Adventitious Virus Testing

What is Adventitious Virus testing and why is it important?

Adventitious agents, such as viruses, present significant risks within biomanufacturing processes through potential contamination and amplification. These threats may emerge at various stages, from the introduction with raw materials to events occurring up to the final packaging. Notably, the highest risks are associated with raw materials of biological origin, like serum, and from viral amplification within the bioreactor. Given risks these adventitious viruses pose to patients, manufacturers must rigorously conduct adventitious virus testing, apply virus purification techniques, and engage in comprehensive virus testing and virus screening to align with strict GMP guidelines and regulations. Additionally, virus characterization is essential to ensure that every viral risk is thoroughly assessed and mitigated, safeguarding the delivery of safe biopharmaceuticals to patients.

Traditional virus testing strategies, including cell-based in vitro detection as well as in vivo adventitious virus testing, have been employed due to their ability to screen for both known and unknown viruses. These tests rely on the virus’s ability to amplify and manifest a detectable effect for identification. Nevertheless, many viruses fail to proliferate or exhibit measurable effects within these systems, making such virus screening methods time-consuming and potentially delaying the release of a batch to patients.

Moreover, the compatibility of in vivo and in vitro detection with the biopharmaceutical is a significant concern, particularly if the drug exhibits toxicity. While this can sometimes be mitigated with a neutralizing antibody, the development of these antibodies can be protracted, and at times, antibody neutralization is not feasible, challenging the traditional virus characterization methods.

Molecular detection methods, in contrast, are generally impervious to the toxicity of the biological sample, obviating the need for neutralizing antibodies and typically requiring less of the valuable biopharmaceutical product. PCR, a highly sensitive virus testing method, excels in identifying known and well-characterized viruses. Yet, it does not detect novel or genetically altered viruses, and extensive PCR testing can deplete substantial quantities of the product.

Next Generation Sequencing (NGS) represents a superior approach for the detection of adventitious viruses. It shares PCR’s insensitivity to potential drug toxicity and goes beyond by sensitively detecting both known and unknown or variant viruses. This makes NGS an optimal virus screening and virus characterization strategy, particularly when speed, sample volume, and the challenge of antibody neutralization are pressing concerns.