{"id":234,"date":"2018-08-27T14:14:54","date_gmt":"2018-08-27T14:14:54","guid":{"rendered":"https:\/\/www.pharmity.com\/?p=234"},"modified":"2019-11-12T15:34:52","modified_gmt":"2019-11-12T15:34:52","slug":"data-integrity-how-to-implement-an-effective-audit-trail","status":"publish","type":"post","link":"https:\/\/www.pharmity.com\/data-integrity-how-to-implement-an-effective-audit-trail\/","title":{"rendered":"Data Integrity – How To Implement An Effective Audit Trail"},"content":{"rendered":"
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Acceptance of data from clinical trials for decision-making purposes depends on the Regulatory Authorities\u2019 ability to verify the quality and integrity of the data.<\/span><\/p>\n Data integrity has become a major priority during regulatory inspections and <\/span>audit trail<\/b><\/span><\/span> deficiencies in particular have been cited in a growing number of observations.<\/span><\/p>\n EU GMP Annex 11, 21 CFR Part 11 and related guidance documents outline the current regulatory requirements for audit trails. <\/span><\/p>\n ICH GCP defines audit trail as <\/span>\u201cDocumentation that allows reconstruction of the course of events\u201d<\/i><\/span>1<\/span><\/sup>.<\/span><\/p>\n The basic definition of an audit trail is a log that contains metadata concerning when and by whom data has been originally entered, changed, or deleted<\/span>2,3<\/span><\/sup>.<\/span><\/p>\n The MHRA guidance on GXP Data Integrity published in March 2018 also covers the Audit Trail topic:<\/span><\/p>\n \u201cThe audit trail is a form of metadata containing information associated with actions that relate to the creation, modification or deletion of GXP records. An audit trail provides for secure recording of life-cycle details such as creation, additions, deletions or alterations of information in a record, either paper or electronic, without obscuring or overwriting the original record. An audit trail facilitates the reconstruction of the history of such events relating to the record regardless of its medium, including the <\/i><\/span>\u201c<\/i><\/span>who, what, when and why<\/b><\/i><\/span><\/span>\u201d<\/i><\/span> of the action<\/i><\/span>\u201d<\/i><\/span>4<\/span><\/sup>.<\/i><\/span><\/p>\n The decision whether to apply audit trails for electronic records should be based on a combination of GXP regulatory requirements and <\/span>assessment of risk<\/b><\/span><\/span> to the <\/span>trustworthiness<\/b><\/span><\/span> and <\/span>reliability<\/b><\/span><\/span> of records<\/b><\/span><\/span>, including the risk of unauthorized or undetectable changes to records<\/span>5<\/span><\/sup>, and the determination <\/span>of the potential effect on <\/span>product quality<\/b><\/span><\/span>, <\/span><\/span>safety<\/b><\/span><\/span> and <\/span>record integrity<\/b><\/span><\/span>6<\/b><\/span><\/sup><\/span>.<\/span><\/p>\n There are many things that should be taken into consideration when setting up audit trails. Many of the controls will be technical in nature and will form part of the functionality of a purchased system; however, a combination of technical and procedural controls may be needed for an adequate level of protection<\/span>7<\/span><\/sup>. <\/span><\/p>\n Whether companies are using a solution that is custom made or they acquire off-the-shelf software from a supplier, they need to consider the following topics:<\/span><\/p>\n Audit only what is necessary<\/b><\/span>: the MHRA GXP Data Integrity Guidance and Definitions states that <\/span>\u201c<\/i><\/span>The relevance of data retained in audit trails should be considered by the organisation to permit robust data review\/verification. It is not necessary for audit trail review to include every system activity (e.g. user log on\/off, keystrokes etc.)<\/i><\/span>\u201d<\/i><\/span> 4<\/span><\/sup>.<\/i><\/span> Only audit trailed those events\/data that are <\/span>critical<\/b><\/span><\/span>.<\/span><\/p>\n The Process Owner and Data Owner (they may be the same person) need to be involved when setting up the audit trail functionality to consider what information they need to review based on its criticality, which should have been defined by the regulated company within a <\/span>Data Governance<\/b><\/span><\/span> framework.<\/span><\/p>\n<\/li>\n<\/ul>\n Audit Trail content.<\/b><\/span> The items included in the audit trail should be those of relevance to permit <\/span>reconstruction<\/b><\/span><\/span> of the process or activity. They will help to reconstruct significant details about study conduct and source data collection necessary to verify the quality and integrity of data<\/span>8<\/span><\/sup> and ensure compliance with the applicable regulation. Audit Trail information should include the following<\/span>4,7<\/span><\/sup>:<\/span><\/p>\n<\/li>\n<\/ul>\n Identity of the person performing the action (this identification must be unique).<\/span><\/p>\n<\/li>\n The detail of the change or deletion, and a record of the original entry (original information should not be obscured).<\/span><\/p>\n<\/li>\n The reason for any GXP change or deletion (to explain why the action was necessary).<\/span><\/p>\n<\/li>\n The Date and Time when the action was performed (changes should be <\/span>dated<\/b><\/span><\/span> and <\/span>time stamped<\/b><\/span><\/span>. They should be implemented with a clear understanding of the time zone referenced and ensuring that the system clocks used for the time stamp are accurate and secure).<\/span><\/p>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n Logical and Procedural Controls. <\/b><\/span>Validated computer systems with enabled audit trails are necessary, but not enough, to meet global regulatory good documentation practice requirements for electronic records. Additional logical and procedural controls need to be implemented. For example:<\/span><\/p>\n Audit trails should be switched on. Users should not be able to amend or switch off the audit trail. Where a system administrator amends or switches off the audit trail a record of that action should be retained<\/span>4<\/span><\/sup>.<\/span><\/p>\n<\/li>\n Periodic checks to verify that audit trails remain enable and effective.<\/span><\/p>\n<\/li>\n Establishment of effective procedures for system use, administration and change management<\/span>7<\/span><\/sup>.<\/span><\/p>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n Report and Review<\/b><\/span>. What is the value of an audit trail solution if the regulated company never review it? By following the steps in the paragraphs above, companies will know they are getting the information they are looking for, but they need to ensure to <\/span>continually review<\/b><\/span><\/span>, follow up, and document the audit trail review process regularly. For this purpose, every GXP organization should implement procedures that outline their policy and processes for review of audit trails in accordance with risk management principles<\/span>2,9<\/span><\/sup>.<\/span><\/p>\n Reviews should be performed of audit trail content that has direct impact on reported values that will be used for product or patient decisions<\/span>7<\/span><\/sup>.<\/span><\/p>\n ICH E6(R2), Section 5.18.1(b) specifies that one of the purposes of trial monitoring is to verify that <\/span>\u201cthe reported trial data are accurate, complete, and verifiable from source documents<\/i><\/span>\u201d. In-process audit trail review is a way of doing this and should be established as part of the monitoring activities of the clinical trial.<\/span><\/p>\n ICH E6(R2), Section 5.18.3 also reinforces the relevance of centralized monitoring as a useful process conducted <\/span>by appropriately qualified and trained persons (e.g., data managers, biostatisticians) <\/span>to help <\/span>distinguish between reliable data and potentially unreliable data. Audit trail reviews conducted by these trained staff can help to identify potential issues that may result in loss of data integrity. Issues may include: erroneous data entry, modifications by unauthorized persons data not entered contemporaneously, falsification of data<\/span>1,7<\/span><\/sup>.<\/span><\/p>\n To comply with the above requirements, it is necessary that audit trails are designed so that the audit trail information relevant to data being reviewed or used is visible on screen or <\/span>easily obtainable<\/b><\/span><\/span>10<\/span><\/sup>.<\/span><\/p>\n Audit trails need to be <\/span>available<\/b><\/span><\/span> and convertible to a generally <\/span>intelligible form<\/b><\/span><\/span>9<\/span><\/sup> and they also need to be viewable\/accessible to end-users.<\/span><\/p>\n For enhanced usability, if available, systems should be <\/span>
\n“The need for and the type of audit trails should be based on a documented and justified risk assessment”<\/b><\/span>7
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\nWhile many regulated companies understand the importance of configuring their computer systems to ensure audit trails are adequate and meet regulatory requirements, many others still struggle to maintain electronic records with a complete and compliant audit trail.<\/span><\/p>\n
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\n<\/span>Including unnecessary information should be avoided since it can increase compliance risk<\/span>4<\/span><\/sup>.<\/span><\/p>\n\n
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