The idea of this article was taking (with permission from the original authors) from Montrium: how-to-avoid-electronic-data-integrity-issues-7-techniques-for-your-next-validation-project
Regulatory agencies around the globe are causing life science companies to be increasingly concerned with data integrity. This comes with no surprise given that Guidance Documents for Data Integrity have been published by the MHRA, FDA (draft), and WHO (draft). In fact, the recent rise in awareness of the topic has been so tremendous that, less than two years after the original publication, the MHRA released a new draft of its guidance whose scope has been broadened from GMP to all GxP data.
Is data integrity an issue of good documentation practices? You can read GCP information about this topic here.
In computerised systems, failures in data integrity management can arise from poor or complete lack of system controls. Human error or lack of awareness may also cause data integrity issues. Deficiencies in data integrity management are crucial because they may lead to issues with product quality and/or patient safety and, ultimately may manifest themselves through patient injury or even death.
I recently was at the vendor qualification tool that uses a hand held device to read data while the physician or expert manually put pressure on someone’s body parts (e..g. pain related). I was not impressed. Even though it seems like a nice device with its own software, the entire process was manual and therefore, questionable data integrity. The measurement seems to be all over the place and you would need the right personnel at the clinical site to perform a more accurate reading since again, it was all manual and dependent of someone else used of the device.
I also questioned the calibration of this device. The sale’s person answer ? “Well, it is reading 0 and therefore, it is calibrated.”….Really? You mean to tell me you have no way of proving when you perform calibration? Where is the paper trail proving your device is accurate? You mean to tell me I have to truth your words? Or your device’s screen that reads ‘0’? Well, I have news for you. Tell that to the regulators when they audit the trial.
What is Data Integrity?
Data can be defined as any original and true copy of paper or electronic records. In the broadest sense, data integrity refers to the extent to which data are complete, consistent and accurate.
To have integrity and to meet regulatory expectations, data must at least meet the ALCOA criteria. Data that is ALCOA-plus is even better.
What is a Computerised System?
A computerised system is not only the set of hardware and software, but also includes the people and documentation (including user guides and operating procedures) that are used to accomplish a set of specific functions. It is a regulatory expectation that computer hardware and software are qualified, while the complete computerised system is validated to demonstrate that it is fit for its intended use.
How can you demonstrate Electronic Data Integrity through Validation?
Here are some techniques to assist you in ensuring the reliability of GxP data generated and maintained in computerised systems.
What to do
Why you should do this
|Outline your expectations for data integrity within a requirements specification.
|Validation is meant to demonstrate a system’s fitness for intended use. If you define requirements for data integrity, you will be more inclined to verify that both system and procedural controls for data integrity are in place.|
|Verify that the system has adequate technical controls to prevent unauthorised changes to the configuration settings.
|The inspection agencies expect you to be able to reconstruct any of the activities resulting in the generation of a given raw data set. A static system configuration is key to being able to do this.|
Verification of Procedural Controls
What to do
Why you should do this
|Confirm that procedures are in place to oversee the creation of user accounts.
|Shared logins or generic user accounts should not be used since these would render data non-attributable to individuals.
System administrator privileges (allowing activities such as data deletion or system configuration changes) should be assigned to unique named accounts. Individuals with administrator access should log in under his named account that allows audit trails to be attributed to that specific individual.
|Confirm that procedures are in place to oversee user access management.
|A security matrix is a visual tool for reviewing and evaluating whether appropriate permissions are assigned to an individual. The risk of tampering with data is reduced if users are restricted to areas of the system that solely allow them to perform their job functions.|
|Confirm that procedures are in place to oversee training.
|People make up the part of the system that is most prone to error (intentional or not). Untrained or unqualified users may use the system incorrectly, leading to the generation of inaccurate data or even rendering the system inoperable.
Procedures can be implemented to instruct people on the correct usage of the system. If followed, procedures can minimize data integrity issues caused by human error. Individuals should also be sensitized to the consequences and potential harm that could arise from data integrity issues resulting from system misuse.
Logical security procedures may outline controls (such as password policies) and codes of conduct (such as prohibition of password sharing) that contribute to maintaining data integrity.
Testing of Technical Controls
What to do
Why you should do this
|Verify calculations performed on GxP data.
|When calculations are part of the system’s intended use, they must be verified to ensure that they produce accurate results.|
|Verify the system is capable of generating audit trails for GxP records.
|With the intent of minimizing the falsification of data, GxP record-keeping practices prevent data from being lost or obscured. Audit trails capture who, when and why a record was created, modified or deleted. The record’s chronology allows for reconstruction of the course of events related to the record.
The content of the audit trails ensures that data is always attributable and contemporaneous.
For data and the corresponding audit trails to be contemporaneous, system time settings must be accurate.
Who can delete data?
Adequately validated and have sufficient controls to
prevent unauthorized access or changes to data.
Implement a data integrity lifecycle concept:
- Activate audit trail and its backup
- Backup and archiving processes
- Disaster recovery plan
- Verification of restoration of raw data
- Security, user access and role privileges (Admin)
Warning Signs – Red Flags
- Design and configuration of systems are poor
- Data review limited to printed records – no review
of e-source data
- System administrators during QC, can delete data (no proper documentation)
- Shared Identity/Passwords
- Lack of culture of quality
- Poor documentation practices
- Old computerized systems not complying with part 11 or Annex 11
- Lack of audit trail and data reviews
- Is QA oversight lacking? Symptom of weak QMS?
Perform Self Audits
- Focus on raw data handling & data review/verification
- Consider external support to avoid bias
- Verify the expected sequence of activities: dates,
times, quantities, identifiers (such as batch,
sample or equipment numbers) and signatures
- Constantly double check and cross reference
- Verify signatures against a master signature list
- Check source of materials received
- Review batch record for inconsistencies
- Interview staff not the managers
FDA 483 observations
“…over-writing electronic raw data…..”
“…OOS not investigated as required by SOP….”
“….records are not completed contemporaneously”
“… fabricating data…”
“…. No saving electronic or hard copy data…”
“…results failing specifications are retested until
acceptable results are obtained….”
- No traceability of reported data to source documents
Even though we try to comply with regulations (regulatory expectations from different agencies e.g. EMA, MHRA, FDA, etc), data integrity is not always easy to detect. It is important the staff working in a regulated environment be properly trained and continuous refresher provided through their career (awareness training of new regulations and updates to regulations).
Companies should also integrate a self-audit program and develop a strong quality culture by implementing lesson learned from audits.
You can read more about data integrity findings by searching the followng topics:
MHRA GMP Data Integrity Definitions & Guidance for the Industry,
MHRA DI blogs: org behaviour, ALCOA principles
FDA Warning Letters and Import Alerts
EUDRA GMDP database noncompliance
The Mind-Numbing Way FDA Uncovers Data
Integrity Laps”, Gold Sheet, 30 January 2015
Data Integrity Pitfalls – Expectations and Experiences
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