High Shear Wet Granulation Process Common Deficiencies Observed in Recently Submitted New and Abbreviated Drug...

Area of Science:

• Pharmaceutical Manufacturing
• Process Chemistry
• Drug Product Quality

Background:

• High shear wet granulation (HSWG) is a standard pharmaceutical manufacturing method for oral solid dosage forms.
• Effective process control is essential for ensuring consistent granulation and final drug product quality.
• Manufacturing process control deficiencies can lead to extended review times for drug applications at regulatory agencies like the U.S. Food and Drug Administration (FDA).

Purpose of the Study:

• To analyze common deficiencies in the control of high shear wet granulation (HSWG) processes within FDA-assessed drug applications.
• To identify specific critical process parameters frequently lacking adequate control in HSWG.
• To provide recommendations for improving HSWG process controls and ensuring drug product quality.

Main Methods:

• Analysis of manufacturing assessment deficiencies from FDA drug applications submitted between 2017 and 2022.
• Focus on applications utilizing high shear wet granulation (HSWG) for oral solid dosage forms.
• Identification and categorization of recurring control deficiencies in the HSWG process.

Main Results:

• Lack of control for granulation endpoint was a frequent deficiency.
• Inadequate control over granulation fluid level and addition rate were commonly observed issues.
• Insufficient control strategies for wet massing time and process scale-up were also identified as significant deficiencies.

Conclusions:

• Common deficiencies in HSWG process control, particularly endpoint determination and fluid management, impact drug product quality.
• Addressing identified control gaps, including scale-up strategies, is crucial for robust pharmaceutical manufacturing.
• Implementing enhanced process controls can improve the efficiency of regulatory reviews and ensure the quality of manufactured drug products.