Meeting product development challenges in manufacturing clinical grade oncolytic adenoviruses.

Oncolytic adenoviruses have been considered for use as anticancer therapy for decades, and numerous means of conferring tumor selectivity have been developed. As with any new therapy, the trip from the laboratory bench to the clinic has revealed a number of significant development hurdles. Viral therapies are subject to specific regulations and must meet a variety of well-defined criteria for purity, potency, stability, and product characterization prior to their use in the clinic. Published regulatory guidelines, although developed specifically for biotechnology-derived products, are applicable to the production of oncolytic adenoviruses and other cell-based products, and they should be consulted early during development. Most importantly, both the manufacturing process and the development of characterization and release assays should be science-driven, use the best available science and technology, and must consider the unique nature of the product: a living, and mutatable, virus. Potentially significant impacts on product quality and safety stem from the possibility of genetic instability related to over-engineering the viruses (as evidenced by their recombination and/or occasional reversion to wild-type virus during manufacturing). This report provides examples of some of the critical components affecting the development and production of clinical grade material and summarizes the significant progress made in recent years.