8 Quality Risk Management Tools Used in the Pharmaceutical Industry

Imagine you have to develop, manufacture, test, and distribute new pharmaceutical or medical device products. Or you have to make changes to an existing manufacturing process. You are going to face risk. Things can and will go wrong and there is a real possibility of causing harm to the patient.

So how do we identify, evaluate and mitigate as many of these risks that could harm the patient? Or how can we uncover these hidden paths to failure before they occur? And it’s often not just one single event but a chain of events where every single event leads you incrementally one step closer to failure.

The methodology for this is called quality risk management or QRM, where we make extensive use of worst-case scenario planning to figure out what could go wrong and come up with steps to mitigate those risks.

Think of it as a way of visualizing catastrophe before it happens and coming up with preventive steps either by designing out the problem (preferred) or procedurilize out the problem (last resort).

More technically, Quality Risk Management (QRM) is defined by the International Conference of Harmonisation (ICH) as a systematic process for the assessment, control and review of risks to the quality of the drug or medicinal product across the product life cycle.

Quality risk management uses many different risk assessment tools to uncover the underlying chain of events (or causes) that lead to failure and harm to the patient.

Let’s take a look at 8 of the most commonly used:

1. Fault Tree Analysis (FTA)
2. Cause and Effect (Fishbone Diagram)
3. Failure Mode Effect Analysis (FMEA)
4. Preliminary Hazard Analysis (PHA)
5. Hazard Operability Analysis (HAZOP)
6. Event Tree Analysis (ETA)
7. Hazard Analysis and Critical Control Points (HACCP)
8. The Five Whys

If you’d like to learn how to use these tools, check out our Conversion Course into Pharma for Scientists

Where it’s used

FTA can be used to investigate complaints or deviations in order to fully understand their root cause and to ensure that intended improvements will fully resolve the issue and not lead to other issues (i.e. solve one problem yet cause a different problem). Fault Tree Analysis is an effective tool for evaluating how multiple factors affect a given issue. The output of an FTA includes a visual representation of failure modes. It is useful both for risk assessment and in developing monitoring programs.

Where it’s used

It’s often used in manufacturing and product development to lay out the different steps in a process, demonstrate where quality control issues might arise, and determine which resources are needed at certain times.

Where it’s used

FMEA can be applied to equipment and facilities and might be used to analyze a manufacturing operation and its effect on a product or process. It identifies elements/operations within the system that render it vulnerable. The output/ results of FMEA can be used as a basis for design or further analysis or to guide resource deployment.

Why are FTA or Cause and Effect Diagrams often used together with FMEA?

FTA or Cause and Effect Diagrams are better at identifying possible faults and FMEA is better at analysing the failure modes for faults that have been identified. So in a work environment, they are often used in tandem with each other when looking to identify and solve potential unknown faults for a new system.
However, FMEA is used by itself when a fault has happened and the failure modes that could have caused it needs to be identified to prevent it from happening again.

Where it’s used

PHA is most commonly used early in the development of a project when there is little information on design details or operating procedures; thus, it will often be a precursor to further studies. It focuses predominantly on identifying and classifying hazards rather than evaluating them in detail. It can be used for product, process and facility design as well as to evaluate the types of hazards for the general product type and the specific product. PHA might be useful where circumstances prevent a more extensive technique from being used. Typically, hazards identified in the PHA require additional follow-up analyses using other tools.

Where it’s used

HAZOP can be applied to manufacturing processes, including outsourced production and formulation as well as the upstream suppliers, equipment and facilities for drug substances and drug (medicinal) products. It has also been used primarily in the pharmaceutical industry for evaluating process safety hazards. The output of a HAZOP analysis is a list of critical operations for risk management. This facilitates regular monitoring of critical points in the manufacturing process.

One of the biggest challenges with HAZOP is that it’s very prescriptive. For example, you use the guide words and process parameters such as no flow, less flow, more flow, no temperature, less temperature, more temperature, time, or any of those elements which can make using this risk management tool tiring, mind-numbing, and difficult to get right.

Where it’s used

Event trees can be used to analyze systems in which all components are continuously operating, or for systems in which some or all of the components are in standby mode or those that involve sequential operational logic and switching.

In the case of standby systems and in particular, safety and mission-oriented systems, the event tree is used to identify the various possible outcomes of the system following a given initiating event which is generally an unsatisfactory operating event or situation.

In the case of continuously operating systems, these events can occur (i.e., components can fail) in any arbitrary order. In the event tree analysis, the components can be considered in any order since they do not operate chronologically with respect to each other.

How it works

HACCP consists of the following seven steps:

1. conduct a hazard analysis and identify preventive measures for each step of the process; determine the critical control points
2. establish critical limits
3. establish a system to monitor the critical control points
4. establish the corrective action to be taken when monitoring indicates that the critical control points are not in a state of control
5. establish a system to verify that the HACCP system is working effectively
6. establish a record-keeping system.

HACCP is not simply a set of seven independent principles; each must build on the other. The output of a HACCP analysis is risk management information that facilitates monitoring of critical points not only in the manufacturing process but also in other life cycle phases.

Where it’s used

HACCP is used to identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination). HACCP is most useful when product and process understanding is sufficiently comprehensive to support the identification of critical control points.

How it works

On the surface, the method is remarkably simple. When a problem occurs, you drill down to its root cause by asking “Why?” 5 times. Each answer forms the basis of the next question, and the final ‘why?’. By then, a preventive measure should have becomes apparent. Then you follow through with it to prevent the issue from recurring.

Where it’s used

This technique is ideal for troubleshooting or resolving simple or moderately difficult, quality improvement and problems. It’s not so suitable if you need to tackle a complex or critical problem because it can lead you to pursue a single track, or a limited number of tracks, of inquiry when, in fact, there could be multiple causes.