Risk-based Methodology for Validation of Pharmaceutical Batch Processes教程.pdfVIP

Downloaded from on August 16, 2013 Risk-based Methodology for Validation of Pharmaceutical Batch Processes Frederick Wiles PDA J Pharm Sci and Tech 2013, 67 387-398 Access the most recent version at doi: 10.5731/pdajpst.2013.00923 Downloaded from on August 16, 2013 TECHNOLOGY/APPLICATION Risk-based Methodology for Validation of Pharmaceutical Batch Processes FREDERICK WILES, ASQ CQE* ProPharma Group, Inc., 10975 Benson Dr. Suite 330, Corporate Woods Bldg. 12, Overland Park, Kansas 66210 ©PDA, Inc. 2013 ABSTRACT: In January 2011, the U.S. Food and Drug Administration published new process validation guidance for pharmaceutical processes. The new guidance debunks the long-held industry notion that three consecutive validation batches or runs are all that are required to demonstrate that a process is operating in a validated state. Instead, the new guidance now emphasizes that the level of monitoring and testing performed during process performance qualification (PPQ) studies must be sufficient to demonstrate statistical confidence both within and between batches. In some cases, three qualification runs may not be enough. Nearly two years after the guidance was first published, little has been written defining a statistical methodology for determining the number of samples and qualification runs required to satisfy Stage 2 requirements of the new guidance. This article proposes using a combination of risk assessment, control charting, and capability statistics to define the monitoring and testing scheme required to show that a pharmaceutical batch process is operating in a validated state. In this methodology, an assessment of process risk is performed through application of a process failure mode, effects, and criticality analysis (PFMECA). The output of PFMECA is used to select appropriat