A Lifecycle Approach to Process Validation

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A history and overview of the 2011 FDA Guidance on Process Validation and the subsequent documentation requirements.

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  • Good learning presentation. Can I get a copy at sunil_doda.78@rediff.com
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  • Great slides. I was following some of the FDA’s process validation concepts when I dropped into this slide. It is an interesting one.
    FDA is now trying to introduce QbD into pre-market processes. In a recent seminar there was a discussion over it and also over the relevance of QbD on process validation. One should check it out.
    In that seminar there was also an introduction of Validator, a software product by Compliance Associates ( www.complianceassociates.ca ) which adhere QbD principles and process validation principles.
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  • Good Presentation. Very updated.
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  • GOOD ANALYSIS ON LIFE CYCLE APPROACH.
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A Lifecycle Approach to Process Validation

  1. 1. VALIDATION BOOT CAMP A LIFECYCLE APPROACH TO PROCESS VALIDATION – PRINCIPLES, IMPLEMENTATION AND PRACTICESSeow Choon How, BSc (Chemistry), MBA, Production Manager,Vela Operations Singapore Pte Ltd25  FEBRUARY  2013   1  
  2. 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. 3. CONTENTI.  Process Validation Lifecycle Approach Overview •  History and development •  FDA’s Process Validation Guidance •  cGMPs and process validation for drug manufacturing25  FEBRUARY  2013   3  
  4. 4. CONTENTII.  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. 5. CONTENTIII.  Critical Documentation Requirements •  Validation policy documents •  Process design documents •  Process qualification documents •  Continued process verification25  FEBRUARY  2013   5  
  6. 6. CONTENTIV.  Interactive Exercise – Case Study •  Attendees participate in an exercise on submission preparation and inspection readiness for the process validation of an API25  FEBRUARY  2013   6  
  7. 7. I. Process Validation Lifecycle Approach Overview25  FEBRUARY  2013   7  
  8. 8. History and Development25  FEBRUARY  2013   8  
  9. 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 comments25  FEBRUARY  2013   9  
  10. 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. 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. 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) product25  FEBRUARY  2013   12  
  13. 13. cGMPs and Process Validation for Drug Manufacturing •  The Validation Process25  FEBRUARY  2013   13  
  14. 14. II. FDA Process Validation Guidance25  FEBRUARY  2013   14  
  15. 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. 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. 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 Verification25  FEBRUARY  2013   17  
  18. 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. 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. 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. 21. II. FDA Process Validation Guidance25  FEBRUARY  2013   21  
  22. 22. III. Critical Documentation Requirements25  FEBRUARY  2013   22  
  23. 23. III. Critical Documentation Requirements25  FEBRUARY  2013   23  
  24. 24. III. Critical Documentation Requirements •  Validation policy documents •  Process design documents •  Process qualification documents •  Continued process verification25  FEBRUARY  2013   24  
  25. 25. III. Critical Documentation Requirements25  FEBRUARY  2013   25  
  26. 26. III. Critical Documentation Requirements25  FEBRUARY  2013   26  
  27. 27. 25  FEBRUARY  2013   27  
  28. 28. IV. Interactive Exercise – Case Study25  FEBRUARY  2013   28  
  29. 29. IV. Interactive Exercise – Case Study Process Validation of an API: An exercise in Submission Preparation and Inspection Readiness25  FEBRUARY  2013   29  
  30. 30. IV. Interactive Exercise – Case Study •  3 Stages of Process Validation25  FEBRUARY  2013   30  
  31. 31. IV. Interactive Exercise – Case Study •  Relationship of Process Validation to Submission Preparation and PAI25  FEBRUARY  2013   31  
  32. 32. IV. Interactive Exercise – Case Study Process Validation of an API25  FEBRUARY  2013   32  
  33. 33. IV. Interactive Exercise – Case Study •  Define the Process to Validate25  FEBRUARY  2013   33  
  34. 34. IV. Interactive Exercise – Case Study •  Phase 1: Define the Manufacturing Process25  FEBRUARY  2013   34  
  35. 35. IV. Interactive Exercise – Case Study •  Phase 2: Process Validation Stage 1 Stage 2 Stage 325  FEBRUARY  2013   35  
  36. 36. IV. Interactive Exercise – Case Study •  Stage 1: Pre-Qualification25  FEBRUARY  2013   36  
  37. 37. IV. Interactive Exercise – Case Study •  Stage 1: Pre-Qualification25  FEBRUARY  2013   37  
  38. 38. IV. Interactive Exercise – Case Study •  Stage 1: Pre-Qualification – Ishikawa Diagram25  FEBRUARY  2013   38  
  39. 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. 40. IV. Interactive Exercise – Case Study •  Stage 1: Pre-Qualification – Critical Process Parameters25  FEBRUARY  2013   40  
  41. 41. IV. Interactive Exercise – Case Study •  Stage 1: Pre-Qualification – API Pre- Qualification Report25  FEBRUARY  2013   41  
  42. 42. IV. Interactive Exercise – Case Study •  Stage 2: Manufacturing Qualification25  FEBRUARY  2013   42  
  43. 43. IV. Interactive Exercise – Case Study •  Stage 2: Manufacturing Qualification – API Manufacturing Report Batch  #1   Batch  #2   Batch  #3  25  FEBRUARY  2013   43  
  44. 44. IV. Interactive Exercise – Case Study •  Stage 3: Life Cycle Qualification25  FEBRUARY  2013   44  
  45. 45. IV. Interactive Exercise – Case Study •  Phase 2: Process Validation – Lists, References and Reports for the Validated Process25  FEBRUARY  2013   45  
  46. 46. IV. Interactive Exercise – Case Study Submission Preparation and Inspection Readiness25  FEBRUARY  2013   46  
  47. 47. IV. Interactive Exercise – Case Study •  API Validation Team Membership25  FEBRUARY  2013   47  
  48. 48. IV. Interactive Exercise – Case Study •  Coordinating Roles and Responsibilities25  FEBRUARY  2013   48  
  49. 49. IV. Interactive Exercise – Case Study API NDA / ANDA Submission Preparation25  FEBRUARY  2013   49  
  50. 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 Operations25  FEBRUARY  2013   50  
  51. 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 Development25  FEBRUARY  2013   51  
  52. 52. IV. Interactive Exercise – Case Study Pre-Approval Inspection Readiness25  FEBRUARY  2013   52  
  53. 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 Equipment25  FEBRUARY  2013   53  
  54. 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 methods25  FEBRUARY  2013   54  
  55. 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 Monitoring25  FEBRUARY  2013   55  
  56. 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 Warehousing25  FEBRUARY  2013   56  
  57. 57. IV. Interactive Exercise – Case Study •  API Site Approval Master Plan 6.  Supply Chain −  Shipping Procedures −  Shipping Validation 7.  Stability25  FEBRUARY  2013   57  
  58. 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 Readiness25  FEBRUARY  2013   58  
  59. 59. Bonus Material25  FEBRUARY  2013   59  
  60. 60. Bonus Material - A  template  of   process  valida;on  protocol  25  FEBRUARY  2013   60  
  61. 61. 25  FEBRUARY  2013   61  

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