in viral spiking runs
in process performance costs*
designing and performing viral clearance studies
Unlock Unprecedented Speed and Efficiency in Viral Spiking
Evaluating CHO-cell-derived biopharmaceutical products can now take less time than ever before. Compared to traditional viral spiking, in which murine leukemia virus (MuLV) and minute virus of mice (MVM) are tested separately, our multi-spike approach combines the processes into one run, freeing up time and resources for more pressing matters.
The same approach is now applicable for vesicular stomatitis virus (VSV) and baculovirus (BV), which both address cell- and production virus-related risks for all kind of Baculovirus/Sf9 produced product types.
The multi-spiking procedure has been tested extensively and is suitable for use in GLP/GMP viral clearance studies, so you can remain confident your viral clearance studies fully evaluate the risk for viral contamination in the drug manufacturing process.
Multi-spike for early phase viral clearance studies (CHO-cell-derived products)
Testing for the MuLV and MVM viruses in early-phase viral clearance studies is the gold standard. Various chromatography, low pH treatment, and virus retentive filtration processes are performed. Overall, our multi-spike approach cuts down starting material utilization and reduces the number of runs performed from the standard 14 down to 7 or 8.
Multi-spike for late-phase viral clearance studies (CHO-cell-derived products)
In late-stage clearance studies, the MuLV and MVM viruses, as well as PRV and Reo-3 viruses, are tested for. Overall, our multi-spike approach lowers the number of runs performed from the average of 52 down to 33.
Multi-spike for viral clearance studies for Baculovirus/Sf9-produced products
Baculovirus (BV)-driven protein expression in insect cells has become a popular choice for biomanufacturing where baculovirus can be used as a helper virus for production of gene therapy AAV vectors. Although it’s an insect virus, BV can be immunogenic and activate the innate immune system, if it was found in the final product. Therefore, removal of this potential contaminant should be demonstrated by viral clearance evaluation.
What about the production cell line? Unlike mammalian cells, insect cells do not replicate human viruses and can be cultivated serum-free, but some insect cells such as those from Spodopera frugiperda (Sf9) have been shown to harbor endogenous Sf-rhabdoviruses. To show that the manufacturing process can eliminate substantially more Sf-rhabdovirus than is estimated to be present in a single-dose-equivalent of unprocessed bulk material, a specific Sf-rhabdovirus model should be addressed in the viral clearance study, e.g., vesicular stomatitis virus (VSV).
Small process intermediate volumes as a result of low product recovery come along with high production costs. Hence, providing enough material for viral clearance study performance is one of the major challenges for this kind of product. We established a multi-spike of VSV and BV to optimize the VC study design and to make the most efficient use of limited resources for this product class.
Accelerating Viral Clearance Studies – A Multi-Virus Spike Approach
In this webinar, we present a new MuLV-MVM multi-virus spike approach that has been developed, and how it can significantly reduce materials, time, and labor required.
Watch Webinar
Why Choose Multi-Spiking?
- Cost-effectiveness: Needing fewer runs and starting materials, multi-spiking can reduce performance process costs by up to 45%**.
- Resource efficiency: Most clients find that the multi-spiking can be performed in just two days, and requires less personnel oversight and other resources compared to traditional spiking.
- End-to-end support: Our multi-spike approach supports the entire drug development life cycle. It can be performed for investigational new drug (IND) and clinical trial application (CTA) filings, all the way to biologic license application (BLA) or marketing authorization application (MAA) filings.
- Quality assurance: Our multi-spike approach was extensively tested in quality assured projects on the basis of already validated methods used for virus quantification. Assay sensitivity and consequent log reduction factors (LRF) are identical to those of standard viral spiking approaches.
- Extensive experience: Over 30 years of experience designing and performing viral clearance studies have gone into the development of this process.
- Specialization: Charles River is one of the few CROs to offer access to a dedicated lab for blood product viral clearance studies.
Viral Clearance Validation Services
Cell line-derived biopharmaceuticals come with an inherent risk of viral contamination. So, it is critically important and mandatory that viral clearance studies are undertaken to ensure patient safety. Our labs in Europe and the US can help you design and perform custom studies. Discover More
Viral Clearance Validation Facilities in Cologne, Germany
The new multi-spike approaches are fully characterized for use in GLP viral clearance studies at our European facility. We offer comprehensive services and support for virus clearance validation studies, from study design, process scale-down, and execution to generation of reports that meet regulatory expectations.
Find out more about our Cologne Facility
Viral Clearance Validation Facility in Wayne, PA, US
The innovative multi-spike approach is GMP-qualified for performance in our North American facility. We offer comprehensive services and support for virus clearance validation studies, from study design, process scale-down, and execution to generation of reports that meet regulatory expectations.
Find out more about our Wayne Facility
Frequently Asked Questions
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What is viral spiking?
Viral spiking is the deliberate spiking of viruses into process intermediates and then demonstrating their inactivation or removal during the subsequent processing steps.
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How is the multi-spike approach different from the single viral spike approach?
With traditional cell-based infectivity assays, viruses are spiked one at a time. With the multi-spike approach, we can spike two viruses for a chromatography procedure simultaneously.
*When Charles River personnel perform the processes, clients who have utilized the multi-spike approach have, on average, realized a 45% reduction in costs when compared to two single-spike runs.
** The performance processes are chromatography and virus retentive filtration.