Concept to risk management ( In context to Q9)

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A Brief concept to Risk assessment analysis…..
(where we stand ?) In context to ICH Q9….

Concept to risk management ( In context to Q9)

  1. 1. A Brief concept to Risk assessment analysis….. (where we stand ?) In context to Q9…. We are living in full of risk…. Risk management not new… Zero risk does not exist anywhere… Presented by Subhakanta Dhal . Mail id-sdhal82@gmail.com 1
  2. 2. Risk of life…. . 2
  3. 3. Examples of Everyday Risk POSSIBLE RISK/ EVENT/ SCENARIO STRATEGIC FINANCIAL OPERATIONAL Including: Governance, Stakeholder Relationships, Reputation, Environment Including Capital Management, Budgeting, Revenue and Expenditure, Reporting CLINICAL (HEALTHCARE) Including Human Resources, OH&S, Procurement, Legislative, Asset Management Changes in services provided Incorrect valuation of capital assets Medication errors Power failure Loss of customers to private sector companies Declining market value of assets Services/ goods not provided within budget Capital assets not maintained/ deterioration Patient aggression Tender evaluation requirements not defined Change in public demand for services/ products Equipment obsolescence Sentinel events Overpayment for goods and services Change in public demand for services/ products Customer revenue/ collections targets not met Incorrect diagnosis Failure to comply with procurement legislation/ processes Loss of customers to other state organisation Unauthorised and irregular expenditure Infection control procedures not followed Conflicts of interest in tender award process Political change Wasteful or unproductive expenditure Failure to report incidents Failure/ closure of service provider Poor market knowledge Changes in funding allocations Patient records not available/incomplete/incorrect Unethical service provider actions Change in interest rates Over/ under spending budget allocations Not upto mark of ethical standards Goods/ services not meeting quality requirements Stakeholders not identified Inaccurate revenue forecasting Terrorist attack/ Bomb threat etc. Non-delivery of goods and services by supplier 3
  4. 4. Contents Concept based • Terminology • Define- Risk & Type • ICH and FDA : Expectation • Identify - what is risk ? • Measure – how to mitigate risk And how much extend ? • Improve & Analysis –how to improve ? Specific method ? • Control – can risk be controlled? If controlled then how ? • Root cause analysis • Opportunities & Benefits. • Potential Applications. • Future prospective Case study • FMEA 4
  5. 5. ICH Framework (Q8,Q9,Q1O).... Product Life Cycle Product Design Process Design Scale-up & Transfer Commercial Manufacture ICH Q8/Q8(R) - Pharmaceutical Development PAT Guidance ICH Q9 – Quality Risk Management ICH Q10 – Pharmaceutical Quality Systems Product
  6. 6. ICH Framework (Q8,Q9,Q1O)....
  7. 7. Product development concept.. In line with Quality Risk Management ?
  8. 8. Product development concept.. Initiate Quality Risk Management Process Formulation & Process design Risk Assessment Risk Identification Risk Analysis Process understanding Risk Evaluation Product release Concept Regulatory strategy Ris k Commun ic at ion Process control Concept unacceptable Risk Control Risk Reduction Risk Acceptance Output / Result of the Quality Risk Management Process Risk Review Review the submission Review Events R isk Ma nage ment t ools Manufacturing Concept
  9. 9. Role of risk Product development concept.. Drug substance properties; prior knowledge Proposed formulation and manufacturing process Research Determination of Cause – Effect relationships (Risk Identification with subsequent Risk Analysis) Phase 1 Risk-based classification (Risk Evaluation) Parameters to investigate (e.g. by DOE) (Risk Reduction 1. proposal; 2. verified) FORMULATION DESIGN SPACE Operation Phase 2 Product and process characteristics on the final drug product CONTROL STRATEGY PROCESS DESIGN SPACE BY UNIT OPERATION Review events Launch Process understanding Re-evaluation and confirmation Formulation understanding Developm. Re-evaluation and confirmation Development Target Product Profile Phase 3 EFPIA PAT TG, 2006
  10. 10. Risk Management approach to focus on critical attributes Unit operation Quality Attributes Dispensing Dissolution Disintegration Hardness Assay Content Uniformity Degradation Stability Appearance Identification Water Microbiology Granulation Drying Blending Tableting Significant influence Initial assessment Prior knowledge First & Second review cycle Formulation and Process understanding Third review cycle Control Strategy EFPIA PAT TG, 2006
  11. 11. What Risks Must Be Managed? Risk to safety of patients, users, handlers Business Regulatory Product liability 11
  12. 12. . Terminology Risk: The combination of the probability of occurrence of harm and the severity of that harm . Risk Acceptance: The decision to accept risk . Hazard: The potential source of harm. Risk Analysis: The estimation of the risk associated with the identified hazards. Risk Assessment: A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. Risk Communication: The sharing of information about risk and risk management between the decision maker and other stakeholders. Risk Control: Actions implementing risk management decisions . Risk Evaluation: The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk. Risk Identification: The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description 12
  13. 13. Terminology . Risk Management: The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating and reviewing risk. Risk Reduction: Actions taken to lessen the probability of occurrence of harm and the severity of that harm. Risk Review: Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. Severity: A measure of the possible consequences of a hazard. Stakeholder: Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority, and industry. Decision Maker(s):Person(s) with the competence and authority to make appropriate and timely quality risk management decisions. Detectability:The ability to discover or determine the existence, presence, or fact of a hazard. Harm: Damage to health, including the damage that can occur from loss of product quality or availability. 13
  14. 14. ICH and FDA :Expectation ICH Q9 Link back to patient risk Opportunities to impact risk using quality risk management Design Process Materials Facilities Manufacturing Distribution Patient
  15. 15. ICH and FDA :Expectation Risk Management across the Product lifecycle for drug (medicinal) products Research Preclinical Phase Clinical Phases End of life cycle Launch Manufacturing & Distribution GLP Safety GCP(clinical) Efficacy GMP GDP (Distribution ) Quality ICH Q9
  16. 16. ICH and FDA :Expectation FDA Pharmaceutical GMP Initiative A Challenge to Industry: (FDA announcement 27 Sep. 2004) At the end of the cGMP Initiative the pharmaceutical community has arrived at a crossroad; one path goes towards the desired state and the other maintains the current state. The path towards the desired state is unfamiliar to many while the current state provides the comfort of predictability. The Agency hopes the pharmaceutical community will choose to move towards the desired state. Why was ICH Q9 ( Quality risk management ) needed? •The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient. •A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product. •The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk. •To facilitate moving to the “Desired State”. •To facilitate communication and transparency. 16
  17. 17. ICH and FDA :Expectation Regulators evaluate category of risk, based on: • Product, process and facility . • Controls to assess & mitigate risk . • Quality system implementation . Regulators determine ‘risk category’ and modify level of oversight accordingly for: • Post-approval change review . • GMP inspections . Result: • Removal of barriers to continuous improvement . • Efficient use of resources by industry & regulators . 17
  18. 18. ICH and FDA :Expectation… Increasing external requirements for best practice, transparency and compliance • Public / Community • Governments • Regulators • Patients • Investors / Creditors The Hurdles Growing complexity and scope of risks ? Increasing efforts and costs for sustainability • Globalisation “Multinational” • Multi-factor approaches • Regulatory expectations • Acceptance of risk and uncertainty • Documentation • Projects • Systems • Interfaces
  19. 19. ICH and FDA :Expectation Initiate Quality Risk Management Process Risk Assessment • Brainstorming Elementary Cause and Effect Assignments – Fishbone (Ishikawa) diagram – Failure mode/effect table • Fault tree analysis • Process map • Flow charts Risk Identification • Risk Analysis Risk Evaluation Risk Communication Risk Control Risk Reduction Risk Acceptance Risk Management Tools unacceptable • Output / Result of the • Quality Risk Management Process Risk Review Process sensors • SOP Data flow optimization • Review Events • FMEA • FMECA Risk ranking
  20. 20. Define risk… RISK = f (severity, probability) Risk has three components: •What could go wrong? •What is the probability of failing to achieve a particular outcome? •What is the impact of failing to achieve a particular outcome? Types of risk... 1. Positive risk and negative risk 2. Pure risk and business risk 3. Residual risk 4. Secondary risk 5. Known risk and unknown risk 6. Etc..... 20
  21. 21. Parameters for “calculating” risks A picture of the life cycle = Risk Priority Number Probability x Detectability x Severity Refers to Refers to Refers to past today future time
  22. 22. Define risk… Impact of risk ?  Individual: Risk is a cognitive and emotional response to expected loss.  Society: Risk is a societal expression of expected harm tempered by expected benefits.  Organizations: Risk is a combination of the probability of occurrence and severity of selected harms.  Technical: Risk is usually based on the expected value of the conditional probability of the event occurring times the consequence of the event given that it has occurred. Quality Risk Management is Not... •Hiding risks •Writing half the truth (e.g. in an investigation report) . •A means of removing industry’s obligation to comply with regulatory requirements . If we do Risk Management properly, we should be able to: • demonstrate that we understand what is important about our business; • have a documented, approved rationale for our decisions; • be proud to share these with regulatory agencies because they demonstrate our knowledge and logical thought processes. 22
  23. 23. Indentify Risk… Quality Degree to which a set of inherent properties of a product, system or process fulfills requirements Risk combination of the probability of occurrence of harm and the severity of that harm Management QRM Systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle
  24. 24. Indentify Risk… (Manage quality risks!....) Consequences What if disaster happens? Prior use of QRM may lower the consequences Nowadays QRM Using QRM Quality management as function of time
  25. 25. Indentify Risk…Who is responsible ? Responsibilities Teams include experts from the appropriate areas • Quality unit, •business development • engineering • regulatory affairs • production operations • sales and marketing • legal, statistics and clinical Decision maker •Take responsibility for coordinating quality risk management across various functions and departments. • Assure that a quality risk management process is defined, deployed and reviewed and that adequate resources are available. Initiating a Quality Risk Management Process •Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk; •Assemble background information and/ or data on the potential hazard, harm or human health impact relevant to the risk assessment; •Identify a leader and necessary resources; •Specify a timeline, deliverables and appropriate level of decision making for the risk management process. 25
  26. 26. Measure Risk… Measure Risk stage Risk assessment Risk identification Risk analysis Risk evaluation Risk Assessment -It consists of the identification of potential hazards and the analysis and evaluation of risks (harm) associated with those hazards. Sources of information.. • Manufacturer’s technical, operation and maintenance manuals • Equipment history cards • Breakdown data- types, frequency, criticality , downtime etc. • Quality Problems • Safety incidents – near misses, accidents • Qualifications status .............................. Etc 26
  27. 27. Measure Risk… Risk identification Identify possible sources of risk (problems , breakdowns etc.) by asking two basic often helpful questions: •What can go wrong? • What are the possible consequences? What can go wrong.. FBD example • Filter bag is damaged. • Bottom air inlet mesh damaged , • Air leaking through base joint. • Blower stops in between . • Required temperature not reached . • Vent joints/pipes developed leaks . • Blower motor jammed. • (Mechanical, electrical, instrument & other problems) ....... 27
  28. 28. Measure Risk… Risk analysis The estimation of the risk associated with the identified hazards. •Basically Two factors.. • Severity (S) ----consequences & Level of impact(s) • Occurrence (O) --- Probability of occurrence • Risk Score = Severity x Occurrence • Risk = S x O Severity & probability ratings.. Qualitative or Quantitative ratings are used to judge the extent of severity and probability of occurrence of the risk. • Qualitative Severity – Minor , Moderate, Critical etc. •Probability – high, medium, Low etc. • Quantitative Rating scales 1-3, 1-5, 1-10 etc. N.B-Guidelines need to be established for assigning appropriate rating. 28
  29. 29. Measure Risk… sample copy Risk Assessment work sheet Potential risk Failure Mode (what can go wrong ) (What can go wrong) Severity Probability (1-10) (10 is very List each failure mode 10 is Worst probable) Risk Score (High scores) Action plan Owner Due Date (need attention) 1.Solution a) b) c) 29
  30. 30. Measure Risk… Risk Evaluation •Risk scores are used to decide whether the risk is significant and requires further actions to reduce the level of risk (or otherwise accept and live with it) • This is done either by analyzing individual risk scores or by preparing “ Risk Evaluation Matrix”. • Appropriate control actions are initiated to reduce or handle the risk (mitigation). 30
  31. 31. Improve & Analysis…. Basic management facilitation method. (flow chart, check sheets, process mapping ,etc)  Failure Mode Effects Analysis (FMEA)  Failure Mode, Effects and Criticality Analysis (FMECA)  Fault Tree Analysis (FTA)  Hazard Analysis and Critical Control Points (HACCP)  Hazard Operability Analysis (HAZOP)  Preliminary Hazard Analysis (PHA)  Risk Ranking and Filtering  Supporting Statistical Tools 31
  32. 32. Improve & Analysis…. Failure Mode Effects Analysis (FMEA) 32
  33. 33. Improve & Analysis…. Failure Mode Effects Analysis (FMEA) •FMEA generates a living document that can be used to anticipate and prevent failures from occurring. FMEA is a systematic method to: 1. Recognize, evaluate, and prioritize potential failures and their effects . 2. Identify actions which could eliminate or reduce the chance of potential failure occurring . 3. Document and share the process . FMEA addresses : •Potential failures of product , process, system or machinery to meet requirements (failure mode) . •Potential consequences (failure effect) . • Potential causes of the failure mode (failure cause) . • Application of current controls . • Level of risk. • Risk reduction (additional controls) 33
  34. 34. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)….. •Types of FMEA System – Potential failure modes between the functions of the system caused by system deficiencies. Design – Failure modes caused by system deficiencies. Process – Failure modes caused by process design. Service – Failure modes caused by system or process deficiencies. 34
  35. 35. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Definition Failure :A proper function or performance (of product, process, equipment etc.) to meet a standard; not performing as required or expected. Failure Mode :The manner of failure . The way in which the product or process could fail to perform its intended function. Failure Effects : the consequences of failure. The outcome of the occurrence of the failure mode on the system, product, or process. Failure effects define the impact on the customer. Ranking is translated into “Severity” score . Failure Causes :Potential causes or reasons the failure mode could occur . •Likelihood of the cause creating the failure mode is translated into an “Occurrence” score Current Controls . •Mechanisms currently in place that will detect or prevent the failure mode from occurring . Ability to detect the failure before it reaches the customer is translated in “Delectability” score. 35
  36. 36. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… When to Use FMEA 1)When a process, product or service is being designed or redesigned. 2) When an existing process, product or service is being applied in a new way. 3) Before developing control plans for a new or modified process. 4) When analyzing failures of an existing process, product or service. 5) Periodically throughout the life of the process, product or service. Concept…A Team Tool • A team approach is necessary. • Team should be led by the Process Owner who is the responsible manufacturing engineer or technical person, or other similar individual familiar with FMEA. The following should be considered for team members: – formulation development team – Operators – Process team – Analytical team – Materials Suppliers – Suppliers – Customers 36
  37. 37. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Occurrence Rating Scale Rating 10 Description Potential Failure Rate Very High: Failure is almost inevitable. High: Failures occur almost as often as not. More than one occurrence per day or a probability of more than three occurrences in 10 events. One occurrence every three to four days or a probability of three occurrences in 10 events . 8 High: Repeated failures. One occurrence per week or a probability of 5 occurrences in 100 events . 7 High: Failures occur often. One occurrence every month or one occurrence in 100 events . 6 Moderately High: Frequent failures. Moderate: Occasional failures. Moderately Low: Infrequent failures. Low: Relatively few failures. Low: Failures are few and far between. One occurrence every three months or three occurrences in 1,000 events . Remote: Failure is unlikely. One occurrence in greater than five years or less than two occurrences in one billion events . 9 5 4 3 2 1 One occurrence every six months to one year or five occurrences in 10,000 events . One occurrence per year or six occurrences in 100,000 events . One occurrence every one to three years or six occurrences in ten million events . One occurrence every three to five years or 2 occurrences in one billion events . 37
  38. 38. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Severity Rating Scale Rating Description 10 9 Dangerously high Extremely high 8 7 6 Very high High Moderate 5 Low 4 Very Low 3 Minor 2 Very Minor 1 None Definition (Severity of Effect) Failure could injure the customer or an employee. Failure would create noncompliance with federal regulations. Failure renders the unit inoperable or unfit for use. Failure causes a high degree of customer dissatisfaction. Failure results in a subsystem or partial malfunction of the product. Failure creates enough of a performance loss to cause the customer to complain. Failure can be overcome with modifications to the customer’s process or product, but there is minor performance loss. Failure would create a minor nuisance to the customer, but the customer can overcome it without performance loss. Failure may not be readily apparent to the customer, but would have minor effects on the customer’s process or product. Failure would not be noticeable to the customer and would not affect the customer’s process or product. 38
  39. 39. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Detection Rating Scale Rating Description Definition 10 Absolute Uncertainty 9 Very Remote 8 Remote 7 Very Low 6 Low Product is 100% manually inspected using go/no-go or other mistake-proofing gauges. 5 Moderate Some Statistical Process Control (SPC) is used in process and product is final inspected off-line. 4 Moderately High 3 High 2 Very High 1 Almost Certain The product is not inspected or the defect caused by failure is not detectable. Product is sampled, inspected, and released based on Acceptable Quality Level (AQL) sampling plans. Product is accepted based on no defectives in a sample. Product is 100% manually inspected in the process. SPC is used and there is immediate reaction to out-of-control conditions. An effective SPC program high. All product is 100% automatically inspected. The defect is obvious or there is 100% automatic inspection with regular calibration and preventive maintenance of the inspection equipment. 39
  40. 40. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… 40
  41. 41. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Procedure 1. For each process input (start with high value inputs), determine the ways in which the input can go wrong (failure mode) 2. Severity (s) --For each failure mode, determine effects  Select a severity level for each effect ( scaled range 1 to 10 , 10-very serious)  Importance of the effect on customer requirements 3. Occurrence (o) ---Identify potential causes of each failure mode  Select an occurrence level for each cause ( scaled range 1 to 10 , 10-high like wood) 4. Detection (D)---List current controls for each cause.  Select a detection level for each cause. ( scaled range 1 to 10 , 10-canot detect)  The ability of the current control scheme to detect or prevent a given cause 5. Calculate the Risk Priority Number (RPN)= S x O x D 6. Develop recommended actions, assign responsible persons, and take actions  Give priority to high RPNs  MUST look at severities rated a 10 7. Assign the predicted severity, occurrence, and detection levels and compare RPNs 41
  42. 42. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… Inputs Outputs Brainstorming C&E Matrix Process Map Process History Procedures Knowledge FMEA List of actions to prevent causes or detect failure modes History of actions taken Experience 42
  43. 43. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… 43
  44. 44. Improve & Analysis…. Failure Mode Effects Analysis (FMEA)… 44
  45. 45. Improve & Analysis…. Failure Mode, Effects and Criticality Analysis (FMECA) Concept… •Failure Mode And Effects Analysis (FMEA ) might be extended to incorporate an investigation of the degree of severity of the consequences, their respective probabilities of occurrence, and their delectability, thereby becoming a Failure Mode Effect and Criticality Analysis . • Failure Modes = Incorrect behavior of a subsystem or component due to a physical or procedural malfunction. • Effects = Incorrect behavior of the system caused by a failure. • Criticality = The combined impact of the probability that a failure will occur & severity of its effect . •Failure Modes effects and Ccriticality Aanalysis (FMECA) = a step-by-step approach for identifying all possible failures in a design, a manufacturing or assembly process, or a product or service . Significance •The FMECA facilitates identification of potential design reliability problems •Identify possible failure modes and their effects •Determine severity of each failure effect •FMECA helps •removing causes of failures •developing systems that can mitigate the effects of failures. .to prioritize and focus on high-risk failures 45
  46. 46. Case study .. 46
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  54. 54. Case study on Risk control 54
  55. 55. Case study on Risk control 55
  56. 56. Case study on sakura tablet (formulation ) 56
  57. 57. case study . 57
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  62. 62. other methodes Improve & Analysis…. Basic management facilitation method. (flow chart, check sheets, process mapping ,etc) Fault Tree Analysis (FTA)  Hazard Analysis and Critical Control Points (HACCP)  Hazard Operability Analysis (HAZOP)  Preliminary Hazard Analysis (PHA)  Risk Ranking and Filtering  Supporting Statistical Tools 62
  63. 63. Improve & Analysis…. Basic management facilitation method. Process Mapping: Process mapping is a workflow diagram to bring a clearer understanding of a process or series of parallel processes. MethodFlowchart- A flowchart is a picture of the separate steps of a process in sequential order. When? • To document a process . • When planning a risk . • To communicate to others how a process is done. • To develop understanding of how a process is done. 63
  64. 64. Improve & Analysis…. Basic management facilitation method… Written Procedures: A written procedure is a step-by-step guide to direct the reader through a task . When? • process is lengthy and complex • process is routine, but it's essential that everyone strictly follows rules. • person wants to know what is going on when a product is being developed. Benefits: • Having written procedures prevent mistakes . • Frees your creativity . • Procedures saves time . • Ensures consistency and improves quality . Work Instruction: Work instructions defines how one or more activities in a procedure should be written in detail, using technology or other resources .The purpose of a Work Instruction is to organize steps in a logical format so that an employee can easily follow it independently . 64
  65. 65. Improve & Analysis…. Fault Tree Analysis (FTA) What ? • FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.  When ? • Root cause analysis of a failure is needed .  Why? - (outcomes) •A better understanding of the root causes of a failure. •A better set of action plans to eliminate those root causes . How to build a Fault Tree 1) Identify a top failure. 2) Brainstorm basic contributors to failure. 3) Link contributors to the top failure •Determine which combination of contributors is needed to cause the top failure. (Ask: How many of the inputs are needed to cause the top failure? ) •Link the contributors to the top failure with the correct gate. (And/Or) Ask: Can we determine contributors for this lower failure ? Yes - repeat cycle making each contributor a top failure, assign gates, etc... No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc... 65
  66. 66. Improve & Analysis…. Fault Tree Analysis (FTA) What ? • FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.  When ? • Root cause analysis of a failure is needed .  Why? - (outcomes) •A better understanding of the root causes of a failure. •A better set of action plans to eliminate those root causes . How to build a Fault Tree 1) Identify a top failure. 2) Brainstorm basic contributors to failure. 3) Link contributors to the top failure •Determine which combination of contributors is needed to cause the top failure. (Ask: How many of the inputs are needed to cause the top failure? ) •Link the contributors to the top failure with the correct gate. (And/Or) Ask: Can we determine contributors for this lower failure ? Yes - repeat cycle making each contributor a top failure, assign gates, etc... No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc... 66
  67. 67. Improve & Analysis…. Fault Tree Analysis (FTA)  Basic symbols: Basic Flow FAULT OR AND  Fault in a box indicates that it is a result of previous faults  Connects preceding fault with a subsequent fault that could cause a failure  Connects two or more faults that must occur simultaneously to cause the preceding fault
  68. 68. Improve & Analysis…. Fault Tree Analysis (FTA)..  Basic symbols: End Points & Connector Root cause  Root cause (= basic fault) (e.g. part failure, software error, human error)  Fault to be further analyzed with more time or information if needed  Transfer-in and transfer-out events
  69. 69. Improve & Analysis…. Fault Tree Analysis (FTA)..  Additional SymbolsExclusive OR Gate:  Fault occurs if only one of the input faults occurs  Priority AND Gate: Fault occurs if all inputs occur in a certain order m  Voting OR Gate: Fault occurs if “m” or more out of “n” input faults occurs
  70. 70. Improve & Analysis…. Fault Tree Analysis (FTA)  Investigation of laboratory failures outlier Production Out of specification result or Lab error others or systematic random Calibration or Interfaces other
  71. 71. Improve & Analysis…. Experiences •Better as a retrospective tool •Visually focused: aid for showing linkages Limitations •Only as good as input . •Time and resource consuming (needs FMEA as a complement ). •Need skilled leader to focus on what is really important •Need significant amount of information •Human errors may be difficult to predict •Many potential fault trees for a system -Some more useful than others -Need to evaluate contribution
  72. 72. Improve & Analysis…. Hazard Analysis and Critical Control Points (HACCP) •HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety & method of identifying and controlling sources of variation at critical process steps that could lead to a hazardous condition. •Similar to a control plan . •Cannot be used effectively without manual or automated process control methods, including statistical process control Uses •New manufacturing process or equipment . •To identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination). Limitations •Requires excellent process knowledge . •FMEA should precede HAACP to identify critical hazards/failure modes (A HAACP could be an action to reduce risk in a FMEA) . •Requires use of more complex statistical tools to be effective (Characterization DOEs, SPC, Capability Matrices) . 72
  73. 73. Improve & Analysis…. Hazard Analysis and Critical Control Points (HACCP) STEPS .... •conduct a hazard analysis and identify preventive measures for each step of the process; •determine the critical control points; •establish critical limits; •establish a system to monitor the critical control points; •establish the corrective action to be taken when monitoring indicates that the critical control points are not in a state of control; •establish system to verify that the HACCP system is working effectively; •establish a record-keeping system. Hazard Tablet Breakage Critical Variable Target Acceptable Comments Control to Control Value Limits Point Tablet CompresForm sion Force 15kN 13 – 18kN Thickness and harness of tablet Monitoring Corrective Record and Control Action Method Automatic Density Measure Eject Tablet On Line Batch Record 73
  74. 74. Improve & Analysis…. Hazard Operability Analysis (HAZOP) •A theory that assumes that risk events are caused by deviations from the design or operating intentions. •Identify potential deviations from normal use . How to perform? A systematic brainstorming technique for identifying hazards using so-called “guide-words” applied to relevant parameters: No, More, Other Than, None. Concept •Focus team discussions by applying “deviations” to specific nodes . •Deviations are generated by applying Guidewords to process parameters . •Examine the process by discussing causes of each deviation •Identify consequences •Evaluate risk and safeguards •Make recommendations, if necessary •Include all parts of the process. Potential Areas of Use(s) 1. Manufacturing processes 2. Equipment and facilities 3. Evaluating process safety hazards 4. Primarily as starter of a HACCP 5. Operator error (“use error”) 74
  75. 75. other methodes Improve & Analysis…. Basic management facilitation method. (flow chart, check sheets, process mapping ,etc) Fault Tree Analysis (FTA)  Hazard Analysis and Critical Control Points (HACCP)  Hazard Operability Analysis (HAZOP)  Preliminary Hazard Analysis (PHA)  Risk Ranking and Filtering  Supporting Statistical Tools 75
  76. 76. Improve & Analysis…. Basic management facilitation method. Process Mapping: Process mapping is a workflow diagram to bring a clearer understanding of a process or series of parallel processes. MethodFlowchart- A flowchart is a picture of the separate steps of a process in sequential order. When? • To document a process . • When planning a risk . • To communicate to others how a process is done. • To develop understanding of how a process is done. 76
  77. 77. Improve & Analysis…. Basic management facilitation method… Written Procedures: A written procedure is a step-by-step guide to direct the reader through a task . When? • process is lengthy and complex • process is routine, but it's essential that everyone strictly follows rules. • person wants to know what is going on when a product is being developed. Benefits: • Having written procedures prevent mistakes . • Frees your creativity . • Procedures saves time . • Ensures consistency and improves quality . Work Instruction: Work instructions defines how one or more activities in a procedure should be written in detail, using technology or other resources .The purpose of a Work Instruction is to organize steps in a logical format so that an employee can easily follow it independently . 77
  78. 78. Improve & Analysis…. Fault Tree Analysis (FTA) What ? • FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.  When ? • Root cause analysis of a failure is needed .  Why? - (outcomes) •A better understanding of the root causes of a failure. •A better set of action plans to eliminate those root causes . How to build a Fault Tree 1) Identify a top failure. 2) Brainstorm basic contributors to failure. 3) Link contributors to the top failure •Determine which combination of contributors is needed to cause the top failure. (Ask: How many of the inputs are needed to cause the top failure? ) •Link the contributors to the top failure with the correct gate. (And/Or) Ask: Can we determine contributors for this lower failure ? Yes - repeat cycle making each contributor a top failure, assign gates, etc... No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc... 78
  79. 79. Improve & Analysis…. Fault Tree Analysis (FTA) What ? • FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.  When ? • Root cause analysis of a failure is needed .  Why? - (outcomes) •A better understanding of the root causes of a failure. •A better set of action plans to eliminate those root causes . How to build a Fault Tree 1) Identify a top failure. 2) Brainstorm basic contributors to failure. 3) Link contributors to the top failure •Determine which combination of contributors is needed to cause the top failure. (Ask: How many of the inputs are needed to cause the top failure? ) •Link the contributors to the top failure with the correct gate. (And/Or) Ask: Can we determine contributors for this lower failure ? Yes - repeat cycle making each contributor a top failure, assign gates, etc... No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc... 79
  80. 80. Improve & Analysis…. Fault Tree Analysis (FTA)  Basic symbols: Basic Flow FAULT OR AND  Fault in a box indicates that it is a result of previous faults  Connects preceding fault with a subsequent fault that could cause a failure  Connects two or more faults that must occur simultaneously to cause the preceding fault
  81. 81. Improve & Analysis…. Fault Tree Analysis (FTA)..  Basic symbols: End Points & Connector Root cause  Root cause (= basic fault) (e.g. part failure, software error, human error)  Fault to be further analyzed with more time or information if needed  Transfer-in and transfer-out events
  82. 82. Improve & Analysis…. Fault Tree Analysis (FTA)..  Additional SymbolsExclusive OR Gate:  Fault occurs if only one of the input faults occurs  Priority AND Gate: Fault occurs if all inputs occur in a certain order m  Voting OR Gate: Fault occurs if “m” or more out of “n” input faults occurs
  83. 83. Improve & Analysis…. Fault Tree Analysis (FTA)  Investigation of laboratory failures outlier Production Out of specification result or Lab error others or systematic random Calibration or Interfaces other
  84. 84. Improve & Analysis…. Experiences •Better as a retrospective tool •Visually focused: aid for showing linkages Limitations •Only as good as input . •Time and resource consuming (needs FMEA as a complement ). •Need skilled leader to focus on what is really important •Need significant amount of information •Human errors may be difficult to predict •Many potential fault trees for a system -Some more useful than others -Need to evaluate contribution
  85. 85. Improve & Analysis…. Hazard Analysis and Critical Control Points (HACCP) •HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety & method of identifying and controlling sources of variation at critical process steps that could lead to a hazardous condition. •Similar to a control plan . •Cannot be used effectively without manual or automated process control methods, including statistical process control Uses •New manufacturing process or equipment . •To identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination). Limitations •Requires excellent process knowledge . •FMEA should precede HAACP to identify critical hazards/failure modes (A HAACP could be an action to reduce risk in a FMEA) . •Requires use of more complex statistical tools to be effective (Characterization DOEs, SPC, Capability Matrices) . 85
  86. 86. Improve & Analysis…. Hazard Analysis and Critical Control Points (HACCP) STEPS .... •conduct a hazard analysis and identify preventive measures for each step of the process; •determine the critical control points; •establish critical limits; •establish a system to monitor the critical control points; •establish the corrective action to be taken when monitoring indicates that the critical control points are not in a state of control; •establish system to verify that the HACCP system is working effectively; •establish a record-keeping system. Hazard Tablet Breakage Critical Variable Target Acceptable Comments Control to Control Value Limits Point Tablet CompresForm sion Force 15kN 13 – 18kN Thickness and harness of tablet Monitoring Corrective Record and Control Action Method Automatic Density Measure Eject Tablet On Line Batch Record 86
  87. 87. Improve & Analysis…. Hazard Operability Analysis (HAZOP) •A theory that assumes that risk events are caused by deviations from the design or operating intentions. •Identify potential deviations from normal use . How to perform? A systematic brainstorming technique for identifying hazards using so-called “guide-words” applied to relevant parameters: No, More, Other Than, None. Concept •Focus team discussions by applying “deviations” to specific nodes . •Deviations are generated by applying Guidewords to process parameters . •Examine the process by discussing causes of each deviation •Identify consequences •Evaluate risk and safeguards •Make recommendations, if necessary •Include all parts of the process. Potential Areas of Use(s) 1. Manufacturing processes 2. Equipment and facilities 3. Evaluating process safety hazards 4. Primarily as starter of a HACCP 5. Operator error (“use error”) 87
  88. 88. Improve & Analysis…. Hazard Operability Analysis (HAZOP) Deviation High temperature in blender Causes Steam heating control malfunction Consequences  Feed material #1 reaches decomposition temperature  Violent reaction with toxic gas generation Safeguards  Diverse high temp. interlock on blender  Blender vented Recommend  Test interlock on quarterly basis  Add steam heating control to monthly PM  Personnel exposure/ injury  Equipment damage Limitations of the model •Applies to specific situations only . •May need to use other models for quantifying risk . •Not a structured approach . •Not designed for quantifiable risk assessment . •Complex output. 88
  89. 89. Improve & Analysis…. Preliminary Hazard Analysis (PHA) Preliminary hazard analysis (PHA) is a semi-quantitative analysis that is performed to: 1. Identify all potential hazards and accidental events that may lead to an accident . 2. Rank the identified accidental events according to their severity . 3. Identify required hazard controls and follow-up actions . The PHA shall consider: 1) The identification of the possibilities that the risk event happens. 2) The qualitative evaluation of the extent of possible injury or damage to health that could result and 3) A relative ranking of the hazard using a combination of severity and likelihood of occurrence, and 4) The identification of possible remedial measures. 89
  90. 90. Improve & Analysis…. Preliminary Hazard Analysis (PHA) Preliminary Hazard Analysis (PHA) Hazard Investigation/ Controls Sev Freq Imp (SxF) Potential Areas • PHA might be useful when analyzing existing systems or prioritizing hazards where circumstances prevent a more extensive technique from being used. • It can be used for product, process and facility design as well as to evaluate the types of hazards for the general product type, then the product class, and finally the specific product. 90
  91. 91. Improve & Analysis…. Risk Ranking and Filtering •Risk ranking and filtering is a tool for comparing and ranking risks. •Risk ranking of complex systems typically requires evaluation of multiple diverse quantitative and qualitative factors for each risk . •The tool involves breaking down a basic risk question into as many components as needed to capture factors involved in the risk. •These factors are combined into a single relative risk score that can then be used for ranking risks. Usage : Risk Ranking and Filtering • Is most suited to compare and manage a “portfolio” of complex risks . •Is facilitated through careful breakdown of a risk into constituent risk scenarios. 91
  92. 92. Improve & Analysis…. Risk ranking and filtering Risk Matrix (1) Risk Ranking Probability High Medium Low Severity Risk Class ONE High Risk Class TWO Medium Risk Class THREE Low
  93. 93. Improve & Analysis…. Risk ranking and filtering Detection Risk Classification High Medium Risk Filtering Low Risk Matrix (2) HIGH priority MEDIUM priority ONE LOW priority TWO THREE
  94. 94. Improve & Analysis…. Supporting Statistical Tools •Control Charts, for example: a. Acceptance Control Charts b. Control Charts with Arithmetic Average and Warning Limits c. Cumulative Sum Charts d. Weighted Moving Average. • Design of Experiments (DOE); • Histograms; • Pareto Charts; • Process Capability Analysis. 94
  95. 95. Control……. Risk control •The purpose of risk control is to reduce the risk to an acceptable level . • Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control. •Risk control might focus on the following questions: •Is the risk above an acceptable level? •What can be done to reduce or eliminate risks? •What is the appropriate balance among benefits, risks and resources? •Are new risks introduced as a result of the identified risks being controlled? Risk reduction • Focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level . • Risk reduction might include actions taken to mitigate the severity and probability of harm. Objectives •Reduce, control or eliminate the risk. • Design away the risk •Take action to reduce severity & probability, or improve detectability of hazard. 95
  96. 96. Control……. Risk acceptance • Decision to accept risk. •Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified. •Risk communication •sharing information regarding information of risk between decision maker and others. •Risk Review •A mechanism to review or monitor events should be implemented. •After risk control in place, carry out new risk assessment to establish potential failures . •Determine whether any new hazards may have been created. hazards may have been created. •Review events that may impact the original decision . 96
  97. 97. Control……. Root Cause Analysis (RCA ) OBJECIVE .. •A structured investigation that aims to identify the true cause of a problem, and the actions necessary to eliminate it. • structured process that uncovers the physical, human, and latent causes of any undesirable event in the workplace. •Process to Discover •what happened • WHY IT HAPPENED • How it can be prevented focus is on understanding , not blaming •Analyses CAUSE & EFFECT Relationships • Emphasis is on SOLUTIONS and System IMPROVEMENT Types of cause •Direct Cause: The cause that directly resulted in the event. (The first cause in the chain.) • Contributing Cause: The cause(s) that contributed to an event but, by itself, would not have caused the event (The cause after the direct cause.) • Root Cause: The fundamental reason for an event, which if corrected, would prevent recurrence. (Last cause in the chain.) 97
  98. 98. Control……. Root Cause Analysis (RCA ) Methods 1. Cause Effect Diagram (fish bone) 2. Why Why Analysis 98
  99. 99. Opportunity for the Industry & Regulators  Using the same guideline apply QRM to  Industry (development, manufacture and distribution)  Competent authorities (reviewer and inspectorate)  Facilitates common approaches to quality risk management in our every day jobs  Supports science-based decision making  Focus resources based on risks to patients  Avoids restrictive and unnecessary requirements  Facilitates communication and transparency
  100. 100. Opportunities & Benefits  Encourages transparency  Create baseline for more science-based decisions  Facilitates communication  Matrix team approach  An aid to convince the stakeholders with trust  Encourages a preventive approach  Proactive control of risks and uncertainty  Benefit of knowledge transfer by team approach  Changes behavior  Better understanding of risk-based decisions  Acceptance of residual risks
  101. 101. Potential Applications •Development; •Facility, equipment and utilities; •Materials management; •Production; •Laboratory control and stability testing; •Packaging and labeling. •Inspection and assessment activities. •Regulatory Operations •Etc..... 101
  102. 102. Next Steps?  From great ideas to practice—how?  Both industry and regulators want to know  Which risks firsts?  Which tools are best?  How will I know “good” from “bad” risk management?  Do we need dept./divisions of risk managers? 102
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