Quantification methods for viruses and virus-like particles applied in biopharmaceutical production processes
Keven Lothert, Friederike Eilts, Michael W. Wolff
Abstract
INTRODUCTION: Effective cell-based production processes of virus particles are the foundation for the global availability of classical vaccines, gene therapeutic vectors, and viral oncolytic treatments. Their production is subject to regulatory standards ensuring the safety and efficacy of the pharmaceutical product. Process analytics must be fast and reliable to provide an efficient process development and a robust process control during production. Additionally, for the product release, the drug compound and the contaminants must be quantified by assays specified by regulatory authorities. AREAS COVERED: This review summarizes analytical methods suitable for the quantification of viruses or virus-like particles. The different techniques are grouped by the analytical question that may be addressed. Accordingly, methods focus on the infectivity of the drug component on the one hand, and on particle counting and the quantification of viral elements on the other hand. The different techniques are compared regarding their advantages, drawbacks, required assay time, and sample throughput. EXPERT OPINION: Among the technologies summarized, a tendency toward fast methods, allowing a high throughput and a wide applicability, can be foreseen. Driving forces for this progress are miniaturization and automation, and the continuous enhancement of process-relevant databases for a successful future process control.