WORKING TOGETHER

Data Integrity in Pharmaceutical Quality Systems

A Presentation by :Brian Sheerin, Hina Amjad and Adam Armiger

Integrity

Trust

Data

• MHRA Definition: Information derived or obtained from raw data

• Decision making on Quality

• Continual Improvement

Importance

FDA Warning Letters (2015)

(Figures from Ungerconsulting.com)

n=19

FDA Warning Letters

(Figures from Ungerconsulting.com)

Total of 15 Warning Letters Concerning Data Integrity Issues (Outside U.S.)

n=15

EMA Non-Compliance Reports 2016

13 Published Reports so far in 2016

5

2

1

3

1

1

n=13

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)

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

Data Life Cycle

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

Recent Violations

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

Example Two - Yunnan Hande Bio-Tech. Co. Ltd.

(China) Warning Letter Date: 6th April 20151.‘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.’

Yunnan Hande Bio-Tech. Co. Ltd

• Unauthorized manipulation of raw data (IR)

• Lack of active audit trail functions

• Insufficient response (CAPA Plan)

• Insufficient investigation

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

What Needs to be Done

1. Actively promote a culture of integrity

2. Establish security protocols

3. Comply with cGMP guidelines

Culture

Data Security

•Who has access?

•Where is the Data Stored?

•Is there a Back-Up?

System Access

• Based on job title

• Unique user ID’s

• Time stamped

• Fully traceable

Data Storage and Back-Up

•Electronic, paper and hybrid systems

•System hard drive

•Server storage

How to record Data (ALCOA)All data should be…

1.Attributable – actions/changes attributable to a particular person2.Legible – data recorded permanently in a durable medium3.Contemporaneous – record of work with date/time stamps which should follow in a logical order4.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.

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™

Audit Trail Deficiencies

Cited in many FDA Warning Letters

1.Inadequate2.Misconfigured3.Not Enabled 4.Unutilized in Data Review

• So to Recap

• 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

Thank You for Listening.

Any Questions?