Zydus Lifesciences Limited

BASICS OF
DATA INTEGRITY
Document No: AT/GMP/02 Version no. 2.0

Prepared By : Reviewed By: Approved By:

Sign / Date: Sign / Date: Sign / Date:

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What is Data Integrity?

• It is the degree to which data (paper records and electronic data) are complete,
consistent, accurate, trustworthy and reliable

……..Shall be maintained throughout the Data life cycle.

Data Life Cycle:

Collection/Creation/Generation Processing(analysis, transformation, migration)

Retrieved Stored/archived Transfer Review/Approval Reporting

continuously monitored until retired/destructed

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Why Data Integrity?

Importance of Data Integrity in Pharmaceuticals

 Data has always been important in pharmaceutical manufacturing and research.

Prime Requirement
Accurate and Reliable Data Ensure safety, Efficacy and Quality of Product
by P’ceutical Industry
& Regulators

Crucial to guarantee ‘Trust’

Customers Industry Regulatory Agencies

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Data Integrity – Key Terminologies

Original records, retained in the format in

• Manual entry on paper
RAW DATA which they were originally generated (i.e.
• Electronic data files
paper or electronic), or as a ‘true copy’.

Describes attributes of other data and

provide the contextual information required 30 mg, Audit trails,
META DATA to understand structure, elements, System generated
interrelationships and other characteristics of messages, Alarms
data.

Complete data set –

All records,
Includes electronic data,
DATA including raw data and metadata and all
audit trails, paper
subsequent transformations and reports.
reports of data etc.

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Data Integrity – Key Terminologies

Static data: Dynamic data:

• Fixed-data document • Allows for an interactive relationship between the user and
• Allows no or very limited interaction between user & record the record content.
content. For e.g. : Chromatographic electronic record for integration,
For e.g. : Paper record, PDF documents, Electronic image zooming

Primary Record/ Raw Data: Secondary Record/Raw Data :

• First time directly generated and not derived from other data
• Data derived from primary data
• Regeneration not possible without repeating the activity
• Can be regenerated multiple times from primary data
For e.g. : Paper record, pH meter print, Electronic data in
For e.g. : Printout from electronic data of software/PLC/SCADA
software

Critical Data: Non Critical Data :

• Does not influence quality & safety of the products
• Directly influences quality & safety of the products
• Does not Influence decisions related to product & unit
• Influences decisions related to product & unit operation
operation
For e.g. : Assay & Dissolution data of tablet
For e.g. : Cleaning record of QC laboratory corridor
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Data Integrity – Key Concepts

Paper Records: PEOPLE

• Batch Records
• Formats
• Logbooks PROCEDURES
i e d to • Labels
l
l ly App
Equa • Protocol/Reports

DATA PRACTICES
GOVERNED AND ACHIEVED THROUGH
INTEGRITY
Equa Electronic Records:
lly A pplie
d to • Electronic data
• Audit trails SYSTEMS
• Alarms
• PLC/SCADA/HMI
• Softwares
FACILITIES

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Data Integrity – ALCOA+

A Attributable
C Complete

L Legible
C Consistent
DATA
INTEGRITY C Contemporaneous
E Enduring
O Original

A Accurate A Available

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Data Integrity – A : ATTRIBUTABLE

 Sign/Date required for each recording.

 Traceable to the person /system generating and modifying the data.
 Indicates who recorded/generated data, who wrote it?
 Linked to source of the data.

Do’s Don’ts
 Put sign/date for each data × Do not sign on behalf of other person.
recorded/reviewed/approved on document.
× Do not record data on behalf of other person.
 Use own login Id password.
× Do not share your login/ID password.
 Keep password complex (not very simple) and
memorize it. × Do not use generic/Common user ID/password.

 Put sign/Date of all doers involved in activity × Do not miss to put sign/date on document.
× Do not write password anywhere.

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Data Integrity – A : ATTRIBUTABLE

Tell me your
Checked password
by sign
done
before
Done by

Sorry, I cannot share it

Missing signature (Not attributable) with anybody

Time My password
Date Time Temp0C Remarks Checked by
Interval is…….

12/10/2017 60 min 18:05 108.4 NA APK

12/10/2017 300 min 22:00 106.4 NA APK
13/10/2017 420 min 00:02 109.6 NA DEV

‘DEV’ recorded entry & Sign/ Date on behalf of ‘APK’.

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Data Integrity – L : LEGIBLE

 Clear, permanent and readable data.

 Shall be accessible throughout data lifecycle.
 Reflects that original records are not obscured

Do’s Don’ts
 Record data which is readable and clear. × Do not overwrite data.
 While correction, original recorded data shall
be readable.
× Do not write in handwriting which is confusing and
not readable.
× Do not use gel/ink pen.

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Data Integrity – L : LEGIBLE

Data recorded is not legible

How you predict for this numeric?

1. 27
2. 24
3. 29

Overwriting

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Data Integrity – C : CONTEMPORANEOUS

 Online entry, Data recorded at the time activity is performed.

 Observed, recorded, documented at the time activity performed.
 Clearly reflect what was done or what was decided and why i.e. what influenced the decision at that time.

Do’s Don’ts
 Record online entries for activity performed. × Do not record data in back date/back time.
 Date and time of the activity shall be recorded × Do not record data in advance (Pre filling).
online while performing activity.
× Do not record data in a manner that time overlay
 Record start time at start of activity and end occurred between two activities by same doer.
time at completion of activity
× Do not record start time and end time together at
the end of actviity.

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Data Integrity – C : CONTEMPORANEOUS

Data recorded in back time.

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Data Integrity – C : CONTEMPORANEOUS

Same person
involved in
two different
activities at
the same
time/date.

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Data Integrity – C : CONTEMPORANEOUS

Sign done in back date,

Doer was absent (On sick leave) on the

said day.

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Data Integrity – O : ORIGINAL

 First recording (source captured) of data or ‘true copy’.

 This preserves content and meaning in unaltered state.
 Data which is directly recorded/generated when GMP activity performed.

Do’s Don’ts
 Record raw data and meta data directly on
authorized approved format only.
× Do not record data on unauthorized unapproved
format,
 Make true copy of original data if it does not
remain unaltered.
× Do not make duplicate documents of same purpose
in unauthorized manner.
× Do not destroy/delete data.
× Do not modify/alter data in unauthorized manner.

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Data Integrity – O : ORIGINAL

Transcription from unauthorized formats to GMP

documents is not right practice

utho rized,
ectly on a
e di r
co rd first tim d format
Re d, issue
ro ve
app

Recording raw data on Unauthorized paper, Blank pages, back of labels,

personal diaries , Excel / Word file in computer is not acceptable
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Data Integrity – O : ORIGINAL

Don’t tear/destroy
GMP documents
which are within
retention period

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Data Integrity – A : Accurate

 Record as observed. “What seen, is recorded”.

 Actual data which is correct, truthful , valid, reliable, honest and free from errors.
 Confirms truth and standard of data.

Do’s Don’ts
 Record as observed. × Do not change data while recording
 Record date, time, values and other items as it × Do not record data other than what observed.
is as observed.
× Do not falsify data.
 If changed, do it with proper supportive
evidence. × Do not manipulate data.

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Data Integrity – A : Accurate

Recording exactly at half an hour, which is not

practical.

Recorded Data is not accurate

Time of recording should be actual, as per defined

frequency and accurate.

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Data Integrity – A : Accurate

Display Record the correct readings as observed.

Shows 6.4 Don’t manipulate the reading to make it
compliant within acceptance criteria

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Data Integrity – A : Accurate

BMS system
Temperature
Date Time (0C) %RH
Recorded Data doesn’t match with electronic data.
04-03-21 07:40 30.1 50
Recording done without performing the activity or what 04-03-21 07:42 29.4 49
observed is not recorded 04-03-21 07:44 28.7 51
04-03-21 07:46 30.2 53

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Data Integrity – C : Complete

 Everything is reported and nothing is omitted for reporting and batch decision
 Dataset having all data and relevant metadata.
 Entire data set with repeated part, re-analysis and each attempt of activity.
 There is No ‘Orphan Data’.

Do’s Don’ts
 Record data for all attempt of activity × Do not omit anything while reporting.
performed.
× Do not report data on selective manner.
 All electronic files generated during activity
shall be reported in paper data.
 Data set include all data and meta data
(original and repeat if any).

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Data Integrity – C : Complete

Report all the electronic files

generated.

For e.g. Here, there are two data

files for same sample:

1.ABVBGH12_11/03/2021.dat
2.ABVBGH12_12/03/2021.dat

Second analysis is not reported in

document and not considered for
batch release

ORPHAN DATA

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Data Integrity – C : Consistent

 Data consistently recorded with date and time stamp in sequential manner.
 Application of ‘GDP’ throughout the process.
 Includes data files, sequence of events and follow on events in sequential manner.

Do’s Don’ts
 Record data in sequential manner of date and
time as well as process steps.
× Do not record data on two different format for same
purpose.
 Record data in same manner on same × Do not record data in manner that is not consistent.
authorized format.
× Do not record data without date and time stamp.
 Follow same pattern of date and time
recording.

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Data Integrity – C : Consistent

14-April-18 at
14/04/18 01:00 pm
at 13:00

Not consistent practice

Data not in sequential date and time manner

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Data Integrity – E : Enduring

 Data recorded on authorized media, maintainable for retention period.

 Permanent and in maintainable form.

Do’s Don’ts
 Record data on authorized approved format
only.
× Do not record data on personal diaries, chit of paper,
sticky notes, unauthorized paper.
 Maintain data up to defined retention period. × Do not store data in an environment which is not
maintainable up to retention period.

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Data Integrity – E : Enduring

Calibration Record
Reading Qty.
S. No. Sign
(In CM) (in L)
1 24.5 116 Ramu
2 25.0 121 Ramu
3 25.5 125 Ramu
4 26.0 135 Ramu
5 26.5 140 Ramu

Unauthorized Format Difference in both data

Data not maintainable – Faded /spoiled

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Data Integrity – A : AVAILABLE

 Data available for review and inspection throughout retention period.

 All data is accessible.

Do’s Don’ts
 Keep all paper raw data and electronic raw × Do not take raw data out of the site.
data at site.
× Do not store raw data in unappropriated manner in
 Manage data in proper manner which is easily
traceable.
which it is difficult to trace and identify the location.

 If it is required to take electronic data outside,

give a copy to site.

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Data Integrity – A : AVAILABLE

Proper paper data management Electronic data at secured location

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Data Integrity – Orphan Data

 Orphan data is the data, which is generated but neither invalidated through applicable
procedures nor included for batch release decision,
­ Or a data generated without any justified purpose.
­ Therefore, data considered for batch release is not complete.

» Orphan data also termed as:

……..Omitted data
……..Data without traceability and documented justification that why it is generated.
………It is like “what generated is not reported”.
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What is Orphan Activity?

 Orphan activity is the activity performed by the doer/data generator but same is not
documented/reported and justified in respective records.

» In other meaning:
……It is like activity is performed but not recorded
……..For e.g. Calibration of platform balance done two times but only reported the
final attempt. (As no printout/electronic data available).

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Orphan Data in laboratory softwares

Other examples:
» Trial runs/Trial injections and single injections/single run
» Analysis repeated on another standalone instrument of same type
(as it has less chance to be caught in review)
» Results which are out of specification – Not reported.
» Data generated with prefix/suffix to the file name or using abnormal file names ( for e.g. using .,/_@\-
in the file name and repeat the analysis)
» Inappropriate processing and modification of electronic data to get desired results.
» Moving, migration or cut-paste of electronic data after generation so as to opt for not reporting.
» Data generated by service engineer which is not reported.
» Data generated by taking remote access of the software which is not reported.
» Data generated during qualification/validation of the computer system which is not reported.
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Orphan Data in PLC/SCADA/HMI Systems

Computer system as PLC/SCADA located at manufacturing, packaging,
engineering/utilities and warehouse departments :

» Trial batch runs in manufacturing and packaging machines.

» Batch processing performed on the machine, batch report available but not
reported.

» Batch processing done for longer duration than defined in the batch record but
same is not reported.

» Batch reprocessing done but not reported.

» Trial run on machine as part of preventive maintenance/breakdown

maintenance which is not reported.

» Failed data not reported in engineering instruments/machines.

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Orphan Data – Other Examples

Other examples of Orphan data across GMP processes:
» Paper printout generated from non-computerized standalone instruments
but not reported. (for e.g. balance, pH meter, autoclave, moisture analyzer).

» Activity performed and electronic data generated in limited memory of non-

computerized instruments but printout not taken and data not reported.

» Activity performed multiple times (more than one time) but only final
attempt reported with respective records.

» Recording on unauthorized media and then discarding the same.

» Replacement of authorized pages and rewriting.

» Duplicate (same set of) documents generated for same activity/same

batch/same purpose and discarding first copy.

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Why Orphan Data generated?

Unintentional Factors Intentional Factors
Lack of training and understanding of To pass failed batch
computer systems/softwares Avoid pain of investigation in
Do not know consequences of not OOS/deviation/laboratory incident
reporting all data Avoid delay in batch release
No guidance available at a time of problem To save time in repeat analysis
occurred. Supervisory pressure for wrongful acts
Doer doesn’t know whether data is generated Individual behaviour to appear good
or not (in case of interruption/error)
Do not want to take QMS and do not want
Lack of defined procedure leads to wrong to increase number of QMS that can impact
practice (for e.g. Trial batch report in department performance (KPIs)
manufacturing)
Lack of personal integrity

From DI and regulatory perspective – “Orphan is anyways an ‘Orphan’ and it is serious DI

breach” – irrespective of factors responsible behind it.....!!!!!!
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Data Integrity and Good Documentation Practices

Basic GDP practices aligning Data Integrity Requirements

Record GMP data by permanent blue ink only × Do not use Pencil/ Eraser/ Ink remover/
Whitener /Water soluble ink

Date Format Time Format

14/03/21 14/03/2021 14-Mar-21 14/3/21 13:00 01:00 am 01:00 pm

× Do not use piece of paper/ Personal diary/ × Do not overwrite to correct any error on a
document
Note book for recording of GMP data

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Data Integrity and Good Documentation Practices

Do’s Don’ts
 Record time in document from
synchronized and calibrated company × Do not record on ‘DRAFT’ document, photocopied or
clock/device provided in area. scanned document.
× Do not record time from personal watches.
 If online data recording is not possible
while performing activity, consult area
× Do not use ____”______ ditto marks for repetitive entries.
supervisor and ask for ‘Checked and × Do not use { } to sign multiple entries. Put signature on each
recorded by”. Ask to add it in data steps.
recording format if not available.
× Do not take print on ‘thermal papers’. If mandatory, make a
true copy as GDP procedure.
 If data required to transcribe, do it from
the parent original document and retain × Do not make photocopy of any document. If required,
both documents. consult area supervisor.

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Data Integrity and Good Documentation Practices

NA

Put Sign
and Date

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Data Integrity and Good Documentation Practices

Correction of error

 Original recorded value/detail shall be readable after correction.

 Make a single line through error. Put code based on type of error. Record correct entry near strike out entry.
Provide reason for correction. Put sign/date
× Never attempt to alter and overwrite original record/value first and then performing GDP corrections.

APREL APRIL
WE : Wrong entry done by mistake

XYZ
/21
14/03

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Data Integrity and Good Documentation Practices

Duplicity of any document is easily identifiable .

Don’t make duplicate documents in unauthorized way.

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Data Integrity Governance Structure

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Data Integrity Framework

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Data Integrity – Handling of failure

HIDING THE
FAILURE IS NOT
ACCEPTABLE

DO NOT HIDE ANY FAILURE/MISTAKE/ISSUE/CONCERN

IDENTIFY DISCUSS RESOLVE

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References
 GxP’ Data Integrity Guidance and Definitions, MHRA, March-2018
 Guideline on data integrity TRS 1033- Annex 4: WHO – 2021
 ‘Data integrity and compliance with Drug CGMP-Questions and answers-Guidance for industry’,
December 2018, US Department of Health and Human services-Food and Drug Administration
 PDA (Parenteral Drug Association - Elements of a code of conduct for data integrity in the
Pharmaceutical industry)
 ‘Data Reliability Guideline’, February-2017, IPA
 PIC/S (Good practices for data management and integrity in regulated GMP/GDP environments) –July,
2021
 ISPE – Records and Data Integrity Guide – 2017
 CQ Policy – “Data Reliability and Governance” – 0101-QP-CEQ-00037

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THANK YOU

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