Q & QA design
- 1. ARUN KUMAR JAIN Quality by Design
- 2. Overview Interpretations of Quality QbD-Juran QbD-Definition ICH Q8-10 Paradigm Shift QbD Attributes Challenges Tools Design Space QbD –Pharmaceutical Development
- 3. Interpretations of Quality Time Cost Fitness for use Performance Features Look & Feel
- 4. Joseph M Juran- QbD Quality by Design (QbD) is a concept first outlined by quality expert Joseph M. Juran Joseph Moses Juran (December 24, 1904 – February 28, 2008) was a Romanian-born American engineer and management consultant The word "quality" as having two meanings: Features that create customer satisfaction The reliability of those features. Failures in features create dissatisfactions, so removing failures is the purpose of quality improvement, while creating features is the purpose of quality by design
- 5. Definition of QbD The pharmaceutical Quality by Design (QbD) is 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
- 6. 6 Q10Q8 Q8, Q9 & Q10 Process Materials Design Manufacturing Distribution Patient Facilities Opportunities to impact risk using quality risk management Q9
- 7. Pharmaceutical Development - Q8(R2) Describes science and risk-based approaches for pharmaceutical product and manufacturing process development Introduced concepts of design space and flexible regulatory approaches Introduced concepts of Quality by Design (QbD) and provided examples of QbD development approaches and design space
- 8. © ICH, November 2010 Quality Risk Management Process - Q9 Process Development Control Strategy Development Continual Improvement of the product
- 9. Q10-Pharmaceutical Quality System The product lifecycle includes the following Technical activities for new and existing products: Pharmaceutical Development: Drug substance development; Formulation development (including container/closure system); Manufacture of investigational products; Delivery system development (where relevant); Manufacturing process development and scale-up; Analytical method development. Technology Transfer: New product transfers during Development through Manufacturing; Transfers within or between manufacturing and testing sites for marketed products.
- 10. Paradigm Shift
- 13. “Quality can not be tested into products; it has to be built in by design”
- 14. From ‘blind compliance’ to ‘science and risk based compliance’ Ajaz Hussain, FDA The Paradigm Change
- 15. ICH Q8, Q9 and Q10 Working Together Formulation Activities: • QTPP Definition • Pre-Formulation Studies • Formulation Screening • Optimization & Selection Process Development Activities: • Process Screening • Lab Scale Development • Scale-Up Studies Manufacturing Activities: • Commercial Scale Manufacturing • Batch Release • Continual Verification & Improvement Q8 PharmaceuticalDevelopment Q9 QualityRiskManagement Q10 PharmaceuticalQualitySystems
- 16. • End User Requirements QTPP • Output Specifications CQA • Input Specifications CMA • Process parameters CPP QbD Terminologies
- 17. QTPP-Quality Target Product Profile Indented Use in Clinical Setting Route of Administration Dosage Form Delivery Systems Dosage Strength Container closure system Drug Product Quality Criteria: Sterility, Purity, Stability etc.
- 18. Target Quality Profiling- A Perspective Customer Market Regulations Research Engineering Business insights Manufacturability Installation & Service Purchasing Suppliers Competitor(s) Corporate Social Responsibility HRM)
- 19. Critical Quality Attributes (CQAs)
- 20. Critical Material Attributes (CMAs) Input Material Quality Attributes Raw material Quality Examples: Water Content/LOD, Assay, Impurities, Colour Value
- 21. Relation between CMA, CPP and CQA
- 22. Process (or Process Step) Design Space Monitoring of Parameters or Attributes Process Controls/PAT Input Process Parameters Input Materials Product (or Intermediate) Product Variability Reduced Product Variability Process Variability Reducing product Variability
- 23. What We Need?
- 24. Key in the Future of Manufacturing Process Understanding
- 25. A Process is well understood when… all critical sources of variability are identified and explained; variability is managed by the process; and, product quality attributes can be accurately and reliably predicted over the design space … http://www.fda.gov/cder/guidance/6419fnl.ht m
- 26. Challenges to ‘Understanding’ Understanding involves Measurements
- 27. Challenges to Analytical Science The need for increased Process understanding is a massive Boost for Analytical Science
- 28. Fritz Erni Challenges to Analytical Science adequate Tools?
- 29. Product Development Tools Computer-aided drafting software Solid modeling software Finite element analysis software Parametric analysis software Rapid prototyping techniques Design for manufacture and assembly techniques Failure mode and effect analysis
- 30. Production Tools Computer-aided Manufacturing Computer numerical controlled tools Continuous process improvement Just-in-time production Virtual manufacturing software Agile manufacturing
- 31. Statistical Tools Design of Experiments Statistical Process Control
- 32. Other Considerations Training is a must Requires money and time Using the tools increases employee retention and satisfaction
- 33. PAT: Process Understanding Improved Process Knowledge to Identify and Remove Sources of Variability Identify Critical to Quality parameters Process understanding as input to Risk Management Control what is critical
- 35. DOE and Design Space DOE is a tool to develop the design space. The outcome of the DOE Identifies the model correlations between CPPs/CMAs and CQAs Helps in establishing the boundaries of the design space. DOE can be used for Scale-up activities. DOE can be used as tool for confirming the design space at manufacturing scale.
- 36. Plackett Burman Design-Screening Run A B C D E F G H I J K 1 - - - - - - - - - - - 2 + - - - + - + + - + + 3 + + - - - + - + + - + 4 + + + - - - + - + + - 5 - + + + - - - + - + + 6 + - + + + - - - + - + 7 + + - + + + - - - + - 8 - + + - + + + - - - + 9 + - + + - + + + - - - 10 - + - + + - + + + - - 11 - - + - + + - + + + - 12 - - - + - + + - + + + - means low, + means high level
- 37. 37 Design Space FACTOR SPACE N dimension X’s X1 X2 X3 X4 X5 XN RESPONSE SPACE M dimension Y’s Y1 Y2 Y3 Y4 Y5 YM
- 38. Inputs: Outputs: P1 P2 P3 M1 M2 CQA1 CQA2 CQA3 Relationships: CQA1 = function (M1) CQA2 = function (P1, P3) CQA3 = function (M1, M2, P1) P2 might not be needed in the establishment of design space Process Parameters Material Attributes Critical Quality Attributes Source:MohebNasr,FDA
- 40. Design Space Vs Changes
- 43. Process Performance / Product Performance Control Charts Performance Indicators