News & Events

Clean Mails – June 2024

Considerations around oncolytic virus manufacturing

Like other Advanced Therapeutic Medicinal Products (ATMP), oncolytic virus manufacturing poses a series of challenges in order to produce safe and robust viral therapies.
Oncolytic virus manufacturing must thus include preliminary development steps such as direct evolution or gene editing methods to generate cancer-specific viruses with adequate lytic properties.

While general biopharmaceutical rationales for virus-based therapies are applicable to oncolytic virus manufacturing and QC testing, some considerations need to be addressed due to their innate attributes or mode of administration. In particular, GMO status can have a big impact on overall regulatory expectations. Oncolytic virus production also requires specific processing to reach the expected concentrations for such products and/or overcome obstacles generated by the size of viruses.

Naobios gathers 20 years of expertise spanning the whole range of virus- and vector-based therapies. Within state-of-the-art cGMP facilities, Naobios supports companies with diverse oncolytic virus manufacturing needs, addressing all hurdles typically encountered by sponsors.

GMO and BSL status of starting material involved in oncolytic virus production.

Effective viral therapies need potent viruses with increased lytic activity on cancer cells. Oncotropism is typically optimized using directed evolution or gene editing.

Overall, oncolytic virus manufacturing needs to take into account safety considerations relating to GMO and BSL status of these engineered strains. With BSL2 facilities, combined with an authorization to handle class 1 & 2 GMOs, Naobios covers all safety situations encountered when working with viral therapies with a keen knowledge on regulatory expectations.

Upstream & Downstream Processing: maximizing concentration and overcoming size constraints.

Oncolytic virus manufacturing draws upon typical upstream processing development strategies. However, to generate the high-titre and highly purified material for clinical trials, downstream processing needs to be adjusted. In particular, tangential flow filtration (TFF) and dead-end filtration may be needed complementary to typical DSP steps of oncolytic virus manufacturing.

Naobios optimized downstream processes for most strains used in viral therapies, including Vaccinia and Measles – which pose unique challenges due to their size. Without the possibility of final aseptic filtration at the end of oncolytic virus manufacturing, other strategies need to be implemented. With two class B clean rooms, Naobios exploits its state-of-the-art facility to circumvent these hurdles and produce safe material in a controlled environment.

QC strategies to assess potency and stability.

Oncolytic virus production requires an adapted QC testing strategy to assess quality attributes, identity, safety profile and potency over the course of production and until final administration.
In addition to typical QC methods applied to virus-based production, specific methods must be implemented to assess identity, retention of transgenes, absence of recombination, potency on a targeted cell line and overall stability of these characteristics.

In close collaboration with sister company Clean Cells, Naobios provides advanced QC services in addition to oncolytic virus manufacturing. This includes development of cytotoxicity read-outs, functional assays, identity assessment using NGS and specific qPCR/dPCR development modalities for integrity and titre assessment. Clean Cells has also implemented a cell cloning platform and is currently involved in the selection of potent cell lines for a virotherapy sponsor.

Overall, Naobios has become a leading expert for the generation of non-GMP and GMP material intended for Ph1/2 up to Ph2b/Ph3. We have successfully developed & optimized processes for multiple modalities while evaluating key attributes all along oncolytic virus manufacturing. Feel free to get in touch with our expert team for a customized assessment of your project.