Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies

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.

KEYWORDS:

• Acceleration
• characterization
• CMC
• first-in-human
• monoclonal antibody
• risk mitigation

Acknowledgments

The authors thank Xuening Li, Xin Pei, Xiaoqing Jin, Yu Ji, and Leo Chan for supporting technology transfer; Oliver Shen and Richard Lu for manufacturing support; Jinsong Feng and Xiaojing Chu for quality assurance; Wenjing Shi, Bo Zhou, Meng Jiang, Chunlong Li, Gaofeng Chen, Yaomin Li, and Shiqi Xu for DP manufacturing support; and Jun-Hsiang Lin for leading the Tox study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

The manuscript was written by Yuqi Wang. All the authors approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19420862.2023.2292305

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.