurate assessment of your processes’ ability to clear or inactivate virus. They can also dramatically increase total log reduction values (LRV) for nanofiltration and other steps. The LRV results from utilizing these stocks often provide the necessary clearance to eliminate low LRV steps, reducing the cost of your viral clearance program and process development efforts. Ultra-pure viruses are purifi­ed using centrifugation and other proprietary process steps. Our standardized process mitigates lot variation, while specially developed quality control assays characterize purity.

With our meticulously developed and highly-re­fined approaches to purifi­cation techniques, we have three classifications of virus for use in studies:

• Ultra 1 (standard)
• Ultra 2 (highly purifi­ed Reovirus, PrV and MuLVs)
• Ultra 3 (highly puri­ed PPV and MVM)

Although widely effective, the Percent Spike Model will produce variable data caused by natural differences in virus preparations.

By focusing on the Viral Removal Filtration step, we pioneered a new approach, the Total Viral Load Challenge which scientifically showcases a repeatable method for robust viral clearance that has been accepted by global regulatory bodies.

View data published on BPI that demonstrates our superior approach

Read an interview that recaps our R&D efforts that led to the service platform creation