Department | Validation/Technical Services | Document no | VAL-185 | ||
Prepared by: |
| Date: |
| Supersedes: |
|
Checked by: |
| Date: |
| Date Issued: |
|
Approved by: |
| Date: |
| Review Date: |
|
APPLICATION
This procedure details the standard methodology used to perform GMP/Quality Risk Assessments during Validation activities.
RESPONSIBILITITY AND AUTHORITY
The Validation Supervisor is responsible for appointing personnel to and coordinating Risk Assessments. The Validation Momager will be responsible for the development of the Validation Risk Management plan, the implementation/execution of the plan and the documentation of the activities associated with the plan.
SAFETY AND PROCESS SPECIFIC INFORMATION
All safety requirements for relevant areas at any GMP facility must be followed at all times.
PROCEDURE
i. Risk Assessment
The Risk Assessment shall be conducted to determine the level of inherit risk within a given process or product. The Risk assessment should be developed to suit the type of Validation undertaken and should be used to determine the level at which Validation is performed. Validation should not be conducted where steps in a process do not impact the safety or quality of the final product and no perceivable risks are identified.
ii. Describe the product and process
A full description of the product and the process should be drawn up, including relevant quality information such as the composition, physical/chemical properties, structure, pH, temperatures, method of cleaning, bactericidal/bacteriostatic treatments (e.g. heat-treatment), drying, screening, mixing, blending, packaging, and the storage conditions. The method of distribution and transport should also be described.
iii. Describe the intended use of the product
The intended use should be based on the expected uses of the product by the end user or consumer. The end use of the product can have a significant impact on the severity of any hazards that are identified and the extent to which Validation may be applied.
iv. Construct a flow diagram
A flow diagram should be constructed and should cover all operations and decisions in a process. When applying risk assessment to a given operation, the steps preceding and following that operation should also be considered. A block-type diagram may be sufficiently descriptive.
v. Identify steps in the process that may impact on safety and product quality
List all the hazards that may be reasonably expected to occur at each step from production, testing and distribution up to the point of use. A hazard analysis should then be conducted to identify which hazards are of such a nature that their elimination or reduction to acceptable levels is essential.
A thorough hazard analysis is required to ensure an effective assessment of all potential risks. A list of the potential hazards which may be introduced, increased or controlled in each step should be drawn up.
In the hazard analysis, the following should be included wherever possible:
– A description of the step in which hazards were identified;
– A description and likely type of occurrence of the potential hazard;
– The qualitative and/or quantitative evaluation of the presence of hazards (see step 4.5.1);
– Define the class and priority of the hazard (see step 4.5.2)
– Consideration of the controls required to eliminate or reduce the identified hazard, and
– The extent to which validation or verification is required.
vi. Qualitative and/or quantitative evaluation of the presence of hazards
Each hazard should be assessed based on the severity, probability and detectability.
vii. Severity Test:
The severity (e.g. adverse impact on health) of a particular risk is assessed as being in one of the following areas LOW, MEDIUM and HIGH. The assessment shall be based on knowledge of the risk. There should be no assumptions.
1. Rate as LOW if the hazard identified relates to situations where:
– The hazard has little or no impact on Identity, Safety, Purity and Effectiveness of the product.
2. Rate as MEDIUM if the hazard relates to situations where:
– The hazard has a likely impact on Identity, Safety, Purity and Effectiveness but is unlikely to cause a health hazard.
3. Rate as HIGH if the hazard relates to situations where:
– The hazard has an obvious impact on Identity, Safety, Purity or Effectiveness of the product and may result in harm to the user.
viii. Probability Test:
This assesses the probability that a Hazard to the safety (harm to the end user) and or quality problem will occur.
1. Rate as LOW if the hazard identified relates to situations where:
The occurrence of the hazard is not likely or controls are in place to eliminate or reduce the likely hood of occurrence.
2. Rate as MEDIUM if the hazard relates to situations where:
The hazard could occur and no controls are in place to eliminate the likely hood of occurrence.
3. Rate as HIGH if the hazard relates to situations where:
The hazard is likely to occur and no controls are in place to reduce the likely hood of occurrence.
ix. Detectability Test:
This assesses the likelihood that a Hazard to the safety (harm to the end user) and or quality problem will be detected.
Rate as HIGH if the hazard identified relates to situations where:
The hazard is likely to be easily identifiable or verification of the step will be conducted each time the step is performed.
1. Rate as MEDIUM if the hazard relates to situations where:
The hazard may be identified through in process checks
2. Rate as LOW if the hazard relates to situations where:
The hazard is not likely to be easily identified.
x. Defining the class and priority of the hazard
The hazard can then be assigned a Risk Class number. To determine the risk class the severity rate and the probability rate are multiplied (See Figure 1 – Risk Class). Once the Risk Class has been assessed the Risk Priority can be determined. The Risk Priority is derived by multiply the Risk Class with the likely hood of hazard detectability (See Figure 2 – Risk Priority).
At the completion of the Hazard assessment process each Hazard should be rated as HIGH, MEDIUM and LOW priority. The following actions should then be conduction for each of the following priorities:
HIGH – Where the hazard has been assessed as high for a given step a Critical Control (CC) should be established and the control Validated or Verified (each time the step is performed).
MEDIUM – Where a hazard has been assessed as medium for a given step a Critical Control (CC) should be considered and the control may be Validated or Verified (each time the step is performed).
LOW – Where a hazard has been assessed as low for a given step procedures the development of procedures to handle the risk should be considered.
xi. Establishing Critical Control Points (CCP)
Once a Hazard has been assessed with a HIGH or MEDIUM Risk Priority a Critical Control Point (CCP) should be considered or implemented for that step. A CCP is a step at which control can be applied and is essential to prevent or eliminate a (patient safety or product quality) hazard or reduce it to an acceptable level. CCPs are where the hazards are being controlled not detected.
Use a decision-tree to determine a CCP (See Figure 4).
If a hazard has been identified at a step where control is necessary for safety, and no control measure exists at that step, or any other, the product or process should be modified at that step, or at an earlier or later stage, to include such a control measure.
xii. Determine the level of Validation or Verification required
The determination of potential hazards within a product / process and the impact on the safety of the end user and affects to product quality are used to determine the level of Validation required and the extent to which verification is required. Where a CCP has been implemented suitable specifications or critical limits should be established and Validation of the control and monitoring activities undertaken. It may be acceptable to forego Validation of the control where ongoing verification is in place.
A decision tree (See Figure 3) should be used to determine whether it is appropriate to validate or verify a control.