Failure Mode and Effects Analysis (FMEA) in Pharmaceuticals

The pharmaceutical industry operates on the preventative principle of failures, which means production failures are avoided before they occur and have an impact on product quality or patient safety. While analyzing deviations, complaints and investigations can provide much needed lessons once the event has already taken place, the best quality systems work on the principle of predicting risks and failures beforehand. This proactive spirit is involved in Failure Mode Effects Analysis (FMEA), which is one of the most widely used risk management mechanisms in the pharmaceutical production area.

FMEA is a practical tool used to analyze how a process, utility, system or equipment can fail, assess the consequences and elaborate measures to bring the risks down. Regardless of whether you are validating the manufacturing process, qualifying equipment, implementing the transfer of a product or introducing a change control, FMEA guarantees that the high risks of production will be detected and dealt with.

I have noticed that FMEA forms are filled out because it is required by the policy of a particular company. However, the real value of the FMEA process lies in the discussions during the evaluation. The well-run FMEA process proves or disproves assumptions, facilitates cooperation between departments and, often, allows pointing out risks that would otherwise be kept unnoticed until some deviation or inspection comes up.

What Does FMEA Mean?

FMEA or Failure Mode and Effects Analysis is a risk analysis tool designed to analyze the potential causes of a failure in a process or procedure, evaluate the damages that stem from it, find the root causes of the breakdowns and come up with ways to minimize the risk level of those problems.

Originally pioneered by the aerospace industry, FMEA is now widely practiced in the pharmaceutical industry since it is in compliance with the ICH Q9 standards of Quality Risk Management.

In a nutshell, FMEA tries to provide answers to the following four questions:

• What fails?
• Why does it fail?
• What are the implications of such failures?
• How can the risks be decreased or avoided?

Knowing the answers to these questions helps firms to allocate their resources to the areas that can pose the highest danger to the quality of products and the safety of patients.

Importance of FMEA in the Pharmaceutical Sector

The modern pharmaceutical industry entails complex processes, advanced technologies, automated systems, utilities and highly regulated atmosphere. This means that any stage of the process may involve risk that might influence the quality of the product if not controlled appropriately.

Using FMEA, companies are able to:
- find the risks before the validation or production
- concentrate on the critical parameters of the process and critical quality attributes
- increase the robustness of the process
- make the change management assessments stronger
- provide scientifically grounded validation decision-making
- cut down the number of deviations and investigations
- increase the preparedness for inspections
- guarantee the safety of the patients
FMEA allows following the principle of actually prioritizing risks instead of treating them equally.

Some Important Terminology Related to FMEA

Key Terminology Used in FMEA
First step in carrying out an FMEA is to be familiar with the terminology associated with FMEA.

1. Failure Mode

A failure mode indicates the manner in which a process, equipment, or system can fail.
Examples include:

• Improper mixing time
• Filter leakage
• Temperature sensor failure
• Insufficient cleaning
• Wrong software configuration

2. Failure Effect

Failure effect consists of the result of the failure.
Examples include:

• Improper blending
• Microbial contamination
• Rejection of product
• Failure to sterilize
• Incorrect documents

3. Failure Cause

Failure cause explains the possible reasons for the failure.
Examples include:

• Mistaken actions of employees
• Degradation of equipment
• Few repairs
• Improper standard operating procedures
• Disruption of utilities

4. Existing Controls

Existing controls are those measures that are already implemented to prevent or identify failures.
Examples include:

• Alarm systems
• Planned maintenance
• Testing during operation
• Calibration
• Management of standard operating procedures
• Training
• Verification of documentation

Three Risk Factors in FMEA

FMEA scores each failure identified using three criteria.

1. Severity (S)

Severity indicates the effects of the failure if it occurs.
Points generally noted include:

• Patient protection
• Product integrity
• Compliance with regulation
• Failure in production

Sample score:
1: No effect
5: Moderate effect requiring follow-up
10: Great effect on patient protection or product recall

2. Occurrence (O)

Occurrence measures how often the failure will occur.
Scores are normally like this:
1: Very unlikely
5: Occurs once in a while
10: Occurs frequently
Historical records, equipment reliability and process capability are important for defining the occurrence score.

3. Detection (D)

Detection shows how probable it is that the failure is going to be detected.
Sample score:
1: Almost certain detection
5: Some chance of detection
10: Very little chance of detection
Lower detection scores indicate stronger process controls.

Calculating the Risk Priority Number (RPN)

The overall risk is calculated by using the following equation:

RPN = Severity × Occurrence × Detection

For example:
Let’s assume that the severity = 5, occurrence = 10, and detection = 5
The value of RPN = 5 × 10 × 5 = 250

The RPN is a measure of how serious the risk is.
In general, companies have predefined thresholds for risk levels, for instance:
If the RPN is lower than 25, the risk is acceptable
If the RPN is between 25 and 125, the risk should be monitored
If the RPN is greater than 125, then management should take steps to reduce risk

A company should set its own standards for acceptable risk based on its risks and internal processes.

Steps to Perform an FMEA

Step 1: Determine the Scope

Identify exactly what needs assessment is to take place.
Some examples may consist of:

• Tablet compression procedure
• Purified water treatment
• HVAC qualification
• Cleaning validation
• Sterilization procedure
• Computerized system
• Packaging line

A properly defined scope enables concentrating on assessment.

Step 2: Gather a Cross-Functional Team

For FMEA to be effective, specialists from various departments should be included in this process.
These might include:

• Production
• Quality assurance
• Quality control
• Engineering
• Validation
• Maintenance
• Process development
• Regulatory affairs

A variety of angles contribute to better risk identification.

Step 3: Outline the Process

Prior to identifying failures, you should divide the whole process into stages.
As for the tablet production, it may have the following stages:

• Dispensing
• Blending
• Granulating
• Sourcing
• Milling
• Compressing
• Coating
• Packaging

Going through the process step by step helps to increase the chances that no significant risks will be missed.

Stage 4: Identify Possible Types of Failure

Ask questions like:

• What could go wrong?
• How can this stage fail?
• What factors can hinder accomplishing the goal of the process?

All possible types of failure should be recorded.

Stage 5: Analyze Each Risk

Assign Severity, Occurrence and Detection ratings using company criteria.
Do not assign ratings based on personal judgments.

Stage 6: Propose Risk Reduction Measures

Identify measures that can be taken in case of the failure types with high risks.
Measures can include:

• Redesigning the process
• Installing additional alarms
• Increasing the sample size
• Updating SOPs
• Training the operators
• Improving preventive maintenance
• Automating the process
• Conducting additional validation studies

After the new measures are implemented, risks must be analyzed again to make sure that RPN became lower.

Practical Example of FMEA

Let's take the example of the process of compressing tablets.
Failure mode: Variations in compression force.
Failure effect: Variable hardness of the tablet leading to problems with dissolution.
Failure cause: Abnormal wear of compression tools and dies.
Existing controls: Preventive maintenance and hardness testing.
Severity: 3
Occurrence: 2
Detection: 2
RPN: 8

Actions recommended:

• Reduction in time intervals for inspecting tools.
• Use of automated compression force measuring.
• Increase in frequency of preventive maintenance.
• Trend development of compression force parameter in production processes.

After implementing these controls, occurrence and detection scores should decline, resulting in a substantial reduction of RPN.

FMEA Applications in Pharmaceuticals

The use of FMEA is widespread during the entire lifecycle of pharmaceuticals.
Some of its common applications are:

• Validation of Processes
• Qualification of Equipment
• Validation of Cleaning
• Validation of Sterilization
• Validation of Water System
• Qualification of HVAC System
• Validation of Analytical Methods
• Validation of Computer Systems
• Design of Facilities
• Qualification of Utilities
• Control of Changes
• Transfer of Technology
• Qualification of Suppliers
• Annual Review of Quality in Products

The flexible nature of FMEA makes it one of the most significant tools used in managing risks in the pharmaceutical sector.

Best Practices for an Efficient FMEA

To get the best from this tool:

• Use scientific data to determine risk scores.
• Involve staff from various departments with experience.
• Make sure to study previous problems and complaints prior to scoring.
• Be ready to challenge assumptions as a group.
• Be prepared to explain the reasons for arriving at your scores.
• Integrate CAPA processes and validation schemes into the FMEA.
• Review FMEA regularly throughout the life of the product.

Make sure to review risk levels once any corrective actions or major process changes are introduced.

The process of Failure Mode and Effects Analysis is more than just an obligatory procedure, but rather a systematic decision-making method that allows pharmaceutical producers to identify potential failures, gauge risks and take steps to assure product quality. When a company examines seriousness, frequency and identification level of potential failures, it can plan the distribution of resources in the best way and establish more reliable manufacturing processes.

In my opinion, successful FMEA sessions are those that stimulate technical discussions instead of merely filling in an FMEA form. When professionals from several fields base their risk assessments on scientific proofs, past experience and operational knowledge, the process takes on the key character in terms of quality risk management.

Share

Tweet

Share

Pin it

Share