Presentation on theme: "ICH Q9: Quality Risk Management"— Presentation transcript:
1 ICH Q9: Quality Risk Management CDER ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE (ACPS)October 5-6, 2006 Rockville, MDH. Gregg Claycamp, Ph.D.Office of New Animal Drug Evaluation
2 Why was ICH Q9 needed?To ensure a common understanding of Quality Risk Management (QRM) by both industry and regulatorsTo facilitate moving to the “Desired State”To facilitate communication and transparencyTo move from ‘fire fighting’ to management of riskICH Q9 explainsA common language and processPotential methodologies for QRMWhere QRM can add value
3 What’s in Quality Risk Management? Q9 has broad risk concepts and principlesPrinciples for implementationElements of Risk Assessment/Management ProcessesDoes not discuss a single tool, but “The Right Tool for the Job” approachRisk Management ToolsHigh-level (Ideas and Concepts)Mid-Level (Quantitative and Qualitative)Low-Level (Real numbers and real time)
4 What’s not in ICH Q9 … A “cookbook” for risk management A specific prescription for your risk management programAn exhaustive treatment of theoryAn exhaustive list of methods and tools
5 Q9’s Sample Process Risk Communication Risk Management Tools Initiate Risk ReviewRisk AssessmentRisk EvaluationunacceptableRisk ControlRisk AnalysisRisk ReductionRisk IdentificationReview EventsRisk AcceptanceInitiateQuality Risk Management ProcessOutput / Result of theRisk CommunicationRisk Management Tools
6 QRM is not a Single Process StartProcess- stepRisk identificationDecisionFeedback procedureRisk analysisSub-Sub- processSub- processStartEndStartEndEtc.End
7 Different Meanings 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.
8 Q9 Overarching Principles “The evaluation of the risk to quality should be based on scientific knowledge and ultimately link back to the protection of the patient; andThe level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk.”
9 Concept: Link Back to Patient Risk Opportunities to impact risk using quality risk managementDesignProcessMaterialsManufacturingFacilitiesDistributionPatient
10 QRM and the Design Space Risk analysts estimate probabilities of being outside (or inside!) of design limits, given various scenarios.v2design spacev1v3What is the chance (probability) of “falling outside” of the design space per unit time?Design parameters and their intersection in a “design space” concept
11 QRM: Another Systems Approach A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecyle.“Systems” thinking and methods!
13 Severity and Probability Risk High RiskIncreasing Probability of OccurrenceMedium RiskLow RiskIncreasing Severity of Harm/Consequence
14 Tools for Risk Management ICH Q9 Includes an Annex of Tools
15 “High-Level” Tools Often rely mixed kinds of information: QuantitativeQualitativeExpert judgmentFocus on systematic thinking:Define the risk questionOrganize information under categories, attributesBuild decision making paths
16 Examples of implementation: FDA CDER/ORA Site Selection process for GMP inspectionsCVM pre-approval decision support system (PAIDSS)Other efforts in progress
18 Risk Ranking –High Level Facility(Risk Ranking)Site MSite TSite CSite DSite XSite AScored and Prioritized Under Multiple CriteriaProcessProductSAMPLE CHART
19 Mid-Level: Combinations of Methods More formula-driven than High-level tools and approachesExpert-driven qualitative with some dataFME(C)ADecision analytic methodsLimitationsWhich experts?Risk-analytical methodsSorting value- and perception-driven assessments with quantitative variables
20 FME(C)A 10 9 8 7 6 5 4 3 2 1 10 9 8 7 6 5 4 3 2 1 Severity of Effect CriticalityS x O109876543211098765432112345678910“SOD” or “Risk Number”S x O x DSeverity of EffectSOOccurrence ProbabilityDetection**Higher detection ability lowers risk score.
22 Present Status of the Guideline Published as US Guidance, June 2006Judging by industry and regulatory conferences, workshops, publications: interest in Q9 remains highSome members of the ICH EWG compiled presentations for information. Now available on ICH website:
23 Next Steps? From great ideas to practice—how? Both industry and regulators want to knowWhich risks firsts?Which tools are best?How will I know “good” from “bad” risk management?Do we need dept./divisions of risk managers?
24 Examples of Implementation: Industry Many presentations at conferences showing examples of:Failure modes and effects analysis (FMEAs)Multivariate models (QC/QA integration)Systems design, modeling and application are readily adaptable to QRM approaches
25 Keys to Implementation Key to implementation: the systems approaches in Q8-Q9-Q10 leverage the best parts of existing knowledge bases and expertise for systematic control of risks to pharmaceutical quality.Gregg’s Pareto principle for QRM: “More than 80% of the expertise for a Quality Risk Management program exists among the domain --i.e., not risk-- experts.”