Viral Contamination Still a Challenge for CGT Industry

Raw material testing will remain the foundation of cell and gene therapy (CGT) sector quality control strategies for the foreseeable future, according to new analysis, which shows the industry still lacks suitable virus detection and inactivation methods.

Biopharmaceutical raw materials—the culture media ingredients, the reagents, and even the production cell lines themselves—are the biggest source of viral contamination in drug manufacturing.

To mitigate the risks, the protein drug industry has developed downstream virus detection, inactivation, and removal strategies to make sure products do not pose an infection risk.

For CGT firms, ensuring products are virus safe is more of a challenge, says Yoshiaki Maruyama, PhD, from the office of cellular and tissue-based products at Japan’s Pharmaceuticals and Medical Devices Agency (PMDA).

“Viral contamination of CGT products may arise from virus-contaminated raw materials or ancillary materials of human or animal origin or from the inadvertent introduction of viruses during the manufacturing process.

“Appropriate raw material controls and robust quality control parameters must be established and maintained throughout the manufacturing process to effectively manage the risk of viral contamination,” he tells GEN.

Inactivation and removal challenges

The big problem is that cell and gene therapies are too sensitive to survive current viral inactivation methods, most of which were developed with protein therapeutics in mind.

Maruyama says, “Most conventional virus inactivation or removal processes inevitably result in cell damage or loss in cell therapy and tissue-engineered products or adversely affect viral vectors in gene therapy products.”

As a result, CGT sector quality control efforts have focused on screening raw materials and finished products, according to Maruyama, who looked at current regulations and common approaches in a recent study.

“In the CGT sector, viral safety is achieved by implementing a comprehensive viral testing program. The use of inactivation and removal processes is challenging for CGT products and raw materials, so quality control strategies relying on screening are generally used,” he says.

Technological solutions?

In future, technologies may play a greater role, according to Maruyama, who says, “

“NGS technologies are expected to be applicable to the detection of adventitious viruses in human or animal cells. NGS offers a powerful, unbiased approach for detecting known and unknown viral contaminants,” they write.

However, as the authors point out, further development will be required as NGS systems detect nucleic acids rather than viable, infectious virus particles.

“Currently, there are no globally accepted NGS-based procedures or validated analytical methods that have reached a consensus on their use as substitutes for conventional viral tests. Therefore, the use of NGS as an alternative to conventional viral tests, including reducing the use of experimental animals, requires further evaluation depending on the specific test to be replaced,” they write.

And in the future, artificial intelligence (AI) systems may also play a role.

“This is largely speculative, and there are currently no concrete examples, but AI-based tools have been applied to manufacturing control for deviation prediction and similar approaches might also be useful for controlling viral contamination risks in CGT products and raw materials,” he says.

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