Correlating product lifecycle and manufacturing site characteristics with product deviations

Although there is awareness among the biopharmceutical industry of the challenges and trade-offs associated with monitoring the safety of drug products, there does not seem to be a clear and consistent understanding of characteristics correlated with the presence of critical-to-quality deviations of a product at the commercial scale (1). The intent of this paper is to initiate an understanding of product and site characteristics that statistically correlate with quality performance of biopharmaceutical commercial products. Towards this objective, a comprehensive survey on related topics is underway at the Massachusetts Institute of Technology (MIT) Center for Biomedical Innovation (CBI). The interim results described in this research represent survey results from 34 commercial-scale biopharmaceutical products at 11 international sites. This research builds on analysis done by the MIT CBI team earlier this year (2). Some regulatory agencies, including FDA, have actively pursued a risk-based approach to manufacturing site inspection because their inspections are site-specific and not restricted to an individual product (1). Explicit inputs that FDA uses for its risk-based selection of sites to inspect include the types of products manufactured (e.g., prescription versus over-the-counter, approved versus unapproved, therapeutic classes); the control and/or contamination potential of the manufacturing environment (e.g., facility size, facility type, number of drug products, sterility requirements); and cost of inspection (e.g., domestic versus international locations). These inputs are logical for consideration of total risk to quality at the level of a site, but, in this research, the focus regarding quality is on the product.