(198b) Establishing Process Control of High Shear Wet Granulation: Insights on Common Deficiencies from FDA Reviewers' Perspective

High shear wet granulation (HSWG) is a critical manufacturing process widely employed in the pharmaceutical industry for producing granules used in solid dosage forms. Establishing proper process control in high shear wet granulation (HSWG) is crucial for ensuring the quality of the drug products. Understanding the impact of process factors such as granulation fluid amounts, spray rate, impeller speed, and wet massing time is essential. From the perspective of FDA drug product manufacturing reviews, deficiencies related to critical process parameters in HSWG have been identified as major causes for extended application review and approval processes. This poster presents a survey of abbreviated and new drug applications (ANDAs and NDAs) submitted between 2018 and 2022, focusing on the most observed deficiencies in HSWG process control. The survey findings consistently highlight deficiencies in the control of granulation endpoint, granulation fluid level, granulation fluid addition rate, and scale-up strategy. The aim of the poster is to present the survey results, discuss the impact of these observed process deficiencies on granulation and final drug product quality, and propose recommended process control strategies. For applications with appropriate process control strategies, it is possible to eliminate multiple review cycle times and improve the approval process, ultimately benefiting patients by ensuring timely access to safe and effective medications manufactured using HSWG.