Biologics, including vaccines and therapeutic proteins, face serious threats from viral contamination due to their reliance on animal- or human-derived materials. Traditional viral detection methods, while effective, are increasingly challenged by the complexity of modern biologics and the need for faster production timelines. A significant shift is occurring in this field, with the introduction of Next-Generation Sequencing (NGS) as a promising alternative to conventional techniques.
The March 2023 revision of the ICH Q5A guideline highlights the potential of NGS in enhancing viral safety testing. This guideline underscores the advantages of NGS, which allows for rapid, unbiased detection and identification of a broad range of viruses. Traditional methods—ranging from animal assays to PCR and electron microscopy—often require weeks to yield results and may miss emerging or mutated viruses, posing risks during biologics production.
Enhanced Detection Capabilities
Current methods like the 9CFR tests are limited in scope, primarily targeting known pathogens within specific species. These tests may fail to identify newly emerging viruses, particularly those that do not replicate in traditional assay systems. In contrast, NGS can analyze all nucleic acid molecules in a sample, significantly broadening the detection capabilities. This technology can identify viral genomes in a variety of biological products, including cell-based therapies, allowing for quicker and more comprehensive safety evaluations.
According to Horst Ruppach, PhD, executive director of scientific and portfolio management at Charles River Laboratories, companies are beginning to recognize the advantages of adopting NGS. “Simply use NGS but maybe not initially in a critical submission,” he advises. “In new product development, use it as an alternative or a supplement to the standard testing to get familiar with the technology.”
NGS can deliver results in just two to three weeks, significantly faster than many traditional methods. This rapid turnaround is especially crucial in the fast-paced biologics market, where even low-level viral contamination can lead to substantial product losses.
Transforming Viral Safety in Cell Therapies
Cell therapies, particularly allogeneic products, present unique challenges in viral safety. Unlike traditional biologics, these therapies are administered directly to patients, leaving no room for the removal or inactivation of potential contaminants. NGS proves invaluable here, as it can detect any viral nucleic acid regardless of whether the virus can grow in culture.
Ruppach emphasizes the necessity of utilizing NGS for allogeneic cell therapies, stating, “In the future, it will be mandatory to use NGS because it has the highest breadth of detection.” Traditional assays often struggle to detect endogenous viruses in primary human cells, which can lead to unanticipated risks.
Recent collaborations between Charles River Laboratories and PathoQuest have demonstrated the effectiveness of NGS. In comparative tests, the NGS method detected multiple viruses that traditional assays missed, underscoring its potential as a standard in viral safety testing.
The economic advantages of NGS are also notable. By reducing the number of different tests required for comprehensive viral safety assessments, manufacturers can lower costs significantly. Ruppach notes, “With NGS, you can replace most of these methods and in the end run two to three assays, one of which is NGS, reducing costs and the timeline.”
As the regulatory landscape increasingly acknowledges the strengths of NGS, its implementation is expected to rise. This shift aligns with global trends toward ethical testing practices, reflecting a commitment to the 3Rs framework—reduce, replace, and refine—in animal testing.
In conclusion, the adoption of NGS in viral safety testing marks a pivotal evolution in the biologics industry. As Ruppach aptly puts it, “In five years, people may wonder why we used the traditional approaches when we had this technology.” The integration of NGS could ultimately redefine standards for safety and efficiency, paving the way for safer biologics in the future.