Genetic and phenotypic markers and their relationship to product quality and consistency

Manufacturers of products derived from biological systems have long sought to identify relevant genotypic and phenotypic markers displayed by production strains and cell lines which could be employed as in-process monitors to predict product quality. Ideally, changes in these markers would signal possible changes in product quality and could be used to ensure batch to batch product consistency. In mammalian cell culture-based manufacturing processes, individual cell lines can exhibit varying genotypes and phenotypes, not all of which are relevant to cellular protein synthesis. In this paper we present data illustrating that two key phenotypic markers, thought to be relevant to protein biosynthesis (specific growth rate and cellular productivity), can vary significantly without causing obvious changes in product characteristics. Additionally, we outline our approach to genotypic characterization at the cell bank and post-process stages and our rationale for this approach.