Dr Pramod Kumar Pandey BSc (Hons), MSc, PhD, founder of PharmaGuru.co, is a highly experienced Analytical Research Expert with over 31 years in the pharmaceutical industry. He has played a key role in advancing innovation across leading Indian and global pharmaceutical companies. He can be reached at admin@pharmaguru.co
What is Root Cause Analysis (RCA)? Root Cause Analysis (RCA) is a structured, systematic approach used to identify the underlying causes of a problem rather than simply addressing its immediate symptoms. By uncovering the fundamental reasons an issue occurred, RCA enables organisations to implement long-term, effective solutions that prevent recurrence. This methodology is widely applied […]
What is Root Cause Analysis (RCA) And How Helpful It In Pharma: Learn With Examples & FAQs
What is Root Cause Analysis (RCA)?
Root Cause Analysis (RCA) is a structured, systematic approach used to identify the underlying causes of a problem rather than simply addressing its immediate symptoms. By uncovering the fundamental reasons an issue occurred, RCA enables organisations to implement long-term, effective solutions that prevent recurrence. This methodology is widely applied across various industries, including quality control, healthcare, engineering, and manufacturing, to enhance processes, products, and systems.
What are the Core Principles of RCA?
Effective RCA is guided by several foundational principles that help ensure accuracy, objectivity, and actionability:
Address root causes, not just symptoms.
Acknowledge the value of treating symptoms to achieve necessary short-term relief.
Recognise that multiple root causes may exist.
Focus on how and why an event occurred—not on assigning blame.
Be systematic and evidence-driven, using verifiable cause-and-effect relationships.
Provide sufficient detail to support meaningful corrective actions.
Consider future prevention or replication of outcomes.
Take a holistic perspective, aiming for analysis that is both comprehensive and actionable.
How Root Cause Analysis Works?
Define the Problem Clearly articulate the issue, including its impact and scope.
Gather Data Collect relevant information—such as measurements, logs, observations, and timelines.
Identify Contributing Factors Use structured tools and techniques to reveal factors that shaped the problem.
Apply RCA Tools
5 Whys: Systematically ask “why?” to drill deeper into cause-and-effect relationships.
Fishbone Diagram (Ishikawa): Visually map potential causes across key categories.
Develop and Implement Solutions Create corrective actions targeting the identified root causes.
Monitor Effectiveness Evaluate the results, verify improvement, and adjust actions as necessary.
What is the 5 Whys Technique?
The 5 Whys method is a simple yet powerful tool for digging beneath the surface of a problem. By repeatedly asking “Why?”—each time probing the previous answer—you progressively move from symptoms toward root causes. While five iterations are typical, the actual number may vary.
Case Study: Peak Splitting in HPLC Analysis
Why is peak splitting occurring? Because the mobile phase was not filtered.
Why wasn’t the mobile phase filtered? Because I was in a hurry.
Why were you in a hurry? Because the analysis results were needed within a short time frame.
Why was the timeframe so short? Because the work was urgent, and I assumed no issues would arise.
Why did you assume no issues would arise? Due to limited analytical experience, additional HPLC training is needed.
Conclusion: The root cause is insufficient analytical skill or training. A corrective action would be to provide comprehensive HPLC training to improve competency and prevent recurrence.
Prevents Recurrence: Addresses the true cause, providing lasting solutions.
Drives Continuous Improvement: Enhances processes, quality, and system reliability.
Reduces Costs: Eliminates repeated failures and minimises waste, downtime, and rework.
What Is a Cause-and-Effect or Fishbone or Ishikawa Diagram?
A Fishbone Diagram—also called an Ishikawa diagram—is a visual brainstorming tool used to categorise and explore potential causes of a specific problem. Its structure resembles a fish skeleton, with the “head” representing the problem and the “bones” representing categories of possible contributing factors.
Common Cause Categories
Depending on the context, categories may include:
Machine (equipment, technology)
Method (procedures, workflows)
Material (raw materials, consumables, information)
Man / Mind Power (skills, labour, knowledge work)
Measurement (inspection, data collection reliability)
Mission (purpose, expectations)
Management / Money Power (leadership, resources)
Maintenance (equipment care, maintenance schedules)
Product / Service
Price
Promotion (marketing or communication)
Process (system performance, process design)
People (staffing, training, competence)
Physical Evidence
Performance (KPIs, quality outputs)
Surroundings (environment or workplace conditions)
Suppliers
Skills
Fishbone Case Study: Low Column Efficiency in HPLC Analysis In Related substances test of an API
Problem (Fishbone Head):Low column efficiency (poor theoretical plates)
Causes
1. Method
Incorrect mobile phase ratio
Flow rate set higher than the validated method
Inadequate column washing and equilibration time
2. Machine (Equipment)
Column temperature not stable
Pump pulsation due to worn pump seal
Detector lamp intensity low
3. Material
Mobile phase not freshly prepared
Buffer pH drifting due to poor pH calibration
Contaminated solvents or reagents
4. Man (chemist)
Improper column handling
Failure to filter and degas mobile phase
Incomplete system flushing between runs
5. Measurement
Incorrect integration settings
Incorrect injection volume entry
6. Environment
Lab temperature fluctuations affecting column performance
Root Cause Identified:
Mobile phase buffer pH was incorrect due to a poorly calibrated pH meter.
Supporting Evidence:
pH meter calibration logs showed one expired buffer standard.
Rechecking pH with a properly calibrated meter corrected the issue.
After preparing fresh buffer with correct pH, column efficiency returned to normal.
Corrective Action:
Calibrate pH meter using fresh buffer standards before mobile phase preparation.
Implement a pre-run checklist for mobile phase preparation and system suitability.
Preventive Action:
Monthly verification of pH meter performance and replacement schedule for buffer standards.
How Is Root Cause Analysis (RCA) Connected to CAPA, OOS, OOT, and Deviations in Pharma?
Root Cause Analysis (RCA) is a core requirement in the pharmaceutical quality system because it helps identify the true reason behind quality failures or process abnormalities. In pharma, RCA is directly connected to CAPA, OOS, OOT, and deviations in the following ways:
OOS (Out of Specification): When test results fall outside established specifications, RCA is performed to determine whether the failure is due to analytical error, instrument issues, sample handling, or a true product quality problem.
OOT (Out of Trend): For results that show abnormal trends over time, RCA helps identify early signals of process drift, equipment wear, or analytical variability—preventing future OOS events.
Deviations: Any departure from approved procedures, processes, or expected outcomes requires an RCA to understand what went wrong and why, ensuring the deviation does not recur.
Corrective actions address the identified root cause.
Preventive actions ensure similar issues do not occur across related systems or processes.
In summary, RCA is the central investigative tool that supports OOS, OOT, and deviation investigations and forms the basis for effective, compliant CAPA in the pharmaceutical industry. It ensures issues are resolved at their source and strengthens overall product quality and regulatory compliance.
Conclusion
Root Cause Analysis (RCA) helps teams move beyond symptom-based fixes to identify and address the true sources of problems. By applying structured tools like the 5 Whys and Fishbone diagrams, organisations can uncover underlying issues, implement effective corrective actions, and prevent recurrence. When done well, RCA strengthens processes, improves quality, and supports continuous improvement across the system.
The five steps are: 1. Define the problem 2. Collect data 3. Identify possible causes 4. Determine the root cause 5. Implement and verify corrective actions
What are the four types of RCA?
The four common types of RCA are: 1. Safety-based RCA 2. Production-based RCA 3. Process-based RCA 4. Failure-based RCA
What are the 5 Whys of root cause analysis?
The 5 Whys is a technique where you repeatedly ask “Why?”—usually five times—to dig deeper into a problem and identify its root cause
