Risk Analysis and Mitigation Matrix (RAMM) – A Risk Tool for Quality Management

Risk analysis and management is the cornerstone of any scienceand risk-based approach1 for modern drug development and manufacturing.2 In order to understand and document processes and products, standard risk analysis tools have been adapted from other industries and academia. These tools include Ishikawa Diagrams,3 P-Diagrams, Preliminary Hazard Analysis (PHA), Failure Modes and Effect Analysis (FMEA4), Failure Modes and Effect Criticality Analysis (FMECA5), Hazard Analysis of Critical Control Points (HACCP6), and several more. The Risk Analysis and Mitigation Matrix (RAMM) was created to provide a pragmatic compromise where other risk tools such as Preliminary Hazard Analysis (PHA) or Failure Mode Effects and Criticality Analysis (FMECA) are maybe either too simple and lacking in detail, or they are maybe too complicated, making it difficult to work consistently with limited resource across all products. The goal of the RAMM was also to align with ICH and FDA guidances (Q8 to Q10 series7, 8, 9 and Process Validation10); especially around tracking Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs) in a pragmatic manner. The tool was designed to be at the heart of any modern quality system with regular review in meetings and as a way of tracking risks and any mitigation actions. The tool had to be simple enough that everyone could use it and provide enough detail that critical risks could be tracked, mitigated, and be time savvy. If it were to take days to go through the risk analysis every time a process review occurred, it would never be as useable as it should be. This article will discuss how the tool works, provide a practical example as applied to a monoclonal antibody (Mab) process, and show how to incorporate the tool into a quality management system.