QMS-140 Root Cause Analysis Investigation Procedure

Purpose

This SOP describes the procedure for initiating, communicating, conducting and documenting Root Cause Investigation related to process, system, raw material, product, facility and laboratory deviations. A detail Investigation is required to identify Root Cause of a deviation or quality trends.

Scope

This SOP covers the use and management of the Root Cause Investigation Tool designed on the principles of DMAIC (Root Cause Investigation Template TEM-315, annexed in this SOP) which may be raised in association of a deviation that needs further investigation or there is a trend in the product complaints, periodic product quality review or trend observed in any other quality aspect.

Root Cause Investigation Tool is used if the root cause of a deviation is not known and there is a necessity to perform an in-depth investigation with an effort to identify root cause(s).

Root Cause Investigation tool does not need to be used in every unplanned deviation situation.

Business Rules

A Root Cause investigation can be raised when one or more of the following occur:

–         The cause of the unplanned deviation cannot be determined.

–         There is a probable cause or set of causes based on available evidence but the causes are not confirmed as the root cause.

–         A number of unplanned deviations that indicates repeated trends or when there are repeated trends indicated by other quality systems, such as complaints, periodic product quality review.

A Root Cause investigation process should follow the DMAIC process, which is described in the ‘Root Cause Investigation Template in attachment A.

A Root Cause investigation is not a substitution of usual unplanned deviation investigation. Rather, the tool should be used as an extended investigation and findings are attached with corresponding deviation.

As the root cause is determined, corrective and preventative actions are assigned in the respective deviation investigation.

Summary and recommendations should be presented periodically at the Site Quality meeting. 

Responsibility

Department Manager:

– The Department Managers are responsible to determine the need for a Root Cause Investigation.

– To identify appropriate Subject Matter Experts (SME) relevant to the scope of the investigation.

– To form an investigation team of at least 3 SMEs, identify the team leader and assign the DI as required.

– To negotiate a date and time with other department heads in order to ensure the presence of all SMEs during the investigation. 

Quality Assurance Manager:

– The Quality Assurance Managers or delegate determine the need for a Root Cause Investigation.

– To train the Subject Matter Experts (SME) (i.e. quality associates, production operations & engineering staffs) about the correct use Root Cause Investigation Tool.

– To review and approve the final investigation report.

– To present progress reports of closed and outstanding investigations, action items & recommendations periodically at the quality meeting.

SMEs:

To carry out the Root Cause Investigation using DMAIC tool Root Cause in (TEM-315, attachment A).

To attend investigation meetings assigned to them and carry out all actions in a timely manner.

To report the progress report of an outstanding investigation including roadblocks and availability of resources to QA Managers and/or the Department Managers.

Safety and Process Specific Information

All safety requirements for relevant areas at any GMP facility must be followed at all times.

Procedure

Quality Assurance Manager in consultation with other department Managers recommends the initiation of a Root Cause investigation when the root cause of a deviation cannot be determined or when there is a repeated trend in deviations, customer complaints, product quality review, internal audit observation or any other adverse trends that can potentially impact the safety and quality of the products.

Department Manager or their delegate identifies the participants (SMEs) and investigation leader to proceed with the investigation.

The soft copy of the blank investigation template is kept in the local drive which is accessible to all employees. The hard copy (A3) template is located in the Master SOP folder alongside the “Root Cause Investigation Procedure” SOP.

The investigation leader prints the template in A3 format and enter investigation reference number (i.e. Deviation no), participants, date and lot numbers.

The DMAIC process gathers facts from interviewing colleagues, batch record review, complaint files, retain samples, procedures and instructions, quality control testing, in-process monitoring, stability data, trends in deviations, previous investigations, change control, product quality reviews, equipment and utility maintenance programs etc. as appropriate.

The investigation might be extended to other batches of the same product, other products, related processing areas and equipment that may be associated with the specific failure or incident as required. Sometime, facts need to be gathered from other manufacturing sites such as Crookwell operations and relevant third party contractors, if required.

The DMAIC investigation process follows a sequential five steps question and answer pattern. It is important to complete each section with specific responses in order to reach to a plausible and true root cause. The DMAIC investigation process includes the following sections in chronological order:

Step 1: DEFINE (problem definition)

This is the first section of the Root Cause investigation. The section is designed with series of questions to define the problem, its history and to outline any work that has been done so far

Step 2: DEFINE / MEASURE (understanding the process)

This step has a grid line space to draw a brief process map to understand the sequential activities involved in the process. As the outline of the process is complete, the participants mark possible area/s where the deviation / incident discovered.

Step 3a: ANALYSIS (process analysis)

This section is designed to list if there were significant changes to process which might have contributed to repetitive incidents. The participants also need to identify and list the process controls and possible non value adding steps. 

Step 3b: ANALYSIS (cause and effect analysis)

This section is designed to perform a cause and effect analysis. The participants brain storm on each of six broad areas or systems such as machine, methods, measurements, materials, people and environments which are related to the defined problem. The process starts from adding the effect (defined problem) at the front of the fish – bone diagram and create branches of possible causes from the six process areas and systems. 

Step 3c: ANALYSIS (5 WHYs, Pareto Chart)

In this section the participants picks the possible causes of the problem. Each of the potential cause is than spread down by asking the question “WHY” up to five successive occasions or up to the point the participants feel the best possible effect / solution is already attained.

* This is an optional step

If found beneficial include a Pareto analysis separately to show the fewest (20%) most significant causes which have been causing the highest (80%) level of effects.  

Step 4: IMPROVE (Evaluate solutions)

As the solutions are identified in the analysis step 3c, each of the solution is placed within a matrix which is best suited based on their weights measured with the degree of benefit and degree of difficulty during the implementation stage. The solutions are grouped into four possible placements within the matrix which are:

– Stars (High benefit, Low difficulty)

These solutions should be implemented with reasonable efforts which can contribute highly to stop recurrence of the incident.

– Quick Wins (Low benefit, Low difficulty)

These solutions should be implemented readily which may contribute to stop recurring incident.

– Extra Effort needed (High benefit, High difficulty)

These solutions are relatively hard and lengthy to implement. However, once implemented, these can effectively prevent such incidents.

– Forget It (Low benefit, High difficulty)

These solutions are perceivably the least effective but harder to implement. These possible solutions can be discarded.

Step 5: IMPROVE / CONTROL (Implement solutions)

This final step list the most effective and reasonable action controls to be implemented with a view to improve the problem areas.

Once the potential root cause would be identified, the investigation participants should ensure the followings are addressed:

– Impact on product quality

– Qualifications or validations of equipment, systems, processes & analytical methods.

During the investigation analysis ask questions such as:

– How does the problem compare to other problems without the particular deviation?

– Does the difference in the problem item suggest a change may have occurred?

– How many units have the problem? Etc.

If the raw material lot is found to be the root cause, participants should check if the same lot has been used in other finished products lots which might already been affected.

Look for the use of common pieces of equipment which could have been used to make other finished products lots. Identify and consider all other similar situations which may not be included in the original deviation.

If the results of a product quality impact assessment pertain to any product in the market, the members of the SQC (Site Quality Committee) need to be notified immediately.

As the investigation is completed a Root Cause report has to be written, identifying the summary, investigation results, impact on product quality, corrective Actions, conclusion, recommendation and disposition.

As part of the investigation report, develop and document all corrective and preventative actions that were taken to solve the immediate problem and measures taken to prevent recurrence. The preventative actions taken should attempt to assure a permanent solution to solving the issue, not a temporary fix.

Update Section C of the Deviation Management (DM) software with the investigation results. Scan the completed Root Cause Investigation and attach with the respective deviation as reference.  

A quality risk assessment may be used to justify the disposition as per the procedure QMS-135 “Quality Risk Management Techniques”.

If after the Root Cause investigation has been completed but the root causes cannot be identified, the investigation will be brought to the attention of the Quality Assurance Manager and subsequently to SQC where it will reviewed and further actions assessed.

APPENDIX A: DMAIC Root Cause Investigation Template

Related Documents

QMS-035 Pharmaceutical Deviation Report System

QMS-055 Product Complaint Procedure

QMS-135 Quality Risk Management Techniques

Revision History