Risk management in pharmaceutical Industry

Risk Managements in pharmaceutical industry. Includes risk management tools for evalution.

1. Risk Management In Pharmaceuticals By, Mahesh Shinde

2. What will cover Objectives Scope Definitions Tools and methodology

3. Identification and mitigation of risks associated with each business unit / function is an important component of proactive management. Any threat to product quality across the supply chain needs to be considered in the risk management exercise; this also includes risk associated with product security, security of supplies as well as compliance to policies / statutory requirements. Risk management includes identification of risks, evaluation of each risk, developing risk mitigation plan, implementation of action plan and review of actions taken to verify their effectiveness . The objective of this training is to describe the Risk Management Process, to define cases when a risk assessment needs to be performed, and to facilitate understanding of quality risk management outputs. OBJECTIVES

4. Applicable to functions that directly or indirectly impacts product quality or security of product & security of supply such as Quality Assurance, R&D, Regulatory, Business Development, Supply chain, Human Resources, IT, Legal, Contract Manufacturing and Pharmacovigilance A quality risk management process may be performed when a decision should be taken or when actions should be prioritized, especially in these cases Deviations Change control Recalls Abnormal restrictions Product quality defects Pharmacovigilance cases Quality Management Review New product introduction projects All activities with potential quality and/or regulatory impacts on Marketing authorization dossier (Regulatory filing), validated status, audits, inspection, transportation etc. SCOPE

5. Definitions (As per ISO ) Physical injury and/or damage to the health of people or damage to property or the environment Harm: Risk: Combination of the probability of occurrence of harm and the severity of that harm - Use of available information to identify hazards and to estimate the risk - It provides the basis for risk evaluation and decisions about the risk reduction. Risk Analysis:

6. Risk Evaluation: Judgement, on the basis of risk analysis, of whether a risk which is acceptable has been achieved in a given context based on the current values of society. Risk Assessment: Overall process of risk analysis and risk evaluation Risk Control: The process through which decisions are reached and implemented for reducing risks to or maintaining risks within specified levels. Risk Management: Systematic application of management policies, procedures and practices to the tasks of analysing, evaluating and controlling risk Definitions (As per ISO )

7. Relationship between Risk Analysis & Other Risk Management Activities Risk analysis Intended use Purpose identification Hazard identification Risk estimation (likelihood x consequence) Risk evaluation: Risk acceptability decisions Risk reduction/control option analysis implementation residual risk evaluation overall risk acceptance Risk monitoring external environment review of risk management experience RISK MANAGEMENT Risk assessment

8. RISK CONTROL Safe design: Build a bridge Protection measures Trains at night Cars in the day Traffic lights Warnings Signals/noise RISK ASSESSMENT Probability that collision happens and degree of severity of the resulting damage RISK MONITORING Check if safety measures work Risk Management (A practical example )

9. Some examples: Engineering Design Reviews Product and Process design (computer) Validation Change Management evaluations Release / Reject / Recall decisions Cross Contamination evaluations Investigations & Corrective / preventive actions GMP impact assessment Most of the time we are managing risk……… (without realising this?) Risk Management in P’ceutical Industry

10. Risk Management Process overview

11. Risk Management Tools & Methodology Risk Management Facilitation Methods FMEA FTA HACCP HAZOP PHA Risk Ranking and Filtering Supporting Statistical Tools

12. Tools Use Scope Risk Steps Risk Controls FTA Identify causes of an undesired event Micro Identification Analysis No Risk Ranking and Filtering Rank items following on criticality level Macro or Narrow system Identification Analysis Evaluation No PHA Identify potentially hazardous Macro or Narrow system Identification Analysis No FMEA Identify potential failures and quote them in order to rank them Narrow system Identification Analysis Evaluation Yes HACCP Appreciate and control risk contamination Narrow system Identification Analysis Evaluation Yes

13. Some simple techniques used to structure risk management by organizing data and facilitating decision-makings are: Flowcharts Check Sheets Process Mapping Cause and Effect Diagrams (Ishikawa diagram or fish bone diagram) Basic Risk Management Facilitation Methods

14. Failure Mode Effect Analysis (FMEA) Allows evaluation of: potential failure modes [ what might go wrong ] for processes the likely effect on outcomes and/or product performance Once failure modes are established, risk reduction can be used to eliminate, contain, reduce or control the potential failures FMEA relies on product and process understanding FMEA methodically breaks down the analysis of complex processes into manageable steps It is a powerful tool for summarizing the important modes of failure, factors causing these failures and the likely effects of these failures

15. To prioritize risks and monitor the effectiveness of risk control activities FMEA can be applied to equipment and facilities and might be used to analyse a manufacturing operation and its effect on product or process It identifies elements/operations within the system that render it vulnerable The output/ results of FMEA can be used as a basis for design or further analysis or to guide resource deployment Areas of use of FMEA

16. Fault Tree Analysis (FTA) An approach that assumes failure of the functionality of a product or process This tool evaluates system (or sub-system) failures one at a time but can combine multiple causes of failure by identifying causal chains The results are represented pictorially in the form of a tree of fault modes At each level in the tree, combinations of fault modes are described with logical operators (AND, OR, etc ). The method relies on expert process understanding to identify causal factors

17. FTA can be used to: establish the pathway to the root cause of the failure investigate complaints or deviations in order to fully understand their root cause ensure that intended improvements will fully resolve the issue and not solve one problem yet cause another (different) problem FTA is an effective tool for evaluating how multiple factors affect a given issue The output of an FTA includes a visual representation of failure modes It is useful both for risk assessment and in developing monitoring programs Areas of use of FTA

18. A tool of analysis based on applying prior experience or knowledge of a hazard or failure to identify future hazards, hazardous situations and events that might cause harm, as well as to estimate their probability of occurrence for a given activity, facility, product or system It involves following steps: 1.List the expected events for each process step 2.Define the dangerous situations (opposite expected events) 3.Enumerate the different causes of each dangerous situation 4 . List consequences of each dangerous situation 5 . List detection, prevention and control measures already in place. 6 . Determine if the dangerous situation is acceptable or not. 7 . If the answer is ‘No’, implement actions and /or do complementary analysis Preliminary Hazard Analysis (PHA)

19. 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 PHA is most commonly used early in the development of a project when there is little information on design details or operating procedures It will often be a precursor to further studies Hazards identified in the PHA are further assessed with other risk management tools such as those in this section Potential Uses of PHA

20. Hazard Analysis & Critical Control Points (HACCP) HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety It is a structured approach that applies technical and scientific principles to analyze , evaluate, prevent, and control the risk or adverse consequence(s) of hazard(s) due to the design, development, production, and use of products It consists of following steps : Assemble a multidisciplinary team with a leader Describe all the detailed steps of the process List all potential hazards associated with each step Determine Critical Control Points ( CCPs) Establish critical limits for each CCP Create a monitoring of critical control points Establish corrective actions when CCP are not under control by the monitoring system Establish verification system to confirm that the HACCP system is effective Establish documentation and record keeping

21. Potential Uses of HACCP To identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination) Most useful when product and process understanding is sufficiently comprehensive to support identification of critical control points The output of a HACCP analysis is risk management information that facilitates monitoring of critical points not only in the manufacturing process but also in other life cycle phases

22. 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. This tool breaks down a basic risk question into as many components as needed to capture factors involved in the risk The factors are combined into a single relative risk score that can then be used for ranking risks Filters in the form of weighting factors or cut-offs for risk scores, can be used to scale or fit the risk ranking to management or policy objectives Risk Ranking & Filtering

23. To prioritize manufacturing sites for inspection/audit by regulators or industry Particularly helpful in situations in which the portfolio of risks and the underlying consequences to be managed are diverse and difficult to compare using a single tool Risk ranking is useful when management needs to evaluate both quantitatively-assessed and qualitatively-assessed risks within the same organizational framework Potential Uses of Risk Ranking & Filtering

24. Relative Risk Ranking System Risk Index Value Level of Risk Action 1 to 8 Low Risk Broadly acceptable risk. No further investigation is needed 9 to 16 Medium Risk Risk is acceptable. Further Investigation may be needed in order to reduce the risk   17 to 25 High Risk Risk is unacceptable. Further Investigation is needed to reduce the risk

25. Consequence & Likehood Categories & Scoring Likelihood  Consequences      Insignificant   1 Minor   2 Moderate   3 Major   4 Catastrophic   5 Almost certain 5     5   10   15   20   25 Likely 4     4   8   12   16   20 Possible 3     3   6   9   12   15 Unlikely 2     2   4   6   8   10 Rare 1   1   2   3   4   5