Process Design to Process Validation
- 1. Process; Design to Validation A Critical Journey Faheem Lakhani Plant Head Platinum Pharmaceuticals
- 2. Flow of Presentation Introduction to Process Design/ QBD Quality Target Product Profile (QTPP) Critical Quality Attributes (CQA’s) Critical Process Parameters (CPP’s) Critical Materials Attributes (CMA’s) Design of Experiments (DOE) Design Space (DP) Control Strategy (CS) Discussion
- 3. Introduction to Process Design/ QBD
- 4. Introduction to Process Design/ QBD How do we fill these quality gaps in Pharmaceutical industry??? By testing???
- 5. Quality of pharmaceutical products, an elephant in the dark
- 6. Are we grappling skewed perceptions of GMP? (Dr.Ijaz) The only source of knowledge is experience. (Albert Einstein)
- 7. The Quality Mantra Quality cannot be tested into PRODUCTS; it has to be built in by DESIGN.
- 8. The Quality Mantra Process validation on 3 batches Not appropriate 30 Batches required for 90% reliability & 95% confidence Not Practical Make the design of experiment strong to demonstrate SCIENCE behind variability
- 9. • A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. (ICH Q8 R2) What is Quality by Design (QbD)?
- 10. What is Quality by Design (QbD)? A systematic Approach Predefined Objectives • Define Quality Target Product Profile (QTPP) • Identify Critical Quality Attributes (CQA) Product and Process understanding • Identify critical material attributes (CMA) and critical process parameters (CPP) • Establish the functional relationships that link • CMA/CPP to CQA Process Control • Develop appropriate Control Strategy, including • justifications Sound Science • Science-driven development (scientific literature, • prior knowledge, DOEs etc.)
- 11. Quality Target Product Profile Critical Quality Attributes Link MA And PP to CQA Establish Design Space Establish Control Strategy Product Life Cycle Management QbD;Stepbystep Approach
- 12. Quality Target Product Profile (QTPP)
- 13. The Quality Target Product Profile (QTPP) provides an understanding of what will ensure the quality, safety, and efficacy of a specific product for the patient Quality Target Product Profile (QTPP)
- 14. Dosage form Tablet Dosage Design Immediate release ,film coated tablet Route of administration Oral Dosage Strength 20mg Stability At least 24 month shelf life at room temperature. Quality Target Product Profile (QTPP)
- 15. The Quality Target Product Profile (QTPP) describes the design criteria for the product, and should therefore form the basis for development of the CQAs, CPPs, and control strategy. Quality Target Product Profile (QTPP)
- 16. Critical Quality Attributes (CQA)
- 17. A physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality (ICH Q8) Critical Quality Attributes (CQA)
- 18. Critical Quality Attributes (CQA) • Physical Attributes • Identification • Assay • Content Uniformity • Dissolution • Degradation Products • Residual Solvents • Water Content • Microbial limits
- 19. Critical Material Attributes (CMA)
- 20. A physical, chemical, biological or microbiological property or characteristic of an input material that should be within an appropriate limit, range, or distribution to ensure the desired quality of output material. Critical Material Attributes (CMA)
- 21. BCS Classification B Chemical Properties Potential for hydrolytic degradation Physical Properties Acceptable API (PSD) for dissolution Product Shelf life 2 years 30c (hydrolysis degradation & dissolution changes controlled by packaging. Critical Material Attributes (CMA)
- 23. A process parameter whose variability has an impact on a CQA and therefore should be monitored or controlled to ensure the process produces the desired quality. (ICH Q8) Critical Process Parameters(CPP)
- 24. Overall Risk Assessment Parameters Drug substance particle size Moisture content in manufactur e Blending Lubrication Compression Coating Packaging In vivo Performance Dissolution Assay Degradation Content uniformity Appearance
- 25. Relationship between CMAs, CPPs & CQAs
- 27. The multidimensional combination and interaction of input variables e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality. Slide 32 May 2008 Design Space (DS)
- 28. Formulation Screening, Optimization & Selection Ingredient Trial-1 Trial-2 Trial-3 Trial-4 API 25mg 25mg 25mg 25mg Avicel Ph-102 64mg _____ 64mg _____ Calcium Hydrogen Phosphate ______ 64mg _____ 64mg Kollidon Cl 5mg ____ 5mg _____ Cross Carmellose Sodium ______ 5mg _____ 5mg Talcum 4mg 4mg 3.5mg 3.5mg Stearic Acid 1.5mg 1.5mg 2.0mg 2.0mg Opadry qs qs qs qs Average weight 100mg 100mg 100mg 100mg
- 29. Multifactorial DOE Study of Variables Affecting Dissolution E# API(PSD) Lubrication Qty Lubrication Time Hardness Dissolution 1 10 3mg 1 60 101.24 2 15 3mg 1 60 87.99 3 5 12mg 1 60 99.13 4 15 3mg 10 60 76.03 5 5 12mg 10 60 79.73 6 15 12mg 10 60 81.04 7 5 3mg 1 100 98.07 8 5 5mg 1 100 97.68 9 15 12mg 1 110 85.47 10 40 3mg 10 110 73.81 11 15 3mg 10 110 84.38 12 1.5 12mg 10 130 64.01 13 5 7.5mg 5.5 85 96.85 14 15 7.5mg 5.5 85 85.13 15 10 3mg 5.5 85 91.87 16 10 12mg 5.5 85 90.72 17 10 7.5mg 1 85 91.95 18 10 7.5mg 10 85 68.94 19 10 7.5mg 5.5 60 92.37 20 10 7.5mg 5.5 110 80.95 21 10 7.5mg 5.5 85 91.95 22 10 7.5mg 5.5 85 90.86 23 10 7.5mg 5.5 85 89
- 30. DOE; Blending Process Parameter Assessment to Develop a Design Space E# Blending Time Rotation Speed Blender Particle size (API) 1 2 10 V Type 5 2 16 10 V Type 40 3 2 30 V Type 40 4 16 30 V Type 5 5 2 10 Drum Type 40 6 16 10 Drum Type 5 7 2 30 Drum Type 5 8 16 30 Drum Type 40 9 9 20 V Type 20 10 9 20 Drum Type 20 11 9 20 V Type 20 12 9 20 Drum Type 20
- 32. Design Space Knowledge Space Control Space Slide 35 May 2008 Control Strategy (CS)
- 33. The control strategy should describe and justify • in-process controls • controls of input materials (drug substance and excipients) • container closure system Slide 36 May 2008 Control Strategy (CS) Contribute to the final product quality
- 34. Take Home Message… Quality by Testing & Inspection Enhanced Product knowledge Process understanding Quality by Design Quality assured by well designed Product & Process