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# Application of Quality Risk Management in Commissioning & Qualifcation

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This presentation presents how Quality Risk management can be applied in Commissioning & Qualification of Facility , System and Equipments in Pharmaceutical Facilities.

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### Application of Quality Risk Management in Commissioning & Qualifcation

1. 1. www.drugregulations.org 1 Presentation prepared by Drug Regulations – a not for profit organization. Visit www.drugregulations.org for the latest in Pharmaceuticals.
2. 2.  This presentation will cover 1. Overview of Quality Risk Management Process 2. Application of QRM in Commissioning & Qualification. www.drugregulations.org 2
3. 3. www.drugregulations.org 3
4. 4. www.drugregulations.org 4
5. 5. www.drugregulations.org 5
6. 6. 6  Individual: Risk is a cognitive and emotional response to expected loss.  Society: Risk is a societal expression of expected harm tempered by expected benefits.  Technical: Risk is usually based on the expected value of the conditional probability of the event occurring X the consequence of the event given that it has occurred.
7. 7.  Risk ◦ Combination of ◦ Probability of occurrence of harm and ◦ Severity of that harm.  Harm ◦ Damage to Health including the damage that can occur from the loss of Product Quality or availability.  Hazard : Potential Source of Harm
8. 8.  Which consequence is more severe? ◦ 300 lives lost in single, fiery plane crash. ◦ 300 lives lost on roads over a weekend. ◦ 300 lives potentially lost from cancer within the next 20 years  Which probability is probable? What does a “30% chance of rain tomorrow” mean? ◦ 30% of the days like tomorrow will have at least a trace of rain. ◦ 30% of the area will have rain tomorrow. ◦ 30% of the time tomorrow, it will rain.
9. 9. Hazard may cause harm Hazard may not cause harm uncertainty Hazard is less likely to cause harm Manage risks in relation to probability Lack of, or inadequate knowledge
10. 10. Time  ProcessParameter Lower Specification Limit (LSL) Upper Specification Limit (USL) today Uncertainty RISK: For a given severity of risk event, what are the chances (probability) of exceeding the USL in the next period of time? Tomorrow ?
11. 11. Time  ProcessParameter Lower Specification Limit (LSL) Upper Specification Limit (USL) today Uncertainty RISK: Control options are scenarios for risk management. Note that this scenario shows the best estimate is below the USL. Tomorrow ?
12. 12. Time  ProcessParameter Lower Specification Limit (LSL) Upper Specification Limit (USL) today Uncertainty Take a cut at a moment in time: Risk has a distribution. Tomorrow ?
13. 13.  Risk Identification What might go wrong? Risk Assessment www.drugregulations.org 13 Risk Review RiskCommunication Risk Assessment Risk Evaluation unacceptable Risk Control Risk Analysis Risk Reduction Risk Identification Review Events Risk Acceptance Initiate Quality Risk Management Process Output / Result of the Quality Risk Management Process RiskManagementtools
14. 14.  System Risk (facility & people) ◦ e.g. interfaces, operators risk, environment, components such as equipment, IT, design elements  System Risk (organisation) ◦ e.g. Quality systems, controls, measurements, documentation, regulatory compliance  Process Risk ◦ e.g. process operations and quality parameters  Product Risk (safety & efficacy) ◦ e.g. quality attributes: measured data according to specifications
15. 15.  Risk Identification What might go wrong?  Risk Analysis What is the likelihood (probability) it will go wrong  What are the consequences (severity)?  Risk Evaluation What is the level of risk? Any mitigating factors? Risk Assessment www.drugregulations.org 15 Risk Review RiskCommunication Risk Assessment Risk Evaluation unacceptable Risk Control Risk Analysis Risk Reduction Risk Identification Review Events Risk Acceptance Initiate Quality Risk Management Process Output / Result of the Quality Risk Management Process RiskManagementtools
16. 16.  Risk Identification What might go wrong?  Risk Analysis What is the likelihood (probability) it will go wrong  What are the consequences (severity)?  Risk Evaluation What is the level of risk? Any mitigating factors? Risk Assessment www.drugregulations.org 17 Risk Review RiskCommunication Risk Assessment Risk Evaluation unacceptable Risk Control Risk Analysis Risk Reduction Risk Identification Review Events Risk Acceptance Initiate Quality Risk Management Process Output / Result of the Quality Risk Management Process RiskManagementtools  Risk Reduction Mitigation or avoidance of quality risk Elimination of risks, where appropriate Risk Control  Risk Acceptance Acceptance of Residual Risk
17. 17. 18 Start End Risk identification Risk analysis Etc. Process- step Decision Feedback procedure Start End Start End Sub- process Sub-Sub- process
18. 18. Should risks be assessed? Are there clear rules for decision making? e.g. regulations Yes “no RM“ Risk assessment not required (No flexibility) Follow procedures (e.g. Standard Operating Procedures) Document results, decisions and actions CONSIDERATIONS 1. What might go wrong? 2. What is the likelihood (probability) it will go wrong? 3. What are the consequences (severity)?No or justification needed Can you answer the risk assessment questions? Yes “informal RM“ Initiate Risk assessment (risk identification, analysis & evaluation) Run risk control (select appropriate measures) Agree on a team (small project) Select a Risk Management tool (if appropriate e.g. see ICH Q9 Annex I) No “formal RM“ Carry out the quality risk management process Document the steps www.drugregulations.org 19
19. 19.  Supporting statistical tools ◦ Acceptance Control Charts (see ISO 7966) ◦ Control Charts (for example)  Control Charts with Arithmetic Average and Warning Limits (see ISO 7873)  Cumulative Sum Charts; “CuSum” (see ISO 7871)  Shewhart Control Charts (see ISO 8258)  Weighted Moving Average ◦ Pareto Charts ◦ Process Capability Analysis ◦ Histograms ◦ Design of Experiments (DOE) ◦ Use others that you are familiar with…. www.drugregulations.org 21
20. 20.  Risk Assessment is not an “Exact science”.  There is no such thing as “Zero” “ Risk”  What you need to decide is “ What is acceptable Risk”  Risk Management is not an “one off” activity.
21. 21. The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk ICH Q9
22. 22. Systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle ICH Q9
23. 23. Applications in Commissioning & Qualifications www.drugregulations.org 25
24. 24. www.drugregulations.org 26
25. 25. www.drugregulations.org 27
26. 26.  Centered around Documentation  Guidance was not Followed as intended  Criteria not used to gain comprehensive understating of the Product , Process and System www.drugregulations.org 28
27. 27. www.drugregulations.org 29 Scope and Extent of Qualification If Everything is critical then nothing is
28. 28. www.drugregulations.org 30
29. 29.  ASTM E 2500 -07  A consensus standard based on sound scientific, engineering and Quality Principles  Focus on product & process design through detailed requirements and mitigating risks in the Design Phase www.drugregulations.org 31
30. 30.  Focus on that which affects Product Quality  Process User Requirements Key to acceptability  Risk Assessment and Process Knowledge used to identify Critical Elements  Only critical features/ functions are qualified  Use of Supplier Documents www.drugregulations.org 32
31. 31.  Science & Risk based approach to assure that GMP Equipment & Systems are ◦ Fit for Intended Use ◦ Have been properly Installed ◦ Are Operating Correctly  Extent of Verification & Level of Detail ◦ Risk to Product Quality ◦ Risk to Patient Safety ◦ Complexity & Novelty of Manufacturing System www.drugregulations.org 33
32. 32.  Critical Quality Attribute ◦ Physical ,chemical, biological or microbiological property that should be within appropriate limit , range or distribution to ensure desired product Quality  Critical Process parameter ◦ A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure process produces desired quality. www.drugregulations.org 34
33. 33.  Critical Aspects are ◦ Functions, Features, abilities and Performance & Quality Characteristics To Ensure Consistent Product Quality & Patient Safety ◦ Should be identified & documented based on scientific product & process understanding. ◦ Verification should focus on these aspects. www.drugregulations.org 35
34. 34. www.drugregulations.org 36 ASTM E 2500 : System Life Cycle & Validation Approach
35. 35. www.drugregulations.org 37 ASTM E 2500 : System Life Cycle & Validation Approach
36. 36. www.drugregulations.org 38 ASTM E 2500 : System Life Cycle & Validation Approach
37. 37. www.drugregulations.org 39 ASTM E 2500 : Life Cycle Phases
38. 38. www.drugregulations.org 40 ASTM E 2500 : System Life Cycle & Validation Approach
39. 39.  Step 1 : Planning and Documentation  VMP  Verification Team and Responsibilities  Document Matrix  Eligible Vendor Documentation  Select Risk Assessment Tool  FMEA can be used to Identify & Evaluate “CRITICAL ASPECTS” of a Manufacturing System.  Engineering Change Notification  Process to document & approve modifications that occur during system design , startup & Verification  Applicability to regulatory laws & expectations must be justified  www.drugregulations.org 41
40. 40.  Step 2 : Identify Subject Matter Expert  SME’s are responsible for Specifications, Design & Verification  Individuals with specific expertise & responsibility in a particular area www.drugregulations.org 42
41. 41.  Step 3 : Requirements Definition  Process Engineering SME’s develop these  Identify specific requirements  Used further for Specifications, Design & Verification www.drugregulations.org 43
42. 42.  Step 4 : Risk Assessment  SME’s conduct FMEA as a design review  Identify “CRITICAL ASEPCTS” that affect systems Installation , Operation and Performance.  Identify Control & Verification techniques to manage risks to an acceptable levels www.drugregulations.org 44
43. 43.  Step 5 : Specification & Design  Leverage Qualified Vendor Expertise ( SME) to identify & document elements which may affect Critical Quality Attributes  Communicate factors that impact product quality to the system designer  Strive to mitigate product quality & patient risks through design  Functional Specifications provide acceptance criteria for functional tests specified in the verification plan  SME’s translate URS into system description & functional specification www.drugregulations.org 45
44. 44.  Step 6 : Verification Plan  Verify the critical Aspects of the Manufacturing System  Design  Properly installed  Operate correctly  Are fit for intended use www.drugregulations.org 46
45. 45.  Step 6 : Verification Plan consists of ◦ Inventory Verification List & Verification Test Matrix  Inventory Verification List  Identifies all necessary system design & Verification documentation  Serves as a Document acquisition checklist  Contains : URS , FS, HSD , SDS , P & ID’s , Electrical & Mechanical Drawings , manuals, a risk analysis report , Verification Testing Matrix , Verification Protocol & Report www.drugregulations.org 47
46. 46.  Step 6 : Verification Plan consists of  Verification Test Matrix  Identifies Critical Testing based on Risk Levels, Design Documentation & SME Input  Identifies Chronological point when testing will be done ◦ Factory , Installation , Start up , Qualification  NON CRITICAL ASPECTS are documented using the IVL checklist .  Do not require SME oversight or QA Personnel.  CRITICAL ASPECTS require SME scrutiny & documented in Verification Test Protocol ◦ www.drugregulations.org 48
47. 47.  Step 6 : Verification Plan consists of  Verification Test Matrix  Acceptance criteria are derived from Functional Requirements in : URS & FS  VTP lists test to mitigate High Risk aspects  Tests to demonstrate system functionality, features, capacity, and output quality.  Critical Tests are generally executed only once. www.drugregulations.org 49
48. 48.  Step 6 : Verification Plan consists of  Verification Test Matrix  VTP contains only the critical testing necessary to verify that  A system is properly installed  It operates correctly  Fit for its intended use www.drugregulations.org 50
49. 49.  Step 6 : Verification Plan consists of  Verification Test Matrix  VTP organizes testing as it pertains to  Installation/ Utility Verification  Startup/ Operation Verification  Functional / Performance Verification  These phases can be used to satisfy Annex 15 requirements. www.drugregulations.org 51
50. 50.  Step 6 : Verification Plan consists of  Verification Test Matrix  The value of VTP is isolation of CRITICAL TESTING needed to verify a system.  CRITICAL TESTING is reviewed by SME & QA  Other testing and documentation are moved to IVL checklist. www.drugregulations.org 52
51. 51.  Step 7 : Verification Plan Execution  Verification Test Matrix identifies when testing document acquisition for the IVL & VTP will happen  Testing may be performed as a part of FAT / SAT protocols or  Performed according to test functions within a VTP  Testing of NON CRITICAL ASPECTS is more simply verified using IVL www.drugregulations.org 53
52. 52.  Step 8 : SYSTEM Verification Report  Reviews testing conducted during System Design , Fabrication , Installation , Start Up & Verification.  Report is written by an Independent SME  Independent review of protocol exceptions , deviations & punch list  Summarizes system performance data  Concludes whether the system is or is not FIT FOR INTENDED USE www.drugregulations.org 54
53. 53.  Step 9 : GMP Release  Performed by QA  QA verifies compliance with other other GMP systems : Training , calibration , maintenance, operating procedures & change Management.  Step 10 : GMP operation & Change Management  Modifications are controlled through Change Management with focus on CRITICAL ASPECTS & SYSTEM PERFORMACE www.drugregulations.org 55
54. 54. www.drugregulations.org 56 ASTM E 2500
55. 55. www.drugregulations.org 57
56. 56. www.drugregulations.org 59 Presentation prepared by Drug Regulations – a not for profit organization. Visit www.drugregulations.org for the latest in Pharmaceuticals.