Sample Size for Tablet Compression and Capsule Filling Events During Process Validation.

Area of Science:

• Pharmaceutical Manufacturing
• Quality Risk Management
• Statistical Process Control

Background:

• Ensuring uniformity of dosage units (UDU) is critical in solid dosage form manufacturing.
• Current UDU testing occurs at blend and compression/filling stages.
• A need exists for a robust sample size selection methodology linked to risk.

Purpose of the Study:

• To propose a sample size selection approach for Process Performance Qualification (PPQ) and Continued Process Verification (CPV).
• To integrate quality risk management principles with UDU testing.
• To link UDU to potential formulation and process risk factors.

Main Methods:

• Bayes success run theorem utilized for PPQ sample size calculation.
• Risk-based reliability levels (99%, 95%, 90%) assigned to high, medium, and low-risk factors.
• Bayesian statistics applied for CPV reduced sampling design.

Main Results:

• Sample sizes for PPQ estimated at 299 (high-risk), 59 (medium-risk), and 29 (low-risk).
• Demonstrated that increased sample size enhances confidence in detecting out-of-specification units at low defect rates.
• Developed a method for CPV sample size calculation based on acquired process knowledge.

Conclusions:

• The proposed risk-based approach optimizes sample size selection for pharmaceutical manufacturing.
• Bayesian statistics provide a flexible framework for both PPQ and CPV sample size determination.
• This methodology enhances the reliability and efficiency of UDU testing during process verification.