9. What are we talking About?
• The completeness, consistency, and accuracy of
data.
1.Attributable,
2.Legible,
3.Contemporaneously Recorded,
4.An Original or a True Copy,
5.Accurate
(FDA.gov)
10. Data Integrity Requirements
• GMP standards published in Eudralex Volume 4 Chapter 4
Annex 11
• European commission directive 2005/62/EC
(Relates to the Storage of Electronic Records)
• FDA - Q7 Good manufacturing practice guidance for active
pharmaceutical ingredients - Guidance for industry
• ICH –Q9 Quality Risk Management
• Essential element of a quality management system
12. Consequences of Data Integrity Issues
•EU statements of non-compliance
•Consent decrees, FDA warning letters
•Importation ban(s)
•Loss of consumer and regulator trust/confidence
•Product applications review suspended
•Market and share price reduction
14. Example One - Novacyl, Ltd (Thailand)
Warning Letter Date: 27th
February 2015
•Inadequate data retention
– Analyst selectively invalidating data
– Failure to retain HPLC raw data required for validation
– Lack of audit trails for HPLC system
•Unauthorised access
– Analysts able to access HPLC files and possibly delete/change
– GC system lacking password protection
•These are serious violations and do not comply with cGMP
15. Example Two -
Yunnan Hande Bio-Tech. Co. Ltd.
(China)
Warning Letter Date: 6th
April 2015
1.‘Failure to prevent unauthorized access or changes to data and
to provide adequate controls to prevent omission of data.’
2.‘Failure of your quality unit to ensure that materials are
appropriately tested and the results are reported.’
3.‘Failure of your quality unit to exercise its responsibility to
ensure the APIs manufactured at your facility are in compliance
with cGMP, and meet established specifications for quality and
purity.’
16. Yunnan Hande Bio-Tech. Co. Ltd
• Unauthorized manipulation of raw data (IR)
• Lack of active audit trail functions
• Insufficient response (CAPA Plan)
• Insufficient investigation
17. Recap: Causes of data integrity breaches
– Lack of audit trails
– Unauthorised access
– Lack of controls to prevent manipulation/deletion
of data
– Actual manipulation/deletion of data
– Selectively choosing which data to review in batch
release decisions
18. What Needs to be Done
1. Actively promote a culture of integrity
2. Establish security protocols
3. Comply with cGMP guidelines
21. System Access
• Based on job title
• Unique user ID’s
• Time stamped
• Fully traceable
22. Data Storage and Back-Up
•Electronic, paper and hybrid systems
•System hard drive
•Server storage
23. How to record Data (ALCOA)
All data should be…
1.Attributable – actions/changes attributable to a particular
person
2.Legible – data recorded permanently in a durable medium
3.Contemporaneous – record of work with date/time stamps
which should follow in a logical order
4.Original – all original data is present/available and is original
record/certified true copy.
5.Accurate – no errors present in data and no changes made
without documented proof of the change.
24. Audit Trail Software
• Software designed to record all actions performed on a piece
of computerized equipment, such as HPLC and GC for the
purpose of complete and accurate recreation
• Examples include:
• Empower 3
• Chromeleon
• SpinChrom
• TotalChrom™
25. Audit Trail Deficiencies
Cited in many FDA Warning Letters
1.Inadequate
2.Misconfigured
3.Not Enabled
4.Unutilized in Data Review
27. • Data Integrity is fundamental to Quality, Safety and Efficacy
of Pharmaceuticals
• A Culture of Integrity must be promoted by Management
• Data Integrity is a requirement and focus of Regulatory
Agencies
• Data Integrity is Everybody's Responsibility
