QUALITY RISK MANAGEMENT

INTRODUCTION

Risk management principles are effectively utilized in many areas of business and government including finance, insurance, occupational safety, public health, pharmaceutical, pharmacovigilance, and by agencies regulating these industries. Risk is defined as the combination of the probability of occurrence of harm and the severity of that harm. However, achieving a shared understanding of the application of risk management among diverse stakeholders is difficult because each stakeholder might perceive different potential harms, place a different probability on each harm occurring and attribute different severities to each harm.

PRINCIPLES OF QUALITY RISK MANAGEMENT

Two primary principles of quality risk management are:

• The evaluation of the risk to quality should be based on scientific knowledge  and
• The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk.

GENERAL QUALITY RISK MANAGEMENT PROCESS

Quality  risk management is a systematic process for the assessment, control, communication and review of risks to the quality of product across the product life-cycle.  A model for quality risk management is outlined in the diagram. Other models could be used. The emphasis on each component of the framework might differ from case to case but a robust process will incorporate consideration of all the elements at a level of detail that is commensurate with the specific risk.

Overview of a typical quality risk management process

Decision nodes are not shown in the diagram above because decisions can occur at any point in the process. These decisions might be to return to the previous step and seek further information, to adjust the risk models or even to terminate the risk management process based upon information that supports such a decision. Note: “unacceptable” in the flowchart does not only refer to statutory, legislative, or regulatory requirements, but also to indicate that the risk assessment process should be revisited.

Responsibilities

Quality risk management activities are usually, but not always, undertaken by interdisciplinary teams. When teams are formed, they should include experts from the appropriate areas such as quality unit, business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics,  in addition to individuals who are knowledgeable about the quality risk management process.

Decision makers should

• take responsibility for coordinating quality risk management across various functions and departments of their organization and
• ensure that a quality risk management process is defined, deployed, and reviewed and that adequate resources are available.

Initiating a Quality Risk Management Process

Quality risk management should include systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk. Possible steps used to initiate and plan a quality risk management process might include the following:

• Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk
• Assemble background information and/or data on the potential hazard, harm or human health impact relevant to the risk assessment
• Identify a leader and critical resources
• Specify a timeline, deliverables, and appropriate level of decision making for the risk management process

Risk Assessment

Risk assessment consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool  and the types of information that will address the risk question will be more readily identifiable. As an aid to clearly defining the risk for risk assessment purposes, three fundamental questions are often helpful:

1. What might go wrong?
2. What is the likelihood (probability) it will go wrong?
3. What are the consequences (severity)?

Risk identification

Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders. Risk identification addresses the “What might go wrong?” question, including identifying the possible consequences. This provides the basis for further steps in the quality risk management process.

Risk analysis

Risk analysis is the estimation of the risk associated with the identified hazards. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.

Risk evaluation

Risk evaluation compares the identified and analyzed risk against given risk criteria.  Risk evaluations consider the strength of evidence for all three of the fundamental questions. In doing an effective risk assessment, the robustness of the data set is important because  it determines the quality of the output. Revealing assumptions and reasonable sources of uncertainty will enhance confidence in this output and/or help identify its limitations. Uncertainty is due to combination of incomplete knowledge about a process and its expected or unexpected variability. Typical sources of uncertainty include gaps in knowledge, gaps in process understanding, sources of harm (e.g., failure modes of a process, sources of variability), and probability of detection of problems.

The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used. Alternatively, risk can be expressed using qualitative descriptors, such as “high,” “medium,” or “low,” which should be defined in as much detail as possible. Sometimes a risk score is used to further define descriptors in risk ranking. In quantitative risk assessments, a risk estimate provides the likelihood of a specific consequence, given a set of risk-generating circumstances. Thus, quantitative risk estimation is useful for one particular consequence at a time. Alternatively, some risk management tools use a relative risk measure to combine multiple  levels of severity and probability into an overall estimate of relative risk. The  intermediate steps within a scoring process can sometimes employ quantitative risk estimation.

Risk Control

Risk control includes decision making to reduce and/or accept risks. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort used for risk control should be proportional to the significance of the risk. Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control.Risk control might focus on the following questions:

• Is the risk above an acceptable level?
• What can be done to reduce or eliminate risks?
• What is the appropriate balance among benefits, risks and resources?
• Are new risks introduced as a result of the identified risks being controlled?

Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level. Risk reduction might include actions taken to mitigate the severity and probability of harm. Processes that improve the detectability of hazards and quality risks might also be used as part of a risk control strategy. The implementation of risk reduction measures can introduce new risks into the system or increase the significance of other existing risks. Hence, it might be appropriate to revisit the risk assessment to identify and evaluate any possible change in risk after implementing a risk reduction process.

Risk acceptance is a decision to accept risk. Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified. For some types of harms, even the best quality risk management practices might not entirely eliminate risk. In these circumstances, it might be agreed that an appropriate quality risk management strategy has been applied and that quality risk is reduced to a specified (acceptable) level. This (specified) acceptable level will depend on many parameters and should be decided on a case-by-case basis.

Risk Communication

Risk communication is the sharing of information about risk and risk management between the decision makers and others. Parties can communicate at any stage of the risk management process. The output/result of the quality  risk management process should be appropriately communicated and documented.  Communications might include those among interested parties (e.g., regulators, industry, within a company, industry, or regulatory authority). The included  information might relate to the existence, nature, form, probability, severity, acceptability,control, treatment, detectability, or other aspects of risks to quality. Communication need not be carried out for each and every risk acceptance. Between the industry and regulatory authorities, communication concerning quality risk management decisions might be effected through existing channels as specified  in regulations and guidance.

Risk Review

Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented. The output/results of the risk management process should be reviewed to take into account new knowledge and experience. Once a quality risk management process has been initiated, that process should continue to be utilized for events that might impact the original quality risk management decision, whether these events are planned (e.g., results of product review, inspections, audits, change control) or unplanned (e.g., root cause from failure investigations, recall). The frequency of any review should be based upon the level of risk. Risk review might include reconsideration of risk acceptance decisions.

RISK MANAGEMENT METHODS AND TOOLS

Quality risk management supports a scientific and practical approach to decision making. It provides documented, transparent, and reproducible methods to accomplish steps of the quality risk management process based on current knowledge about assessing the probability, severity, and, sometimes, detectability of the risk. Traditionally, risks to quality have been assessed and managed in a variety of informal ways (empirical and/or internal procedures) based on, for example, compilation of observations, trends, and other information. Such approaches continue to provide useful information that  might support topics such as handling of complaints, quality defects, deviations, and allocation of resources. An organization can can assess and manage risk using recognized risk management tools and/or internal procedures (e.g., standard operating procedures). Below is a non exhaustive list of some of these tools

1. Basic Risk Management Facilitation Methods

   Some of the simple techniques that are commonly used to structure risk management by organizing data and facilitating decision making are:
   • Flowcharts
   • Check Sheets
   • Process Mapping
   • Cause and Effect Diagrams (also called an Ishikawa diagram or fish bone diagram)

2. Failure Mode Effects Analysis (FMEA)

   FMEA  provides for an evaluation of potential failure modes for processes and their 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. FMEA can be used to prioritize risks and monitor the effectiveness of risk control activities. FMEA can be applied to equipment and facilities and might be used to analyze 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.

   Template  of  FMEA

3. Failure Mode, Effects, and Criticality Analysis (FMECA)

   FMEA might be extended to incorporate an investigation of the degree of severity of the consequences, their respective probabilities of occurrence, and their detectability, thereby becoming a Failure Mode, Effects, and Criticality Analysis (FMECA). In order for such an analysis to be performed, the product or process specifications should be established. FMECA can identify places where additional preventive actions might be appropriate to minimize risks.
   FMECA application  should mostly be utilized for failures and risks associated with manufacturing processes; however, it is not limited to this application. The output of an FMECA is a relative risk “score” for each failure mode, which is used to rank the modes on a relative risk basis

   Template  of  FMECA

4. Fault Tree Analysis (FTA)

   The FTA tool  is an approach that assumes failure of the functionality of a product or process. This tool evaluates system (or subsystem) 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.). FTA relies on the experts’ process understanding to identify causal factors.
   FTA can be used to establish the pathway to the root cause of the failure. FTA can be used to investigate complaints or deviations in order to fully understand their root cause and to ensure that intended improvements will fully resolve the issue and not lead to other issues (i.e. solve one problem yet cause a different problem). Fault Tree Analysis 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.

   Example of Fault tree analysis

5. Hazard Analysis and 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.
   HACCP consists of the following seven steps:
   
   1. conduct a hazard analysis and identify preventive measures for each step of the process
   2. determine the critical control points
   3. establish critical limits
   4. establish a system to monitor the critical control points
   5. establish the corrective action to be taken when monitoring indicates that the critical control points are not in a state of control
   6. establish system to verify that the HACCP system is working effectively
   7. establish a record-keeping system
   HACCP might be used to identify and manage risks associated with physical, chemical, and biological hazards (including microbiological contamination). HACCP is 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 lifecycle phases.

   Template  of  HACCP

6. Hazard Operability Analysis (HAZOP)

   HAZOP  is based on a theory that assumes that risk events are caused by deviations from the design or operating intentions. It is a systematic brainstorming technique for identifying hazards using so-called guide words. Guide words (e.g., No, More, Other Than, Part of) are applied to relevant parameters (e.g., contamination, temperature) to help identify potential deviations from normal use or design intentions. HAZOP often uses a team of people with expertise covering the design of the process or product and its application.
   HAZOP can be applied to manufacturing processes, including outsourced production and formulation as well as the upstream suppliers, equipment and facilities for drug substances and drug products. It has also been used primarily in the pharmaceutical industry for evaluating process safety hazards. As is the case with HACCP, the output of a HAZOP analysis is a list of critical operations for risk management. This facilitates regular monitoring of critical points in the manufacturing process.

   Example of HAZOP

7. Preliminary Hazard Analysis (PHA)

   PHA is 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. The tool
   consists of:
   1. the identification of the possibilities that the risk event happens,
   2. the qualitative evaluation of the extent of possible injury or damage to health that could result,
   3. a relative ranking of the hazard using a combination of severity and likelihood of occurrence, and
   4. the identification of possible remedial measures
   PHA might be 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; thus, it will often be a precursor to further studies. Typically, hazards identified in the PHA are further assessed with other risk management tools such as those in this section.

   Example of Preliminary Hazard Analysis Report

8. Risk Ranking and Filtering

   Risk ranking and filtering is a tool for comparing and ranking risks. Risk ranking of complex systems typically involves evaluation of multiple diverse quantitative and qualitative factors for each risk. The tool involves breaking down a basic risk question into as many components as needed to capture factors involved in the risk. These 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 and filtering can be used to prioritize manufacturing sites for inspection/audit by regulators or industry. Risk ranking methods are 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 for management to evaluate both quantitatively-assessed and qualitatively-assessed risks within the same organizational framework.

   Templete of Risk ranking

9. Supporting Statistical Tools

   Statistical tools can support and facilitate quality risk management. They can enable effective data assessment, aid in determining the significance of the data set(s), and facilitate more reliable decision making. A listing of some of the principal statistical tools commonly used  is provided:
   • Control charts, for example Acceptance control charts,Control charts with arithmetic average and warning limits,Cumulative sum charts ,Shewhart control charts,Weighted moving average.
   • Design of experiments (DOE)
   • Histograms
   • Pareto charts
   • Process capability analysis