Risk-Based Approach in Qualification and Validation
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NISHANTA RAMESHANRisk-Based Approach in Qualification and Validation
Uploaded by
NISHANTA RAMESHANRisk-Based Approach in Qualification and Validation
Prepared By- Under the guidance of –
Nishanta Rameshan ,M.Pharm,1st Sem (PA) Dr.Zanza Patel(Assoc prof.)
Parul Institute Of Pharmacy, Parul University
Parul Institute Of Pharmacy , Parul University
CONTENTS
• Qualification and Validation
• What is a Risk-Based Approach (RBA)?
• Principles of Risk-Based Approach.
• Risk Based Approach in Qualification and Validation .
• Risk Assessment.
• Regulatory and Industry guidance supporting Risk Based Approach.
• Benefits regulators see in Risk Based Approach .
• Continuous Improvement and Reassessment.
• Pros and cons of the Risk-Based Approach.
• Conclusion.
• References.
Qualification and Validation
Qualification and Validation are two distinct but interrelated processes in the pharmaceutical and biotechnology industries that ensure
facilities, equipment, systems, and processes meet regulatory requirements and produce products of the desired quality. Here are the key
differences:
Qualification
• It a regulated and documented process that demonstrates that equipment, systems, and facilities are installed correctly and operate as
intended for their specific usages.
• It applies only to equipment, systems, and utilities that directly or indirectly impact product quality and patient safety.
• Qualification is focused on by regulatory authorities like the FDA and EMA to ensure compliance.
Validation
• Validation is a broader concept establishing documented evidence that a process consistently produces a product that meets its
predetermined specifications and quality attributes.
• It encompasses the entire process lifecycle, including process design, qualification of equipment/systems, and continued process
verification.
• Validation ensures that the equipment and systems are qualified and the entire process is controlled to produce the desired final product.
Summary
In summary, qualification demonstrates suitability for intended use, and validation provides a high degree of assurance that the process
will consistently produce a quality product. These activities are interconnected, with commissioning often leveraged during qualification and
qualification being a subset of the overall validation process.
What is a Risk-Based Approach (RBA)?
• Risk-Based Approach (RBA) is a systematic framework for
identifying, evaluating, and prioritizing risks to enable informed
decision-making.
• It is widely used in the pharmaceutical, life sciences, and
biotechnology sectors to ensure patient safety, product quality, and
regulatory compliance.
• RBA helps allocate resources efficiently by focusing on high-risk
areas while minimizing oversight on low-risk activities.
• This approach aligns with global standards such as ICH Q9, as well as
regulatory expectations from agencies like the FDA and EMA.
• It promotes a proactive and data-driven way to manage risks throughout
the product lifecycle—from development to post-market monitoring.
• The ultimate goal is to enhance product safety, improve quality, and
ensure operational efficiency
Principles of Risk-Based Approach.
• Risk Identification: Proactively recognizing potential risks across
product development, manufacturing, and distribution.
• Risk Prioritization: Using tools like Failure Mode Effects Analysis
(FMEA) or Fault Tree Analysis (FTA) to rank risks based on severity,
occurrence, and detectability.
• Risk Mitigation: Implementing measures to reduce unacceptable risks
to an acceptable level, leveraging approaches such as design controls
or process safeguards.
• Continuous Monitoring: Regularly updating risk management
strategies based on real-world data, deviations, or changes in
regulations.
• Lifecycle Approach: Ensuring risk management processes are applied
consistently throughout the product lifecycle, from development to
post-market activities.
Risk Based Approach in Qualification and Validation.
Risk Identification & Assessment
• Uses systematic tools like Failure Mode and Effects Analysis (FMEA) to pinpoint hazards, failure modes, or process
variations that could adversely affect product quality or compliance.
Risk Prioritization
• Risks are ranked by severity, likelihood, and detectability, ensuring critical areas receive maximum attention.
• Lesser risks may require reduced qualification or validation efforts.
Control Measures
• Methods such as design improvements, validated procedures, training, and robust SOPs are implemented to mitigate
top-priority risks, ensuring they remain at acceptable levels.
Validation Strategy
• The extent and scope of qualification or validation are determined by the risk assessment.
• Activities focus more on critical quality attributes (CQAs) and parameters essential for product safety and efficacy.
Risk Assessment:
Risk assessment involves identifying hazards and analyzing and evaluating risks associated with exposure to those
hazards.
• Starting Point: Begin with a clear problem description or risk question to focus the assessment.
• Fundamental Questions:
• What might go wrong?
• What is the likelihood (probability) it will go wrong?
• What are the consequences (severity)?
• Hazard Identification: Systematically identify hazards related to the risk question using data such as historical
information, theoretical analysis, expert opinions, and stakeholder concerns.
• Risk Analysis: Estimate the risk by linking the likelihood of occurrence and severity of harm, sometimes including the
detectability of the harm.
• Risk Evaluation: Compare identified and analyzed risks against predefined risk criteria, considering evidence strength,
uncertainties, and limitations.
• Sources of Uncertainty: Include gaps in knowledge, process variability, failure modes, and detectability challenges.
• Risk Output: Risk can be expressed qualitatively (e.g., high, medium, low) or quantitatively with numerical
probabilities or risk scores.
• Quantitative Risk Estimation: Useful for evaluating specific consequences and sometimes integrated into scoring
systems combining severity and probability.
Regulatory and Industry Guidance Supporting Risk-Based Approach
• ICH Q9 (Quality Risk Management) provides a robust framework for risk management in pharmaceuticals,
applicable through the product lifecycle.
• EU GMP Annex 15 emphasizes risk-based qualification and validation, requiring a formal documented risk
assessment to determine the scope and extent of activities.
• WHO Guidelines support risk management throughout qualification and validation phases, highlighting lifecycle
considerations and change control.
STEPS OF IMPLEMENTATION.
• Facility, equipment and utilities.
• Development.
• Materials management.
• Production.
• Laboratory control and stability testing.
• Packaging and labeling.
• Supply chain control.
• Inspection and assessment activities.
Continuous Improvement and Reassessment.
Initial Risk Assessment:
Identify and prioritize risks early in the process based on
their potential impact.
Continued Process Verification (CPV):
Use real-time monitoring and data analysis during
routine production to ensure processes remain in a
validated state.
Periodic Reviews:
Regularly review the validated state of systems and
processes, analyzing performance data and changes to
confirm ongoing compliance.
Annual Product Quality Review (APQR):
Conduct annual evaluations of product data to identify
trends, inconsistencies, and areas for process
optimization.
Change Control and CAPA:
Assess all changes using a risk-based approach and
implement corrective and preventive actions (CAPA) to
drive improvements.
Benefits of the Risk-Based Approach
• Efficient Resource Allocation
• Resources are focused where risk is greatest, saving time and reducing costs while maintaining
compliance.
• Streamlined Documentation & Faster Approval.
• Less critical systems require minimal qualification, lowering documentation burdens and allowing
quicker product launches.
• Regulatory Alignment.
• Compliant with ICH Q9, Q10, and FDA guidance, ensuring modern best practices.
Pros and Cons of Risk-Based Approach
Pros Cons
• Optimizes resources by focusing on high-risk areas. • Requires strong risk management expertise.
• Regulatory alignment with current global standards. • Risk of underestimating risks if assessments are
• Encourages innovation and flexibility in approach. incomplete.
• Initial setup and cultural change can be
challenging.
Conclusion
A risk-based approach in qualification and validation is recognized globally as a best practice for ensuring
pharmaceutical quality and patient safety. It improves efficiency and regulatory compliance by focusing efforts
on critical risks while enabling continuous lifecycle management and adaptation to changes. Successful
implementation depends on sound risk assessment, regulatory alignment, and organizational commitment to
quality risk management.
REFERENCES