Failure mode and effect analysis (FMEA) is a commonly used risk assessment tool to evaluate potential failure modes, causes, and likely effects on pharmaceutical manufacturing processes and products. FMEA relies on product and process knowledge and experience, it breaks down the analysis of complex processes into measurable items and steps, once the failure modes are established and risks are identified, risk control methods can be placed to reduce or eliminate potential failures. FMEA follows the principle of ICH Q9 (quality risk management) and the tool is applicable to manufacturing process, equipment, and systems such as water and HVAC systems. The analysis includes 5 steps (below figure), and after risk reduction methods are completed, FMEA form will be reviewed by the project team again to determine if the risk is reduced to acceptable levels.

FMEA evaluates the level of failure mode using severity (S), likelihood of occurrence(O), and detectability (D). Risk Priority Number (RPN) is then calculated (RPN = S x O x D) to determine risk levels as “High”, “Medium”, or “Low”. Severity, Occurrence, and detectability can be rated by a 5 score system as shown in below table.

Process FMEA is one of the most commonly used technical documents generated by biological drug manufacturers to thoroughly analyze risks in manufacturing process of a product. Examples of process FMEA risk assessment and risk control table is presented below, and they can be divided into separated documents to cover cell culture, purification, and drug product processes.