The biggest concern in this Regulatory Challenging Environment is to apply risk-based thinking for implementing, deploying and maintaining a quality management system with limited resource

There is a significant concern of every pharmaceutical professional who is responsible to ensure the consistent quality of products and who are responsible for deploying & implementing the quality management system (QMS) throughout the product life-cycle.

Risk Management concept is not new, this tool is used for a long time in the pharmaceutical industries but now it is used differently to identify the risk and apply the risk-based thinking approach in every function of pharmaceutical industries i.e in the process, QMS, during the preparation of any procedure, etc.

This article will present requirements about the process and quality management system. Here are some definitions of risk management defined in standards and guidelines.

Definition & Background of Risk-Based Approach

There are some international guidelines and standards that provide directions or guidance to successfully implement a workable solution to make a robust quality management system. Following requirement are defined in different standard and regulation but not limited to:

“ISO 13485:2016 Medical devices — Quality management systems — Requirements for regulatory purposes
The organization shall:
  • a) determine the processes needed for the quality management system and the application of these processes throughout the organization taking into account the roles undertaken by the organization;
  • b) apply a risk based approach to the control of the appropriate processes needed for the quality management system;
  • c) determine the sequence and interaction of these processes”
Similarly, 21 CFR 820.75 also suggest following

21 CFR 820.75 – Process validation.

(b) Each manufacturer shall establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met.
(1) Each manufacturer shall ensure that validated processes are performed by qualified individual(s).
(2) For validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented.
(c) When changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate. These activities shall be documented.

As per 21 CFR 820.100

(b) Each manufacturer shall analyze service reports with appropriate statistical methodology in accordance with 820.100.

Trend Analysis & Effective Resource Utilization

By using the right statistical tools and correct analysis, the potential risky area within the process, QMS, service, etc. can be identified and in all these areas resources can be used effectively. We all know that there is an unlimited need but resources are limited so, in that situation, effective resource utilization is a big question.

There are different tools for trend analysis and out of all the statistical tools, the most common tool is used – Control Chart. This control chart is very often used in the pharmaceutical/healthcare industries to understand the behaviors of process and analytical results and on the basis out of trends, limits are defined.

A survey with the help of Pulse has been done by Pharmawhiz. As per the survey result, 76% of people are using trend analysis in QMS to apply risk-based approach however 24% are not using any kind of trend analysis tool in QMS to apply risk-based thinking. 

Disclaimer: Results may vary if more participants will take part in the survey.

Pulse Survey- Risk based thinking
Pulse Survey- Use of Trend analysis tools in Risk-based thinking 









Thoughtfully utilization of all these statistical techniques make the effective utilization of limited resource and with the help of all these techniques, good quality of product with improved productivity can be produced.

Generally, limit set based on the standard deviation 2σ & 3σ and trending chart constructed using threshold limit – Alert Limit & Action Limit.

Type of variance exists in the process

Generally, there are two types of variance exist in the process:

  1. Common cause
  2. Special cause

Common Causes:

These type of variance is inherent in the process and exist permanently and these type of variance affect the process every time i.e yield of the product. You have might see that for any product you always found yield limit within a range and maximum time it is not 100% so now you can understand there are some losses always remain in the process which is due to the common cause and known as common cause variance but if suddenly you have encountered with surprise increment or decrement in the yield from its routine trends then it indicates that this is not due to common cause. These types of variance are not due to the common cause, it is something different which is due to a special cause, and these types of variances known as special cause variance.

Special Cause:

As stated above these types of causes are not exist in the process commonly so it means it is generated due to any process error, human error, material error, etc. These types of causes are generally called assignable causes.

Any drift in the process indicating the presence of special cause in the process. Any such outlier shall be treated as special cause variance and it should be investigated thoroughly. Any outlier should be removed from the data used to calculate the process centerline and it should not be used to make trend analysis.
Line chart - Outlier Identification
Line chart – Outlier Identification
From the above explanation, now you can understand where should we more focused to make the process well with-in control. Of-course, you should deploy your resources to analyze the process, identify the special cause, investigate it, and fix the problem which will give you a controlled process and good productivity.
There are other statistical tools also which can be used on QMS elements i.e. deviation, market complaint, self-inspection, supplier management, etc.

Pareto Analysis

Pareto analysis tools can be used on the identified root cause, inspection deficiencies to understand what are the key factors/area which contributes 80% in the non-conformance.

Trends Analysis- Risk based Thinking
Trends Analysis- Risk-based Thinking in QMS or Process














This tool can be used by selecting the column chart in the MS-Excel sheet and with the help of this chart you can easily identify the 80% contributory factors and utilize your resource effectively to control all these risky areas. By focusing all these 80% contributory factors and fixing all these gaps you can also improve your compliance level.


It is recommended to do the trend analysis of each critical process and QMS element i.e. Change Control, Deviations, Market Complaints, Out of Specification, Self-Inspection, Supplier related non-conformance, etc. and basis that identifies the risky area or repetitive failure area and deploys the resource on these areas for further improvement.

Now you can understand the “Importance of Risk-Based thinking” & “How to apply it”

Statistical Tools: “Use It, Identify Cause, Fix It and Improve the Compliance