Data Integrity and Audits

Preparing for Successful Data
Integrity Audits
Mary Chris Easterly & Richard D. Schlabach

13 October 2017
Integrity Audits
• U.S. Food & Drug Administration
and other regulatory agencies
found major issues beginning in
2014
• Data Integrity has been a major

concern for pharmaceutical and
medical device companies since
2014
October 12 - 13, 2017

Integrity Audits
Session General data

Data integrity
focus of
integrity concepts regulatory
One inspections
Session How to audit

paper and
electronic records
Two for data integrity
October 12 - 13, 2017

General Data Integrity Concepts
October 12 - 13, 2017

Data is Recorded…
Electronic
Paper
Systems
October 12 - 13, 2017
General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
RAW DATA DATA

Original records and All original records, including source data,
documentation, retained in metadata, subsequent transformations
the format in which they and reports, generated or recorded at the
were originally generated time of the activity. Allows full and
(paper or electronic) complete reconstruction and evaluation
of the activity.
October 12 - 13, 2017

General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
ORIGINAL RECORD
Data as the file or format in which it was originally
generated, preserving the integrity (accuracy,
completeness, content and meaning) of the record
• original paper record of manual observation

• electronic raw data file from a computerized system
October 12 - 13, 2017

General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
Which of these is an original paper record?

• Printout from pH Meter or • Report printed from
balance Ethylene Oxide monitoring
It depends:
– With data storage
system
– No data storage • Printed chromatogram

from automated system
such as FTIR (Fourier
• Photocopy of autoclave cycle
Transform Infrared
report: Spectroscopy), HPLC
– Autoclave does not store data (High Performance Liquid
– Report was originally printed on Chromatography)
thermal paper
October 12 - 13, 2017

Data Integrity:
The extent to which all data
are complete, consistent
and accurate throughout
the data lifecycle
October 12 - 13, 2017

October 12 - 13, 2017

Error is made:
Acknowledge
error so it can
Action is taken that
be addressed
is not compliant
Mistake with cGMP to save
time, for instance
Bad Practice
Intention
Procedures Or Fraud
and/or
cGMPs are
bypassed
knowingly
Data Integrity
October 12 - 13, 2017
Issue
Prevent Detect
October 12 - 13, 2017

General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
Data must be: ALCOA, with additional

• Attributable to the emphasis on data being:
person generating the •Complete
data •Consistent
• Legible •Enduring
• Contemporaneous •Available
• Original record
• Accurate
October 12 - 13, 2017

General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
Good Doc Practices Paper Electronic
Principle
• Initials/signature by person who • Electronic signature (username +
Attributable performed activity password)
• Indelible ink • Data is visible in fields
Legible • No erasure or correction
fluid/tape
• Changes are corrected properly
• Recorded at time of activity • Record is saved when data is entered
Contemporaneous • No pre- or post-dating • Time/date stamps
• Synchronized time (for accuracy)
• Paper form • Data generated by computerized system
Original • No post-its or temporary method Includes metadata
of recording then transcribing • Not able to modify original data
data
• Data recorded is accurate • Data transfers from original data system
Accurate • Calculations are checked accurately (e.g., to LIMS, archival)
• Second person verification • Calculations correct
• Second person verification
October 12 - 13, 2017

General
GeneralData
DataIntegrity
IntegrityConcepts
Concepts
• DI is not a new expectation of regulatory bodies.

• Predicate rules: 21 CFR 211, ICH Q7, 21 CFR Part 11, EudraLex Annex 11
Examples of predicate rules related to data integrity:

§211.68: • Changes in records are made by authorized personnel
• Backup data are exact and complete, and secure from alteration,
inadvertent erasures, or loss
§211.160 • Laboratory activities are documented at the time of performance
§211.188 • Documentation that significant steps were accomplished including
identification of person performing and supervising the steps
§211.194 • Laboratory records include all data secured in the course of each test
EudraLex Vol. 4, 4.9 • Changes made to entry are signed and dated; alteration permits
reading of original information
EudraLex Vol. 4, • Audit trails (record of all GMP-related changes and deletions) need to
Annex 11 be available and regularly reviewed
October 12 - 13, 2017

Data Integrity Requirements
Title Organization Link Date
GMP Data Integrity Definitions MHRA https://www.gov.uk/government/uploa March,
ds/system/uploads/attachment_data/fil
and Guidance for Industry (Medicines & e/412735/Data_integrity_definitions_an 2015
Healthcare d_guidance_v2.pdf
Products
Regulatory
Agency, United
Kingdom)
Draft GxP Data Integrity MHRA https://www.gov.uk/government/uploa July,
ds/system/uploads/attachment_data/fil
Definitions and Guidance for e/538871/MHRA_GxP_data_integrity_c 2016
Industry onsultation.pdf
Draft Data Integrity and U.S. Food & https://www.fda.gov/ucm/groups/fdago April,

v-public/@fdagov-drugs-
Compliance with GMP Guidance Drug gen/documents/document/ucm495891. 2016
for Industry Administration pdf
October 12 - 13, 2017

Data Integrity Requirements
Title Organization Link Date
Guidance on good data and World Health http://www.who.int/medi May,
record management practices Organization cines/publications/pharmp 2016
rep/WHO_TRS_996_annex
05.pdf
Draft Good Practices for Data PIC/S https://picscheme.org/en/ August,
Management and Integrity in (Pharmaceutical publications 2016
Regulated GMP/GDP Inspection Scroll to document title
Environments Convention
Pharmaceutical
Inspection Co-
operation
Scheme)
October 12 - 13, 2017

Data Integrity Focus of
Regulatory Inspections
October 12 - 13, 2017

DI Focus of Regulatory Inspections
Primary Considerations for cGMP Enforcement:

• Is drug adulterated?
• Most important factor – is there risk to patient?
– High risk: FDA takes quick action
• Sub- or super-potent
• Contamination
• Sterility concerns
• Other defects
cGMP = current Good Manufacturing Practices
Adulterated = fails to conform to compendial standards of quality, strength or purity
- Paula R. Katz, CDER, India Pharmaceutical Forum

October 12 - 13, 2017
2016 Warning Letters:
• 19 - Data Integrity
– Lack of control over access
to computerized systems
– Non-contemporaneous 54 warning letters
record-keeping
– Deletion, falsification,
alteration, or other 47 import alerts
manipulation
4 untitled letters
2016 OMQ Enforcement Actions
- Paula R. Katz, CDER, India Pharmaceutical Forum

October 12 - 13, 2017
FDA concerns with data integrity:

Shared login accounts Cannot identify a unique individual
System administrator role not Assigned to personnel responsible for record
independent content
cGMP record not complete All electronic data generated to satisfy a CGMP
requirement is not included
Testing into compliance Actual samples were used during “system

suitability,” test, or equilibration runs
- Paula R. Katz, CDER, PDA Data Integrity Workshop

October 12 - 13, 2017
FDA recommends With each record
audit trails that
capture changes to
Audit Trails critical data be Before final approval
reviewed: of the record
History of finished
product test results
Regular review of Sample run

audit trails sequences
should include,
at a minimum,
changes to: Sample identification
Critical process
parameters
- Paula R. Katz, CDER, PDA Data Integrity Workshop

October 12 - 13, 2017
Deadline for Audit Trails
• If no audit trailed system exists:

– Paper based audit trail is permitted (if equivalent to integrated
audit trail in Annex 11 of EudraLex) until a fully audit trailed
system becomes available
– Facilities should upgrade to an audit trailed system by the end
of 2017 if equivalence cannot be demonstrated
- MHRA GMP Data Integrity Definitions and Guidance for Industry, March, 2015
October 12 - 13, 2017
Deadline for Unique Logins
• If a computerized system supports one or limited

number of user logons:
– Upgrade to computerized system that can provide the required
number of unique logons by the end of 2017
– Paper based traceability is permitted if no suitable alternative
computerized system exists
- MHRA GMP Data Integrity Definitions and Guidance for Industry, March, 2015
October 12 - 13, 2017
Mgmt
Mfg Lab
• 2 kinds of data integrity problems Oper Oper Analyst
– Top down, pervasive, dictated by management

– Bottom up, isolated, one or a few operators or
analysts
• If FDA finds DI issue in one place…

– Assume data integrity is an issue everywhere,
unless a credible audit determines otherwise
October 12 - 13, 2017 - Takahashi: Look Out for These Data Integrity Issues
DI Focus ofFocus
Regulatory Regulatory Inspections
for Inspections
– When something doesn’t look right, take a tangent and zero

in on it. Examples:
• Test results for one batch used to release other batches
– Test file has same date and time as other tests
– Too many tests run in the time available
• Audit trail disabled until passing test results were obtained
• Failing and passing batches of active pharmaceutical ingredient
blended to produce passing results
– Lab and management knew about this practice
• Created falsified training records that were requested during the
inspection
- Takahashi: Look Out for These Data Integrity Issues
DI Focus ofFocus
for Inspections
• Look for data that is too good

– No complaints, deviations, or out-of-specification
investigations
– Handwritten data that looks too neat
October 12 - 13, 2017 - Takahashi: Look Out for These Data Integrity Issues
DI Focus ofFocus
for Inspections
26 Active Pharmaceutical Ingredient (API) FDA warning

letters
• 12 focused primarily on data integrity concerns
• 4 focused secondarily on data integrity concerns
• Quality System records
– Only 2 of 17 complaints in complaint log; complete list found on
warehouse floor
– Many production deviations in a GMP Anomalies folder that were
not investigated or reported
October 12 - 13, 2017 - Bowman Cox, FDA GMP Warning Letters Review
Regulatory
DI Focus ofFocus for Inspections
API FDA warning letters

• Laboratory records and computerized systems
– Unofficial test records and deleted unknown peaks in
chromatograms – potential impurities
– Reference standard tested instead of 12 month stability
sample
– Retested samples until in-specification results were reported
Regulatory
DI Focus ofFocus
Regulatory
for Inspections
Inspections
API FDA warning letters
– Microbiologist did not record test results
contemporaneously
– QC worksheet completed after FDA investigators asked
for it
– Gas chromatograph clock set back to make it appear
stability test was done months earlier; failing tests deleted
– HPLC system configured to automatically delete aborted
tests, and turn back clock for passing results
- Bowman Cox, FDA GMP Warning Letters Review

October 12 - 13, 2017
Regulatory
DI Focus ofFocus for Inspections
2 Drug Product FDA warning letters focused on data

integrity concerns
– Trial HPLC injections; data stored separately from reported test
results
– Administrator privileges given to analysts, who changed time and
date settings then overwrote and deleted HPLC test data
– Unreported gas chromatography results, including out of
specification test results for a raw material
DI Focus ofFocus
for Inspections
2 Drug Product FDA warning letters focused on data

integrity concerns
• Other records
– Batch record pages destroyed and replaced with backdated revised
pages
– Workers in production failed to record activities contemporaneously
– Workers incinerated GMP documentation
FDA Warning Letters from FY2015
• Requirements approaching those of a consent

decree
• Boilerplate text was included in warning letters

for serious data integrity deficiencies
- Barbara W. Unger, Data Integrity: Surveying the Current

Regulatory Landscape, Pharmaceutical Online
October 12 - 13, 2017
1. A comprehensive investigation into the extent of the inaccuracies in data

records and reporting
• A detailed investigation protocol and methodology
o Summary of all systems to be covered by the assessment
o A justification for any systems excluded
• Interviews of current and former employees

o Identify the nature, scope, and root cause of data inaccuracies
o Interviews conducted by a qualified third party
• Determine extent of data integrity deficiencies

o Identify omissions, alterations, deletions, record destruction, non-contemporaneous record
completion, and other deficiencies
o Identify operations where data integrity lapses were discovered
• A comprehensive retrospective evaluation of the nature of all data integrity

deficiencies
o Conducted by qualified third party
o Specific expertise in the area where potential batches were identified

October 12 - 13, 2017
2. A current risk assessment of the potential effects of the

observed failures on the quality of your drugs.
• Your assessment should include:
• Risks to patients caused by the release of drugs affected by a lapse of
data integrity
• Risks posed by ongoing operations

October 12 - 13, 2017
3. A management strategy for your firm that includes the details of your
global corrective action and preventive action plan. Your strategy should
include:
• A detailed corrective action plan that describes how you intend to ensure
the reliability and completeness of all of the data you generate, including:
o analytical data,
o manufacturing records, and
o all data submitted to FDA.
• A comprehensive description of the root causes of your data integrity

lapses, including evidence that the scope and depth of the current action
plan is commensurate with the findings of the investigation and risk
assessment.
o Indicate whether individuals responsible for data integrity lapses remain able to
influence CGMP-related or drug application data at your firm.

October 12 - 13, 2017
3. Your management strategy should include:

• Interim measures describing the actions you have taken or will take to protect
patients and to ensure the quality of your drugs, such as:
o notifying your customers,
o recalling product,
o conducting additional testing,
o adding lots to your stability programs to assure stability,
o drug application actions, and
o enhanced complaint monitoring.
• Long-term measures describing any remediation efforts and enhancements to
procedures, processes, methods, controls, systems, management oversight, and
human resources (e.g., training, staffing improvements) designed to ensure the
integrity of your company’s data.
• A status report for any of the above activities that are already underway or
completed.

October 12 - 13, 2017
Completion of these activities

will not happen quickly and
will take a concerted effort
on the part of the firms involved.

October 12 - 13, 2017
DI Observations - EU
• Uncontrolled documentation was noted throughout
production engineering notebooks with setup details and
passwords, crib notes on the wall of the Goods In area,
scraps of paper containing numbers of components
brought onto line.
• Printouts of particle count data from HEP filter testing were

not transferred from thermal paper to non-volatile media to
ensure the integrity of the record throughout the retention
period.
October 12 - 13, 2017

• Following a software update, data was lost from an autoclave

control system. The system backup was unable to recover lost
data as the backup was only performed on a 3 monthly basis.
• The backup CD/DVD for the autoclave control system was not
stored within a controlled environment to assure its integrity.
• Data from the integrity test was not backed up. The system was
observed to overwrite previous data.
• Backups were permitted to be made on the same computer

drive which failed to ensure that a separate copy was available
following drive failure or corruption.
October 12 - 13, 2017

• Access to files and the system clock on the hard drive was
available to all users
• The lock screen used a shared password. If a user had logged

into the software behind the lock screen and another user
opened the computer, they could perform actions under the
initial user’s login.
• Users had more authorisation on the chromatography data

system than was permitted according to the SOP.
• Access control systems were not considered GMP systems

despite their intended purpose to control access to GMP areas.
October 12 - 13, 2017

• HPLC software in the laboratory was not
configured for GMP compliance:
– Unique user passwords were not enforced
– Users were permitted to:
• Change the default audit trail
• Change the default “require user comments”
• Copy non-related projects
• Use annotation tools
October 12 - 13, 2017

• Control of dosimeter readings was deficient:

– Dosimeters could be reread and individual thicknesses
be input into the system if a variation of 6% was
identified for a location; this did not result in a deviation
to review the validity of previous acceptable results
– New thickness readings had no second person
verification to ensure accuracy of the data used
October 12 - 13, 2017

Additional Sources of Information
• MHRA GMP Inspection Deficiency Data Trend 2016

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/609030/MHRA_GMP_Insp
ection_Deficiency_Data_Trend_2016.pdf
• Current Expectations and Guidance, including Data

Integrity and Compliance With CGMP, Sarah Barkow,
PhD, Team Lead, CDER/OC/OMQ Guidance & Policy,
ISPE DI Workshop, June 5, 2016
https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm518
522.pdf
• Compliance Trends, Paula R. Katz, J.D., Dir., Mfg.

Quality Guidance & Policy Staff, Office of Mfg. Quality,
Office of Compliance, CDER, India Pharmaceutical
Forum, Mumbai, India, Feb. 24, 2017
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/U
CM549445.pdf
October 12 - 13, 2017

• Regulatory Perspective: Data Integrity

Guidance, PDA Data Integrity Workshop, Paula
R. Katz, J.D., Dir., Mfg. Quality Guidance and
Policy Staff, CDER/Compliance, Sep. 14, 2016
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTo
bacco/CDER/UCM539554.pdf
• Takahashi: Look Out for These Data Integrity

Issues, Pink Sheet & Gold Sheet, by Bowman
Cox (subscription required), Mar. 28, 2014
• FDA GMP Warning Letters Review: API

Supplier Warnings Surge on Data Integrity
Concerns, Pink Sheet, by Bowman Cox
(subscription required), Apr. 26, 2017
October 12 - 13, 2017
• FDA GMP Warning Letters Review:

Foreign Drug Product Firms Hit Hard on
GMP Basics, Pink Sheet, by Bowman Cox
• Data Integrity: Surveying the Current

Regulatory Landscape, Pharmaceutical
Online, Barbara W. Unger, Aug. 4, 2016
October 12 - 13, 2017

Preparing for Successful Data Integrity Audits
Questions?
October 12 - 13, 2017

Integrity Audits
Mary Chris Easterly & Richard D. Schlabach

13 October 2017
Integrity Audits
• U.S. Food & Drug Administration
and other regulatory agencies
found major issues beginning in
2014
• Data Integrity has been a major

concern for pharmaceutical and
medical device companies since
2014
October 12 - 13, 2017

Integrity Audits
Session General data

Data integrity
focus of
integrity concepts regulatory
One inspections
Session How to audit

paper and
electronic records
Two for data integrity
October 12 - 13, 2017

How to Audit Electronic and
Paper Records for Data Integrity
October 12 - 13, 2017

How to Audit for Data Integrity
• Every quality audit is a data integrity audit.

– Outside auditors have the lowest probability of finding
Data Integrity Issues
– Internal auditors have the highest probability of finding
DI Issues
October 12 - 13, 2017

Request auditee to provide at opening meeting:

– List of all GMP computerized systems
Laboratory • LIMS (Laboratory Information Management System)

• Chromatography, including HPLC, GC
• Standalone vs. networked systems
Manufacturing • Manufacturing Requirements Planning
• Building Automation Systems – monitor and alarm for
environmental conditions
• Automated production equipment
Enterprise/ • Complaints, training, deviations, change control,
Quality System document control
Data Storage • Backups, archiving, retrieval of data after retirement
October 12 - 13, 2017


• Procedures for laboratory data generation, review, and approval;
Certificate of Analysis generation
• Certificate of Analysis (CofA) for specific released batch
– Select a test that uses computerized systems
– Trace from generation of data to CofA
October 12 - 13, 2017


• Procedure for providing, changing, and removing user access to
e-systems
• Procedure for investigating deviations
• Does the procedure include how to address data integrity
issues?
If you have concerns about putting

instructions for how to handle DI issues
into an SOP, know that all companies
have some type of DI occurrence. It’s
part of human nature.
October 12 - 13, 2017

During opening meeting, select automated test from CofA:

• For specific instrument:
– SOPs for use of equipment, data archival, system
administration, user access/security levels
– Qualification of equipment showing how aspects of system use
were qualified
– Flowchart of data flow for computerized system, including data
backup and archival
• Who has access to modify or delete data from generation to
archival?
October 12 - 13, 2017

Data Governance/Data Management:
• Procedure/Program/Plan for Data Integrity

– Computerized systems not fully compliant?
• Gap analysis and remediation plan
• Employee training on DI principles and their

responsibilities
October 12 - 13, 2017

Data Governance/Data Management:

• Oversight of contractors and suppliers
– Ensure contract laboratories and manufacturers have
Data Integrity program and procedures
– DI included in audits of contractors and suppliers
– DI included in quality agreement with contractors and
suppliers
• DI included in all Internal Audits
October 12 - 13, 2017

During audit walkthrough, for selected system:

• Ask for system administrator, user, and second person
reviewer to be present
• Ask for demonstration of system to generate, manipulate,

and review data
• Review related paper logbooks

– Equipment maintenance
– Equipment use
October 12 - 13, 2017

During audit walkthrough:

• Review configuration settings for computerized system
– Password changes:
• Required to change at first logon
• Number of days before required to change
– Users with specific access types
• Generic system administrator username should not be enabled
• Number of people with system administrator access (should be
minimal)
• Which people have system admin access (personnel with
responsibility for data generated?)
– Functions that specific access types (e.g., reviewer, analyst)
can perform
October 12 - 13, 2017


• Users with active accounts – current employees?
– Training and access approval records
• Unique username/password (not shared)

– Recorded password - under keyboard, behind monitor, in drawers
• Audit trail turned on; users cannot turn it off

• Contents of trash can
– Data files that did not pass testing specifications
• User ability to change computer or server time/date
October 12 - 13, 2017


• Data folders & files
– Look at data chronologically
• Aborted runs – reason documented in e-record or paper
record
• Sequential files with same or slightly modified name
– Files hidden in folders separate from official test data
– Dates and times on files
– Tests performed match paper use logbooks for
instrument
October 12 - 13, 2017


• Paper records:
– Documents posted, on counters, in trash cans, in
drawers
– Personal notebooks in production and laboratory
areas
• Do they include GMP information?
– Controlled issuance and reconciliation of
laboratory forms
– ALCOA plus principles
October 12 - 13, 2017

• Management Responsibility
– Work environment:
• Staff encouraged to communicate failures and mistakes, including data
reliability issues
– Corrective and preventive actions taken

– Ensure adequate information flow between staff at all levels
– Actively discourage management practices that might inhibit
the active and complete reporting of such issues
• Hierarchical constraints
• Blame cultures
October 12 - 13, 2017

Our computer
systems are
Part 11
compliant
We have never
had a data
The FDA
integrity issue
reviewed our
computer
systems and had Our
no observations employees
would never
falsify data
– Data that is too good to be true

– Paper records from computerized systems are
mistakenly considered original (raw) data although
they do not include metadata
October 12 - 13, 2017
• Auditors need to determine:
– Is occurrence of a data integrity issue isolated or a
pattern for an individual, operational unit, or an entire
organization?
– Is occurrence a bad practice or intentional
manipulation?
What is the risk to the

product quality?
October 12 - 13, 2017

• MHRA GMP Inspection Deficiency Data Trend 2016

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/609030/MHRA_GMP_Insp
ection_Deficiency_Data_Trend_2016.pdf
• Current Expectations and Guidance, including Data

Integrity and Compliance With CGMP, Sarah Barkow,
PhD, Team Lead, CDER/OC/OMQ Guidance & Policy,
ISPE DI Workshop, June 5, 2016
https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm518
522.pdf
• Compliance Trends, Paula R. Katz, J.D., Dir., Mfg.

Quality Guidance & Policy Staff, Office of Mfg. Quality,
Office of Compliance, CDER, India Pharmaceutical
Forum, Mumbai, India, Feb. 24, 2017
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/U
CM549445.pdf
October 12 - 13, 2017

• Regulatory Perspective: Data Integrity

Guidance, PDA Data Integrity Workshop, Paula
R. Katz, J.D., Dir., Mfg. Quality Guidance and
Policy Staff, CDER/Compliance, Sep. 14, 2016
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTo
bacco/CDER/UCM539554.pdf
• Takahashi: Look Out for These Data Integrity

Issues, Pink Sheet & Gold Sheet, by Bowman
Cox (subscription required), Mar. 28, 2014
• FDA GMP Warning Letters Review: API

Supplier Warnings Surge on Data Integrity
Concerns, Pink Sheet, by Bowman Cox
October 12 - 13, 2017
• FDA GMP Warning Letters Review:

Foreign Drug Product Firms Hit Hard on
GMP Basics, Pink Sheet, by Bowman Cox
• Data Integrity: Surveying the Current

Regulatory Landscape, Pharmaceutical
Online, Barbara W. Unger, Aug. 4, 2016
October 12 - 13, 2017

Preparing for Successful Data Integrity Audits
Questions?
October 12 - 13, 2017

Data Integrity and Audits

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Preparing for Successful Data

Mary Chris Easterly & Richard D. Schlabach

• Data Integrity has been a major

October 12 - 13, 2017

Session General data

Session How to audit

October 12 - 13, 2017

October 12 - 13, 2017

RAW DATA DATA

October 12 - 13, 2017

• original paper record of manual observation

October 12 - 13, 2017

Which of these is an original paper record?

– No data storage • Printed chromatogram

October 12 - 13, 2017

October 12 - 13, 2017

October 12 - 13, 2017

October 12 - 13, 2017

Data must be: ALCOA, with additional

October 12 - 13, 2017

October 12 - 13, 2017

• DI is not a new expectation of regulatory bodies.

Examples of predicate rules related to data integrity:

October 12 - 13, 2017

Draft Data Integrity and U.S. Food & https://www.fda.gov/ucm/groups/fdago April,

October 12 - 13, 2017

October 12 - 13, 2017

October 12 - 13, 2017

Primary Considerations for cGMP Enforcement:

cGMP = current Good Manufacturing Practices

Adulterated = fails to conform to compendial standards of quality, strength or purity

- Paula R. Katz, CDER, India Pharmaceutical Forum

2016 OMQ Enforcement Actions

- Paula R. Katz, CDER, India Pharmaceutical Forum

FDA concerns with data integrity:

Testing into compliance Actual samples were used during “system

- Paula R. Katz, CDER, PDA Data Integrity Workshop

Regular review of Sample run

- Paula R. Katz, CDER, PDA Data Integrity Workshop

Deadline for Audit Trails

• If no audit trailed system exists:

Deadline for Unique Logins

• If a computerized system supports one or limited

• 2 kinds of data integrity problems Oper Oper Analyst

– Top down, pervasive, dictated by management

• If FDA finds DI issue in one place…

– When something doesn’t look right, take a tangent and zero

• Look for data that is too good

26 Active Pharmaceutical Ingredient (API) FDA warning

API FDA warning letters

- Bowman Cox, FDA GMP Warning Letters Review

2 Drug Product FDA warning letters focused on data

2 Drug Product FDA warning letters focused on data

FDA Warning Letters from FY2015

• Requirements approaching those of a consent

• Boilerplate text was included in warning letters

- Barbara W. Unger, Data Integrity: Surveying the Current

1. A comprehensive investigation into the extent of the inaccuracies in data

• Interviews of current and former employees

• Determine extent of data integrity deficiencies

• A comprehensive retrospective evaluation of the nature of all data integrity

- Barbara W. Unger, Data Integrity: Surveying the Current

2. A current risk assessment of the potential effects of the

- Barbara W. Unger, Data Integrity: Surveying the Current