Gunnar Danielson, Mettler Toledo GmbH, Switzerland
Dr Markus Dathe, F. Hoffmann-La Roche, Switzerland
Travis Frick, GlaxoSmithKline Vaccines, Belgium
Dr Bob McDowall, ECA Data Integrity Working Group, R D McDowall Ltd
Dr Danilo Neri, PQE, Italy
Dr Siegfried Schmitt, PAREXEL International, UK
Dr Franz Schönfeld, GMP Inspector, Government of Upper Franconia, Germany
Data integrity in the GMP analytical laboratory continues to be THE major global topic amongst both regulatory agencies, pharmaceutical companies and suppliers. Although the headlines are still gabbed by warning letters and non-compliances involving cases of falsification and fraud from a minority of organisations this is the tip of the iceberg. The majority of data integrity issues seen in warning letters and 483 observations are still due to poor data management practices where records created are not adequately documented, electronic records that are poorly protected or not protected at all and / or there is still a reliance on paper printouts from computerised systems as raw data.
Since 2015 there has been a tsunami of regulatory guidance and advice from MHRA, FDA, WHO, PIC/S, EMA and even the Chinese FDA. In addition, ECA have issued a draft guidance for comment and the April 2017 release of the GAMP guidance on Records and Data Integrity that is a companion to GAMP 5. Do these guidances say the same things or are there contradictions? How should laboratories and suppliers respond to the WHO suggestion that „replacement of
hybrid systems should be a priority“?
The second Laboratory Data Integrity conference is designed to present, from a practical
perspective, the following areas:
- Laboratory data integrity where are we now?
- Regulator talk
- Review of the GAMP Guide on Records and Data Integrity
- Scope of the Second person review
- Instruments with integrated software – quo vadis?
- Data integrity audits
- Data integrity from research to manufacturing
- Developing metrics for laboratory data integrity
- Using data flow mapping to identify data integrity concerns
- Instrument Supplier’s perspective of data integrity
In addition, there will be a Discussion Forum at the end of day 1 where all delegates will have the opportunity to ask specific questions to benefit from the speakers’ experiences in this field.
The conference is intended for the technical and managerial personnel who deal with data integrity issues including analytical development and quality control analytical laboratories in pharmaceutical companies, contract research and manufacturing organisations. QA personnel responsible for quality oversight of data integrity work will also find the conference invaluable.
All participants get a free copy of the current version of the ECA „Data Governance and Data Integrity for GMP Regulated Facilities“ Guidance.
Introduction – Laboratory Data Integrity: Where Are We Now?
Regulatory Requirements and Expectations
- Overview of data integrity since October 2016 conference
- Warning letter update
- Regulatory guidance update
- GAMP Guide on Records and Data Integrity
Mitigating Data Integrity Risks in Pharmaceutical Manufacturing
- Legal requirements, European and international guidelines and guidance documents
- Case study: data integrity in the quality control lab and how it relates to the continuous
- improvement process
- Inspection findings
Metrics for Laboratory Data Integrity
- What is “data integrity”?
- What is “metadata”?
- What primary data integrity risks are associated with data systems (paper, electronic, and hybrid)? How can these risks be mitigated?
- How can manipulation of electronic records be detected?
- What are the requirements of/best practices for validating a computer system/
- electronic records?
- What are the most important things for companies to do or recognize regarding
- manufacturing data integrity?
Case Study: Data Integrity from Research to Manufacturing: Balancing Analytical
- What are metrics?
- Metrics will change throughout a data integrity programme: assessment and
- remediation phases
- Suggested metrics for routine chemical analysis
Science and Regulatory Compliance
Instruments with Integrated Software and Data Integrity
- Patient safety, freedom of research and speed to market: the dilemma of development
- DI in the development lifecycle – phase appropriate requirements
- Is it just regulations or common sense?
- The TITO principle and how to avoid it
- Benefits of data integrity measures
- Data ownership as a key prerequisite for DI compliance
Scope and Detail of a Second Person Review
- The new USP <1058> and the Lab Instrument classes
- The class B and Data Integrity
- The hubris of hybrids – paper complicates everything!
- Criticality: how critical is critical?
Using Data Flow Mapping to Identify Data Integrity Concerns
- US and EU regulatory requirements for second person review
- Responsibilities and SOP for the review
- Key requirement for the review: objective evidence
- Paper record review
- Hybrid system review problems
- Electronic system set up – is the software up to the job?
- Assays where second person review can be problematic
Data Integrity: An Instrument Suppliers Perspective
- What is ‘Data Flow Mapping’?
- How to execute ‘Data Flow Mapping’?
- The benefits of ‘Data Flow Mapping’
- Examples of ‘Data Flow Mapping’ detecting data integrity concerns
Data Integrity Audits – An Analytical Perspective
- The extent to which all data are complete, consistent and accurate throughout the
- data lifecycle“ – the lifecycle starts at the beginning – at the source of the data
- It‘s about the controls throughout the whole process
- Common misconceptions of benchtop instruments
- Start with correct data – finish well.
Review of the GAMP Guide: Records and Data Integrity
- What to expect when preparing an audit for data integrity
- The analytical laboratory - from the clinical setting to the certified laboratory
- (50 shades of grey?)
- How to plan the audit (access to site, systems and records; length of audit, location
- of audit, etc.)
- Performing the audit (access to staff, access to systems and records - let the hunt begin!)
- From black holes to compliant records - where to draw the line?
- The audit report - explaining the unexplainable, the difficult and the obvious
Laboratory Control Systems: how to prevent Data Integrity violations
- Overview of the new guide
- Review and Discussion of key sections of the Guide: Data governance framework
- Data life cycle, Risk management, Management, development and operation appendices
Post Conference Workshop Audit Trail Review for Laboratory Systems
Why Is An Audit Trail and Its Review Important?
- Strongly enforced Data Integrity Requirements in the latest 3 years by almost every
- Regulated Agency in the latest guidances issued by MHRA, WHO, FDA and recently
- by PIC/S.
- Particularly importance in the laboratory environment where data created within the
- analytical processes are relied upon to ensure the Product Quality
- Requirement to implement every control measure oriented to prevent Data Integrity
- violation either through automatic functionalities and interim manual procedures
- Need to routinely monitor the effectiveness of these measures in pharmaceutical
What is in a Name?
- Part 11 and Annex 11 / Chapter 4 requirements for audit trail
- Regulatory requirements for audit trail review
- Guidance documents for audit trail review
- Do I really need an audit trail?
Workshop 1: Which Audit Trail to Review?
- What do we look for in an application for auditing?
- Pros and cons for event logs and audit logs?
- Audit trail(s) ?
- Part 11 compliant system - does this help data integrity?
Attendees will be presented with an overview of the audit trails within an application and
the content of each log. Which audit trails should be reviewed and when in the context
of the work performed by the laboratory data system?
What are GMP-Relevant Data?
Workshop 2: Identifying GMP Relevant Data
- Annex 11 requires that audit trails monitor GMP-relevant data – what are GMP relevant data?
- Critical data?
Attendees will be presented with a list of records to identify if they are GMP records and
how critical they are to help focus the second person review of audit trail data.
Review of Audit Trail Entries
- What are we looking for in an audit trail review?
- Process versus system: avoiding missing data integrity issues
- Regulatory requirement is “frequent review” of audit trails
- What do we need to validate and what to check?
- Suspected data integrity violation - What do we need to do?
Workshop 3: Reviewing Audit Trail Entries
Attendees will be provided with the output of an audit trail to review and see if any
potential issues are identified for further investigation.
- Controls to Aid Second Person Review of Audit Trails
- Procedural controls for data review
- 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?