Validation deviation does not only mean a deviation in the steps of its realization. Refer to such deviations as events that can influence the legitimacy of the conducted study and hence the validity of relevant results and existence of valid state of process, equipment, utility, cleaning operation or analysis method.
In order to manage the validation deviations properly, it is necessary to do more than only document what had happened and carry out the test in an identical manner. The firm needs to figure out why the deviation occurred, whether the validation aim has been accomplished, what danger or risk this can bring and whether additional qualification and validation work is required.
The quality of the assessment and report presented on the deviation can often be even more important than the validation.
Take, for example, an operational qualification study for a temperature-controlled chamber. If a temperature excursion happens during one of the tests due to an unexpected opening of the door, that might not invalidate the qualification. But the investigation must answer the following questions:
To begin, the original data have to be preserved. The executed protocol, raw data, electronic records, equipment status, alarms, audit trails (if relevant), calibration status, environmental conditions, operator entries and other similar documents have to be examined.
In case the deviation involves a computer system, the logs and audit-trail information are of utmost importance. Data should not be reset due to the disappointment in the original execution.
From the standpoint of QA, it goes without saying that original happening has to be reconstructed before the repeat testing begins.
The repeat test will give some useful evidence, but it does not mean that the original result loses its importance.
An example is provided below. If a sample from validation fails a defined acceptance criterion, it can be said that "Analyst did wrong sampling" presented valid immediate cause. However, the investigation should not stop there.
The root cause must be established based on evidence. Just saying that it was a "human mistake" without trying to understand the circumstances that caused it is not enough for thorough investigation.
Deviations in validation may influence:
So if the batch of process validation experiences an unexpected halt, the specialists have to consider whether the halt is a normal course of actions or represents some extraordinary state that is within the limits expected of the process or a halt that exceeds the previously established working conditions of the process.
FDA recommendations on validation of processes underscore the need for a lifecycle approach and risk-based evaluation of knowledge concerning the process, parameters of the process and how it affects the product's quality.
That's why mere repeating of the test in question may not be enough.
The investigation level is dependent on the extent of risk posed to product quality and validation activities. According to ICH Q9(R1), quality risk management refers to systematic decision-making. Assessment effort is aligned with the risk level.
For example, in case of high-risk deviation, further qualification, additional validation testing, increased sampling or technical assessment could be needed.
In contrast, low-risk events could be resolved by a documented assessment.
The key point in this regard is to ensure enough clarity in the justification, so it could be easily followed by an independent reviewer catching the reasons behind this conclusion drawn by the company.
For example, if there was a validation deviation because the instrument was not available in the calibration status it needed, then only recalibrating the instrument would alleviate the immediate situation. It will be necessary to assess the CAPA to check if the calibration management system, scheduling system, equipment status management or pre-execution checking had an influence on this event.
Preventive actions could be:
Validation is the process that gives evidence of the ability of a particular method, process, equipment or system to perform as it is supposed to. Hence it is quite clear that any failures or strange results are part of the evidence that needs to be assessed scientifically.
As it is noted in the recommendations of the FDA, purposeful studies based on scientific principles and an understanding of the life cycle is important instead of focusing just on getting reasonable results.
If the repetition of a test is justified, the justification of the repetition of the test, its connection to the first test and the original test result need to be documented.
The guidance documents of the FDA on the process validation contain the same lifecycle approach with continued follow up of process ability after the qualification.
It is also worth mentioning a significant development for companies following the PIC/S guidelines. The PIC/S issued PI 006-4 Recommendations on Qualification and Validation in July 2026 as it replaces PI 006-3 and is expected to come into force from 01 October 2026.
Good management practices imply the preservation of original evidence, finding out what actually happened, determining what caused the deviation, understanding how it affects the validation conclusion, applying appropriate risk management practices and making sure that CAPA measures are effective.
The quality of the assessment and report presented on the deviation can often be even more important than the validation.
First Determine What the Deviation Actually Means
When a deviation happens during validation, the first question should not be "Can we carry on with the study?" Instead, it should be "What was impacted and whether this event invalidates any part of the evidence that is being generated"?Take, for example, an operational qualification study for a temperature-controlled chamber. If a temperature excursion happens during one of the tests due to an unexpected opening of the door, that might not invalidate the qualification. But the investigation must answer the following questions:
- What happened and when?
- Was the event within the acceptance criteria laid down in the protocol?
- Was the process that was followed appropriate?
- Was the excursion relevant for the other test results?
- Was the equipment working properly?
- What caused the deviation: equipment, method, technique or people?
- Should the impacted tests be repeated?
Protect the Original Evidence Before Starting the Investigation
A frequent flaw in the validation process is the rush to perform test replication following a failed experiment.To begin, the original data have to be preserved. The executed protocol, raw data, electronic records, equipment status, alarms, audit trails (if relevant), calibration status, environmental conditions, operator entries and other similar documents have to be examined.
In case the deviation involves a computer system, the logs and audit-trail information are of utmost importance. Data should not be reset due to the disappointment in the original execution.
From the standpoint of QA, it goes without saying that original happening has to be reconstructed before the repeat testing begins.
The repeat test will give some useful evidence, but it does not mean that the original result loses its importance.
Investigate the Cause, Not Just the Event
A proper investigation of validation distinguishes between an immediate event and a root cause.An example is provided below. If a sample from validation fails a defined acceptance criterion, it can be said that "Analyst did wrong sampling" presented valid immediate cause. However, the investigation should not stop there.
- Did the protocol adequately define the sampling location?
- Was the analyst well-trained?
- Did the equipment differ from the validated equipment?
- Were there problems in conducting the sampling?
- Was the swabbing properly controlled?
The root cause must be established based on evidence. Just saying that it was a "human mistake" without trying to understand the circumstances that caused it is not enough for thorough investigation.
Assess the Impact on the Validation Study
Assessment of the implications of the validation is the most vital part of the study.Deviations in validation may influence:
- A single trial.
- Particular acceptance criteria.
- Some factors of the qualification or validation protocol.
- The validatory conclusion as a whole.
- Previously acquired information in validation.
- The current validated condition.
So if the batch of process validation experiences an unexpected halt, the specialists have to consider whether the halt is a normal course of actions or represents some extraordinary state that is within the limits expected of the process or a halt that exceeds the previously established working conditions of the process.
FDA recommendations on validation of processes underscore the need for a lifecycle approach and risk-based evaluation of knowledge concerning the process, parameters of the process and how it affects the product's quality.
That's why mere repeating of the test in question may not be enough.
Use Risk Assessment to Support the Decision
It is important to note that not all validation deviations necessitate the same degree of scrutiny.The investigation level is dependent on the extent of risk posed to product quality and validation activities. According to ICH Q9(R1), quality risk management refers to systematic decision-making. Assessment effort is aligned with the risk level.
For example, in case of high-risk deviation, further qualification, additional validation testing, increased sampling or technical assessment could be needed.
In contrast, low-risk events could be resolved by a documented assessment.
The key point in this regard is to ensure enough clarity in the justification, so it could be easily followed by an independent reviewer catching the reasons behind this conclusion drawn by the company.
CAPA Should Address the System Weakness
The corrective action should resolve the root cause that was identified and not just fix the problem.For example, if there was a validation deviation because the instrument was not available in the calibration status it needed, then only recalibrating the instrument would alleviate the immediate situation. It will be necessary to assess the CAPA to check if the calibration management system, scheduling system, equipment status management or pre-execution checking had an influence on this event.
Preventive actions could be:
- Changing the validation protocols or SOPs
- Improving the pre-execution control
- Strengthening the equipment status management
- Changing the trainings
- Improving automated systems’ operation
- Changing the sampling plan
- Adding the verification steps
- Checking similar validations for the same violation.
Avoid the Repeat Until Pass Approach
Among the most troubling practices is the notion of treating validation as an experiment that can simply be repeated until satisfactory performances have been obtained.Validation is the process that gives evidence of the ability of a particular method, process, equipment or system to perform as it is supposed to. Hence it is quite clear that any failures or strange results are part of the evidence that needs to be assessed scientifically.
As it is noted in the recommendations of the FDA, purposeful studies based on scientific principles and an understanding of the life cycle is important instead of focusing just on getting reasonable results.
If the repetition of a test is justified, the justification of the repetition of the test, its connection to the first test and the original test result need to be documented.
What Should QA Review Before Closing the Deviation?
I expect QA and the appropriate validation department to have established the following before closing the deviation:- The event is properly described.
- Raw data documentation has been preserved and examined.
- There is a scientific rationale for the cause of the event.
- Assessment of product, process, equipment or system impact has taken place.
- Impact on the validation conclusion has been identified and recorded.
- Rationale for additional testing or requalification has been provided.
- The CAPA plan resolves the cause of the problem.
- The effect on other relevant validation activities has been examined.
- All the actions have been done or controlled.
- The final validation report clearly shows the deviation and what actions have taken place.
Regulatory Perspective
According to the European Union Good Manufacturing Practices (EU GMP) Annex 15, the process of qualification and validation must take place during the entire lifecycle of a production process as a part of quality risk management and any change that influences facilities, equipment, utilities and/or processes has to be documented and the extent of its effect on the validated status must be evaluated.The guidance documents of the FDA on the process validation contain the same lifecycle approach with continued follow up of process ability after the qualification.
It is also worth mentioning a significant development for companies following the PIC/S guidelines. The PIC/S issued PI 006-4 Recommendations on Qualification and Validation in July 2026 as it replaces PI 006-3 and is expected to come into force from 01 October 2026.
Good management practices imply the preservation of original evidence, finding out what actually happened, determining what caused the deviation, understanding how it affects the validation conclusion, applying appropriate risk management practices and making sure that CAPA measures are effective.
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