Best Root Cause Investigation tools and their benefit in Pharmaceuticals

The root cause is the very common procedure adopted by most of the industry to identify the issue/problem. Most of the industry follow the standard procedure to identify the root cause. Some of the common tools are used to identify the root cause. These tools are the way to identify the main cause. After identification of the main root cause take appropriate action and plan corrective action and preventive action (CAPA). It doesn’t matter which tools are using for root cause analysis.

Root cause investigation is a problem-solving method to identify the main cause of the nonconformity/defect/issue/problem/nonconformance.

Example of a tree to understand the root cause.

Root cause Analysis / Root cause Investigation Example of tree

Root cause Analysis / Root cause Investigation
Example of tree

The root of a tree plays a very important role to grow or develop the tree.

Assume the tree is problem/nonconformity/nonconformance/defect/issue then identify the root (factors/causes) which responsible for the development or growth of that nonconformity.

Another side of the picture shown that the cause (root) is responsible for effect (tree).

Identify these root causes from the resources like man, material, method, machine, etc.

The following methods may be used to support the identification and analysis of root causes:

1. Ishikawa Diagram/Fishbone Diagram/Cause and Effect Diagram / 6M:

1.1 Ishikawa Diagram is the most popular tools for root cause investigation.

1.2 This tool is also known as the fishbone diagram or cause and effect diagram or 6M.

1.3 This tool is mainly categorized in 6M i.e. Man, Materials, Machine Method, Measurement, Mother nature / Milieu (Environment).

1.4 Possible causes are usually grouped into major categories (e.g. 6M) to identify the sources of variation.

1.5 Below are the main 6M causes:

1.5.1 Man: Responsible persons who involved in the process or activity.

1.5.2 Materials: Raw materials, items, parts used or involved in the process or activity.

1.5.3 Method: It includes all procedures, rules, policy, regulation, and specific requirement for the activity or process and

1.5.4 Measurements: Data generated during the a process which measures the quality of products.

1.5.5 Machines: Any equipment, instrument involved in the activity or process.

1.5.6 Mother nature / Milieu (Environment): This include environmental conditions like temperature, humidity, pressure differential etc. and culture in which process or activity performed.

Ishikawa Diagram / Fishbone Diagram as per below:


Ishikawa Diagram / Fishbone Diagram / Cause and Effect Diagram / 6M
Ishikawa Diagram / Fishbone Diagram / Cause and Effect Diagram / 6M

2. Brainstorming / Grouping Technique:

In this technique focus on the most probable resource or cause first:

2.1 Grouping / Set of similar causes:

2.1.1 If some ideas will seem to be very similar then prepare a set of probable causes by grouping or removing duplicates.

2.2 Selection of cause:

2.2.1 Identify the cause as per the priority.

2.2.2 Give preference to the uppermost cause.

2.2.3 Failure Mode Effect Analysis

3. Identifying inconsistency by logic

3.1 By using the rules of logic identify the inconsistency with data.

3.2 Create a chain of logic or reasoning and identify the facts.

3.3 Prepare rationale for selection of logic and verify this from the QA department.

3.4 Verify the identified facts for consistency and resolve inconsistencies.

4. Hypothetical Technique

4.1 Generate assumptions based on the collected data.

4.2 Start assumption, how the nonconformance occurred.

4.3 Generate the sequence of events.

4.4 Identify the root cause.

5. Failure Mode Effect Analysis (FMEA):

5.1 Failure Mode and Effects Analysis (FMEA) is a potential failure identifying and evaluation procedure.

5.2 After identification of failure, create failure mode.

5.3 Created failure mode is helpful for risk reduction and eliminate, reduce or control the potential failures.

5.4 Benefits of Failure Mode Effect Analysis (FMEA):

5.4.1 FMEA is helpful to manage and break down the complex process steps into simplified steps.

5.4.2 Reduction of potential failures

5.4.3 Saving lives by improving quality

5.4.4 Cost reduction and save time

5.5 How to use the Failure Mode Effect Analysis (FMEA):

5.5.1 Failure Mode Effect Analysis (FMEA) is evaluated by Risk Priority Number (RPN).

5.5.2 Risk Priority Number (RPN) is calculated by occurrence, detectability, and severity of the risk.

5.6 Potential Areas of Use(s)

5.6.1 Used in risk control

5.6.2 Applied to equipment, facilities, system, operation and its effect on the product.

6. 5-Why Root Cause Investigation tool

6.1 The 5 Why questioning technique is a useful tool for discovering cause and effect relationships.

6.2 If the problem is simple or involves humans then this questioning technique is helping to identify the root cause.

6.3 Combination of fishbone diagram and 5 why is a more effective technique to identify the root cause. Take any resource of fishbone diagram and ask “Why”.

E.g. Previous product traces found on the duct. The main cause is related to “Machine”

  1. Why product traces found?

Ans. Because duct is not clean.

  1. Why duct is not clean?

Ans. Because duct cleaning is not part of the cleaning procedure.

  1. Why duct cleaning is not part of cleaning procedure?

Ans. Because by mistakenly person is not incorporated this part of the cleaning procedure.

  1. Why mistake happened by a person?

Ans. Because that person is not qualified or trained for that particular work.

6.4 In 5 why technique asks a series of questions to identify the proper root cause.

6.5 Each time ask “why” to answer to get the root cause.

6.6 This tool is not helpful for a complex problems.

6.7 In “5 Why” technique ask 5 questions. If needed ask more, depends on the requirement.

5 why analysis tool, root cause investigation tool
5 Why root cause analysis tool

7. Kepner – Tregoe / K-T Rational Thinking

7.1 Kepner and Tregoe developed problem-solving and decision-making method.

7.2 Six main steps are involved in this method:

7.2.1 Define the Problem:

Briefly describe the problem statement which includes

  • What – Identify exact issue
  • Where – Location of issue
  • When – Timing of issue
  • Depth – Size / complexity of issue
7.2.2 Identify the differences and changes: The description of the problem should include both “Is” and “Is Not” data. Identify the differences and changes.

Example of the problem: rust observed on the inner sidewall of reactor but not at the bottom of the reactor.

Is – Rust on the inner sidewall

Isn’t – Rust not at the bottom of the reactor






1. What happened with reactor?

2. Specify the problem.


1. What similar reactor could have an issue, but it does not?

What is specific about the reactor?


1. Where is the rust on the reactor?

2. Where is the problem observed during the process?

1. Where other possibly will the problem be observed, but it is not?

2. Where other possibly will it be on the reactor, but it is not?

3. Where other possibly will the defect be observed in the process, but it is not?

What is specific about the location?


1. When the defect was observed?

2. How long the reactor observed in a problem?

3. When in the reactor life cycle was?

1. When other possibly will it have been observed, but it wasn’t?

2. What other times possibly will it have been observed, but wasn’t?

3. When other possibly will it have been seen in its life cycle, but wasn’t it?

1. What is specific about the timing?

2. What has changed?


1. How many reactors facing a similar problems?

2. Severity or complexity of the problem?


1. When other possibly will it have been observed but was not?

2. What other times possibly will it have been observed but was not?

3. When other possibly will it have been seen in its life cycle but was not?


7.2.3 Detect possible causes:

Use 5 why, brainstorming, Ishikawa Diagram etc. for identification of possible causes.

7.2.4 Test possible causes against the fact: Each cause should be tested against the problem description, facts and each cause have able to explain both “Is” and “Isn’t” data. Eliminate causes that are not supported to “Is” and “Isn’t” data.

7.2.5 Prove true cause:

Explain cause by experiment, verifying assumptions, correct the problem and monitoring recurrence.

7.2.6 Prevent the true cause:

Extend the analysis beyond the immediate true cause with the aim to prevent problems in other areas for reoccurrence.

8. Process Mapping – workflow diagram

8.1 Process Mapping helps to understand the sequential process.

8.2 Construct a process workflow diagram for a process flow, process currently use,

8.3 Construct a Process Flowchart

Step 1: Determine the Start point and endpoint of process

Step 2: Sequentially arrange steps – General process flow

Step 3: Diagram the process

Step 4: Finalize the Flowchart

8.5 After finalizing the flowchart confirm whether the the process is running as per the process flowchart.

8.6 Person involved in the activity is following the procedure as per process flowchart.

8.7 Identify the missing points.

8.8 Sample Process Map Flowchart:

Process mapping / workflow diagram, root cause investigation tool

Process Mapping / Process workflow Diagram

9. If….then logic / Cause and effect analysis

9.1 Cause and effect analysis starts with most potential causes, prioritize the causes.

9.2 By applying rules of logic built a cause-effect relationship.

9.3 ‘Real’ cause should be verified and express by ‘if…..then’ statement.

9.4 Check for failure and missing elements.

9.5 Identify the other causes which may cause the same effect in the future. Hence, the same problem will not occur.

10. Fault Tree Analysis

10.1 This tool is helpful to identify the logical relationship between the nonconformity/harm and root causes.

10.2 Fault should be described in the form of a tree diagram.

10.3 This analysis assumes knowledge of known and potential adverse events (harm) or safety concerns that are inherent in the product being analyzed.

11. Distinguishing root Causes from probable Causes

11.1 Identify the probable root causes and distinguish the root cause from the multiple probable root causes. If the action plan is able to prevent recurrence then consider the root cause.

Distinguishing root cause from probable causes

Distinguishing root cause from probable causes



1. What are the tools used in root cause analysis?

1. Ishikawa Diagram / Fishbone Diagram / 6 M
2. 5 Why technique
3. Fault tree analysis
4. Cause-effect analysis
5. Brain storming / Grouping Technique
6. Hypothetical Technique
7. Kepner – Tregoe Technique
8. Process Mapping – Workflow diagram
9. Selecting root Causes from probable Causes
10. Identifying Inconsistency
11. Failure mode effect analysis (FMEA)

2. What if the root cause (s) cannot be identified?

If you do not find any root cause even after investigation then you should consider the most probable root cause which may be the fundamental cause of nonconformance. You should take CAPA on it.

3. What is root cause analysis and why is it important?

A class of a problem-solving technique for identifying the basic factors or root causes of problems that trigger possible the occurrence of an adverse event on a process or product. The main goal of root cause analysis (RCA) is to prevent a recurrence.
Importance of root cause analysis:
1. To maintain the flow of the system, consistency in product quality.
2. Identify the fundamental cause which triggers the nonconformance.
3. After identification of root cause you can able take appropriate CAPA to eliminate the cause.
4. Root cause is a regulatory requirement.

4. What is the best tool for getting to a problems root cause?

Total 11 root cause tools are available. In that most popular investigation tools are Ishikawa / Fishbone diagram, 5 why analysis, Failure mode effect analysis (FMEA), Fault tree analysis, Brainstorming and KT rational thinking.

5. What is difference between RCA and RCFA?

RCA is Root cause analysis and RCFA is Root cause failure analysis.
RCA – A class of a problem-solving technique for identifying the basic factors or root causes of nonconformance. E.g. OOS, deviation occured during manufacturing.
RCFA – A class of a problem-solving technique for identifying the basic factors or root causes of failure. E.g. equipment failure, process failure, system failure, etc.

Leave a Reply

Google Translate »
error: Content is protected !!