ISPE Guidance Documents

• 1 Introduction
• 1.1 Objectives
• 1.2 Scope
• 1.3 Benefits
• 1.4 Key Concepts
• 1.5 Definitions
• 1.5.1 Specification
• 1.6 Guidance Structure
• 2 Variability and Sampling
• 2.1 Variability
• 2.1.1 Variability of Analytical Measurement
• 2.1.2 Overall Process Variability
• 2.1.3 Distribution of Data
• 2.2 Sampling
• 3 Establishment and Application of a Process Performance and Product Quality Monitoring System
• 3.1 Introduction
• 3.2 Establishment and Implementation of a Control Strategy as a Basis for a PP&PQMS
• 3.3 Provide the Tools for Measurement and Analysis of Parameters and Attributes
• 3.3.1 Simple Descriptive Statistics
• 3.3.2 Statistical Process Control
• 3.3.3 Process Capability
• 3.4 Analysis of Parameters and Attributes
• 3.4.1 Management Review Process
• 3.5 Identify Sources of Variation
• 3.5.1 Example of Application of Different Out of Trend Considerations
• 3.5.2 Example of Use of Statistical Tools
• 3.5.3 Management Issues Involved in Identifying Sources of Variation
• 3.6 Include Feedback on Product Quality from both Internal and External Sources
• 3.6.1 Product Review
• 3.6.2 More Frequent Management Review in Addition to Annual Product Review
• 3.6.3 Monitoring for Multiple Manufacturing/Packaging/Testing Sites
• 3.7 Provide Knowledge to Enhance Process Understanding
• 3.7.1 Model Effectiveness and Improvement (Enrich Design Space)
• 3.7.2 Regular Re-evaluation of the Risk Assessment
• 3.7.3 Modern Approaches to Process Validation
• 3.7.4 Innovation
• 4 Roles and Responsibilities of Quality Stewards
• 4.1 Introduction
• 4.2 Quality Steward Role
• 4.2.1 Example Quality Steward Role 1 (Product Design Owners)
• 4.2.2 Example Quality Steward Role 2 (Product Quality Steward)
• 5 Appendix 1 - Considerations for Analytical Procedures and Data
• 6 Appendix 2 - General Considerations for Establishing a Control Strategy
• 7 Appendix 3 - Analytical Procedures Potentially Used in a PP&PQMS
• 8 Appendix 4 - References
• 9 Appendix 5 - Glossary
• 9.1 Acronyms
• 9.2 Definitions

• Winston R. Brown, Alcon Research, Ltd. – A Novartis Division, USA
• Chunsheng Cai, PhD, Vertex Pharmaceuticals, Inc., USA
• Joseph Famulare (Co-Lead), Genentech Inc., USA
• Jennifer Gehle-Novak, Fresenius Kabi USA, LLC, USA
• Jaspreet Gill, Baxter Healthcare Corp, USA
• Rob Hughes, Rob Hughes Associates, United Kingdom
• Claudia Q. Lin, PhD, Bayer Healthcare, USA
• Bryan Liptzin, Amgen Inc., USA
• Steven J. Martino, Johnson & Johnson, USA
• George P. Millili, PhD (Co-Lead), Merck & Co., Inc., USA
• Jason J. Orloff, PharmStat, USA
• Christopher Potter, PhD, ISPE PQLI Technical Project Manager, United Kingdom
• Ronald C. Stellon, AstraZeneca, USA
• Dr. Thirunellai G. Venkateshwaran, PhD, Genentech Inc., USA

The ISPE Product Quality Lifecycle Implementation (PQLI) Good Practice Guide (GPG): Process Performance and Product Quality Monitoring System (PP&PQMS) is Part 4 of the ISPE Guide Series: PQLI from Concept to Continual Improvement, which is a product of the ISPE PQLI program.

The modern pharmaceutical quality system described in ICH Q10 is a holistic approach which helps to facilitate the consistent development and production of high quality pharmaceutical products. The ISPE PQLI GPG: Process Performance and Product Quality Monitoring System considers process performance and product quality monitoring systems established to support products and processes developed using the enhanced, Quality by Design approach. This Guide is intended to be compatible with the process validation guidance issued by the FDA and the draft guideline on process validation issued by the EMA.

This Guide is relevant to the development and manufacture of drug substance and drug product for both small and large molecules. It is also applicable to new and existing products.