A Practical Analytical Risk Survey Program for Active Pharmaceutical Ingredient Synthesis that Enhances Analytical Control Strategies for Early and Mid-Stage Development

摘要

Active pharmaceutical ingredient (API) process development requires a comprehensive analytical control and a set of wide-ranged analytical methods. In the early to mid-stages of development, i.e., at phase I and II clinical trials, the analytical controls in manufacturing processes are still evolving. The analytical methods designed to gather data on APIs, intermediates, starting materials, and reagents are also progressing, but knowledge regarding method robustness is limited. Despite being in clinical development, there is a requirement for scientifically sound data to provide confidence in key decisions, establish reproducible testing at contract manufacturing organizations (CMOs), and, most importantly, guaranteeing consistent quality to ensure patient safety. As every project is different, how do we drive consistency between projects in handling and learning from risk mitigation?To address this, an analytical risk survey program to evaluate common risk factors was developed. In this article, we introduce a new workflow that is simple and widely applicable to assess analytical gaps and risks for early- to mid-stage projects. The workflow combines a checklist with common risk factors and a spreadsheet with scored ranking to facilitate the collation of an experimental 'to do' list for evolution of analytical method conditions and optimization of controls.The impact of this risk survey program has shown to be value added for both the analytical teams and overall portfolio development at Bristol Myers Squibb.