Dr Markus Dathe, F. Hoffmann-La Roche AG, Basel, Switzerland
Dr Bob McDowall, Member of the ECA IT Compliance Interest Group
Dr Frank Sielaff, GMP Inspector, Regional Authority, Darmstadt, Germany
The objectives of this ECA educational course are to provide:
- An understanding of the regulatory requirements for audit trail review of laboratory computerised systems
- Understand what is meant review by exception
- Who should perform the second person review?
- Discuss audit trail examples for attendees to identify potential data integrity issues
- Present examples of audit trail entries for attendees to identify potential data integrity issues
EU GMP Annex 11 on computerised systems has required “regular review” of audit trail entries since its publication in 2011. In addition, the data integrity guidance documents issued by MHRA, WHO, FDA, EMA and PIC/S over the past few years reiterates the need for review of audit trail entries as part of a second person review of analytical data. However, like all regulations and guidance these documents emphasise the “what” that must be done but leave the “how” to each laboratory to interpret and then implement. For example:
- Do I need an audit trail function for all software?
- How regular is a regular review of audit trail entries?
- In some organisations, there is confusion about who should review audit trail entries - is this a laboratory or quality assurance role?
- What does a risk-based or review by exception of audit trail entries really mean and do all laboratory informatics applications offer this approach?
This is also compounded by the fact that most laboratory software applications were initially designed before data integrity issues took centre stage in the eyes of the regulators. How can GMP regulated organisations influence software suppliers?
This course is designed to help GMP organisations understand what is involved in a review of audit trail entries and how to conduct a risk based review.
- Managers and staff from Quality Control and Analytical Development Laboratories of pharmaceutical companies
- Contract Research Organisation and Contract Manufacturing Organisation laboratory personnel
- Quality Assurance staff involved in reviewing laboratory data or performing data integrity audits
- Auditors (internal and external) responsible for performing self-inspections or external audits and needing to understand and assess data integrity
Introduction to the Course
Regulations and Guidance for Audit Trails and their Review
Audit Trail Review as Part of a Data Integrity Strategy
- An overview of the regulatory framework: EU, FDA, MHRA, WHO and PIC/S regulations
- Data life cycle in Analytical Laboratories
- Audit Trails in GMP Inspections: What are the expectations of the inspector?
Validation of Audit Trail Functionality
- Define ATR as element of the DI Strategy
- Risk-based Approach – how to apply
- Apply a systematic approach to define ATR
- Audit Trail Review concepts
Workshop 1: Validation of Audit Trail Functionality
- Specification of audit trail requirements in the URS: dos and don’ts
- Documentation of the application configuration for audit trail functionality
- Leveraging the supplier’s development and testing into your validation effort
- User acceptance testing of audit trail functionality
The attendees will review user requirements for audit trail functions to highlight good and bad practices and from good requirements design tests to verify correct functionality
Documenting the assumptions, exclusions and limitations of your chosen test approach
Audit Trail Review in Context of second Person Review
When is an Audit Trail not an Audit Trail?
- Overview of the analytical process from sample to reportable result
- Highlight the use of computerised systems and audit trails
- Use technical controls to focus review effort
- Audit trail review issues for manually entered data into a laboratory system and electronic transfer between systems
Where do Suppliers help us and where do they let us down?
- What do we look for in an application for auditing?
- Which audit trail(s) should I review?
- Event logs vs. audit logs
Workshop 2: Which Audit Trail to Review?
- What do we expect from the suppliers to support data and audit trail review?
- Identify and avoid typical pitfalls
- Data ownership
- Data packaging and storage – supplier vs. business
Attendees will be presented with an overview of the audit trails within a chromatography data system and the content of each one.
Which audit trails should be reviewed and when?
What are GMP-relevant Data?
Workshop 3: Identifying GMP-relevant Data
- Annex 11 requires that audit trails monitor GMP-relevant data – what are GMP-relevant data?
- What are critical data and how can they be determined?
- Direct/indirect, static/dynamic data
- Data, Audit Trail and criticality?
Using facilitated discussion, attendees will develop a matrix for risk based audit trail review. Then they will apply the principles to a list of laboratory records to identify if they are GMP records to help focus the second person review of audit trail data.
Review of Audit Trail Entries
Workshop 4: Reviewing Audit Trail Entries Part 1
- Guidance for “regular review” of audit trails
- Process versus system: avoiding missing data integrity issues when only focussing on a per system review
- What are we looking for in an audit review?
- Suspected data integrity violation - What do we need to do
Attendees will be provided with a series of audit trail entries at the system level to review. Are there any potential data integrity issues to be followed-up?
Workshop 5: Reviewing Audit Trail Entries Part 2
Attendees will be provided with a series of audit trail entries at the data capture and interpretation level to review. Are there any potential data integrity issues to be followed-up?
Controls to aid Second Person Review of Audit Trails
Open Discussion: Bring us your Audit Trail Problems
Key Learning Points and Final Discussion
- Technical considerations for audit trail review e.g.
- Identifying data that has been changed or modified – how the system can help
- Documenting the audit trail review has occurred
- Review by exception – how technical controls can help
- Have you specified and validated these functions?