From ATP to QC: A Risk-Based Assessment Workflow to Enables Robust Commercial Analytical Methods

Late-stage API development and commercial manufacture require analytical control strategies that support release, IPCs, and lifecycle trending across sites and CMOs. Although analytical target profiles (ATPs) define required method performance per ICH Q14, teams need a consistent way to evaluate residual method risk and prioritize robustness work before validation and transfer. We describe a risk-based analytical method assessment workflow implemented at Bristol Myers Squibb to strengthen commercial analytical control strategies and improve QC readiness. The approach is a bottom-up risk assessment performed on the intended final operating conditions and established conditions for a method/technique. Templated spreadsheets with technique-specific checklists capture common failure modes (e.g., sample preparation complexity, solution stability, selectivity and system suitability sensitivity, instrument/vendor variability, and data processing controls). Risks are ranked to identify knowledge gaps and generate an experiment “to-do” tracker. Outputs provide transparent risk acceptance/mitigation rationale for PPQ readiness, ICH Q2 validation planning, and method transfer. This workflow has been implemented for small molecule projects in BMS portfolio successfully for several years. Case examples demonstrate improved cross-functional alignment and earlier identification of robustness limitations that can reduce transfer burden and investigations.