This document provides an agenda for a conference on ensuring product quality and patient safety. The agenda includes sessions on data integrity risk management, data integrity in clinical research, data quality management in clinical research, regulations impacting data integrity, creating a culture of quality for data integrity, data management perspectives and challenges for the pharmaceutical MSME sector in India, data integrity from an analytical laboratory perspective, an overview of data integrity non-conformances from regulators, data integrity as an essential part of quality, the regulatory perspective on data integrity and challenges, MHRA and US FDA requirements for data integrity in clinical studies, data integrity on the manufacturing floor, and other topics. Various experts from the pharmaceutical industry will speak in the different sessions.

1. Dr. Santosh Kumar Narla,
Senior Manager,
Formulation Regulatory Affairs,
Laurus Labs Limited, Hyderabad.
 santoshmph@yahoo.com
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2. Key points of discussion:
 Data Integrity: Beware or Be aware?,
 Decades of regulatory history,
 International regulatory perspective and collaboration,
 Common misconceptions,
 Enforcement actions,
 Inspections and ANDA approvals,
 Risk reducing strategies,
 Regulatory challenges.
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3. Data Integrity: Beware or Be aware
 It is not new … don’t be panic ….. BUT .. be aware of the requirements…
 Treat EVERYDAY as a AUDITABLE DAY…
 Know the BASIC regulatory requirements…
 Refresh your company policies / systems (SOPs/handling procedures)..
 Always consult your superiors / guide your sub-ordinates…
 Learn from the Audit findings…
 Stay on regulatory updates and warning letters…
 Watch with your EARS too ….
 ALWAYS follow your company policies……
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4. Decades of Regulatory History………
It is not a new requirement… and not only related to some regulated countries…
Above 60% of Warning Letters in 2015 and 2016 involved data integrity lapses
Problem is continuing to till date………….
USFDA:
 21 CFR Parts 11, 211, 803: Electronic Records, Signatures - 1997, 2003.
 Data integrity key concepts are inherited from 21 CFR 11, 210, 211 and 212.
 “Data Integrity and Compliance with cGMP”, draft guidance for industry (April 2016).
EMA: EudraLex Vol 4 Chapter 4 Documetation & Annex 11: Computerized systems: 2011.
GMP guidance (Q&A) to ensure the integrity of data: Aug 2016.
MHRA: MHRA GxP Data Integrity Definitions and Guidance for Industry 2015/2016.
WHO: WHO Technical Report Series 996 Annex 5, Guidance on good data and record
management practices: May 2016.
Health Canada: Letter to Stakeholders -Responsibilities and Obligations with Respect to the
cGMP – Feb 2015.
ICH: Q7: Computerized Systems (5.4) & Q9: Quality Risk Management: 2005.
PIC/S: Good Practices for Data Management and Integrity In Regulated GMP/GDP Environments,
Aug 2016.
India: CDSCO Offers Risk-Based Checklist for Indian Pharma Manufacturing Inspections
The above list is not limited ……….. There are MORE country requirements and guidelines.
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5. 5

6. In 2015: “a new look at an old topic”
In 2003, TGA suspended 219 products of Pan Pharma, Australia and instructed to recall immediately…..due to DI
WORLD BIGGEST PRODUCT RECALL – 219 products recalled, 1650 export products cancelled……
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Data integrity issues and importance is increasing….

7. Warning Letters Citing Data Integrity Deficiencies
FY2013 FY2014 FY2015 FY2016
Total warning letters 38 22 19 46
US sites with DI
deficiencies
0% 0% 33% 73%
(0 of 13) (0 of 4) (1 of 3) (8 of 11)
Outside US sites with DI
deficiencies
40% 67% 81% 81%
(10 of 25) (12 of 18) (13 of 16) (29 of 35)
Total number of warning
letters citing DI
deficiencies
26% 55% 74% 79%
(10 of 48) (12 of 22) (14 of 19) (37 of 46)
Note: Compounding
warning letters excluded.
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8. 2016 — A year of data integrity issues and pharma non-compliances
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9. 9

10. International Regulatory Perspective and Collaboration
 International convergence in data integrity guidance
 Cooperation between regulators
 Exchange of information
 Joint inspections
 Coordinated market actions
 Inspectorates better equipped to
 Identify data integrity failures
 Manage post-inspection actions and remediation plans
 Widespread inspectorate training in DI principles and techniques
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11. Common Misconceptions
Why we need to worry?
It is important ONLY in Pharma? 2015: Volkswagen Emission scandal for diesel cars in US
The result: VW’s CEO lost his job; billions were wiped from the company’s shares; and the German economy
faced a bigger threat than the Greek crisis.
My department is perfect… 1000 drugs reviewed/ 700 rejected: May 2014.
Over 700 medicines were recommended for suspension by
the EMA based on DI concerns, over clinical studies
conducted at GVK Biosciences.
Volkswagen GVK Biosciences
Timeline September 18, 2015 May 19, 2014
The issue Installation of a ‘defeat device’ software on cars
to fool emission tests
Falsification of electrocardiograms detected in
each and every one of the 9 trials inspected
The regulator US Environmental Protection Agency (EPA) French agency on medicinal products (ANSM)
The impact About 11 million cars About 700 different medicines suspended
The financial
impact
EPA penalties could reach US $ 18 billion India’s export loss estimated US $ 1.2 billion
Severity of
problem
Car engines emitted nitrogen oxide pollutants
up to 40 times above what is allowed in the US
Falsification of ECGs was performed by at least 10
individuals and took place between 2008 and 2013
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12. Enforcement actions
Enforcement
tool
Action
2016
statistics
Regulatory
Meetings
FDA may use the regulatory meeting after a follow-up re-inspection 27
Injunctions FDA may seek injunctions against individuals / corporations to
prevent them from violating the Act
Consent
Decrees
Agreement between FDA and drug maker, proving via third party. 27
Import Alerts Prevent violated products from being distributed in the US. 47
Seizures Removal of specific violated goods from commerce.
Warning
Letters
Noted violations, requesting a written response. 54
Untitled
Letters
Noted violations (not in the threshold of warning letter), requesting a
written response.
4
FDA Form 483
Official Action Indicated (OAI)
Voluntary Action Indicated (VAI)
No Action Indicated (NAI)
Office of Compliance Office of Manufacturing Quality (OMQ)
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13. 13

14. Inspections and ANDA Approvals
14

15. 15
Where and When, Data Integrity is applicable…….
Applies to Entire Product Lifecycle

16. Risk Reducing Strategies
 Internally identified DI issue:
 Disclose to regulators, documented evidence of remediation or commit to voluntary
remediation.
 Discrepancy found in the batch record / QC document:
 Report it with a valid risk assessment and detailed justification – Follow SOPs.
 Identify the resources where risk is HIGH :
 Risk based approaches /Internal audits /double review need to be utilized.
 Follow ALCOA+ (Used by FDA, MHRA and WHO):
 A – Attributable: Records and data linked to the individual or system performing the action
 L – Legible: Records and data, readable and traceable across the lifecycle
 C – Contemporaneous: Records and data reported at the time it has occurred
 O– Original: Records and data are the primary source (or true copy)
 A – Accurate: Records and data are correct and free from errors/manipulations
 + - WHO added: complete, consistent, enduring and available .
 Stay UPDATED:
 Always stay updated with recent audit news, warning letters …..
 Stay tuned for guidelines and regulation updates …..
 Fine tune your SOPs / policies based on your Internal Audit Findings….
 Plan Data Integrity Specific Internal Audits…
 Beware / Be Ready for Whistle-Blowers ……….
Whistle Blowers:
2016: Ranbaxy: Dinesh Thakur
2014: GVK: Narayan Konduru Reddy
2010: GSK: Cheryl Eckard
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17. Data Integrity
R&DQA
Soft wares, Systems and Audits
Quality culture and Training
Policies and User controls
Management and department leads
Individuals
OperationsQC RA
Pillars of Data Integrity
All other parties linked with development, manufacturing, distribution and selling are also responsible.
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18. Regulatory Challenges
 In 2016, 40% ANDAs approval is delayed due to manufacturing issues (received CRL).
 2016: Semler’s data integrity concerns made regulators question the equivalency of over 110 generic
drug applications. Concerns were raised by the US FDA, EMA and the WHO.
 In 2015, USFDA issued a warning letter to Sipra Labs, a testing laboratory. There are also
instances of lapses on data integrity.
Regulatory department will also play an important role:
 Data integrity checks before dossier submission.
 Internally identified data integrity issues:
 Understand the out come and analyze the impact on dossiers/Product
 Propose required regulatory action (product recall? / Notification to agencies?)
 Review of Deviations, OOS and validation summaries..
 Supporting during regulatory audits with submitted information…..
FDA's Pre Approval Inspection Program 7346.832:
18
Incorrect Handling of OOS Results found in 10 FDA Warning Letters in 2011

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20. 20
Cost of Data Integrity Lapses………
FDA-483 Observations
Warning letters
Import alerts
Withheld product approvals
Cancellation of government contracts
Product recalls
Seizure
Consent decree of permanent
injunction
Civil money penalties
Suspension or revocation of licenses
Prosecution (temporary or permanent
debarment, if found guilty)
Damage to company’s reputation
Loss of sales
Loss of jobs
Loss of Share Value
Closing or take-over company

21. Data integrity is about more than compliance with regulations; it’s about
protecting life-saving research and products for human use.
Cost of compliance is cheaper than facing non-compliance issues…
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22. - November - Hyderabad
Conference Workshop
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Ensuring Product Quality And Patient Safety
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23. Ensuring Product Quality And Patient Safety
EXPERT SPEAKERS
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Dr.Ambrish Srivastava
VP Medical Affairs,Clinical
Research and Regulatory
Alkem Labs Ltd
Suveer Shrivastava
Vice president-Quality
Mylan Laboratories
Yogesh Joshi
Associate VP-QC
Ajanta Pharma
Sophia Lily
Head Quality,
API and Nutrition
Piramal Enterprises Limited
Chandra Sekhar
VP Quality
Reliance life sciences Pvt.Ltd.
Dr. Upendra k Jani
VP- Quality Assurance
Hester Biosciences
Dr Nimita Limaye
CEO
Nymro Clinical
Consulting Services
Dr Ravisekhar Kasibhatta
Sr.VP -Clinical Research
Lupin Limited
Arun Mendiratta
Associate VP-QC
Aurobindo pharma
Dr.Prashant Pandya
GM-Program Management
Reliance Lifesciences Pvt.Ltd.
Kiran Kumar Merusomayajula
Senior Manager, CQA
Aurobindo Pharma
Dr.Mahesh Bhalgat
Executive Director COO
Sanofi
Dr. Santosh Kumar Narla
Group Head- Europe
Laurus Labs
Dr. Jayam Ravi
Global Compliance Head
Clinical Pharmacovigilance
Dr. Reddy s Laboratories
Sanjit Ghosh
Works Manager
Shine Pharmaceuticals
Raghuvirsinh Parmar
Sr Executive, Analytical Quality
Sunpharma
Tapas Joshi
Executive Mirobiology
Lupin
Arani Chatterjee
Senior Vice President,
Clinical Research
Aurobindo Pharma
Dr.Sambi Reddy Kurre
Associate Vice President
Aurobindo Pharma
For Speakers Contact
RACHNA TIWARI
Conference Manager
rachna.tiwari biotrains.com
+

24. Ensuring Product Quality And Patient Safety
AGENDA
www.thedataintegrity.com info biotrains.com + -
SESSION
SESSION SESSION
SESSION
SESSION
SESSION
SESSION
SESSION
Data Integrity risk management Data Integrity in Clinical Research
Why Data integrity issues happen
Data integrity risk factors
Consequences of non-compliance
Approach to Data Integrity compliance
Risk Management strategies
Dr.Prashant Pandya
GM-Program Management
Reliance Lifesciences Pvt.Ltd.
CRO Sponsor Relationship
Protocol EC Local FDA Investigator management
Subjects Volunteers ICF Process
GxP Implementation
Regulatory Inspection readiness
Dr Ravisekhar Kasibhatta
Sr.VP -Clinical Research
Lupin Limited
Data Integrity and cGMP compliance for successful Inspections
DI audit trends through review of recently issued s
warning letters on Data Integrity
Case study: How to respond to s and Warning lettersSatya Chandra Sekhar
VP Quality
Reliance Lifesciences Pvt.Ltd.
Data Quality Management in Clinical Research
End to End Process for Managing Quality, Validity and Integrity of Data
Basis of GCP
Data Management Plan
Data Safety Monitoring in Clinical Trials
Role of QA QC
Bringing it All Together
Dr.Ambrish Srivastava
VP Medical Affairs,Clinical
Research and Regulatory
Alkem Labs Ltd
SESSION
SESSION
SESSION
SESSION
SESSION
SESSION
SESSION
SESSION
SESSION SESSION
Regulations Impacting Data Integrity:
The Cost of Poor Data Integrity
Dr Nimita Limaye
CEO
Nymro Clinical
Consulting Services
Industry reaction on DI
Beginning of DI issues..
Understanding DI…
Industry understanding s at the beginning
Preparing from Others Mistakes.
Types of reaction based on size
… Business volume
Entire industry got together to address DI
Today s Industry stand on DI
Formation of Remediation teams..
Mock audits and role of Management ,
Consultants as out come to address DI
Yogesh Joshi
Associate VP-QC
Ajanta Pharma
Creating A Culture of Quality For Data Integrity
Discussing GCP GMP GLP
leadership emphasis, message creditability,
peer involvement and employee ownership of quality issues.Dr. Upendra k Jani
VP- Quality Assurance
Hester Biosciences
Data management perspective & challenges for the
Pharmaceutical MSME Sector in India
Sanjit Ghosh
Works Manager
Shine Pharmaceuticals
Data integrity - Analytical Laboratory perspective
The increasing focus of FDA on Data integrity.
Data integrity and Human factor.
Case study and Examples of recent Data integrity highlights.Raghuvirsinh Parmar
Sr Executive, Analytical Quality
Sunpharma
Overview of DI non conformance from regulators,
impact and remediation perspective or
Cultivating the culture to avoid DI shortfalls
Sophia Lily
Head Quality,
API and Nutrition
Piramal Enterprises Limited
Data integrity-Essential Part of Quality:
Reduce manual entries possibilities
Continual state of validation
Security of electronic data
Adherence of SOP to guidelines regulations
Adherence of practices to SOPs
Arun Mendiratta
Associate VP-QC
Aurobindo Labs
Data Integrity: Regulatory Perspective and Challenges
Data Integrity: Beware or Be aware ,
Decades of regulatory history,
International regulatory perspective
and collaboration,
Common misconceptions,
Enforcement actions,
Inspections and ANDA approvals,
Risk reducing strategies,
Regulatory challenges.Dr. Santosh Kumar Narla
Group Head- Europe
Laurus Labs
MHRA , US FDA requirements for data integrity
in clinical studiesArani Chatterjee
Senior Vice President,
Clinical Research
Aurobindo Pharma
Data Integrity on the Manufacturing floor:
SAP, MES, DCS, PLC
Dr.Sambi Reddy Kurre
Associate Vice President
Aurobindo Pharma
Mahesh Bhalgat
Executive Director and Chief Operating Officer
Shantha Bioethics
Tapas Joshi
Executive Mirobiology
Lupin
Dr. Jayam Ravi
Global Compliance Head Clinical Pharmacovigilance
Dr. Reddy s Laboratories
Kiran Kumar Merusomayajula
Senior Manager, CQA
Aurobindo Pharma
SESSION
Suveer Shrivastava
Vice president-Quality
Mylan Laboratories