Quality Risk Management Quiz

Regulatory Science: Risk Management Tools and Techniques

• Regulatory Science is a discipline focused on the risk management tools and techniques used in the pharmaceutical industry.
• The presentation uses ICH Guidelines Q9 for Quality Risk Management; it details the principles and applications for different aspects of pharmaceutical quality.
• Includes considerations for development, manufacturing, distribution, and inspection and submission/review processes of drugs, including those from biotechnology.
• Importance is placed on scientific knowledge and linking the risk evaluation to patient protection.
• The document emphasizes the need for the level of effort in the quality risk management process to be commensurate with the degree of risk.

What is Risk?

• Risk is the combination of the probability of harm and the severity of that harm. (ISO/IEC Guide 51)
• A hazard is something with the potential to harm someone.
• Risk is the likelihood that a hazard will cause harm.

Stakeholders

• Achieving a shared understanding of risk management among diverse stakeholders is challenging, as each stakeholder may have unique perceptions of potential harms, their likelihood, and severity.
• Key stakeholders in the pharmaceutical industry include medical practitioners, government, industry professionals, and patients.
• Patient protection, by managing the risk of quality, is a primary concern.

Who is Responsible for Risk Management?

• Interdisciplinary teams are tasked with carrying out quality risk management activities, although this isn't always the case.
• Teams should include experts from various relevant areas, such as quality units, business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics, and clinical experts.
• Individuals knowledgeable of the quality risk management process are also essential.

Systematic Approach to Risk Management

• Quality risk management (QRM) is designed for coordinating, facilitating, and improving science-based decision-making regarding risks.
• Steps in the process are defining the risk problem, gathering background data/information, identifying resources, assigning a timeframe for the process, and determining the decision-making level.

Critical Process Parameters (CPPs) and Critical Material Attributes (CMAs)

• Critical Material Attributes (CMAs) are physical, chemical, biological, or microbiological properties of input materials; these properties must be within specified parameters in order to ensure quality output.
• Critical Process Parameters (CPPs) are process parameters whose variability impacts Critical Quality Attributes (CQAs). To ensure quality, they are monitored and controlled.

Risk Analysis

• Risk analysis relates CPPS and CMAs to CQAs based on experience and scientific understanding.
• The risk evaluation of quality should reflect scientific knowledge linking to the protection of the patient.
• Risk analysis involves evaluating the impact of attributes on CQAs by assessing the likelihood of effect.
• The process should have a level of effort proportionate to the risk level.
• Different levels of detail exist in risk analysis (e.g. simplified traffic light approach vs. detailed FMEA).

Identifying CQAs

• Critical Quality Attributes (CQAs) are characteristics that directly impact the safety and effectiveness of pharmaceutical products (e.g. Safety, Efficacy, Identity, Potency, Purity, and Other properties relevant to the specific product).
• QTPP (Quality Target Product Profile) is reviewed for possible CQAs
• Identifying CQAs are needed across the development/manufacturing process

Risk Analysis - Ranking

• Risk ranking involves categorizing risks as High, Medium, or Low.
• Risk analysis should focus on the most critical factors to reduce cost and time by prioritizing high-risk factors.

How is a Quality Attribute Deemed Critical?

• A quality attribute is deemed critical when it impacts safety, efficacy and product quality.
• A change in criticality happens only with a change in severity.

When is a Quality Attribute a CQA?

• A quality attribute is a CQA when it affects the patient. This involves issues like incorrect dosage, harmful by-products, or damaged product.

Risk Control

• The goal of risk control is to reduce risk to an acceptable level.
• The amount of effort should correspond to the significance of the risk (high/medium/low) to be managed and controlled.
• Acceptable risk may be dependent on other variables.

Risk Reduction/Risk Acceptance

• Risk reduction involves mitigating risk.
• Sometimes a decision to accept risk is necessary in cases where the best practices to control the risk might not fully eliminate the risk, or the impact of the risk is low.
• Risk control needs to be documented and assessed

Risk Communication

• Risk communication involves sharing risk and risk-management information among stakeholders.
• The results of the quality risk management process need to be communicated and documented accurately.
• Communication should happen at each step of quality risk management.

Review Risk Management

• Risk management review is a continuing, ongoing factor of the quality management process.
• Review is necessary to monitor and evaluate events to determine root cause for corrective action.
• Reviews should be structured to handle and learn from both planned and unplanned events, and used to identify additional risks that may arise as a result of controlling a risk factor.

Basic Risk Analysis Tools

• FMEA (Failure Mode and Effect Analysis),
• Flowcharts,
• Check Sheets,
• Process Mapping,
• Cause-and-effect Diagrams,
• Fishbone Diagrams.
• Pareto charts,
• Statistical Tools (e.g., to organize data)

Fault Tree Analysis (FTA)

• FTA is a system to identify causal factors and pathways of failure by producing a visual representation.
• It uses logical operators like AND or OR in different levels and combinations
• Can aid the identification of the root cause of a failure
• Can help to understand how multiple factors affect a problem

Hazard Analysis and Critical Control Points (HACCP)

• HACCP is a proactive and preventive tool that helps with product quality assurance and safety.
• Consists of seven key steps including a hazard analysis and identification of preventive steps for each step of a process, identifying critical control points, establishing critical limits, monitoring control points, and establishing corrective actions when control points are not within specification.
• Useful for managing risks associated with physical, chemical, and biological hazards.

Failure Modes and Effects Analysis (FMEA):

• FMEA is a thorough failure identification procedure, used to prevent possible failures.
• It includes steps in identifying all possible process failures, the consequences of each failure, and methods of preventing these failures from occurring once identified.
• This method requires a multidisciplinary team.

FMEA Steps

• Outline all process steps
• Identify potential failures for each step
• Specify the potential outcomes of each failure
• Evaluate the likelihood and severity of issues using a Risk Priority Number (RPN) calculation, to prioritize issues and direct corrective actions
• The results can be analyzed by Pareto method.
• Implement corrective actions
• Revisit the FMEA after implementing corrective actions.

FMEA Case Study

• The presentation includes a case study examining the use of FMEA in the pharmaceutical industry. The case study uses an example of blending, granulation, milling, lubricant blending, sieving, and tabletting in the creation of a pharmaceutical tablet.