Evaluating Novel Strategies for Viral Filtration in an End-to-End Continuous Process
The importance of viral filtration studies
Biological therapeutics need to meet strict safety criteria. Virus safety is ensured through complementary manufacturing and quality control measures. Virus filtration is a critical element in this process, and viral filtration studies have become a key step in bioprocessing over the past decades. They are required by most regulators to bring a biologic to the market. The purpose is to assure that the final medicinal product is safe from the potential risk of viral contamination.
The quality of the design of such studies is key: when inappropriately designed, they may lead to undesired results such as non-representative filter fouling or virus breakthrough.
The characteristics of end-to-end continuous filtration
Continuous processing is a modern manufacturing method for biologicals, e.g. monoclonal antibodies (mAb). Consequently, also continuous viral clearance has to be investigated. Compared to batch filtration, continuous end-to-end processes present new challenges to the operation and validation of the viral filter:
- Higher loadings are required to maximize filter utilization and decrease filter swap outs, thereby reducing process risk;
- Higher loadings and continuous operation can lead to viral clearance assessments lasting several days and potentially overloading the filters with virus causing either non-representative filter fouling or non-representative virus breakthrough;
- Novel filter evaluation and assessment strategies are needed to maximize filter utilization while still demonstrating safety.
Consequences for assessing viral clearance in continuous end-to-end filtration
This, in turn, means that assessment of viral clearance in continuous viral filtration may require studies spanning over several days and also novel virus-spiking strategies. This type of assessment is needed to adequately demonstrate a high level of viral clearance while ensuring the filters are not overloaded with virus and are consistent with real-life manufacturing conditions.
A team of scientists at Just- Evotec Biologics has performed studies to identify a robust virus filter that retains virus despite high load challenges and low operation pressures. Key findings were:
- There are multiple filter options suitable for continuous processing;
- The use of surrogates for virus particles can give clues to filter behavior, however, the assay still needs optimization in terms load challenge.
- Alternatives to traditional virus spiking techniques such as a bracketed, integrity test approach can simplify viral clearance assessment while still demonstrating virus safety.
Summary and outlook
While bioprocessing technologies have evolved rapidly during the past decades, multiple factors such as increased cost, quality and production pressures are calling for further advances. At the same time, regulatory requirements are evolving and sophisticated safety testing has become a key prerequisite for market approval of novel biologics.
The team at JUST – Evotec Biologics has therefore kicked off an initiative to spearhead the development of next-generation bioprocessing technologies such as continuous end-to-end viral filtration.
Future work of the group will include optimization of the surrogate virus spiking and testing techniques as well as testing other virus filters for robustness of virus clearance at low flux/pressure conditions.
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