Viral Clearance Validation
Greater Log Reduction Values in Fewer Steps
Viral clearance is a critical component of regulatory submissions as it helps demonstrate the overall product safety of your biopharmaceutical. Through thousands of studies, we have developed a service platform that supports regulatory success.
Developed service platform optimized for peak performance across multiple runs and products
Created a more effective method for achieving higher log reduction values in less steps compared to the “percent spike model”
Ensures regulatory success by leveraging intelligent study design, database, platform, and decades of experience
On-premise, remote, or continuous chromatography study capabilities
Flexibility – Expertise to work with equipment from multiple vendors
Viral Clearance Validation Platform Overview
- Database with over 20,000 entries used for study design
- Large-Volume Testing and Sensitive Plaque Assays
- High-Titer Virus Stocks
- Ultra-Purified Preparations of Virus Spikes
- Consistent data by enhancing Viral Removal Filtration
- Virus spiking strategy based on total viral load compared to percent spike delivers better results
Viral Clearance Validation Platform Overview
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.
Viral Clearance Database
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.
- Recombinant proteins
- Monoclonal antibodies
- Tissue and plasma products
- Gene therapy vectors
- Raw materials
- 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
Large Volume Virus Detection Methods – Viral Plaque Assay vs TCID50
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.
High Titer, Ultra Purified Virus Stocks
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)
Total Viral Load Challenge Spiking Strategy
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.