GMP Documentation Errors and Solutions in Pharmaceuticals

The foundation of quality systems in the manufacturing and distribution of pharmaceuticals is based upon the documentation of work performed. Work that is not documented is deemed not to be done in a regulated environment.
Because of this principle, documentation practices play a significant role in determining product quality, whether companies are compliant with the law, the ability to release production batches and provide assurance regarding the integrity of data produced through the manufacturing process.

In my experience, documentation deficiencies are one of the most common items observed during regulatory inspections, internal audits and customer audits. Facilities with state-of-the-art systems and equipment have trouble following good manufacturing practices (GMP) with regard to documentation even when they are following other GMP.

Many companies have yet to understand how the smallest of documentation mistakes can lead to major regulatory issues. Health authorities such as the United States Food and Drug Administration, European Medicines Agency and World Health Organization are starting to evaluate documentation from the standpoint of data integrity, as opposed to procedural compliance.

Poor documentation practices can create concerns with:

• Traceability of product
• Reputation of batch
• Integrity of data
• Quality of culture
• Credibility of investigation

If severe enough, documentation deficiencies can lead to warning letters, import alerts, batch rejects and regulatory actions.

Why GMP Documentation is Critical

Pharmaceutical documents do much more than just record a transaction. Paperwork proves that:

• The right things are done in the right way in manufacturing
• Approved methods are used
• Critical process parameters have been controlled
• Deviations were investigated
• Scientists have justification for making quality decisions

Reliable records also serve as support for:

• Product traceability
• Regulatory inspections
• Batch Review
• Product Investigations
• Recall management

Without complete records, pharmaceutical companies cannot prove compliance with GMP, Good Manufacturing Practices.

The Real Problem Behind Documentation Errors

I see many people assume that mistakes made while documenting information are just mistakes made at the time of documentation. However, they tend to be rooted in larger, systemic problems within an organization, including:

• An inadequately defined Good Manufacturing Practices (GMP) culture
• Poor management of staff by supervisors
• Insufficient amount of training carried out prior to production
• Pressure and stress placed on production teams
• Ineffective quality systems within the organization
• Lack of accountability of reviewers for their work

Regulators are also increasingly viewing documentation failures as a warning sign that a facility may not be manufacturing products in accordance with the regulations and guidelines required.

Common GMP Documentation Errors in Pharmaceutical Plants

Mistakes in GMP documentation are commonplace because there are few common problems between facilities.

1. Incomplete Documentation Entries

Many inspectors find that not only do they see incomplete documentation entries as one of the top deficiencies for GMP documentations but also find it very difficult to properly evaluate whether an event took place or not based solely off incomplete documentation (i.e., missing dates, missing signatures, blank fields, etc.) Including all the required entries into a batch manufacturing record is critical for timely disposition of a batch. Even the smallest missing document entry in a batch manufacturing record could result in a significant delay in disposition of a batch.

2. Backdating/Delayed Records

Data must be documented as close to the timing (contemporaneously with the completion of an event) in order to meet the expectations of regulators. However, backdating/delayed recording of records is widely reported in the industry. Examples of this would include: data from cleanings completed hours later, recording temperature from a previous shift, or completing batch record documents after all other associated documentation is completed.

In my experience, backdating/delaying completion of documentation records is typically a quick way to raise data integrity concerns during an inspection.

3. Improper Corrections in GMP Records

The most commonly cited issues with improper corrections occur in regulatory audits. Examples of unacceptable correction practices include:

• Use of correction fluid
• Erasing entries
• Overwriting data
• Scribbling out information completely

Correcting GMP records requires:

• Preservation of the original documentation
• Justification (if required) for the correction
• Signature and date (as appropriate)

Improper corrections to GMP records raise confidence in the reliability of the record.

4. Missing Signatures and Initials

The issue of unsigned entries is still a fairly common issue with GMP records even within mature GMP facilities. While unsigned entries do not affect the traceability of a batch, these entries may impact:

• Verification activities
• Accountability of a process

A reviewer should identify missing signatures prior to the approval of a GMP record.

5. Recording Data Before Activity Completion

Documenting data before an activity is complete is a violation of GMPs and is seen as a significant risk to data integrity because there is no proof that something that has been documented has been actually done. Examples of this are:

• Signing a cleaning record before completing the cleaning
• Completing environmental monitoring forms in advance of taking a sample from the environment
• Signing the logbook prior to completing an activity

6. Use of Uncontrolled Documents

Use of uncontrolled or expired forms continues to present a significant compliance risk. The most common examples of this are:

• Copying uncontrolled forms
• Utilizing obsolete versions of an SOP
• Using unapproved forms

Documentation that has not been controlled leads to inconsistent performance in regards to procedures.

7. Illegible Handwriting

The issue of unclear entries is often disregarded within the organization, but unclear entries can present additional challenges during a review process. Illegible handwriting can result in:

• Misunderstanding during data entry
• Calculation errors
• Traceability problems
• Delays in the completion of investigations

The majority of times when inspectors question records it is due to them being illegible.

8. Electronic System Errors

As organizations transition to an electronic format for their processes, the risk associated with electronic documentation is continuing to increase. Some of the many issues associated with electronic documentation are:

• Use of Shared Passwords
• Disabled Audit Trails
• Unmonitored Access
• Incomplete Electronic Review
• Missing Electronic Signatures

Many electronic systems are expected to meet data integrity expectations and regulations.

Why Documentation Errors Increase During High Production Pressure

Reasons for rising errors in documentation when productive output is required - the need to increase documentation error rates during periods of high product demand is a trend that I regularly note. As the production schedule is put under more pressure, the operator's behavior can change, leading to:

• Delaying of entries
• Increased pressure to complete documentation review quickly
• Skipping of verification steps
• Prioritizing output over compliance

All of this creates an environment where documentation quality will deteriorate gradually over time. A strong management oversight is critical during busy workload periods.

GMP Documentation and Data Integrity

Today, regulatory authorities are primarily looking at the principles of data integrity for all modern regulatory inspections. The evaluation of documentation practices today is based on the following principles as outlined in the ALCOA principle of Data Integrity:

• Attributable
• Legible
• Contemporaneous
• Original
• Accurate

There are many additional expectations that could be put forth as follows:

• Complete
• Consistent
• Enduring
• Accessible

Documentation practices that are poor can be treated under the category of “data integrity” failure, not as procedural deviation.

Root Causes of Documentation Errors

Reasons for errors in documentation are mostly due to system flaws rather than one-time operator error. Some of the most common causes are:

• Lack of training
• Poorly written SOPs
• Too much manual data entry
• Complexity of the documentation process
• Reviewer's fatigue
• Insufficient oversight

When true root cause analysis is not performed, we will see repeated occurrences of errors.

Solutions for Reducing GMP Documentation Errors

Most successful pharmaceutical companies employ a combination of procedural, technical and cultural initiatives to achieve success.

1. Create and Improve GMP Training Programs

Training shows how to fill out documents but should also educate employees on:

• The importance of documentation
• Regulatory standards
• These risks are connected to data integrity
• What could happen due to improper documentation

I find that when operators realize that the documents they create will ultimately impact someone and/or the health of a patient, the quality of their documentation improves.

2. Simplify Documentation Formats

Complex forms lead to increased errors when documenting activities. Good GMP forms must:

• Be easy to read
• Only have the necessary fields
• Have clear instructions
• Limit calculations to be completed manually

Good form design minimizes operator confusion as well as the amount of time spent reviewing the form.

3. Enhancing Reviewer Accountability

The quality of documentation continues to lack in quality mostly because an evaluator is only evaluating based on the technical data provided and does not evaluate the overall quality of documents created. In addition, when an evaluator reviews documentation, there are five areas that should be checked.

• Completeness
• Readability
• Timeliness of the entries
• Correcting the errors
• Verifying the signatures

A strong review process with standards and controls will limit the number of repeat violations.

4. Implement Electronic Documentation Systems

If an electronic documentation system has been designed and implemented appropriately, it should significantly reduce many of the manual documentation problems. The benefits of these systems include:

• Improved Traceability
• Audit Trails
• Control of Who Has Access
• Reduced Issues with Handwriting
• Automated Calculating Functions

If an electronic documentation system is poorly controlled, additional compliance issues will develop with the electronic systems.

5. Conduct Routine Documentation Audits

Conducting periodic audits of documentation items allows for the identification of weaknesses in the documentation processes prior to regulatory inspections. Audit area examples may include:

• Correction Practices
• Logbook Entries
• Batch Records
• Equipment Logs
• Electronic Audit Trails

Trend analysis of documentation deviations over time, will assist in recognizing areas producing repeated problems.

6. Encourage Quality Culture

An organization having a strong culture of quality generally has effective long-term solutions to the issue of documentation compliance. Organizations having mature quality cultures will usually display a documented history with respect to:

• Procedural Discipline
• Accountability
• Data Integrity Awareness
• Deviations

The overall quality of documentation reflects the culture of the entire organization.

Documentation Errors Frequently Observed During Inspections

Regulatory Inspectors often find the following documentation errors during inspections:

• Un-explained overwrites
• Missing data entries
• Incomplete investigation records
• Back dating of records
• Uncontrolled work-sheets
• Inconsistent time/date stamps

In several of my recent inspections, the number of documentation issues that expanded into other investigation areas related to data integrity across various systems.

The Role of Management in Documentation Compliance

Documentation quality is greatly affected by the involvement of senior management. The senior management role involves several areas of responsibility:

• Providing adequate resources for staffing
• Supporting a culture of GMP
• Avoiding unrealistic expectations for production output
• Providing adequate training of all employees
• To ensure that the quality of the product is maintained

When senior management has prioritized both productivity and compliance equally, the quality of the documentation system typically sees a large improvement.

Best Practices for GMP Documentation Control

To follow good documentation practices, an organization must have a solid documentation system by employing the following good shred documentation practices.

Best Practices Recommended

• Document on an immediate basis following the completion of the activity
• Document utilizing only controlled documentation
• Review records in a timely fashion
• Utilize a proper method for making corrections to documentation
• Train your employees on a routine basis
• Audit your documentation system on a routine basis
• Implement awareness of data integrity in your organization.

Implementing these good shred practices consistently will reduce compliance risks and increase the efficiency of your overall operation.

Documentation errors have become a primary risk of compliance in pharmaceutical manufacturing because of how important documentation is as evidence for product quality, traceability and regulatory credibility. While many companies incorrectly perceive these types of mistakes as minor clerical issues, regulators have begun to view recurring deficiencies as a sign of a larger systemic defect with quality and possible data integrity concern.

From my experience, creating a sustainable improvement to documentation practices requires more than just changes of procedure; it requires a commitment to and support of, a strong quality culture, accountability for the effectiveness of reviewers, continuous training, full management commitment and process discipline. Companies that treat documentation as a key component of their quality function rather than simply an administrative task are well positioned for inspections and investigations and for long-term regulatory compliance.

Regulatory References

1. FDA Guidance for Industry: Data Integrity and Compliance With Drug cGMP
2. WHO Guidance on Good Data and Record Management Practices
3. MHRA GMP Data Integrity Guidance and Definitions
4. EU GMP Guidelines Volume 4
5. US FDA 21 CFR Part 211 Current Good Manufacturing Practice

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