The occurrence of failures in GMP compliance is often linked to a contribution of multiple weak links rather than being a result of a single occurrence of an error or violation in procedures or SOPs. Rather severe GMP compliance problems normally indicate the presence of deficiencies related to pharmaceutical quality system, defects in management supervision, weaknesses with investigation, data integrity problems, etc.
When it comes to complying with the applicable regulatory requirements, the manufacturers of pharmaceutical products cannot only be focused on checking their compliance with the requirements of the applicable regulations. This implies the need to have stable systems which ensure that the pharmaceutical products complying with standards are produced.
In this connection, we can refer to the previous warning letters issued by FDA. For instance, some of the issues raised in its 2026 inspections are related to lack of adequate quality unit monitoring, insufficient reliability of records and defects in the investigation process.
Issues may arise in both paper and electronic formats. These include records that are incomplete, entries that are backdated, master spreadsheets that are left uncontrolled, the destruction of an original record, shared accounts, improper audit trail, unauthorized notebooks and actions undertaken that would not allow reproducing test results.
According to the FDA, cGMP data must be correct and trustworthy throughout its existence.
A letter of warning of the FDA against Dabur India Limited is evidence of the tremendous danger associated with this issue. The FDA detected inaccuracies and lack of control over quality assurance departments of the enterprise and concluded that the company’s reply has been too narrow, having missed an essential systemic flaw in data governance.
From the viewpoint of quality assurance, it isn't enough to merely answer the question of whether any incorrect record has been discovered. The following pertinent inquiries also need to be made.
In normal course of weak investigation, the reason of an operator's error is found and the deviation is closed through retraining. The problem with this approach is that there is no proof that the cause of the operator's error and the occurrence of a failure in the system have been understood.
A good investigation must study the incident, measure its magnitude, identify scientifically valid reasons, assess the impact on the product and develop proper CAPA.
The FDA OOS guidance provides an indication that OOS result cannot be explained as an analytical error without proper investigation proving the laboratory error as the cause. If this is not done, an investigation should lead to its through study including assessment of manufacturing and production factors.
When I evaluate investigations, I am not satisfied with simply reading the root-cause statement. The evidence presented must show the link between the suspected reason and the failure that occurred.
Changing an SOP, performing refresher training or delivering a warning may be appropriate, but this does not mean that the actual problem has been solved.
Take as an example repeated deviations arising from errors in batch records. If a company continues retraining its operators without being able to correct the underlying problem, the investigation must be aimed at determining whether the root cause lies in poor documentation, insufficient line clearance, lack of supervision, workload, unclear instruction or weak control.
According to ICH Q10, a pharmaceutical quality system should also ensure continuous improvement, monitoring of processes, managers’ accountability, as well as risk-based quality management.
Thus, effectiveness of CAPA should be demonstrated on the grounds of objective proof rather than simply confirming that an action was performed.
FDA letters highlight many cases of failure of the quality unit in providing oversight. In the warning letter addressed to Intas Pharmaceuticals in 2026 the agency pointed out failures regarding investigations and CAPA, electronic batch records and responsibilities of the quality unit.
This issue is especially relevant in case the company's plans for production contradict quality unit decisions. QA must be able to stop the process, block, escalate or investigate the issue and act under quality unit’s authority free from commercial impacts.
Strong quality culture exists when it is demonstrated by the decisions that were taken when everything is at stake.
A commonly found problem is the gap between the procedure that has been approved and the actions of employees. The gap could be caused by difficulty in following procedures, them becoming obsolete or employees not being adequately trained on them.
The FDA’s cGMP guidance sets out a general approach to the quality system meant to ensure compliance with 21 CFR parts 210 and 211.
In my audit comparisons, I would analyze the following:
The procedure → the practice → the evidence.
If those three do not correspond, the organization will run compliance risks.
In case of numerous breaches of the procedure, there is a need to analyze whether the procedure is actually right.
Continuous supervision is necessary to demonstrate that the processes in question are still capable and controlled. High process variability, unusual trends in yield, recurrence events of equipment malfunction or the emergence of unfavorable tendencies related to essential quality characteristics may show impairment of process control.
The FDA’s process validation approach is based on cycle control and ongoing verification processes. Moreover, in numerous cases of FDA enforcement actions, improper monitoring processes for process operations and quality of the produced goods were discovered.
Hence, a mature CPV program should be aimed at monitoring trends instead of waiting for the failure of the batch.
To investigate an OOS result, laboratory personnel conduct an examination of, among other things, instrument function, calculations, sample preparation and reagents. If, however, the laboratory root cause is not identified, then the investigation should also take into consideration the factors related to manufacturing and sampling.
Similarly, the same principle applies to OOT results and deviations.
Even in the situation when a result is within specification, it can still have scientific significance if it is indicative of an unusual tendency. Thus, an experienced QA and QC team also takes into account historical data, process capability and past trends in deviations and previous analytical data.
There may be errors in the batch documents, absence of proper forms, improper notebooks, destroyed documents or incomplete information which makes it impossible for quality control to find out if the production and testing process was conducted in a proper way.
Cases of discarded documents and uncontrolled books are referred to in the letters from FDA. According to the agency’s letters, the personnel wrote records in the books that were not approved.
The practical test of documentation efficiency is the following: Can an independent auditor organize all the documents and reconstruct the situation with the help of only the original GMP documents? If no, then it makes sense to investigate the system of documentation seriously.
Some key signs are:
If there are three departments that have similar issues with documentation, treating every one of them as an independent occurrence may lead to missing a common issue with training, procedures, management or data governance.
Inspectors may scrutinize the scope of investigation, the assessment of the impacted product, the history of data, the affected batches, the effectiveness of CAPA measures and the existence of the same problems.
Thus, the response to the inspection observation should cover the fundamental system, not only its visible symptom.
Remember that according to ICH Q9, the quality risk management should be based on science and risk.
When it comes to serious failures of the GMP compliance system, it can usually be said that such problems are of systemic nature. Issues related to data integrity, weak investigations, ineffective CAPA, low-level QA management, poor documentation, uncontrolled processes and implementation of suitable measures in case of deviations allow these problems to reinforce each other, gradually undermining the entire pharmaceutical quality system.
While working in the field of quality assurance, it is important to emphasize that there is no need for extensive documentation. Instead, what matters is the establishment of a reliable recording system and the fact that investigations are based on various evidence in terms of CAPA.
Finally, the companies capable of evaluation of their systemic weaknesses beforehand are more likely to comply with regulatory requirements and thus we can conclude that they are interested in delivering the medicines of appropriate quality to patients.
In this connection, we can refer to the previous warning letters issued by FDA. For instance, some of the issues raised in its 2026 inspections are related to lack of adequate quality unit monitoring, insufficient reliability of records and defects in the investigation process.
1. Failures in Data Integrity
Data integrity continues to be one of the biggest threats to adherence to GMP guidelines as any important decision related to quality relies on accurate data.Issues may arise in both paper and electronic formats. These include records that are incomplete, entries that are backdated, master spreadsheets that are left uncontrolled, the destruction of an original record, shared accounts, improper audit trail, unauthorized notebooks and actions undertaken that would not allow reproducing test results.
According to the FDA, cGMP data must be correct and trustworthy throughout its existence.
A letter of warning of the FDA against Dabur India Limited is evidence of the tremendous danger associated with this issue. The FDA detected inaccuracies and lack of control over quality assurance departments of the enterprise and concluded that the company’s reply has been too narrow, having missed an essential systemic flaw in data governance.
From the viewpoint of quality assurance, it isn't enough to merely answer the question of whether any incorrect record has been discovered. The following pertinent inquiries also need to be made.
- How big is the extent of the problem?
- What systems and departments are being impacted?
- Are there any other processes which can produce similar results?
- Has any product which has been released been affected?
- Are records of the transactions and originality of the record kept?
- Was management informed about this practice?
2. Weak or Incomplete Investigations
Poor compliance with GMP can also be manifested in cases where companies investigate deviations, OOS results, complaints and failures at shallow level only.In normal course of weak investigation, the reason of an operator's error is found and the deviation is closed through retraining. The problem with this approach is that there is no proof that the cause of the operator's error and the occurrence of a failure in the system have been understood.
A good investigation must study the incident, measure its magnitude, identify scientifically valid reasons, assess the impact on the product and develop proper CAPA.
The FDA OOS guidance provides an indication that OOS result cannot be explained as an analytical error without proper investigation proving the laboratory error as the cause. If this is not done, an investigation should lead to its through study including assessment of manufacturing and production factors.
When I evaluate investigations, I am not satisfied with simply reading the root-cause statement. The evidence presented must show the link between the suspected reason and the failure that occurred.
3. Inefficacious CAPA
CAPA could be considered a compliance issue when organizations mistake action for efficacy.Changing an SOP, performing refresher training or delivering a warning may be appropriate, but this does not mean that the actual problem has been solved.
Take as an example repeated deviations arising from errors in batch records. If a company continues retraining its operators without being able to correct the underlying problem, the investigation must be aimed at determining whether the root cause lies in poor documentation, insufficient line clearance, lack of supervision, workload, unclear instruction or weak control.
According to ICH Q10, a pharmaceutical quality system should also ensure continuous improvement, monitoring of processes, managers’ accountability, as well as risk-based quality management.
Thus, effectiveness of CAPA should be demonstrated on the grounds of objective proof rather than simply confirming that an action was performed.
4. Inadequate Quality Unit Oversight
The quality unit will fail if it is limited to reviewing documents only. The quality unit must be given enough authority, independence, resources and participation in the working process.FDA letters highlight many cases of failure of the quality unit in providing oversight. In the warning letter addressed to Intas Pharmaceuticals in 2026 the agency pointed out failures regarding investigations and CAPA, electronic batch records and responsibilities of the quality unit.
This issue is especially relevant in case the company's plans for production contradict quality unit decisions. QA must be able to stop the process, block, escalate or investigate the issue and act under quality unit’s authority free from commercial impacts.
Strong quality culture exists when it is demonstrated by the decisions that were taken when everything is at stake.
5. Failure to Follow Written Procedures
Having an SOP does not automatically mean compliance.A commonly found problem is the gap between the procedure that has been approved and the actions of employees. The gap could be caused by difficulty in following procedures, them becoming obsolete or employees not being adequately trained on them.
The FDA’s cGMP guidance sets out a general approach to the quality system meant to ensure compliance with 21 CFR parts 210 and 211.
In my audit comparisons, I would analyze the following:
The procedure → the practice → the evidence.
If those three do not correspond, the organization will run compliance risks.
In case of numerous breaches of the procedure, there is a need to analyze whether the procedure is actually right.
6. Poor Control of Manufacturing Processes
The process validation phase does not conclude once qualification batches have been completed.Continuous supervision is necessary to demonstrate that the processes in question are still capable and controlled. High process variability, unusual trends in yield, recurrence events of equipment malfunction or the emergence of unfavorable tendencies related to essential quality characteristics may show impairment of process control.
The FDA’s process validation approach is based on cycle control and ongoing verification processes. Moreover, in numerous cases of FDA enforcement actions, improper monitoring processes for process operations and quality of the produced goods were discovered.
Hence, a mature CPV program should be aimed at monitoring trends instead of waiting for the failure of the batch.
7. Poor Handling of OOS, OOT and Deviations
One of the most harmful actions is identifying a negative result as a laboratory issue prior to enough proof being available.To investigate an OOS result, laboratory personnel conduct an examination of, among other things, instrument function, calculations, sample preparation and reagents. If, however, the laboratory root cause is not identified, then the investigation should also take into consideration the factors related to manufacturing and sampling.
Similarly, the same principle applies to OOT results and deviations.
Even in the situation when a result is within specification, it can still have scientific significance if it is indicative of an unusual tendency. Thus, an experienced QA and QC team also takes into account historical data, process capability and past trends in deviations and previous analytical data.
8. Inadequate Documentation and Record Control
Many do not consider that documents may fail to pass tests even though the product itself appears satisfactory. Nevertheless, in accordance with GMP, documents have to serve as proven evidence of what has been done.There may be errors in the batch documents, absence of proper forms, improper notebooks, destroyed documents or incomplete information which makes it impossible for quality control to find out if the production and testing process was conducted in a proper way.
Cases of discarded documents and uncontrolled books are referred to in the letters from FDA. According to the agency’s letters, the personnel wrote records in the books that were not approved.
The practical test of documentation efficiency is the following: Can an independent auditor organize all the documents and reconstruct the situation with the help of only the original GMP documents? If no, then it makes sense to investigate the system of documentation seriously.
How Companies Can Detect Major Compliance Weaknesses
Companies need to avoid waiting for a regulatory inspection to identify such issues. Internal audits and management evaluations should look for systemic signs.Some key signs are:
- Recurrent deviations that arise from the same underlying issues
- Repeated OOS or OOT results
- CAPAs that consistently keep being extended or reopened
- Anomalies detected in audit trails
- Records that rarely exist or have to be reconstructed
- Frequent breakdowns of equipment or utilities
- Trends in processes that cannot be explained
- Quality reviews that lack sufficient evidence
If there are three departments that have similar issues with documentation, treating every one of them as an independent occurrence may lead to missing a common issue with training, procedures, management or data governance.
What Inspectors Usually Examine
Inspectors care about not only what has gone wrong but whether the quality system of the company has the ability to detect the problem and deal with it.Inspectors may scrutinize the scope of investigation, the assessment of the impacted product, the history of data, the affected batches, the effectiveness of CAPA measures and the existence of the same problems.
Thus, the response to the inspection observation should cover the fundamental system, not only its visible symptom.
Remember that according to ICH Q9, the quality risk management should be based on science and risk.
When it comes to serious failures of the GMP compliance system, it can usually be said that such problems are of systemic nature. Issues related to data integrity, weak investigations, ineffective CAPA, low-level QA management, poor documentation, uncontrolled processes and implementation of suitable measures in case of deviations allow these problems to reinforce each other, gradually undermining the entire pharmaceutical quality system.
While working in the field of quality assurance, it is important to emphasize that there is no need for extensive documentation. Instead, what matters is the establishment of a reliable recording system and the fact that investigations are based on various evidence in terms of CAPA.
Finally, the companies capable of evaluation of their systemic weaknesses beforehand are more likely to comply with regulatory requirements and thus we can conclude that they are interested in delivering the medicines of appropriate quality to patients.
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