Ensure

integrity of
GxP data by
fostering good
data reliability
practices

DATA INTEGRITY
Foundation for Creating Sustainable Trust

Webcast - April 20th, from 2.30 pm to 3.30 pm (CET)

Data integrity is a
widespread risk

Régis de Montardy,
Global Quality Strategy & Systems
Why is GxP Data Integrity a TOPIC ?
● GxP Data Integrity has become a global problem in recent years,
following multiple cases of fraud in our industry
● Health regulatory authorities worldwide are highly concerned and
are taking enforcement actions

● Objective of this webcast :

● Bring awareness of the risk of non-compliance related to GxP data integrity

● Inform you about the initiatives we have engaged for risk mitigation
● Request your full support to these initiatives

Data Integrity Webcast - April 20th 3

Decisive agency actions on data integrity
breaches

2012 – Ranbaxy (India) – Four facilities of Ranbaxy placed under consent 2015 – Hisun (China) – “Systemic data manipulation” in Quality Control
decree for GMP and data integrity violations, extended later to 2 other laboratory, 15 products banned from import, causing chemotherapy
facilities. 27 marketing authorizations removed. 500 M$ settlement for drug shortage
criminal charges.

2014 – GVK (India) – ANSM identifies 5-years falsification of 2015 – Kaketsuken (blood products and vaccines manufacturer,
electrocardiograms used in clinical trial. 700 marketing authorizations Japan) - Falsification of production records for decades to hide the
suspended by EMA. use of unauthorized ingredients

Data Integrity Webcast - April 20th 4

What are inspectors seeing ?

Discarding
Data Not recording
Repeated
activities
testing to obtain
contemporaneously
passing result

Releasing
Not saving
failing product
original data
(paper or electronic)
Backdating

Copying Fabricating
existing data Data
as new data

Data Integrity Webcast - April 20th 5

What is data integrity?

Degree to which
● Preclinical
we can rely on our ● Clinical
● Manufacturing
GxP DATA ● Quality control
● Distribution
to DEFEND ● Pharmacovigilance

Quality of our products Safety of our patients

20 April 2016 Data Integrity Webcast - April 20th 6

Quotes from regulatory authorities
• “Data integrity is one of today’s Why is it important?
most important issues because it Lack of Data Integrity
gets to the foundation of the
relationship between industry and
the FDA,”
Thomas Cosgrove, JD
Acting Director, Office of Manufacturing and
undermines breaks
Product Quality, FDA/CDER PRODUCT TRUST
safety, efficacy, with regulators
& quality

• “Senior management cannot be left

off the hook by claiming ‘we did not makes
REGULATORY
know,’” ACTION
more likely
Carmelo Rosa
Director, FDA/DIDQ
Based on: PDA Annual Meeting - March 7, 2014
Karen Takahashi , Senior Policy Advisor
FDA/CDER/Office of Compliance

Data Integrity Webcast - April 20th 7

GxP Data integrity is considered as a
widespread RISK
Reinforced Regulations Stronger Enforcement Policy

●1997 – 21 CFR part 11 “Electronic ●Unannounced inspections

Records, Electronic Signatures (domestic & foreign, e.g. ANSM, FDA)

●2012 – Revised European GMP ●Limiting access to data = product

Annex 11 adulteration (FDASIA)

●2015 – MHRA guidance on data ●‘On the spot’ import alerts

integrity
●FDA can stop review of applications
●2015 – WHO guidance on good data (AIP)
and record management principles
(draft) FDA focus on Data
Integrity
●2016 – EMA work plan includes
GMP guidance for data integrity 22 Warning Letters
in 2014-2015
●2016 – FDA: Data Integrity and (doubled compared to
2012-2013)
Compliance With CGMP – Guidance
for Industry (draft)

Data Integrity Webcast - April 20th 8

Data integrity is not only about FRAUD!

IGNORANCE SLOPPINESS FRAUD

Organizational & Zero tolerance

Awareness
technical message from
& training
controls the top!

Data Integrity Webcast - April 20th 9

Sanofi commitment to data integrity
● Data Integrity identified as a key 2016 priority for Global Quality
● Today you will hear about:
● Sanofi action plan to increase awareness and operational support
● Strong link between data integrity and business integrity
● Testimonies from our manufacturing sites on their inspection experiences
● Examples of best practice approaches from R&D

Data Integrity Webcast - April 20th 10

Toronto site testimony

Ron Hudcosky,
Site Quality Head, Toronto
The Sanofi action plan

Nader Shafiei,
Global Quality Strategy & Systems
RECAP - what is data integrity?

Degree to which
● Preclinical
we can rely on our ● Clinical
● Manufacturing
GxP DATA ● Quality control
● Distribution
to DEFEND ● Pharmacovigilance

Quality of our products Safety of our patients

Data Integrity Webcast - April 20th 13

What makes GxP data reliable?

Data Integrity Webcast - April 20th 14

Key attributes of reliable GxP data

Accuracy Completeness

Consistency Contemporaneity

Inconsistency
= Confusion

Data Integrity Webcast - April 20th 15

Key attributes of reliable GxP data

Legibility Originality
tamper proof

initial & date

changes
independent review
(when required)

Traceability Trustworthiness

Data Integrity Webcast - April 20th 16

How to safeguard integrity of GxP data?

Organizational Controls Technical Controls

Operational Controls

Data Integrity Webcast - April 20th 17

More on organizational & technical controls

Organizational Controls Technical Controls

Global Quality Documents Facility and System Design

Training and Education Computerized Systems

Compliance

Inspection Readiness Tools Electronic Data Handling

Creation
Authentication
Human Factors
ethical conduct Protection
Retention

Data Integrity Webcast - April 20th 18

Action Plan – what are we doing?

Global Operational
Quality Units

• Global Quality standard established

• Data Integrity Ensure
• Good Documentation Practices in-place
in-use
• Local implementation in progress

• e-Learning deployed Train

• Translations in multiple languages Industrial:
80% coverage in 2016
• Train the trainer program defined
Other Units:
• Worldwide Webcast under definition

• Inspection readiness tools deployed

• Transferring knowledge and expertise to Leverage
Tools and expertise in
operational units
support for GxP
• Deploying validated Global ITS tools inspections
(e.g. Laboratory Information Mgmt. System)

Data Integrity Webcast - April 20th 19

Action Plan – what are other relevant initiatives?

• Global Quality training

• Computerized Systems Compliance
• Knowledge transfer on controls safeguarding integrity of
electronic data

• Global Quality training

• Human error prevention
• Help with prevention/reduction of data handling errors

• Global Ethics & Business Integrity awareness programs

• Will help with prevention of data fraud

Data Integrity Webcast - April 20th 20

What immediate actions can you take?

Data Integrity e-Learning Inspections Readiness tools

http://qdms-navigator-p.pharma.aventis.com/QDMS-
Navigator/index.html?bu=gq&locale=en#

https://apps.sanofi.com/gz/qualityacademy/Pages
/Data-Integrity-Awareness.aspx

Data Integrity Webcast - April 20th 21

How ITS addresses Data
Integrity challenges
Use case: Implementation of a Storage
Capability for Laboratory Data in R&D

Rose-Marie Cousin Miralles,

ITS Quality & Compliance
Hand Ramdani
ITS R&D / CMO – Hubs & Labs Domain
What does Data Integrity mean from ITS
perspective?

Educate ITS associates and Key external partners on the stakes of Data Integrity
•Leverage training materials developed by Global Quality

Deliver and Maintain Computerized Systems Compliant with applicable regulations

•Project Methodology – PUMA
•Design must include necessary provisions to safeguard integrity of GxP data
•Validation Process
•Change & Release Management Process
•…

Ensure that ITS Operation Activities & Services are executed in compliance with
applicable regulations and that appropriate controls are in place
•User Access Management
•Data Backup & Restore
•Incident & Problem Management
•…

Data Integrity Webcast - April 20th 23

Use case: Laboratory Data in R&D
Context & Background

Multiple & Diverse

Sources of Data Type of Files Storage locations
Lab Instruments, Applications, Raw Data, Processed Data, Images, Local drive, File Share, eRoom,
Reports… Video, Spreadsheets, PDF… Sharepoint, EDMS…

Leading to High risk on Data Integrity

Difficult to ensure Lack of clear
Data owner not easy to
appropriate User access identification of GxP
identify
management control data versus non GxP Data

Data Integrity Webcast - April 20th 24

Electronic Research Data Store (eRDS*)
To address Business Needs and contribute to Data Integrity

Centralized Lab Data Secured Service

Repository Repository on Request

Storage of all lab data in User access management Self-service portal for user
one platform access management
Periodic access review for
Data categorization, GxP Data
naming convention…
Data Backup & Recovery

*: Capability available to-day in the R&D sites of Vitry, Chilly-Mazarin and Strasbourg

Data Integrity Webcast - April 20th 25

… To be successful, the Technical Solution must be
sustained by a robust Data Governance process

Business Representative for determining,

describing and enforcing the business
rules and definitions for the data

Subject Matter Expert knowledgeable of

Data Sources and Data Flow

Liaison between Business and ITS

Data Integrity Webcast - April 20th 26

What are the Benefits of eRDS from Data
Integrity perspective?

Clear identification of GxP versus non GxP data

⇒ Storage of GxP Data in a dedicated space

Clear Data Ownership

Access management controls

⇒ Specific Access Rights, modification and/or deletion of data is not allowed,
Periodic Review of Accesses

Highly secured data storage

⇒ Data duplication, Backup & Recovery procedures in place and tested

Data Integrity Webcast - April 20th 27

Jurong site testimony

Matthieu Caillod,
Jurong Site Head
Data Integrity is part of
business integrity

Laurent Maunier,
Chief Anti Fraud Officer / Ethics & Business Integrity
Chief Anti-Fraud Officer’s mission

● Design and implement a comprehensive Fraud Risk

Management Program based on four anti-fraud pillars:
● Prevention
• Foster Fraud definitions, enhance awareness & trainings / Implement a
pragmatic Fraud Risk Assessment
● Detection
• Coordinate all detections initiatives supporting the anti-fraud program
● Investigation
• Supervise and coordinate all fraud investigations across the Group
● Analysis & Reporting
• Global reporting to the ECC and Audit committee

Data Integrity Webcast - April 20th 30

What is Fraud?

● In many countries, the concept of fraud derives from a

legal definition often from both civil and/or criminal
laws.

● International Standards Accounting 240 - "An

intentional act by one or more individuals among
management, employees, or third parties, involving the
use of deception to obtain or maintain an unjust or
illegal advantage“

● Error: unintentional misstatement

Data Integrity Webcast - April 20th 31
What are the various types of Fraud?
Covers cash & non cash Covers financial & Covers private &
items non financial items public bribes and
includes also COI

Fraudulent
Assets misappropriation

disbursements

Fraudulent reporting

Corruption
Cash Financial Bribery

Non financial (R&D

Inventory Conflicts of interest
and Production)

Intangible assets
misappropriation

GxP Data
Integrity

Data Integrity Webcast - April 20th 32

Impact of fraud...collateral damages
Decrease of market capitalization

Raising costs of capital

Financial
Exclusion from tender business

Fine

Investigation costs

Damages

Reputation damage

Loss of trust from patients and civil society…

Non financial Time exposure : press, public, competitors

Absorption of management’s attention

Frustration and job change

Uncertainty for other employees

Data Integrity Webcast - April 20th 33

Data Integrity - fraudulent examples
● 2013 – A former Aptuit employee sentence by 3 months
imprisonment after been found guilty of altering pre-
clinical trial data.
● 2014 – 14 employees from NECC charged for criminal
charges following FDA investigation discovering
numerous cased of falsification of cleaning logs
● Ranbaxy pleaded guilty to felony charges in 2013 after
FDA accused it of falsifying data used to obtain approval
for some of its generic drug products. A $500 million
fine against the company now stands as the largest in
US history against a pharmaceutical manufacturer for
fraud.
Data Integrity Webcast - April 20th 34
The fraud triangle

The opportunity to commit

Fraud (poor control, lack of
governance, complex
transactions…)

Opportunity
The motivation to commit
fraud (greed, ego, fear…) The justification to
commit fraud (“I’ll
never be caught”,
“everyone else does
it”, “I am not paid
enough”, “that has
Rationalization
Pressure no impact”…)

Donald R. Cressey, Other People's Money (Montclair: Patterson Smith, 1973) p. 30.

Data Integrity Webcast - April 20th 35

Compliance Helpline
http://mysanofi.sanofi.com/sites/Global-Compliance/Pages/ExvTUHd8/Compliance%20Helpline_EN.aspx

Data Integrity Webcast - April 20th 36

Global Disciplinary Policy

● Corrective and / or disciplinary actions

co-signed by Roberto Pucci and Dante
Beccaria – doc ID GDPOL-013848

FRAUD

Zero tolerance
message from
the top!

Data Integrity Webcast - April 20th 37

Data integrity challenges in
clinical trials

Jean-Christophe Cabrillac,
R&D Quality
Clinical Trials: current environment
Study Protocol

Central lab Treatment Investigator

allocation
Service Management
Patient
providers
System
medical file

Patient data

Clinical Study
Safety
Database Report
Database

Data Integrity Webcast - April 20th

From protocol design to patient treatment
allocation: end to end data integrity

Randomization
Technical
specifications Treatment allocation Protocol
management system design

Packaging
Packaging & labeling
specifications

Interactive response
technology
(IRT) Investigator
Treatment dispensed
Emergency code
breaking

Data Integrity Webcast - April 20th

Process analysis & action plan

Study Risk
Analysis

IRT Peer
Team
Computerized
Specifications & Systems
data consistency:
Quality Controls
& Quality Release

IRT Service
Provider Training
Governance

Data Integrity Webcast - April 20th

IRT peer team: who they are?

Subject Matter Experts

c
Procurement
c
Ensure Data Integrity along the
Packaging process from study design to
patient allocation

c
Biostatistics Governance with
c IRT providers
Study
Management
c
Guidance &
IS Solutions
Support to the
study team

Data Integrity Webcast - April 20th

Key success factors

Subject matter Computerized system

experts validation

Data Integrity

Transversal
collaboration New process and
governance model
Provider involvement

Data Integrity Webcast - April 20th

Conclusion

Thierry Bourquin,
Group Chief Quality Officer
Fundamental aspects of data integrity

• A world wide issue

• Not just limited to fraud!

• Hot topic for regulatory authorities globally

• Concerns everyone in Sanofi

• Basis of sustainable trust with our regulators & patients

Data Integrity Webcast - April 20th 45

What do we expect from you?
● Use Communication materials to raise awareness of your
teams (Webcast videos, posters, etc.)
● Deploy E-learning in your respective organisations
● Apply Inspection readiness tool
● Assess Vulnerabilities in your key processes
● Review Compliance status of your critical computerised
systems
● Support Implementation of validated global information
systems
● Escalate Any data integrity breaches using the applicable
process (quality or compliance in case of fraud)
Data Integrity Webcast - April 20th 46
THANK YOU ALL FOR ATTENDING THIS WEBCAST
***
This webcast will be published in the coming weeks
on our Global Quality website

Data Integrity Webcast - April 20th