Risk Assessment for Drug Products with Device Components

Transcription

1 Risk Assessment for Drug Products with Device Components Khaudeja Bano, M.D. Senior Medical Director, Medical Device Safety Head, Pharmacovigilance and Patient Safety AbbVie Inc.

2 Process consisting of: well-defined steps which, Risk Management when taken in sequence, support better decision making by contributing to a greater insight into risks and their impacts. It includes elements such as risk identification, assessment, mitigation, elimination and communication. Establishes a systematic, well-informed and thorough method of decision making which leads to greater transparency and predictability

3 Components Risk management planning Launch product Preliminary risk assessment Risk review/monitoring Risk control Yes Increase in residual risk? No Residual risk evaluation Justification Yes Residual risk Acceptable? No Residual risk reduction No Yes Benefit/risk assessment Overall residual risk evaluation Risk management process review

4 Risk Management Risk Management Planning Risk Management Plan Identify risk management activities to be performed and Establishes the process to Manage the inputs and expected outputs Preliminary Risk Assessment/Risk Assessment Preliminary Hazard Analysis/Hazard Analysis Identify and assess risks early in the product realization process, and Continuous update to assess additional risks identified during a product s design and development

5 Risk Management Risk Control Product Design FMEA, Manufacturing Process FMEA, Use FMEA, Test Method FMEA, Facility/Utility/Equipment FMEA, Distribution FMEA, Identify causes and effects Contributing to and resulting from failures of a product s design and its associated processes, and the control measures to prevent, reduce and/or detect the causes and failures Residual Risk Evaluation Updated Preliminary Hazard Analysis/Hazard Analysis Evaluate the residual risk once controls have been applied

6 Risk Management Risk Acceptability Risk Acceptability Matrix Establish the criteria, based upon the severity and probability of occurrence of a harm, for evaluating the acceptability of the risk associated with a given hazard Benefit / Risk Assessment Benefit /Risk Analysis Report Determine if the benefit(s) of the product outweigh individual risks evaluated to be unacceptable Overall Residual Risk Evaluation Overall Residual Risk Evaluation Report Evaluate the overall residual risk for the product once all controls have been applied

7 Risk Management Risk Management Process Review Risk Management Report Ensure all activities have been completed in alignment with the Risk Management Plan and that systems are in place to monitor product information post-launch Risk Review/Monitoring Process Analysis of production and post-production information and records of escalated issues Analyze production and post-production information to identify issues that could result in an unacceptable change to product s risk and escalating issues for action as appropriate

8 Preliminary Risk Assessment Identification of a listing of known and foreseeable hazards based upon an understanding of the intended users, use, and reasonably foreseeable misuse of the product in both normal and fault conditions Identification of hazardous situations resulting from the occurrence of each hazard Identification of a listing of harms resulting from the occurrence of each hazard-hazardous situation combination Estimation of the severity for each harm Estimation of the probability of occurrence for each harm Evaluation of the pre-mitigated risk resulting from the occurrence of each hazard-hazardous situation combination

9 Inputs / Outputs Inputs Identification of the users, intended use, and user needs Scope of the product design and development process (i.e. new product, change to an existing product, class of product) Identification and general description of the product being designed and developed Criteria for evaluating risk acceptability defined -Risk Management Plan Estimates of the probability and severity for each harm Outputs Preliminary Hazard Analysis During the course of risk management activities, the Preliminary Hazard Analysis is updated until it evolves into the Hazard Analysis at the time of product launch.

10 Risk Severity Probability Risk

11 Hazard analysis Hazard Hazardous situation Harm

12 Risk Management Tools 1. Process mapping 2. Preliminary Hazard Analysis (PHA) 3. Hazard Analysis of Critical Control Points (HACCP) 4. Hazard Operability Analysis (HAZOP) 5. Fault tree analysis (FTA) 6. Failure Mode Effects Analysis (FMEA) 7. Failure Mode, Effects and Criticality Analysis (FMECA) 8. Risk Ranking and Filtering 9. Informal Risk Management 10. Taguchi, variation risk management method 12

13 FMEA / FMECA Failure Mode Effects Analysis Failure Mode Effects & Criticality Analysis Adds criticality analysis to FMEA Tools to identify known or potential failure modes

14 FMEA / FMECA Benefits: Used to examine a variety of high-level systems or small components Scalable Quantitative or semi-quantitative Limitations Each event is a separate occurrence Does not show interactions

15 FMEA / FMECA 1. Define what is being analyzed 2. Identify the potential or known failure modes 3. Identify the effects of each failure mode 4. Rate each effect for: Probability of occurrence Severity Detectability Calculate Risk Priority Number RPN = probability x severity x detectability*

16 FMEA / FMECA 5. Prioritize the effects based on RPN and determine risk acceptability 6. If risk acceptable, continue monitoring 7. If risk must be modified or eliminated, consider appropriate control or mitigation strategies 8. Prepare report and retain documentation

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18 FMEA Product Design FMEA Manufacturing Process FMEA Test Method FMEA Facility/Utility/Equipment FMEA Distribution FMEA Use FMEA

19 Drug with device component - guiding principles Product as a whole / system Assess drug product and device component risks Critical to assess the interactions Cross functional team of experts Design out risk mitigate Label as risk mitigation Cross functional collaboration Data flow

20 Balance Benefit Risk Risk Benefit

21 Drug + Delivery System = Product Drug Hazard contamination / extraneous matter Hazardous situation administration of contaminated product Harm serious injury requiring medical / surgical intervention Delivery system Hazard damaged Hazardous situation delay in therapy Harm serious injury requiring medical / surgical intervention due to delay in therapy

22 Severity Rating Estimation of harm to the patient/ user for each hazard associated with the product. all indications for the product. all populations impacted based on the worst-case scenario reasonably likely to occur both the long-term and short-term effects of the harm Severity Rating 5 Death or life threatening injury. Justification 4 Reversible and/or temporary serious injury or a permanent injury that may result in disability or have a medically significant impact to patient/user safety or health. 3 Event requiring medical intervention but is not expected to result in disability or have a medically significant impact on patient/user safety or health. 2 Event not requiring medical intervention. 1 Inconvenience or cosmetic. No risk to patient/user safety.

23 Probability Rating Probability Frequent (5) Probable (4) Occassional (3) Remote (2) Unlikely (1) Qualitative Definition Has occurred and/or is likely to occur regularly during the life of the product under specified conditions. Has occurred and/or is likely to occur several times during the life of the product under specified operating conditions. Has occurred and/or will occur infrequently during the life of the product under specified operating conditions. Has occurred and/or will rarely occur during the life of the product under specified operating conditions. Has not occurred and/or is not expected to occur during the life of the product under specified operating conditions.

24 Sample product risk acceptability table Risk Acceptability Probability of Occurrence of Harm Severity

25 Sample product risk acceptability table Risk Acceptability Probability of Occurrence of Harm Severity ALARP Unacceptable 2 1 Acceptable

26 EXERCISE A drug / device combination product preliminary hazard analysis Hazards Hazardous situations Harm Severity - Scale 1-5 Probability - Scale 1-5 Risk

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