A validation report review is performed to verify if an accomplished validation investigation was executed as per its sanctioned protocol, produced good quality evidence, implemented remediation and satisfied previously set acceptance criteria. Validation report endorsement is the official conclusion that documented data are valid and permissible according to the pharmaceutical quality assurance system.
In the field of pharmaceutical manufacturing approval for the report should not be made just because all pages of the protocol have been filled or the end results look satisfactory. Quality assurance and technical reviewers have to make sure there is enough evidence to draw conclusions, limitations are being considered and the issue has been investigated to make a valid verdict that was executed.
Ensure that the report mentions all the equipment, utilities, processes, analysis methods, ways of cleaning or computer systems that have been used. Ensure that the protocol number and revision, report number, dates of study, data about the product or process and number of the corresponding equipment are the same.
A common documentation problem is that the report shows good execution of the research process, but does not prove if the original aims of the study were achieved. For example, a report on cleaning validation can say that all the samples were accepted, but fail to show if the chosen sampling points represented the places which were hard to clean, or if the analytical method was suitable to detect the necessary residue.
In case there was a modification in the scope of the research during the course of its implementation, the report must include the evidence of the approved changes in the change control or any other authorized documents. A reviewer has to reject the case of discrepancy in the approved protocol and the work done performed without any justification.
Depending on what kind of validation is involved, the following documents shall be reviewed:
Data quality is equally important. Documentation should be relevant, legible, done at the same time as the process, original or certified and correct, with due consideration of principles of ALCOA+. Lack of information, unforeseen mistakes during transcription, tests done multiple times without any explanation, or inconsistency in timestamps must be analyzed rather than automatically considered as mistakes in documentation.
The reviewer must ensure that each deviation is recorded, investigated appropriately and assessed in terms of the impact on its validity. A proper report must indicate the deviation number and whether any corrective action, testing, or repeat testing is needed.
Take for example, an instance where a parameter in a process validation batch exceeds the range of the accepted value for a short time. The report should not simply state that the value was disregarded or that the batch made the grade in finished product testing. Instead, it should indicate the reason behind the finding, how long it occurred, its impact on the process and any relevant quality aspects or implication of the validation conclusion.
In case of repeated experiments following a failure, the report must include the original result and the repeat results and the rationale for repeating the experiment. Receiving a successful outcome in later experiments does not invalidate the failure from the first experiment.
Quality assurance must decide whether the available procedure allows approving the results with specified actions if some deviations remain open, or whether any outstanding problems rule out the validity of conclusions.
The conclusion should include:
Also, the conclusion should be in accordance with the type of the study. For example, installation and operational qualifications do not guarantee that the manufacturing process can consistently produce the product that meets the specifications.
1. Technical/Validation Owner: Reviews conformity of the protocol application, data completeness, computation the deviations and interpretations.
2. Reviewers from concerned departments: Experts from production, QC, engineering, microbiology and IT, who comprehend their area of competence.
3. Quality Assurance: Reviews the compliance of the processes with GMP rules, confirms document traceability and carries out deviation approval as well as change process analysis and evaluation of the interpretation.
4. Authorized approver: Confirms the approval of the documents in accordance with the responsibilities and procedures set at the site.
No reports need to necessarily be approved by all departments. Any review board should correspond with the activity itself and its risks. For instance, for computerized systems, opinion from IT or the owner of the system may be required, whereas expertise in microbiology and aseptic manufacturing is guaranteed for aseptic simulation processes.
Comments arisen in the course of the review must be resolved and registered. The final version must be identifiable through a specific signature or some electronic approvals still confirming that the approval has happened. If there is a need in some amendments to be made after an approval, the site should follow its own document-control and change-management procedures instead of simply replacing the approved version.
Another common obstacle is turning the approval of report into admin target. Reviewers may pay attention only to formatting of the report and ignore the correct implementation of the sampling technique and the adequacy of acceptance threshold.
Thus suitable review checklist shall include the following questions:
The consequences of a comprehensive evaluation of validation reports need to be understood as the result of a scientific and quality-informed approach rather than a mere verification of the document. Validation reports must provide evidence of the realization of the validation study as planned, data credibility assessment, analysis of deviations and conclusions supported by facts. Use of these principles by QA and technical reviewers leads to validation reports being relevant documents of information control.
Establish What the Study Aimed to Prove
The first step in reviewing a validation report is to check if the study was conducted according to the approved protocol. The reviewer should have a good understanding about the aim, objectives, criteria of acceptance, sampling plan, important parameters and responsibilities before carrying out the study.Ensure that the report mentions all the equipment, utilities, processes, analysis methods, ways of cleaning or computer systems that have been used. Ensure that the protocol number and revision, report number, dates of study, data about the product or process and number of the corresponding equipment are the same.
A common documentation problem is that the report shows good execution of the research process, but does not prove if the original aims of the study were achieved. For example, a report on cleaning validation can say that all the samples were accepted, but fail to show if the chosen sampling points represented the places which were hard to clean, or if the analytical method was suitable to detect the necessary residue.
In case there was a modification in the scope of the research during the course of its implementation, the report must include the evidence of the approved changes in the change control or any other authorized documents. A reviewer has to reject the case of discrepancy in the approved protocol and the work done performed without any justification.
Examine the Evidence, Not Just the Summary
The findings of the report are valid to the extent that evidence and information are solid. As such, people reviewing the document should look through the documents from which the findings have been derived in order to understand whether the summary indeed reflects the data.Depending on what kind of validation is involved, the following documents shall be reviewed:
- Completed protocols, raw results, reports on investigation and sampling process.
- The state of the tools and equipment involved in the study.
- The qualifications of the people involved in the study.
- The conditions of the place where data has been collected.
- Papers describing the methodology of research and the process of evaluation of the gathered data.
Data quality is equally important. Documentation should be relevant, legible, done at the same time as the process, original or certified and correct, with due consideration of principles of ALCOA+. Lack of information, unforeseen mistakes during transcription, tests done multiple times without any explanation, or inconsistency in timestamps must be analyzed rather than automatically considered as mistakes in documentation.
Review Deviations and Unexpected Results Before Approval
A validation study can comprise of deviations, failures, unusual findings, or results outside established acceptance criteria. Before the report can be utilized to form a defensible conclusion, these deviations should be reviewed.The reviewer must ensure that each deviation is recorded, investigated appropriately and assessed in terms of the impact on its validity. A proper report must indicate the deviation number and whether any corrective action, testing, or repeat testing is needed.
Take for example, an instance where a parameter in a process validation batch exceeds the range of the accepted value for a short time. The report should not simply state that the value was disregarded or that the batch made the grade in finished product testing. Instead, it should indicate the reason behind the finding, how long it occurred, its impact on the process and any relevant quality aspects or implication of the validation conclusion.
In case of repeated experiments following a failure, the report must include the original result and the repeat results and the rationale for repeating the experiment. Receiving a successful outcome in later experiments does not invalidate the failure from the first experiment.
Quality assurance must decide whether the available procedure allows approving the results with specified actions if some deviations remain open, or whether any outstanding problems rule out the validity of conclusions.
Assess Whether the Conclusions Match the Results
A credible validation report does much more than provide results. It analyzes results against the established acceptance criteria and also states whether or not the goals in the initial plan have been achieved.The conclusion should include:
- Whether the acceptance criteria were met.
- Whether deviations or unexpected results influence the outcome.
- Whether the evidence produced suggests that the validated or qualified state has been achieved.
- Any restrictions, conditions, or further actions that should be taken into account.
- Whether follow-up validation or qualification is needed.
Also, the conclusion should be in accordance with the type of the study. For example, installation and operational qualifications do not guarantee that the manufacturing process can consistently produce the product that meets the specifications.
Define Review Responsibilities and Approval Sequence
It is required that validation SOP, document-control and authorization matrix be used in the review and approval procedures of the experimental site. Depending on the organization and study format, the roles and obligations of the following professionals can differ. However, the following sequence can work properly:1. Technical/Validation Owner: Reviews conformity of the protocol application, data completeness, computation the deviations and interpretations.
2. Reviewers from concerned departments: Experts from production, QC, engineering, microbiology and IT, who comprehend their area of competence.
3. Quality Assurance: Reviews the compliance of the processes with GMP rules, confirms document traceability and carries out deviation approval as well as change process analysis and evaluation of the interpretation.
4. Authorized approver: Confirms the approval of the documents in accordance with the responsibilities and procedures set at the site.
No reports need to necessarily be approved by all departments. Any review board should correspond with the activity itself and its risks. For instance, for computerized systems, opinion from IT or the owner of the system may be required, whereas expertise in microbiology and aseptic manufacturing is guaranteed for aseptic simulation processes.
Comments arisen in the course of the review must be resolved and registered. The final version must be identifiable through a specific signature or some electronic approvals still confirming that the approval has happened. If there is a need in some amendments to be made after an approval, the site should follow its own document-control and change-management procedures instead of simply replacing the approved version.
Common Weaknesses That Delay Validation Report Approval
Some of the usual flaws are absence of the sources of raw data, poor assessments of the effect of deviations, absence of uniform identifiers for equipment, sentences without adequate support, absence of records of the changes and vague definition of follow-up tasks.Another common obstacle is turning the approval of report into admin target. Reviewers may pay attention only to formatting of the report and ignore the correct implementation of the sampling technique and the adequacy of acceptance threshold.
Thus suitable review checklist shall include the following questions:
- Are the results traceable back to the source?
- Was the study conducted according to the protocol and the acceptance threshold?
- Were deviations and unexpected results thoroughly analyzed?
- Does the conclusion correlate with the evidence?
- Are required actions in place?
The consequences of a comprehensive evaluation of validation reports need to be understood as the result of a scientific and quality-informed approach rather than a mere verification of the document. Validation reports must provide evidence of the realization of the validation study as planned, data credibility assessment, analysis of deviations and conclusions supported by facts. Use of these principles by QA and technical reviewers leads to validation reports being relevant documents of information control.
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