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+ GDP Quality Management Risk Based Approach Frank Peeters, Ph.D. GDP Responsible Person Raes Pharmaceutical Logistics Senior Consultant, Tobeas bvba Nimfenstraat 1, B-2800 Mechelen +32 479 299103 frank.peeters@tobeas.be Slide 2 + Overview of GDP Regulations Slide 3 + Globalized Production: Potential Risk Slide 4 + Good Distribution Practices The New EU Regulation EU GDP Act - Guidlines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01) 5 Nov 2013 2013/C 343/01 Although the act specifically states products for Human use, the authorities and pharma clients extend it to veterinary products and IMPs (investigational medicinal products) Slide 5 + The difference between GDP Compliance and Certification Products are stored and distributed in a GDP-compliant manner. This ensures control over the distribution chain and consequently maintains the quality and integrity of medicinal products All storage & distribution activities require GDP compliance Certain activities require certification by the competent authorities, while others are only controlled by the marketing authorization holders (MAH) themselves Only storage activities currently require a GDP license GDP license required Warehousing Storage: Months Warehousing Storage: Months Storage in view of Transport Days -Weeks Storage in view of Transport Days -Weeks Cross Docking Storage: Hours Cross Docking Storage: Hours Tran sport Exempt of GDP license Slide 6 + EU GDP Act 2013/C 343/01 Effective 5 November 2013 1. Quality Management System 2. Personnel 3. Premises and Equipment 4. Documentation 5. Operations 6. Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Product Recalls 7. Outsources Activities 8. Self-Inspection 9. Transportation 10. Specific Provisions for Brokers New in the regulation: Risk Based Approach Slide 7 + Risk Based Approach: where does it apply for me? Slide 8 + Risk in the GDP Regulation: 23 times Slide 9 + Risk in the GDP Regulation: 23 times Slide 10 + Risk in the GDP Regulation: 23 times Slide 11 + Risk in the GDP Regulation: 23 times Slide 12 + Risk Management Avoid all risks that can have an impact on the product quality and on patient safety Risk Management: Dont try to do everything Focus on the high risks The residual risk is ALARP: As Low As Reasonably Possible Slide 13 + How to Comply? Risk Management Guidelines Medicinal Products: Eurdralex Annex 20 Quality Risk Management Equals ICH Q9 Quality Risk Management adopted 2005, in operation March 2008 Tripartite: EU, US & Japan FDA initiative, Pharmaceutical cGMPs for the 21st Century A Risk-Based Approach Sep 2004 Medical Devices: ISO 14791:2000 2007 Slide 14 + Link ICH Q8 (Pharmaceutical Development) with ICH Q10 (Pharmaceutical Quality Sytem) Slide 15 + Definition of Risk IEC 1508 1.25 The likelihood of a specific hazardous event occuring within a specific period or in specific circumstances IEEE A measure of the probability and severity of undesired effects. Often taken as the simple product of probability and consequence ISO Guide 51 Combination of probability of harm and severity of harm Slide 16 + Definition of Risk IEC 1508 1.25 The likelihood of a specific hazardous event occuring within a specific period or in specific circumstances IEEE A measure of the probability and severity of undesired effects. Often taken as the simple product of probability and consequence ISO Guide 51 Combination of probability of harm and severity of harm Slide 17 + Slide 18 Slide 19 Slide 20 Slide 21 Slide 22 + Different Risk Classes GDP Risk (Product) Business Risk Relating to the product (eg unavailability) Relating to the company (financial, reputation) Safety risk (Safety Health Environment) Cosmetic Impact, Comfort Slide 23 Risk Management Tools (see ICH Q9) Basic risk management facilitation methods questionnaires check sheets flowcharts Risk ranking and filtering Failure Mode Effects Analysis (FMEA) Failure Mode, Effects and Criticality Analysis (FMECA) Hazard Analysis and Critical Control Points (HACCP) Fault Tree Analysis (FTA) Hazard Operability Analysis (HAZOP) Preliminary Hazard Analysis (PHA) Supporting statistical tools Slide 24 Top-down Risk Assessment: Risk Ranking Example: GDP criticality on equipment: Which Areas are GDP critical (eg Pharmaceutical vs Food) Which Systems are GDP critical Which Hardwore & Software Components are GDP critical Which User Requirements and Functions are GDP critical Slide 25 Intermezzo: What are GDP Critical Systems? which maintain the correct temperature conditions whereby there is a risk for contamination or mixup whereby an adequate turnover is assured (FEFO) that assure a safe and secure storage including during transportation that assure the delivery of the right products to the right addressee to perform planning tasks that may have impact a on timely delivery that are involved in tracing of faulty products that are involved in recall processes. Slide 26 Top-down Risk Assessment: Risk Ranking Example: GDP criticality on equipment: Which Areas are GDP critical (eg Pharmaceutical vs Food) Which Systems are GDP critical Which Hardwore & Software Components are GDP critical Which User Requirements and Functions are GDP critical Slide 27 Risk Classification Slide 28 Prioritization based on risk Period 1 Period 2 Period 3 Period 4 Slide 29 Risk Quantification Slide 30 FMEA Tool (prior to actions) Slide 31 FMEA tool (after actions) Slide 32 Low Medium High Risc Probability Low Medium High Reduce Avoid Accept Slide 33 + Risk Acceptance After every Risk Analysis: Take a Time Out Ask yourself: DOES THIS FEEL RIGHT? Professionally Morally Ethically Is your Risk Reduced? Mitigation of the Severity? Reduction of the Probability? Increase of the Detectability? and then RISK ACCEPTANCE Slide 34 + The Swiss Cheese Approach: Building in safety measures Slide 35 + Conclusion: RISK BASED APPROACH = RISK KNOWLEDGE + RISK REDUCTION STRATEGY + RISK BASED DECISION Slide 36 + Risk Based Decision Making Hard DataSoft Data (Facts) Experience Hard Data + Soft Data + Experience = JUDGEMENT Slide 37 + Slide 38 + Slide 39 + Slide 40 + Decision Making: Facts Risk accompanies every decision You will never know all the facts some assumptions must be made Most decisions are made at the emotional level (does it feel right?) Our brain is wired for speed, not for accuracy Beware of patterns never confuse fact with assumption The decision making environment has a big impact Stress kills effective decision making Time is always your enemy Slide 41 + Understand the problem Obtain Hard Data and information: The WHO The WHAT The WHY The HOW The WHEN Slide 42 + Understand the problem Obtain Hard Data and information: The WHO The WHAT The WHY (ask 5 times WHY) The HOW The WHEN BUT AVOID PARALYSIS BY ANALYSIS Slide 43 + Remove Risk Increasing Factors Structural Causes Inconsistent process, Unreliable equipment, Poor design/layout, Failure to standardize, Workload, Fatigue, Time pressure, Interruptions Prevention Workspace (Ergonomics) Lighting, Noise, Workflow not logical, Inadequate segregation of areas, Discomfort, Duration of Tasks, Inadequate maintenance of premises, Temperature too hot/cold, Visual distractions, Smells & pollutants Prevention Environmental Causes Cultural & Organization: Poor communication, Hierarchy, Bureaucratic, KPIs encourage Under-reporting Accountability Slide 44 + Remove Risk Increasing Factors Process Related Causes Unclear Procedures, Over dependency on memory, Relying on human vision, Too many checks and too often, Only see what you expect Prevention Information Related Causes Too many documents, too complex, inaccurate or not suited for the purpose Latest versions of instructions not available Inappropriate use of assumptions, only verbal communication Communication not given to all staff Staff who is using the documentation does not consult it Staff doesnt understand the risk for the patient Prevention Individual (Physical, Mental) Tiredness, Illness, Hangovers & Drug abuse Slide 45 November 13, 2008Interactive Round Table Quality Risk Management 45 Initiate Quality Risk Management Assessment Output/result of the Quality Risk Management Process Risk Identification Risk Reduction Risk Evaluation Risk Analysis Risk Acceptance Review Events Unacceptable Risk Assessment Risk Control Risk Communication Risk Management Tools Risk Review Typical Quality Risk Management Process Slide 46