In the production of drugs, the validated state is important to ensure that products produced are of high quality, safe to use and in compliance with regulations set by the governing bodies. In the manufacturing area there will be changes. These changes could include equipment, process or system changes or material changes and will occur during production. If changes are not managed appropriately, the validity of the process being followed may be compromised.
Change control is one of the key ways to manage changes effectively. Change control is a structured process for evaluating, approving and implementing, as well as documenting, changes to a process. A comprehensive change control program will help ensure that changes to the manufacturing process will not adversely affect the quality of the product produced or the manufacturer’s compliance with regulatory requirements.
Another area to consider is that validation involves verifying the system's condition. There are many factors that can affect a validated system; therefore, every change must be evaluated per Good Manufacturing Practices.
- Equipment
- Utilities
- Configuration of the Manufacturing Process
- Raw materials and suppliers
- Analytical Methods
- Computer Systems (Electronic) used in Manufacturing
Validation of a system occurs when verified that the operation consistently meets the requirements set before the use of the equipment after it has been modified by use of change controls. The relationship of validation and change control is simple a validated system will function properly and the validated state of the system must be maintained after any changes have occurred to the equipment or process. If a validated system has had changes made, without the appropriate change control process, the validated state may have been lost and not detected in a timely manner.
Consider these examples:
The fundamental principle is that the impact of a change is determined by its associated risk rather than its size.
An impact assessment must take into consideration the following:
For example:
Examples of such changes that require further assessment for 21 CFR Part 11 Compliance include:
Key docs include:
Some frequent issues are:
Best Practices include:
Therefore, during inspection, Inspectors will typically look for:
When companies establish a structured approach to managing changes through an effective, complete impact assessment of each proposed change and by keeping accurate and detailed records, they will maintain their validated state.
In a highly regulated environment such as the pharmaceutical industry, the challenge lies in balancing change so that the company can achieve products, services and processes that meet expectations for continued improvement and compliance while maintaining product quality and patient safety.
Another area to consider is that validation involves verifying the system's condition. There are many factors that can affect a validated system; therefore, every change must be evaluated per Good Manufacturing Practices.
Understanding Change Control and Validation
A structured approach that allows for modification in a controlled way and is adequately documented following:- Equipment
- Utilities
- Configuration of the Manufacturing Process
- Raw materials and suppliers
- Analytical Methods
- Computer Systems (Electronic) used in Manufacturing
Validation of a system occurs when verified that the operation consistently meets the requirements set before the use of the equipment after it has been modified by use of change controls. The relationship of validation and change control is simple a validated system will function properly and the validated state of the system must be maintained after any changes have occurred to the equipment or process. If a validated system has had changes made, without the appropriate change control process, the validated state may have been lost and not detected in a timely manner.
Why Even Small Changes Matter
Many mistakenly believe that validation is solely affected by large scale changes. While this is true, even minor scale changes also can influence validation on a major scale.Consider these examples:
- A minor part replacement of your equipment may alter product performance.
- A patch on your software may cause a change in the method of data handling or storage.
- A process change that alters or improves one step of the manufacturing process may produce a change in the overall quality of the finished product.
The fundamental principle is that the impact of a change is determined by its associated risk rather than its size.
The Role of Impact Assessment
Impact assessment is the most important part of the change control process. This will determine if validation has been affected and what necessary actions need to be taken.An impact assessment must take into consideration the following:
- Targeted products or product line and their intended use
- Critical process parameters and the effect on those parameters
- Equipment performance and whether the change will affect operational performance
- Integrity of data prior to and following change and if necessary, revalidation of data.
Where Changes Usually Impact Validation
Changes can have a far-reaching impact across multiple areas of validation, frequently in a connected manner.1. Equipment Qualification
Changes to equipment-related elements such as replacement, relocation and/or modification could necessitate (at minimum):- Re-execution of IQ (installation qualification)
- Retesting as part of OQ (operational qualification)
- Verification as part of PQ (performance qualification)
2. Process Validation
Changes to processes are extremely sensitive; even slight changes in process parameters can result in undesirable changes to product quality.For example:
- Changing the mixing speed
- Altering the drying temperature
- Changing the batch size
3. Cleaning Validation
Cleaning validation generally is affected by:- Introduction of a new product
- Change in cleaning agents
- Modification of equipment design
4. Computerized Systems
Computer systems must be evaluated thoroughly due to their potential for impacting the integrity of data.Examples of such changes that require further assessment for 21 CFR Part 11 Compliance include:
- Change in software applications or versions
- Change in system configuration
- Replacement of hardware components
Documentation and Traceability
When it comes to managing validation impacts, documentation is critical. Every change must have a trail from initiation to completion.Key docs include:
- Request and justification for change
- Report on impact assessment
- Approval documentation
- Documentation of validation efforts
- Final conclusion
- Each change can be traced back to validation activities
- All decisions have supporting evidence
- Documentation is available for an audit
Common Pitfalls Companies Face
Many organizations struggle with managing change control processes.Some frequent issues are:
- Minimizing the effect of change
- Not enough cross-functional involvement
- Insufficient/unclear documentation
- Failure to revise validation documentation
- Failure to revise validation documents without justification
How to Increase Change Control Effectiveness
Successful change control requires a structured, methodic approach to improve success rate.Best Practices include:
- Involve QA early
- Use a Risk-Based Approach
- Provide Scientific Justification
- Train individuals
- Conduct Regular (as in once a year) Review of Change Control Effective Operations
What Regulators Expect
Regulatory Agencies expect an established, standardized Process of Change Control that all aspects have been properly documented, validated and maintained according to current Good Manufacturing Practices.Therefore, during inspection, Inspectors will typically look for:
- Impact assessments that are complete and properly documented
- Validation decisions that are supported with a clear justification as to why the validation decision was made
- Where applicable, evidence to support that validation has been approved through the process of revalidation
- Compliance with Current Good Manufacturing Practices
- Regulatory observance(s)
- Warning Letters
- Product Recall(s)
When companies establish a structured approach to managing changes through an effective, complete impact assessment of each proposed change and by keeping accurate and detailed records, they will maintain their validated state.
In a highly regulated environment such as the pharmaceutical industry, the challenge lies in balancing change so that the company can achieve products, services and processes that meet expectations for continued improvement and compliance while maintaining product quality and patient safety.
Frequently Asked Questions on Change Control Impact on Validation Status
Q1. What is change control in pharmaceuticals?
Answer: Change control in pharmaceutical companies defines how to assess or modify changes in processes, equipment or systems.Q2. What is validation status?
Answer: Validation status is an indicator of a system being used within the approved/validated limits.Q3. How do changes affect validation?
Answer: A change can affect the performance of a system and may require revalidation depending on the risk associated with that change.Q4. Is revalidation always required after a change?
Answer: Not every change requires revalidation, only changes that are significant enough to have the potential to influence quality or performance.Q5. What is impact assessment?
Answer: An impact assessment is a process that assesses the potential impact of a change on product quality and compliance.Q6. Which guideline supports risk-based approach?
Answer: ICH Q9 – Quality Risk Management is the guideline that supports implementing a risk-based approach in the pharmaceutical industry.Q7. Why is documentation important in change control?
Answer: Because documentation provides traceability and evidence for audits, written documentation is essential in the change control process.Q8. What happens if change control is ignored?
Answer: Change control is significant because it protects against non-compliance and risk to products and regulatory action.
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