Statistics for FDA Process Validation (3.0 days):

Statistics for FDA Process Validation (3.0 days):

This course focuses on how to establish a systematic approach to implementing statistical methodologies into a process development and validation program consistent with the FDA guidance. This course teaches the application of statistics for setting specifications and assessing measurement systems (assays), using design of experiments (DOE) for process design, establishing a strategy for process qualification, and ensuring process control/capability. All concepts are taught within the three-stage product cycle framework defined by requirements in the process validation regulatory guidance documents.

Statistics for FDA Process Validation Objectives:

• apply statistics to set specifications and validate measurement systems (assays)
• develop appropriate sample plans based upon confidence and power
• implement suitable statistical methods into a process validation program for each stage:

Stage 1 – Process Design
◦ utilize risk management tools to identify and prioritize potential critical process parameters
◦ define critical process parameters and operating spaces for the commercial manufacturing process using design of experiments (DOE).

Stage 2 – Process Qualification
◦ assess scale effects while incorporating large (pilot) scale data
◦ develop process performance qualification (PPQ) acceptance criteria by characterizing intra and inter-batch variability using process design data and batch homogeneity studies
◦ develop an appropriate sampling plan for PPQ.

Stage 3 – Continued Process Verification
◦ develop a control plan as part of a risk management strategy
◦ collect and analyze product and process data
◦ ensure your process is in (statistical) control and capable.

Outline:
1. Introduction to Statistics for Process Validation
• Process Validation principles
• Stages of Process Validation

2. Primer on Statistical Analysis
• Basic statistics
• Statistical intervals and hypothesis testing
• ANOVA and regression
• Time series charts

3. Foundational Requirements for Process Validation
• Setting specifications
• Analytical methodology
• Sampling plans

4. Stage 1 – Process Design
• Steps to DOE
• Defining critical-to-quality attributes (CQAs)
• Identifying and prioritizing potential process parameters
• Screening designs
• Response surface designs
• Establishing a strategy for process control

5. Stage 2 – Process Qualification
• Batch homogeneity
• Setting PPQ acceptance criteria
• Scale effects
• Characterizing inter and intra-batch variability

6. Stage 3 – Continued Process Verification
• Developing a control plan as part of a risk management strategy
• Statistical process control
• Process capability

7. Advanced Methodologies (Optional)
• Advanced DOE
• Advanced Process Control
• Advanced Process Capability

Appendix A – Capstone Exercise
Appendix B – Reference Material