Biosafety Testing And Quality Control Requirements For Lentiviral Vectors With A Focus On Replication Competent Testing And Infectious Titer

The use of lentiviral (LV) vectors to deliver genetic material in the treatment of diseases refractory to other therapies has become a familiar and successful form of gene therapy over the past decade. Most frequently based on human immunodeficiency virus (HIV), LV vectors have a large genetic capacity with relatively low immunogenicity and a preference for transducing cells that are non-proliferating or are slowly proliferating. This latter attribute not only increases the possibility of persistence of the gene modified cells but may also reduce oncogenic potential.

Due to the unique nature and application of lentiviral vectors, it is critical to plan for, and properly perform the complete testing requirements to ensure safety and consistency of your LV based ex vivo gene therapy. Interpreting and applying the relevant regulations and guidelines can be a challenge, but with the right expertise and guidance you can avoid unwelcome surprises and reduce the time it takes for your therapy to reach awaiting patients.

In this paper we cover the key manufacturing principles of LV vectors, regulatory considerations specific to the testing requirements of LV vectors, and testing strategies for LV vectors, with particular focus on the replication competent virus assay and infectious titer assay.