QUALITY RISK MANAGEMENT (QRM) AS PROCESS FLOW
Quality Risk Management (QRM) is a vital part of Quality Assurance (QA) in the
pharmaceutical industry, ensuring that risks to product quality, safety, and efficacy are
identified, assessed, and mitigated. By integrating process flow diagrams into QRM,
pharmaceutical companies can better understand each step of their manufacturing process and
proactively manage risks that could compromise product quality or patient safety.
Steps for Implementing QRM with Process Flow in Pharmaceutical QA:
1. Define the Process Flow:
Create a detailed process flow diagram representing all stages of the pharmaceutical
manufacturing process, including:
• Material Procurement: Sourcing of raw materials and APIs (Active Pharmaceutical
Ingredients).
• Manufacturing: Compounding, mixing, and production processes.
• Quality Control (QC): In-process testing and sampling for quality compliance.
• Packaging and Labeling: Final product packaging, labeling, and batch release.
• Storage and Distribution: Warehousing and shipping logistics.
2. Identify Risks at Each Process Step:
At each stage of the process flow, identify potential risks to product quality and patient
safety. Examples of risks include:
• Material Procurement: Contamination or adulteration of raw materials.
• Manufacturing: Cross-contamination between different products, operator error, or
equipment malfunction.
• Quality Control: False-negative or false-positive results in testing.
• Packaging: Incorrect labeling or improper sealing.
• Storage: Temperature excursions or humidity fluctuations during storage.
Common tools for risk identification:
• Failure Mode and Effects Analysis (FMEA)
• Fishbone diagrams (Ishikawa)
• Brainstorming sessions with cross-functional teams
• Process Hazard Analysis (PHA)
3. Risk Assessment:
• Severity: How critical is the risk to patient safety or product efficacy?
• Likelihood: How probable is the occurrence of this risk?
• Detection: What is the likelihood of detecting the risk before it impacts the product?
A Risk Priority Number (RPN) or a Risk Matrix (combining severity, likelihood, and
detection) is commonly used to evaluate risks.
Example:
• Risk: Contamination during compounding
• Severity: High (could lead to product recall and patient harm)
• Likelihood: Moderate (with existing controls)
• Detection: Low (contamination may not be detected immediately)
• RPN/Score: High priority for risk mitigation.
4. Risk Control Measures:
Implement risk control measures to reduce the likelihood, severity, or improve detection of
risks. In the pharmaceutical industry, these may include:
• Preventive Measures:
o Supplier qualification programs for raw materials to ensure consistent quality.
o Use of closed systems and validated cleaning protocols to minimize
contamination.
o Regular calibration and maintenance of equipment to prevent breakdowns
during production.
• Detective Measures:
o In-process controls such as sampling and testing during critical steps (e.g.,
sterility testing, dissolution testing).
o Automated monitoring systems (e.g., temperature and humidity control in
storage facilities).
5. Risk Communication and Documentation:
Ensure that all risk assessments, identified controls, and actions are communicated across
relevant departments (e.g., production, QC, QA). This is vital for ensuring that everyone
understands the risks involved and the measures in place to mitigate them.
Key documentation to maintain includes:
• Risk assessment reports
• Control strategies and procedures
• Validation protocols and results
• Change control documentation when process changes are made.
6. Risk Review and Continuous Monitoring:
Risk management is a continuous process. Regularly review the risk management plan and
process flow, especially when changes occur, such as:
• New suppliers for raw materials.
• Changes to equipment or processes.
• Updated regulatory requirements (e.g., FDA or EMA guidelines).
Process Step Identified Risk Risk Assessment Control Measure
Supplier audits,
Material High severity,
Contaminated API batch incoming material
Procurement moderate likelihood
testing
Cleaning validation,
Manufacturing Cross-contamination High severity, low
dedicated equipment
(Mixing) between product batches likelihood
for high-risk products
Calibration and
Quality Control False test results due to Moderate severity,
maintenance schedule
(Testing) equipment malfunction moderate likelihood
for testing equipment
Barcode scanning and
Incorrect labeling of High severity, low
Packaging double-check
product likelihood
procedures
Temperature excursion Automated temperature
High severity, low
Storage during cold chain monitoring and alarm
likelihood
storage system
Regulatory Context in the Pharmaceutical Industry:
Regulatory agencies like the FDA, EMA, and ICH have established guidelines for QRM
in the pharmaceutical sector. Two key documents include:
• ICH Q9: Quality Risk Management: Provides a structured approach to managing
risks related to product quality, including risk assessment, control, communication, and
review.
• ICH Q10: Pharmaceutical Quality System: Incorporates risk management as a core
component of the overall pharmaceutical quality system.
Benefits of Using QRM with Process Flow in QA:
1. Improved Product Quality: By identifying and controlling risks, companies ensure
that products consistently meet quality standards.
2. Regulatory Compliance: A robust QRM system aligned with process flow diagrams
helps meet regulatory expectations, reducing the likelihood of non-compliance.
3. Efficiency Gains: QRM helps streamline processes by focusing efforts on high-risk
areas, leading to more efficient use of resources.
4. Patient Safety: Proactive risk management ensures that patient safety is prioritized,
reducing the chances of recalls or adverse events.
5. Continuous Improvement: Regular reviews of the process flow and risk assessments
promote continuous improvement and adaptation to new challenges.
Conclusion:
Integrating Quality Risk Management (QRM) with a process flow in the QA
department of the pharmaceutical industry is essential for safeguarding product quality,
ensuring compliance, and enhancing patient safety. By using systematic tools like process flow
diagrams, risk assessments, and control measures, pharmaceutical companies can proactively
identify risks and implement strategies to mitigate them, ensuring reliable and high-quality
product delivery.
