Hazard Analysis and Critical Control Point, commonly known as HACCP, is a systematic preventive technique for identifying hazards and assuring that they are controlled before they threaten product quality. HACCP was developed for food production but the principles can be equally effective when applied in pharmaceutical manufacturing as part of the Pharmaceutical Quality System.
In casting the net for hazards in the field of pharmaceuticals, the aim is not to list every possible hazard. The question is which hazards will need to be controlled, in what way and how to substantiate the fact that the control is effective.
I have noticed that HACCP proves to be especially useful when it is paired with the knowledge of the process and risk assessment, instead of being simply regarded as another quality document. A solid HACCP study should show the manufacturing people what potential problems are and what preventive controls should go into place.
There are various potential hazards in the pharmaceutical industry which consist of:
ICH Q9(R1) describes a scheme for quality risk management, within which HACCP is applied as one of the techniques of risk analysis.
In fact, a pharmaceutical HACCP study may be linked to:
A complicated equipment failure might offer better insights when using FMEA. In the case of a process in which hazards can be mapped stepwise, HACCP would be a more applicable technique.
For instance, in sterile production, hazards related to preparation of components, sterilization, loading and container sealing may be reviewed.
The hazard analysis should consider how likely the hazard is to manifest as well as what its impact could be.
It is important to note that not every step of the process becomes a Critical Control Point.
This is the area where less qualified HACCP teams tend to complicate matters. When practically every step is termed as critical, there will be no opportunity to identify truly important controls.
Depending on the process, these limits may include:
The monitoring system must define:
The response may include:
Activities that may take place in this step include:
The documents that should be produced:
The potential risks may include contamination coming from chemicals or microorganisms, as well as the loss of effective control over the system.
The team implementing HACCP could analyze each phase of the process:
Water Generation → Water Storage → Water Distribution → Water Use
At each phase of the water treatment system, risks are analyzed.
Control measures may include:
Some of the hazards that might arise in this process include:
As a reminder, HACCP should support, rather than replace, the all-encompassing Contamination Control Strategy employed by the facility.
The multidisciplinary nature of the team might have the following participants:
Sometimes the most profitable HACCP projects are those which reveal the risks that were previously taken for granted by the team members.
It is important to note that HACCP is not a substitute for GMP, validation, FMEA, or any Pharmaceutical Quality System. HACCP is an effective method that can be used in the system of quality risk-management strategy.
A successful HACCP analysis helps to understand important risks and differentiate between real critical points and ordinary process controls, to indicate standards, develop the methods of supervision and guarantee that the methods are used in an efficient way.
HACCP does not aim to create a new risk-management document. Its main goal is to make the process of manufacturing safer and more predictable by managing the significant risks at the early stages of process carrying out.
I have noticed that HACCP proves to be especially useful when it is paired with the knowledge of the process and risk assessment, instead of being simply regarded as another quality document. A solid HACCP study should show the manufacturing people what potential problems are and what preventive controls should go into place.
What Is HACCP?
The HACCP system consists of strategies that help identify hazards and assess their severity through the establishment of critical points and limits, monitoring and taking action if something goes wrong.There are various potential hazards in the pharmaceutical industry which consist of:
- Microbial contamination
- Cross-contamination
- Mixing up of drugs
- Failing to identify the materials
- Presence of foreign materials
- Temperature fluctuations
- Mistake in process parameters
- Equipment contamination
- Utility failures
- Insufficient cleaning
HACCP and Pharmaceutical Quality Risk Management
HACCP should not be considered apart from pharmaceutical quality risk management.ICH Q9(R1) describes a scheme for quality risk management, within which HACCP is applied as one of the techniques of risk analysis.
In fact, a pharmaceutical HACCP study may be linked to:
- Process design
- FMEA
- Cleaning validation
- Process validation
- Contamination Control Strategy
- Environmental monitoring
- Deviation management
- CAPA
- Change control
A complicated equipment failure might offer better insights when using FMEA. In the case of a process in which hazards can be mapped stepwise, HACCP would be a more applicable technique.
The Seven Principles of HACCP
Classic HACCP comprises of seven key principles.1. Carrying Out a Hazard Analysis
The initial step is to detect any hazards that may exist in each stage of the production process.For instance, in sterile production, hazards related to preparation of components, sterilization, loading and container sealing may be reviewed.
The hazard analysis should consider how likely the hazard is to manifest as well as what its impact could be.
2. Identifying Critical Control Points
Critical Control Point (CCP) is a stage at which control can be established and vital for avoiding, eliminating, or diminishing hazardous factors to an appropriate extent.It is important to note that not every step of the process becomes a Critical Control Point.
This is the area where less qualified HACCP teams tend to complicate matters. When practically every step is termed as critical, there will be no opportunity to identify truly important controls.
3. Determine Critical Limits
The identification of a critical control point must lead to defining measurable critical limits.Depending on the process, these limits may include:
- Temperature
- Time
- Pressure
- Concentration
- pH
- Sterilization parameters
- Any other parameters that can be measured
4. Create a Monitoring System
Monitoring is needed to ensure that the critical control point stays within its limits.The monitoring system must define:
- What is being monitored
- How and when it must be found
- Monitoring frequency
- Who conducts the monitoring
- Where results are recorded
5. Determine Corrective Actions
There must be a predetermined response when a critical limit is exceeded.The response may include:
- Stopping the process
- Segregating unsafe material
- Repeating a procedure
- Starting a deviation
- Investigating the reasons behind the deviation
- Evaluating the results
6. Establishing Verification Procedures
Verification is the process to reveal if the HACCP system is continuing to work the way it was planned.Activities that may take place in this step include:
- Reviewing records
- Calibration
- Qualification of the equipment
- Monitoring of the environment
- Conducting internal audits
- Trend analysis
- Validation
- Periodic revision
7. Documenting and Keeping Records
The HACCP system must provide production of controlled documents that indicate how a hazard was identified and controlled.The documents that should be produced:
- HACCP study
- Hazard identification
- Identifying CCPs
- Records in monitoring
- Taking corrective actions
- Records in verification
- Approval
- Revision history
Example of HACCP Application
Let’s take a pharmaceutical water system as an example.The potential risks may include contamination coming from chemicals or microorganisms, as well as the loss of effective control over the system.
The team implementing HACCP could analyze each phase of the process:
Water Generation → Water Storage → Water Distribution → Water Use
At each phase of the water treatment system, risks are analyzed.
Control measures may include:
- Sanitation
- Temperature monitoring
- Constant circulation
- Proper pipe design
- Regular analysis of microbiological indicators
- Chemical analysis
- Preventive maintenance
HACCP in Sterile Manufacturing
In sterile manufacturing, contamination risk assessment can also be aided by HACCP.Some of the hazards that might arise in this process include:
- Microbial contamination
- Personnel contamination
- Inadequate sterilization
- Inadequate material transfer
- Loss of environmental control
- Closure-in-container problems
As a reminder, HACCP should support, rather than replace, the all-encompassing Contamination Control Strategy employed by the facility.
Common HACCP Mistakes
A number of weak points can decrease a pharmaceutical HACCP study’s efficiency.1. Considering HACCP a Paperwork Activity
An HACCP report may be nicely formatted but still mean nothing if the team fails to grasp the technology.2. Transforming All Stages into CCPs
Over-classification hinders distinguishing real controls from normal controls.3. Using Unexplored Parameters
The critical limits should be determined by scientific data and not by the convenience of given parameters.4. Underestimating the Role of Human Factors
Process workers and different interventions, training and the complexity of procedures have a heavy impact on the presence of dangers in pharmacies.5. Not Upgrading the Study
The HACCP study should be changed if there have been substantial changes, deviations and validation results, or if one has acquired new knowledge about the process.Making HACCP More Efficient
A good HACCP project must be carried out by a team that actually knows the process.The multidisciplinary nature of the team might have the following participants:
- Manufacturing
- QA
- QC
- Engineering
- Validation
- Microbiology
- Regulatory Affairs
Sometimes the most profitable HACCP projects are those which reveal the risks that were previously taken for granted by the team members.
It is important to note that HACCP is not a substitute for GMP, validation, FMEA, or any Pharmaceutical Quality System. HACCP is an effective method that can be used in the system of quality risk-management strategy.
A successful HACCP analysis helps to understand important risks and differentiate between real critical points and ordinary process controls, to indicate standards, develop the methods of supervision and guarantee that the methods are used in an efficient way.
HACCP does not aim to create a new risk-management document. Its main goal is to make the process of manufacturing safer and more predictable by managing the significant risks at the early stages of process carrying out.
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