{Reference Type}: Journal Article
{Title}: Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies.
{Author}: Wang Y;Quan Q;Gleason C;Yu H;Peng L;Kang Y;Jiang L;Wu K;Pan J;Bao M;Zhu Q;Yi M;Fang M;Zheng Y;Qiu L;Xu B;Li X;Song J;Sun J;Zhang Z;Su Z;Lin J;Xie Y;Xu A;Song X;Huang C;Shen Z;Wang L;Song J;
{Journal}: MAbs
{Volume}: 15
{Issue}: 1
{Year}: 2023 Jan-Dec
{Factor}: 6.44
{DOI}: 10.1080/19420862.2023.2292305
{Abstract}: Pharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4-5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of "fast-to-FIH" approaches in combination with BeiGene's de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.