1. RQM (26.04.2024) eng.pdf

Quality Management  Program 4 Lectures + Exercises Lecturer: Dr. Detlef Behrens Exam: 90 min. written exam, open book Quality Management │ Dr. Detlef Behrens │ 2024 2 Dates 26.04. Introduction to Risk Management (90 Minutes) 17.05. Business Continuity Manageme...

Quality Management  Program 4 Lectures + Exercises Lecturer: Dr. Detlef Behrens Exam: 90 min. written exam, open book Quality Management │ Dr. Detlef Behrens │ 2024 2 Dates 26.04. Introduction to Risk Management (90 Minutes) 17.05. Business Continuity Management / Lean Management / Pareto / HAZOP Exercises (2 x 90 Minutes + 15 minute break) 28.06. Quality Management Exercises (2 x 90 Minutes + 15 minute break) 05.07. Quality Management in GxP-Environments Exercises (2 x 90 Minutes + 15 minute break) Quality Management │ Dr. Detlef Behrens │ 2024 3  Definition „risk“ Risk [it. risico] - peril, loss - Probability of occurrence (likelihood, L) of an event (E) and its severity (S) R(E) = L(E) * S(E) Quality Management │ Dr. Detlef Behrens │ 2024 4  Risk through Hazard-damage-causality Cause Hazard Human Machine Environment Hazardousness Damage = 0 Threat Coincidence (space-time- Methoden Impact Action & action-equality) RM in Unternehmen suddenness Literatur Harm Damage = 1 Human Harmfulness Machine Outcome Environment Damage Quality Management │ Dr. Detlef Behrens │ 2024 8  Definition residual risk Residual risk addresses hazards that Have been assessed and risks that have been accepted Have not yet been identified Are not yet linked to the customer/patient/society risk Is the risk transferred to an acceptable level? Consider current scientific knowledge & techniques Fulfill all legal and internal obligations Zero risk is never possible [Source: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] Quality Management │ Dr. Detlef Behrens │ 2024 6  Terms regarding „risk management“ „Management“ Coordinated activities to lead and direct an organization „Organization“ Group of people and institutions with a given structure of responsibilities, powers and relationships „System“ Set of correlative or interactive elements Quelle: DIN EN ISO 9000:2005 Quality Management │ Dr. Detlef Behrens │ 2024 7  Meaning of „risk management“? Coordinated activities to identify, direct and manage risks The goal of risk management is, To avoid risks To reduce risks preventive To shift risks To assure risks curative To account for risks Quality Management │ Dr. Detlef Behrens │ 2024 8 Example: Projekt-risk management Risiken vor Maßnahmen Einheit [€ oder d] Schaden [€] Eintritts- oder Potentielle Störung und Folge wahrscheinlichkeit vor Risikowert Verzögerung Maßnahme [%] [d] Baustellenkosten erhöht durch nutzerseitige 300.000 € 10% 30.000,00 Verzögerung Verspätete Inbetriebnahme durch 30 d 50% 15,00 Lieferverzug eines Lieferanten Diebstahl auf der Baustelle 100.000 € € 20% 20.000,00 Summe Risikowert Tage (ohne Maßnahmen) 15,0 Tage Summe Risikowert € (ohne Maßnahmen) 50.000,00 € Risiken nach Maßnahmen Einheit [€ oder d] Art der Kosten der Schaden [€] oder Eintritts- Risikowert Entscheidung für Maßnahme Maßnahme Maßnahme Verzögerung [d] wahrscheinlichkeit nach nach Maßnahme Risikorückstellung präventiv (p) [€] nach Maßnahme Maßnahme Prävention (j/n) kurativ (k) Einsatz eines Claim-Managers zur Abwehr der p 20.000 € 100.000,00 € 5% 5.000,00 j 25.000,00 Forderungen Vereinbarung einer Pönale mit dem Lieferanten bei p 0€ 15,00 d 10% 1,50 j 1,50 Auftragsvergabe Versicherung k 15.000 € - € € 20% - j 15.000,00 Summe Risikorückstellung Tag (mit Maßnahmen) 1,5 Tage Summe Risikorückstellung € (mit Maßnahmen) 40.000,00 € Quality Management │ Dr. Detlef Behrens │ 2024 9  Legal requirements for risk assessments(I) KonTraG „Law on control and transparency in the corporate sector“, § 91 (2) AktG: „The management board must take suitable measures, in particular set up a monitoring system, for an early recognition of developments that endager the continued existence of the company.“ Handelsgesetzbuch, § 317 (4) HGB: „The auditor must investigate whether the required measures for an early recognition of detrimental developments have been taken by the board. Quality Management │ Dr. Detlef Behrens │ 2024 10  Legal requirements for risk assessments (II) Environment protection 12. BImSchV „Störfallverordnung“ (Major Accidents Ordinance): safety concepts, safety management systems Machine- and system safety 9. GPSGV „Maschinenschutz-Richtlinie“ (Machine safety guideline): Hazard analysis/ risk analysis Occupational health & safety ArbSchG, GefStoffV, BioStoffV, BetrSichV: „Gefährdungsbeurteilungen“ (hazard assessment) Pharmaceutical AMG: GMP implementation, attachment 20 „QRM“ Medical devices MPG: Risk assessment Quality Management │ Dr. Detlef Behrens │ 2024 11  Standards and regulations(I) ISO 31000 „Risk management“ DIN EN ISO 14971 „Risk management for medical devices“ DIN EN ISO 14121-1 „Machine safety – Risk assessment“ BS 25999 „Business Continuity Management“ VDI/VDE 2180-2 „System safety in process engineering by means of process control engineering-Managementsystems“ DIN EN 61511, VDE 8010 „Functional safty – safety systems in the process industry“ EU-GMP Teil III „Quality risk management (RQM)“ (ICH Q9; ex GMP Anhang 20) … The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Quality Management │ Dr. Detlef Behrens │ 2024 12  RQM-Concepts DIN EN ISO 14971 and GMP part III (ICH Q9) Initiate Quality Risk Management Process Risk Assessment Risk Identification Risk Analysis Risk Evaluation unacceptable R isk Management tools Ris k Communic ation Risk Control Risk Reduction Risk Acceptance Output / Result of the Quality Risk Management Process Risk Review Review Events Quality Management │ Dr. Detlef Behrens │ 2024 13  Risk management implementation after GMP-guidelines part III (ICH Q9) („Züricher Methode“) Initiate Quality Risk Management Process Establish a team Risk Assessment Step 1 Basic Data Risk Identification Step 2 Process Conditions Risk Analysis Step 3 Hazard Identification Step 4 Hazard Assessment Risk Evaluation unacceptable R is k Manag ement tools Ris k C ommun ic ation Step 5 Risk Evaluation Risk Control Risk Reduction Step 6 Risk Reduction Measures Risk Acceptance Step 7 Residual Risk Output / Result of the Quality Risk Management Process Summary Risk Review Requirement by a Quality Review Events Management System [Quelle: Zurich insurance company in: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] 14 Quality Management │ Dr. Detlef Behrens │ 2024  Methods Visualization methods (flowcharts, Checklists etc.) FMEA (Failure Mode Effects Analysis) FMECA(Failure Mode, Effects and Criticality Analysis) FTA (Fault Tree Analysis) HACCP hazard analysis and critical control points PAAG/HAZOP Hazard and operability study Risk assessment and filtering Supporting statistical methods …. Quality Management │ Dr. Detlef Behrens │ 2024 15  FMEA, FMECA DIN EN 60812 (Replacement for DIN 25448) Used for systems, processes and products Implementation in a team FMECA (Failure Mode and Effects and Criticality Analysis): extended FMEA by quantified probability of default Occurrence Severity Detectability ➔ Action Priority Number APN APN = O x S x D Approach 1. Evaluation of potential error types 2. Estimate the expected impact 3. Determine their cause 4. Define measures of risk reduction 5. Verification of effectiveness? 6. Renewed risk assessment Quality Management │ Dr. Detlef Behrens │ 2024 16  FMEA FMECA Quality Management │ Dr. Detlef Behrens │ 2024 17  Implementation in practice (I) Quality Management │ Dr. Detlef Behrens │ 2024 18 Implementation in practice (II) Quality Management │ Dr. Detlef Behrens │ 2024 19  FTA DIN EN 61025 Error analysis up to the cause (causal chain) Illustration as a fault tree Combination of error types by logical operators (AND, OR etc.) Determination of failure probability of systems Implementation in a team of system experts Possible applications Usually used for technical systems (e.g. space and aviation, automotive, electronics) Examine complaints or deviations to understand their root cause Approach 1. Define system or subsystem 2. Based on possible errors „ask“ the cause 3. Link with „AND“ or „OR“ operators 4. Develop a fault tree 5. Arrange failure probabilities 6. Determine system failure Quality Management │ Dr. Detlef Behrens │ 2024 20 Syntax of a fault tree [Quelle: relyence.com Quality Management │ Dr. Detlef Behrens │ 2024 21  Ishikawa-/ Fishbone-Diagram Source: https://www.pharmaguideline.com/2017/06/fishbone-tool-of-investigation.html Quality Management │ Dr. Detlef Behrens │ 2024 22  HACCP Origin food industry Concept of critical (risky) points in the process (Hazardous and Critical Control Point) Implementation in seven steps: 1) Implement a hazard analysis and identify preventive measures for all process steps 2) Define critical control points 3) Establish critical limits 4) Establish a system to monitor the critical control points 5) Establish appropriate corrective actions when monitoring indicates, that the critical control points are not under control? 6) Set up a system that demonstrates the effective operation of the HACCP- system 7) Establish a documentation system Quality Management │ Dr. Detlef Behrens │ 2024 23  HACCP - Example Product / Measures for risk Risk under Link to Risk Critical Function reduction control? document grill for 5 minutes - if Meat temperature Burger Grill yes temperature < 75 °C add yes SOP xy to low 3 more minutes Quality Management │ Dr. Detlef Behrens │ 2024 24  PAAG/ HAZOP Prognose, Auffinden der Ursachen, Abschätzen der Auswirkungen, Gegenmaßnahmen or Hazard and Operabilty Studies Systematic brainstorming process Guide word method Hazard identification with „guide words“ (e.g. none, more, except, a part of etc.), which are related to relevant parameters (like contamination, temperature) Implementation as a team of people with experience Application for designing a plant, a process or a product and its application Quality Management │ Dr. Detlef Behrens │ 2024 25  Realization of risk management in companies Risk assessment at strategic level (analysis + assessment) Implement improvement measures Implement operational risk considerations into or as QM processes in the QM system Implement regular risk assessments Audit processes of risk considerations [Quelle: DIN EN ISO 14971] Quality Management │ Dr. Detlef Behrens │ 2024 26  Classification of the Probability of Occurrence frequent e.g. once in 2 years / 50 % possible e.g. once in 5 years / 20 % rare e.g. once in 20 years / 5 % Very rare e.g. once in 50 years / 2 % Unlikely e.g. once in 100 years / 1 % The determination of the frequency is based on the lifetime of the analyzed unit. Another example: [Quelle: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] Quality Management │ Dr. Detlef Behrens │ 2024 27 Quality Management │ Dr. Detlef Behrens │ 2024 28  Classification of the impact Category Definition of the term value in k€ insignificant negligible considering the size of the analyzed unit e.g. 50‘000.- small Damage consequences are limited e.g. 200‘000.- noticable Financial result visiably affected, in the amount of an e.g. 1‘000‘000.- annual profit critical Financial result sustainably affected, in the amount of e.g. 5‘000‘000.- several annual profits catastrophic Existence of the analyzed unit is threatened, equity is e.g. 10‘000‘000.- consumed in whole or in part Focus is on company value! 29 Quality Management │ Dr. Detlef Behrens │ 2024  Risk Evaluation Prepare a risk profile: Consequences eratur [Quelle: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] Quality Management │ Dr. Detlef Behrens │ 2024 30  Risk Evaluation Prepare a risk profile: Consequences Risiko- und Qualitäts- management Einführung Grundlagen Regelwerke/ Konzeption Methoden RM in Unternehmen [Quelle: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] Literatur Quality Management │ Dr. Detlef Behrens │ 2024 31  Result of the risk assessment Risk-Map Preventive action/s Consequence: Measures, project/s Budget Resources (time, personal) Verification of effectiveness Quality Management │ Dr. Detlef Behrens │ 2024 32  Risk-Map Actual-state Target-state frequent Probability of occurrence 2 9 possible 1 5 4 3 1 3 5 rare 6 9 2 6 very rare 7 8 7 4 unlikely 8 Impact Impact Quality Management │ Dr. Detlef Behrens │ 2024 33  System documentation Law, regulations, requirements Existing internal documentation Where to be in system future? (Mission, Policy) What to do? (e.g. Directives) How to do? (e.g. Guidelines) Detailed instructions Records (e.g. Standard Operating Procedures) Rules & Procedures Records & (internal regulations) Reports [Quelle: ICH Q9 “QUALITY RISK MANAGEMENT”, 07/2006] Quality Management │ Dr. Detlef Behrens │ 2024 34  Additional Reading ISO/IEC Guide 73:2002 - Risiko-Management - Wörterbuch - Leitfaden für die Berücksichtigung von Termini zum Risiko-Management in Normen. ISO/IEC Guide 51:1999 - Leitfaden für die Aufnahme von Sicherheitsaspekten in Normen. Process Mapping vom American Productivity & Quality Center, 2002, ISBN 1928593739. IEC 61025 - Fehlerbaumanalyse (Fault Tree Analysis, FTA). IEC 60812 Analysetechniken für die Funktionsfähigkeit von Systemen - Verfahren für die Fehlzustandsart- und Auswirkungsanalyse (FMEA). Failure Mode and Effect Analysis, FMEA from Theory to Execution, 2. Ausgabe 2003, D. H. Stamatis, ISBN 0873895983. Guidelines for Failure Modes and Effects Analysis (FMEA) for Medical Devices, 2003 Dyadem Press, ISBN 0849319102. The Basics of FMEA, Robin McDermott, Raymond J. Mikulak, Michael R. Beauregard 1996, ISBN 0527763209. WHO Technical Report Series Nr. 908, 2003, Annex 7 Application of Hazard Analysis and Critical Control Point (HACCP) methodology to pharmaceuticals. IEC 61882 - Gefäh:rdungs- und Betreibbarkeitsuntersuchung (HAZOP). ISO 14971:2000 - Anwendung des Risikomanagements auf Medizinprodukte. ISO 7870:1993 - Control Charts (Qualitätsregelkarten). ISO 7871:1997 - Cumulative Sum Charts (Cusumkarten - Anleitung zu Qualitätslenkung und Auswertung von Daten mit Cusumtechniken). ISO 7966:1993 - Acceptance Control Charts (Annahme-Qualitätsregelkarten). ISO 8258:1991 - Shewhart Control Charts (Shewhart-Qualitätsregelkarten). What is Total Quality Control?; The Japanese Way, Kaoru Ishikawa (Translated by David J. Liu), 1985, ISBN 0139524339. Quality Management │ Dr. Detlef Behrens │ 2024 35