Validation audit evaluates a pharmaceutical site's validation process to determine if the validation program is scientifically acceptable, appropriately documented and implemented in accordance with authorized processes and remains throughout the lifecycle of equipment, utilities, processes and systems. Validation Audit Checklist allows auditors to assess whether enough validation documents exist and provide evidence that the facility operates in a validated and controlled manner.
Good audit should connect the validation master plan (VMP) and risk evaluations, qualification files, protocols carried out, validation reports, changes to operation and changes brought about by controls. If documents are examined one by one and connections are not checked, the examination does not uncover any hazards.
While conducting an audit, verify if the VMP:
It is necessary to analyze from where the site gets the information about critical machines, process parameters, quality features, sampling places, etc. It should be ensured that the risk assessment is based on knowledge of the product and the production process and is not just taken from other projects.
As an example, it should be stated that in cleaning validation, the choice of the worst-case product is based on the necessary knowledge related to the product, i.e., cleaning efficiency, solubility, potency, toxicity of the source, equipment sharing.
Make sure during the audit that there are indications of risk assessment reviews occurring when there are important changes. The introduction of a new product can alter the previous assumptions or the introduction of changes in process, equipment, or cleaning agent can have a similar effect.
In the audit, you need to check if the validation method has been justified. The number of batches for the process validation, the sampling frequencies and the criteria should be established based on the relevant requirements, process knowledge and the risk assessment that has been carried out properly. Do not forget that the same number of batches cannot replace the scientific justification.
Checking the documentation for DQ, IQ, OQ and PQ should reveal whether the different stages of the qualification process have been planned correctly taking into consideration the design and purpose of the unit in question.
What to check:
One of the points to be considered by me is whether the instruments were calibrated while performing the qualification tests. If the tests generated positive results, the only challenge is to justify that the instrument used was fit for measurement.
In conducting process validation, attention should be paid to:
For cleaning validation, check that the documented justification for worst-case selection is appropriate, that limits of residue are defined, that sampling techniques are identified and that recovery studies and suitability of analytical techniques are determined. Confirm that the locations of the sampling activities and the results of the analysis match laboratory records.
One of the common problems during audits is cleaning validation reports showing successful analytical reports that do not provide adequate explanations of the sampling strategy or recovery efficiencies.
When validating analytical methods, it is important to consider certain crucial properties such as specificity, accuracy, precision, linearity, range, robustness, etc. Check math calculations, chromatograms, system suitability tests, integration changes, as well as documented studies on unexpected results.
Validation of computerized systems differs from that of analytical instruments. The assessment of computerized systems includes a description of the subject of the system use, definition of user needs, risk assessment, validating approach, access to data, backup arrangements, etc.
Choose a few instances of validation deviations and make sure that the analysis shows the occurrence of the problem, assessment of the results following the event and the presentation of reliable scientific evidence for validation.
As an example, in the case of lab chromatography data systems, the auditor must ensure that user privileges are managed according to procedures, electronic data are protected from unauthorized access, audit trails are examined according to standard procedures and changes in the validated configuration are properly analyzed.
The fact that there is a validation certificate does not mean that the computerized system remains in control. The audit should investigate the evidence of operation and the validation records used during validation.
Control of change is also very important. This includes changes relating to equipment and utility, manufacturing processes and methods of analysis, use of computer software, purification process and modifications made in a given site.
You should establish whether impact evaluation points out the need for additional analysis, partial re-certification, or revalidation. You also have to check whether the actions were completed prior to the change implementation, if such requirement is specified by the site.
The corrective and preventive actions (CAPA) should focus on addressing the root cause of significant or repetitive shortages. Addressing the same deviation multiple times without effective corrective measures may be indicative of the gaps in the validation management procedures.
Check if the documents are correct and can be retrieved without difficulties once approved. Make sure that executed documents are also complete, signed and can be tracked back to the relevant system.
The integrity is to be verified through the examination of origin documents and electronic records, audit traces and related corrections. ALCOA+ shall be adhered to when determining if documents are traceable, legible, contemporaneous, original and correct.
Additionally, the triggers for revalidation and reassessment should be understood. It can be, for example, a significant equipment change, repeatedly occurring nonconformances, negative monitoring deviations and any changes related to the product quality.
Categorize findings according to the site’s already approved auditing procedure. Evaluate their probable consequences for product quality, patient safety, data credibility and GMP compliance. Define responsible owners and realistic deadlines. CAPA must be aimed at eliminating the problem found and sending the same problem from happening again.
During the inspection, auditors may reserve the question as to how the site knows about validity of its manufacturing process after it has changed equipment, caused deviations, or experienced negative trends. The facility must be able to demonstrate this by means of its connected records rather than just have the approved VMP submitted.
Begin with the Validation Master Plan
The validation master plan (VMP) details the organization’s overall approach to qualification and validation. The VMP should include the scope of the VMP, the functional divisions in the organization accountable for its execution and the strategy for implementation of validation activities.While conducting an audit, verify if the VMP:
- Relevant sites, facilities, systems, processes, cleaning methods, analytical procedures and computerized machinery have been taken into account.
- It lays out tasks and availability of authority.
- It describes the risk management model applied for definition of the scope of validation.
- It indicates validation activities that are being carried out or planned.
- It specifies the procedures for support of the validated status.
- It has a mechanism for revision of the VMP.
Review Risk Assessment and Validation Planning
Risk evaluation is needed to be documented so as to state what to validate, how much to validate and to determine a control mechanism if required.It is necessary to analyze from where the site gets the information about critical machines, process parameters, quality features, sampling places, etc. It should be ensured that the risk assessment is based on knowledge of the product and the production process and is not just taken from other projects.
As an example, it should be stated that in cleaning validation, the choice of the worst-case product is based on the necessary knowledge related to the product, i.e., cleaning efficiency, solubility, potency, toxicity of the source, equipment sharing.
Make sure during the audit that there are indications of risk assessment reviews occurring when there are important changes. The introduction of a new product can alter the previous assumptions or the introduction of changes in process, equipment, or cleaning agent can have a similar effect.
In the audit, you need to check if the validation method has been justified. The number of batches for the process validation, the sampling frequencies and the criteria should be established based on the relevant requirements, process knowledge and the risk assessment that has been carried out properly. Do not forget that the same number of batches cannot replace the scientific justification.
Check Equipment and Utility Qualification Records
The equipment and utilities should be qualified for use in the production; the relevant qualification documentation demonstrates that the installation, functioning and quality of the units in question have been duly evaluated.Checking the documentation for DQ, IQ, OQ and PQ should reveal whether the different stages of the qualification process have been planned correctly taking into consideration the design and purpose of the unit in question.
What to check:
- User requirements and technical specifications approved.
- Details on equipment identification and installation.
- Critical equipment and instruments verified.
- Calibration state of measuring instruments checked.
- Testing of the alarms, interlocks and the range of operation performed.
- Acceptance criteria approved and testing results registered.
- Changes and deviations evaluated.
One of the points to be considered by me is whether the instruments were calibrated while performing the qualification tests. If the tests generated positive results, the only challenge is to justify that the instrument used was fit for measurement.
Examine Process and Cleaning Validation
The process validation should be able to show that the manufacturing process can produce products that are compliant with the predetermined quality standards. The audit must cover the entire life cycle of the process and not only look at the final report of the validation process.In conducting process validation, attention should be paid to:
- Understanding of process design and development that supports the commercial process.
- Determination of critical process parameters and critical quality attributes.
- Existing process qualification protocols and standards.
- Documentation of the validation batches.
- In-process results and finished product results.
- Deviations from the process and their effect on the validation results.
- Processes of Continued Process Verification (CPV).
For cleaning validation, check that the documented justification for worst-case selection is appropriate, that limits of residue are defined, that sampling techniques are identified and that recovery studies and suitability of analytical techniques are determined. Confirm that the locations of the sampling activities and the results of the analysis match laboratory records.
One of the common problems during audits is cleaning validation reports showing successful analytical reports that do not provide adequate explanations of the sampling strategy or recovery efficiencies.
Evaluation of Analytical Method and Computerized System Validation
Analytical methods are used for generating data required for material testing, in-process control, stability studies and batch release. Therefore, it is necessary to examine whether the analytical methods have been validated or verified in relation to their intended use. It is also necessary to check the adequacy of supporting data required for fulfilling the relevant validation characteristics.When validating analytical methods, it is important to consider certain crucial properties such as specificity, accuracy, precision, linearity, range, robustness, etc. Check math calculations, chromatograms, system suitability tests, integration changes, as well as documented studies on unexpected results.
Validation of computerized systems differs from that of analytical instruments. The assessment of computerized systems includes a description of the subject of the system use, definition of user needs, risk assessment, validating approach, access to data, backup arrangements, etc.
Evaluate Deviations, Change Control and CAPA
Validation operations seldom happen without unforeseen issues arising. A crucial query to ask during an audit is whether these issues were identified, reviewed and analyzed regarding their influence on the validation result.Choose a few instances of validation deviations and make sure that the analysis shows the occurrence of the problem, assessment of the results following the event and the presentation of reliable scientific evidence for validation.
As an example, in the case of lab chromatography data systems, the auditor must ensure that user privileges are managed according to procedures, electronic data are protected from unauthorized access, audit trails are examined according to standard procedures and changes in the validated configuration are properly analyzed.
The fact that there is a validation certificate does not mean that the computerized system remains in control. The audit should investigate the evidence of operation and the validation records used during validation.
Control of change is also very important. This includes changes relating to equipment and utility, manufacturing processes and methods of analysis, use of computer software, purification process and modifications made in a given site.
You should establish whether impact evaluation points out the need for additional analysis, partial re-certification, or revalidation. You also have to check whether the actions were completed prior to the change implementation, if such requirement is specified by the site.
The corrective and preventive actions (CAPA) should focus on addressing the root cause of significant or repetitive shortages. Addressing the same deviation multiple times without effective corrective measures may be indicative of the gaps in the validation management procedures.
Verify Documentation and Maintenance of Validated Status
Validation is not considered complete with the approval of the initial report. Validation cannot be valid until it is preserved through ongoing monitoring, periodic assessment as needed, change control, maintenance tools and techniques and re-validation processes.Check if the documents are correct and can be retrieved without difficulties once approved. Make sure that executed documents are also complete, signed and can be tracked back to the relevant system.
The integrity is to be verified through the examination of origin documents and electronic records, audit traces and related corrections. ALCOA+ shall be adhered to when determining if documents are traceable, legible, contemporaneous, original and correct.
Additionally, the triggers for revalidation and reassessment should be understood. It can be, for example, a significant equipment change, repeatedly occurring nonconformances, negative monitoring deviations and any changes related to the product quality.
Practical Validation Audit Checklist
This checklist can be used to start the internal audit of Good Manufacturing Practice. This implies that the scope of internal audit should be modified depending on the facility, products manufactured, the systems established and requirements of regulation.| Audit area | Key questions |
| Validation master plan | Is it up to date/valid? |
| Risk assessment | Are the decisions based on science? |
| Equipment qualification | Is there a set of documentation related to DQ, IQ, OQ, PQ wherever it is applicable? |
| Utilities | Is there a sufficient number of documents proving qualification and routine monitoring? |
| Process validation | Have all the critical parameters and quality attributes been assessed? |
| Cleaning validation | Is there a proof of worst case selection and residue limits justified? |
| Analytical methods | Are the methods selected fit the purpose and the supporting data is traceable? |
| Computer controls | Is the access and audit trails backup functioning properly? |
| Deviations | Are there sufficient proofs of investigation and analysis? |
| Change control | Are the validation effects examined before the plan is implemented? |
| Documents | Are protocols, reports and raw data being controlled at all times? |
| Validated state | Are monitoring and qualification activities effective? |
How to Report Audit Findings
Audit results must indicate the demanded specification or sanctioned procedure, the detected situation and supporting objective evidence. Don’t use obscure phrases such as “validation records aren’t sufficient” without specifying the exact unachieved or insufficient documentation.Categorize findings according to the site’s already approved auditing procedure. Evaluate their probable consequences for product quality, patient safety, data credibility and GMP compliance. Define responsible owners and realistic deadlines. CAPA must be aimed at eliminating the problem found and sending the same problem from happening again.
During the inspection, auditors may reserve the question as to how the site knows about validity of its manufacturing process after it has changed equipment, caused deviations, or experienced negative trends. The facility must be able to demonstrate this by means of its connected records rather than just have the approved VMP submitted.
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