A Lifecycle Approach to Process Validation
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The document outlines a lifecycle approach to process validation in pharmaceutical manufacturing, detailing stages as defined by FDA guidance: process design, process qualification, and continued process verification. It includes critical documentation requirements and an interactive case study exercise for process validation related to active pharmaceutical ingredients. The author, Seow Choon How, emphasizes the importance of establishing a scientific basis for consistent quality in drug manufacturing.
A Lifecycle Approach to Process Validation
- 1. VALIDATION BOOT CAMP A LIFECYCLE APPROACH TO PROCESS VALIDATION – PRINCIPLES, IMPLEMENTATION AND PRACTICES Seow Choon How, BSc (Chemistry), MBA, Production Manager, Vela Operations Singapore Pte Ltd 25 FEBRUARY 2013 1
- 2. Seow Choon How BSc MBA Vela Operations Singapore Pte Ltd Choon How is a Process and Produc9on Professional with exper9se in Plant Management and Opera9ons, Technology Transfer, Valida9on, Lean Manufacturing, Change Control, Con9nuous Improvement, current Good Manufacturing Prac9ces (cGMP) and CAPA. In the past 13 years, he has worked with Schering-‐Plough (SP), Ecolab (ECL) and currently with Vela Diagnos9cs (VelaDx) within the Pharmaceu9cal, Hygiene Chemicals and Medical Devices industries. Choon How has a Specialist Diploma in Biomedical Engineering from Singapore Polytechnic (SP), a MBA from Southern Cross University (SCU) and Bachelor of Science (BSc) from Na9onal University of Singapore (NUS). He is one of the recipients for SCU’s top academic achievement award and valedictorian in SCU Gradua9on 2008. He is an ac9ve member of the Community of 25 February 2013 Prac9ces (CoPs) within the industries and in sharing the 2 best prac9ces and technologies.
- 3. CONTENT I. Process Validation Lifecycle Approach Overview • History and development • FDA’s Process Validation Guidance • cGMPs and process validation for drug manufacturing 25 FEBRUARY 2013 3
- 4. CONTENT II. FDA Process Validation Guidance • Stage 1 – Process design may be generally described as “process understanding” • Stage 2 – Process qualification may be described as “validation performance” • Stage 3 – Continued process verification may be simply described as “maintaining validation” 25 FEBRUARY 2013 4
- 5. CONTENT III. Critical Documentation Requirements • Validation policy documents • Process design documents • Process qualification documents • Continued process verification 25 FEBRUARY 2013 5
- 6. CONTENT IV. Interactive Exercise – Case Study • Attendees participate in an exercise on submission preparation and inspection readiness for the process validation of an API 25 FEBRUARY 2013 6
- 7. I. Process Validation Lifecycle Approach Overview 25 FEBRUARY 2013 7
- 8. History and Development 25 FEBRUARY 2013 8
- 9. FDA’s Process Validation Guidance • Notified industry in 2006 • Issued in draft Nov 2008 • Most recent issue Jan 2011 Rev 1 • “reflection of industry practice” • PDA SAB formed a committee to collect and collate member comments 25 FEBRUARY 2013 9
- 10. FDA’s Process Validation Guidance • Introduction “This guidance outlines the general principles and approaches that FDA considers appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances), collectively referred to in this guidance as drugs or products. This guidance incorporates principles and approaches that all manufactured can use to validate manufacturing processes.” 25 FEBRUARY 2013 10
- 11. FDA’s Process Validation Guidance • Introduction “The lifecycle concept links product and process development, qualification of the commercial process, and maintenance of the process in a state of control during routine commercial production.” 25 FEBRUARY 2013 11
- 12. FDA’s Process Validation Guidance • Introduction This guidance covers the following categories of drugs: − Human drugs − Veterinary drugs − Biological and biotechnology products − Finished products and active pharmaceutical ingredients (APIs or drug substances) − The drug constituent of a combination (drug and medical device) product 25 FEBRUARY 2013 12
- 13. cGMPs and Process Validation for Drug Manufacturing • The Validation Process 25 FEBRUARY 2013 13
- 14. II. FDA Process Validation Guidance 25 FEBRUARY 2013 14
- 15. II. FDA Process Validation Guidance • Process validation (FDA 1987) is defined as establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. 25 FEBRUARY 2013 15
- 16. II. FDA Process Validation Guidance • For purpose of the guidance, process validation (FDA 2011) is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product. 25 FEBRUARY 2013 16
- 17. II. FDA Process Validation Guidance • Process validation involves a series of activities taking place over the lifecycle of the product and process. The guidance describes process validation activities in three stages. o Stage 1 – Process Design o Stage 2 – Process Qualification o Stage 3 – Continued Process Verification 25 FEBRUARY 2013 17
- 18. Stage 1 – Process Design • The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities. • Process design may be generally described as “process understanding” and “pre-qualification”. 25 FEBRUARY 2013 18
- 19. Stage 2 – Process Qualification • During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing. • Process qualification may be described as “validation performance” and “manufacturing qualification”. 25 FEBRUARY 2013 19
- 20. Stage 3 – Continued Process Verification • Ongoing assurance is gained during routine production that the process remains in a state of control. • Continued process verification may be simply described as “maintaining validation” or “life cycle qualification”. 25 FEBRUARY 2013 20
- 21. II. FDA Process Validation Guidance 25 FEBRUARY 2013 21
- 22. III. Critical Documentation Requirements 25 FEBRUARY 2013 22
- 23. III. Critical Documentation Requirements 25 FEBRUARY 2013 23
- 24. III. Critical Documentation Requirements • Validation policy documents • Process design documents • Process qualification documents • Continued process verification 25 FEBRUARY 2013 24
- 25. III. Critical Documentation Requirements 25 FEBRUARY 2013 25
- 26. III. Critical Documentation Requirements 25 FEBRUARY 2013 26
- 27. 25 FEBRUARY 2013 27
- 28. IV. Interactive Exercise – Case Study 25 FEBRUARY 2013 28
- 29. IV. Interactive Exercise – Case Study Process Validation of an API: An exercise in Submission Preparation and Inspection Readiness 25 FEBRUARY 2013 29
- 30. IV. Interactive Exercise – Case Study • 3 Stages of Process Validation 25 FEBRUARY 2013 30
- 31. IV. Interactive Exercise – Case Study • Relationship of Process Validation to Submission Preparation and PAI 25 FEBRUARY 2013 31
- 32. IV. Interactive Exercise – Case Study Process Validation of an API 25 FEBRUARY 2013 32
- 33. IV. Interactive Exercise – Case Study • Define the Process to Validate 25 FEBRUARY 2013 33
- 34. IV. Interactive Exercise – Case Study • Phase 1: Define the Manufacturing Process 25 FEBRUARY 2013 34
- 35. IV. Interactive Exercise – Case Study • Phase 2: Process Validation Stage 1 Stage 2 Stage 3 25 FEBRUARY 2013 35
- 36. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification 25 FEBRUARY 2013 36
- 37. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification 25 FEBRUARY 2013 37
- 38. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification – Ishikawa Diagram 25 FEBRUARY 2013 38
- 39. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification – Critical Process Parameters (CPPs) CPP is the identification of process parameters as critical based on the review of current data for acceptable and operating ranges for these parameters. 25 FEBRUARY 2013 39
- 40. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification – Critical Process Parameters 25 FEBRUARY 2013 40
- 41. IV. Interactive Exercise – Case Study • Stage 1: Pre-Qualification – API Pre- Qualification Report 25 FEBRUARY 2013 41
- 42. IV. Interactive Exercise – Case Study • Stage 2: Manufacturing Qualification 25 FEBRUARY 2013 42
- 43. IV. Interactive Exercise – Case Study • Stage 2: Manufacturing Qualification – API Manufacturing Report Batch #1 Batch #2 Batch #3 25 FEBRUARY 2013 43
- 44. IV. Interactive Exercise – Case Study • Stage 3: Life Cycle Qualification 25 FEBRUARY 2013 44
- 45. IV. Interactive Exercise – Case Study • Phase 2: Process Validation – Lists, References and Reports for the Validated Process 25 FEBRUARY 2013 45
- 46. IV. Interactive Exercise – Case Study Submission Preparation and Inspection Readiness 25 FEBRUARY 2013 46
- 47. IV. Interactive Exercise – Case Study • API Validation Team Membership 25 FEBRUARY 2013 47
- 48. IV. Interactive Exercise – Case Study • Coordinating Roles and Responsibilities 25 FEBRUARY 2013 48
- 49. IV. Interactive Exercise – Case Study API NDA / ANDA Submission Preparation 25 FEBRUARY 2013 49
- 50. IV. Interactive Exercise – Case Study • Drug Substance – Chemistry, Manufacturing and Controls Information A. Manufacturers B. Description of Manufacturing Process and Process Controls 1. Flow Diagram 2. Description of the Manufacturing Process and Process Controls 3. Reprocessing, Reworking and Other Operations 25 FEBRUARY 2013 50
- 51. IV. Interactive Exercise – Case Study • Drug Substance – Chemistry, Manufacturing and Controls Information C. Control of Materials 1. Starting Materials 2. Reagents, Solvents, and Auxiliary Materials 3. Diluents D. Control of Critical Steps and Intermediates E. Process Validation and / or Evaluation F. Manufacturing Process Development 25 FEBRUARY 2013 51
- 52. IV. Interactive Exercise – Case Study Pre-Approval Inspection Readiness 25 FEBRUARY 2013 52
- 53. IV. Interactive Exercise – Case Study • API Site Approval Master Plan 1. Product Description 2. Process − Manufacturing Instructions − Historical Batch Performance − Process Development − Support Validations − Process Equipment 25 FEBRUARY 2013 53
- 54. IV. Interactive Exercise – Case Study • API Site Approval Master Plan 3. Analytical − Lab Practices − Analytical Equipment − Lab Investigations and Method Issues − Method Validation and Qualification: Site specific and Outsourced methods 25 FEBRUARY 2013 54
- 55. IV. Interactive Exercise – Case Study • API Site Approval Master Plan 4. Facility − Systems and Utilities − PM/Calibration − Change Over / Cleaning − Support Equipment (ie Freezers, stopper and glass washers etc) − Environmental Monitoring 25 FEBRUARY 2013 55
- 56. IV. Interactive Exercise – Case Study • API Site Approval Master Plan 5. Quality and Compliance − Quality Agreements − Investigations/Deviations Review/Remediation − CAPA closeouts − Training − Raw Material and Component Management − Storage and Warehousing 25 FEBRUARY 2013 56
- 57. IV. Interactive Exercise – Case Study • API Site Approval Master Plan 6. Supply Chain − Shipping Procedures − Shipping Validation 7. Stability 25 FEBRUARY 2013 57
- 58. IV. Interactive Exercise – Case Study • Summary 1. Define Manufacturing Process prior to the start of Process Validation. 2. Officiate a Validation Team including members from Process, Manufacturing, QA and RA. 3. Review of protocols and reports to ensure the 3 stages of Process Validation are completed 4. Coordinate with the team on the validation document for Submission Preparation and Inspection Readiness 25 FEBRUARY 2013 58
- 59. Bonus Material 25 FEBRUARY 2013 59
- 60. Bonus Material - A template of process valida;on protocol 25 FEBRUARY 2013 60
- 61. 25 FEBRUARY 2013 61