Validation shows that a pharmaceutical process, method, system, facility, or equipment can operate consistently. Validation can mean various things depending on the article that is validated, where it is within its lifecycle, what the company knows about the process, and what its regulatory strategy is.
Traditionally, pharmaceutical professionals sum up types of process validation into four groups: prospective validation, concurrent validation, retrospective validation, and revalidation. Today’s GMP requirements put these types together and describe them as process lifecycle which implies process design, process qualification, and continual process verification activities. The FDA process validation guidance states that validation should be considered a lifecycle activity divided into three stages: process design, process qualification, and continual process verification.
The understanding of the difference between various terms is important because otherwise companies may use incorrect validation techniques which would lead to ineffective validation results.
It is usually the method of choice when it comes to introducing either a new product, manufacturing process, major change in the process, or a new plant or equipment configuration.
An example of a typical prospective process validation exercise would involve:
FDA defines the process qualification stage as the point where the process design is assessed to identify whether it can provide commercially reproducible manufacturing processes.
In the past, this method was successfully applied in some situations in which prospective validation was impossible or where it was reasonable to ensure the validation of processes underway during production. Yet, it should be understood as more than a quicker method of prospective validation.
The WHO validation guidelines state that concurrent validation consists of the validation involving the collected during a particular process data and that the decision about its use should be made by properly authorized people.
For example, in a well-known process a concurrent validation can be required while the production is still being carried out in controlled conditions. Nevertheless, the protocol, adequate controls, suitable equipment, valid data, etc. still have to be available.
As a QA engineer, I would always want to know why concurrent validation was chosen rather than prospective one and whether it was properly justified.
In contrast to it is prospective validation, here the evidence is relevant to verification since it already exists before the proof begins.
Historical information includes data such as:
According to WHO counsel, it must be applied only to the most exceptional cases of well-established processes and where sufficient information about historical cases has been accumulated and changed.
FDA Q7A recommends retrospective validation only under sufficient conditions in case of well-established API.
It's applicable because of:
How extensive the revalidation is supposed to be will depend on the scale of the change and possible threats to the quality of the end product.
According to the FDA's process validation stages, the following stages of process validation exist:
This concept is of great importance for many pharmaceutical companies that have been working for a considerable time. The fact that manufacturing process was originally validated does not mean it is validated forever.
Some of the examples include the following:
1. Process validation: Proves that a certain process of production continually yields a product with the desired quality.
2. Cleaning validation: Proves that a certain cleaning method is capable of producing the necessary level of cleanliness.
3. Analytical method validation: Proves that an analytical process is suitable for its aims.
4. Computer system validation: Proves that a computerized system works for its regulated purpose.
5. Sterilization validation: Proves efficacy and consistency of the sterilization process.
6. Equipment and utility qualification: Proves that the equipment is suitable for use.
The actions mentioned above are related to each other but should not be mixed. For instance, process validation cannot be replaced by equipment qualification in the same way as analytical method validation can’t establish the validated state of the manufacturing process.
QA should be able to answer the following questions:
Prospective validation entails acquiring planned evidence before commercial production. Ongoing validation employs manufacturing process activities to create validation evidence. Retrospective validation is the evaluation of historical evidence in some situations. Revalidating happens when some change or new evidence determines the need.
In reality, the goal is not philosophical validation. The goal is to maintain the documented evidence of the fact that once validated, the process, system, method, or equipment continues to be fit for use over its lifecycle.
The understanding of the difference between various terms is important because otherwise companies may use incorrect validation techniques which would lead to ineffective validation results.
1. Prospective Validation: Evidence Before Routine Production
Prospective validation occurs before routine commercial production of a product or process. The protocol for this validation has been approved beforehand and acceptance criteria agreed upon, and the validation process is evaluated with the help of a preplanned validation batch.It is usually the method of choice when it comes to introducing either a new product, manufacturing process, major change in the process, or a new plant or equipment configuration.
An example of a typical prospective process validation exercise would involve:
- process development and scale-up knowledge
- identification of CQAs and CPPs
- risk assessment
- qualification of equipment and utilities
- approval of manufacturing processes
- defined sampling and testing
- predetermined acceptance criteria
- implementation of the validation batches
FDA defines the process qualification stage as the point where the process design is assessed to identify whether it can provide commercially reproducible manufacturing processes.
2. Concurrent Validation: Validation During Routine Manufacturing
Concurrent validation refers to the concept of the collection and evaluation of validation data while the process is being executed during the actual manufacturing process.In the past, this method was successfully applied in some situations in which prospective validation was impossible or where it was reasonable to ensure the validation of processes underway during production. Yet, it should be understood as more than a quicker method of prospective validation.
The WHO validation guidelines state that concurrent validation consists of the validation involving the collected during a particular process data and that the decision about its use should be made by properly authorized people.
For example, in a well-known process a concurrent validation can be required while the production is still being carried out in controlled conditions. Nevertheless, the protocol, adequate controls, suitable equipment, valid data, etc. still have to be available.
As a QA engineer, I would always want to know why concurrent validation was chosen rather than prospective one and whether it was properly justified.
3. Retrospective Validation: Historical Evidence
Retrospective validation is the use of historical data on manufacturing and quality, which confirm that a process has been operating in accordance with its design.In contrast to it is prospective validation, here the evidence is relevant to verification since it already exists before the proof begins.
Historical information includes data such as:
- Manufacturing and testing records
- Process parameters results
- Results of the final product
- Incidents
- Out-of-specification (OOS) and Out-of-trend (OOT) analyses
- Complaints
- Trends of the process
- History of equipment
- Maintenance data
According to WHO counsel, it must be applied only to the most exceptional cases of well-established processes and where sufficient information about historical cases has been accumulated and changed.
FDA Q7A recommends retrospective validation only under sufficient conditions in case of well-established API.
4. Revalidation: Confirming Continued Suitability
Revalidation is necessary when it is required to affirm the validity of an existing validation due to changes, acquired evidence, or other issues that might affect the validated status.It's applicable because of:
- Serious alterations to the equipment
- Significant changes in the process
- Revisions in the composition or raw materials
- Reorganization of the building or the utility system
- Changes in critical parameters of the process
- Multiple incidents of deviations
- Major repairs or changes
- Adverse tendencies in the process
- Change in conditions that may affect the validity of the assumptions validated
How extensive the revalidation is supposed to be will depend on the scale of the change and possible threats to the quality of the end product.
Validation Approaches Under the Modern Lifecycle Model
One major change in pharmaceutical validation is moving away from the idea of validation being a one-time activity and towards the concept of lifecycle validation.According to the FDA's process validation stages, the following stages of process validation exist:
Stage 1: Process Design
The final commercial manufacturing process is established based on the knowledge gained during the process development and scale-up.Stage 2: Process Qualification
Different aspects of manufacturing, including the design of the facility, equipment, utilities, and the process itself are tested in order to provide evidence that it (the process) is capable of being executed repeatedly.Stage 3: Continued Process Verification
Various data obtained during the manufacturing operations need to be tested and monitored to make sure that the manufacturing process is under control.This concept is of great importance for many pharmaceutical companies that have been working for a considerable time. The fact that manufacturing process was originally validated does not mean it is validated forever.
Validation Types Also Depend on What Is Being Validated
The phrase, “validation types,” is used for validation actions depending on the subject being validated.Some of the examples include the following:
1. Process validation: Proves that a certain process of production continually yields a product with the desired quality.
2. Cleaning validation: Proves that a certain cleaning method is capable of producing the necessary level of cleanliness.
3. Analytical method validation: Proves that an analytical process is suitable for its aims.
4. Computer system validation: Proves that a computerized system works for its regulated purpose.
5. Sterilization validation: Proves efficacy and consistency of the sterilization process.
6. Equipment and utility qualification: Proves that the equipment is suitable for use.
The actions mentioned above are related to each other but should not be mixed. For instance, process validation cannot be replaced by equipment qualification in the same way as analytical method validation can’t establish the validated state of the manufacturing process.
How QA Should Decide Which Approach Applies
When evaluating a validation strategy, I do not begin by determining which type of validation is the most convenient. Instead, I begin with the lifecycle stage, knowledge of the process involved, associated risks, change being attempted, commitments in regard to the regulations, and the objective evidence available.QA should be able to answer the following questions:
- What is being validated?
- What is the purpose of the process?
- What are the previously known facts?
- What risks are known?
- How was this method selected?
- Are the systems properly qualified?
- Is there a definition of the acceptance criteria?
- What is the potential effect of divergence?
- What monitoring will help ensure that the process remains stable?
A Practical Way to View Validation
The conventional definitions are still valuable but pharmaceutical companies should refrain from treating them as distinct definitions.Prospective validation entails acquiring planned evidence before commercial production. Ongoing validation employs manufacturing process activities to create validation evidence. Retrospective validation is the evaluation of historical evidence in some situations. Revalidating happens when some change or new evidence determines the need.
In reality, the goal is not philosophical validation. The goal is to maintain the documented evidence of the fact that once validated, the process, system, method, or equipment continues to be fit for use over its lifecycle.
Get ready to use editable Validation Protocols in MS-Word FormatView List
No comments:
Post a Comment
Please don't spam. Comments having links would not be published.